Molnupiravir March 31, 2021 Opposition by Entrepreneurship Development Center

IN THE MATTER OF:
THE PATENTS ACT 1970,

THE PATENTS (Amendment) RULES 2016
IN THE MATTER of a Pre-grant Opposition

under Section 25(1)
IN THE MATTER OF:
IN201717025098 filed on 14/07/2017, by EMORY UNIVERSITY
In the matter of:
Entrepreneurship Development Center

…OPPONENT
VS.
EMORY UNIVERSITY,
…………. RESPONDENT/APPLICANT
STATEMENT OF CASE OF THE OPPONENT
1. The Opponent herein is on behalf of Entrepreneurship Development Center, a not for
profit registered company, having it’s Registered office at Pune, having place of business
at 100, NCL Innovation Park, Dr Homi Bhabha Rd, Pune, Maharashtra 411008.
Entrepreneurship Development Center (aka Venture Center) is a DSIR
approved Scientific and Industrial Research Organization that aims to nurture science
based innovation and entrepreneurship. It also hosts projects related to National Missions
including the National Biopharma mission.
2. Entrepreneurship Development Center serves as the Nerve Center supporting the
activities of the Task Force for Repurposing of Drugs for COVID19 created by the Office
1
of PSA, Govt of India under the aegis of the S&T Core Group on COVID19. Thus, the
Petitioner has real and substantial interest in the matter at hand.
3. The Petitioner has learnt that the Applicant has filed Indian Application No.
201717025098 on July 14, 2007 which is currently pending before the Patent Office.
The said application has been filed in respect of an invention for “N4
HYDROXYCYTIDINE AND DERIVATIVES AND ANTI VIRAL USES RELATED
THERETO” filed by Emory University (hereinafter referred to as “Applicant”).
4. The Petitioner has learnt, the application has been published on November 03, 2017 with
publication number 44/2017. First examination report has been issued on Dec 20, 2019
and replied on Sept 18, 2020. FER and reply to the FER attached as Annexure 1.
5. The claims on record as in response to FER filed on Sept 18, 2020 as per the IPO website
attached as Annexure 2.
For sake of convenience the claims on records which Opponent has contests are as following:
CLAIM 1: A pharmaceutical composition comprising a pharmaceutically acceptable excipient
and a compound having Formula I
Formula I, or salt thereof, wherein

Q is O, -O(C=O)-, -O(C=O)V-, or NR7;
V is O, NH, NR7, CH2, or CHR7;
W is O;
X is CH2,CHMe, CMe2, CHF, CF2, or CD2;
Y is CR”;
Z is CR”;
each R” is independently selected from is H, D, F, Cl, Br, I, CH3, CD3, CF3, C1-22alkyl, acyl,
C2- 22alkenyl, C2-22alkynyl, hydroxyl, formyl or SCH3;
R1 is
2
Monophosphate ester,
diphosphate ester
alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl,
carbanoyl, esteryl, alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-
C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-
C12)aryl, or heterocyclyl, or phosphoramidyl wherein R1 is optionally substituted with one
or more, the same or different, R20;
Y1 is O or S;
Y2 is OH, OR12, OAlkyl, or BH3 - M+; Y3 is OH or BH3 - M+;
R2 is hydrogen or hydroxy;
R3 is hydrogen, hydroxy, (C1-C22)alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto,
formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio, , (C1-C22)alkylamino, ((C1-
C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-
C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl;
R4 is hydrogen, hydroxy,(C1-C22)alkyl, fluoromethyl, difluoromethyl, trifluoromethyl,
hydroxymethyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy,
carbamoyl, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino, ((C1-
C22)alkyl)2amino,(C1-C22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-
R5 is hydrogen, hydroxy, or halogen;
R6 is hydrogen, hydroxy, (C1-C22)alkoxy, (C1-C22)alkyl, ethynyl, allenyl, halogen, nitro,
cyano, amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, (C1-C22)alkylamino,
((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-
C6)carbocyclyl, (C6- C12)aryl,orheterocyclyl;
each R7 is independently selected from absent, hydrogen, -(C=O)Oalkyl(C1-C22), -
(C=O)alkyl(C1- C22), -(C=O)NHalkyl(C1-C22), -(C=O)N-dialkyl(C1-C22), -(C=O)Salkyl(C1-C22),
hydroxy, (C1-C22)alkoxy, (C1- C22)alkyl, halogen, nitro, cyano, amino, mercapto, formyl,
carboxy, carbamoyl, (C1-C22)alkoxy, (C1- 127 C22)alkylthio, (C1-C22)alkylamino, ((C1-
C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-
C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein each R7 is optionally substituted with
one or more, the same or different, R20;
R8 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2-C22)alkynyl, halogen, nitro,
cyano, hydroxy, benzyloxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-
C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-
C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-
C12)aryl,orheterocyclyl, wherein R8 is optionally substituted with one or more, the same or
different, R20;
R9 is hydrogen, methyl, ethyl, tert-butyl, (C1-C22)alkyl, halogen, nitro, cyano, hydroxy,
amino, mercapto, formyl, carboxy, carbamoyl, cycloalkyl, (C1-C22)alkoxy, (C1-C22)alkylthio,
(C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R9 is optionally
substituted with one or more, the same or different, R20;
R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, lipid, methyl, ethyl, isopropyl, cyclopentyl,
cyclohexyl, butyl, pentyl, hexyl, neopentyl, benzyl, halogen, nitro, cyano, hydroxy, amino,
mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-
C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-
3
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl,
wherein R10 is optionally substituted with one or more, the same or different, R20;
R11 is hydrogen, deuterium, (C1-C22)alkyl, methyl, halogen, nitro, cyano, hydroxy, amino,
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl,
R12 is hydrogen, (C1-C22)alkyl, (C6-C12)aryl, phenyl, 1-naphthyl, 2-naphthyl,aromatic,
heteroaromatic, 4-substituted phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl,
naphthyl, or heterocyclyl, wherein R12 is optionally substituted with one or more, the same
or different, R20;
cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1-
C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-
C12)aryl, or heterocyclyl,
C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, alkylsulfinyl, (C1-
C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl,
R20 is deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano,
hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1-
C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-
C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl;
and wherein the lipid comprises a C6-22 alkyl, (C1-C22)alkoxy, polyethylene glycol, or (C6-
C12)aryl substituted with an (C1-C22)alkyl group, heterocyclylis acarbocyclylcomprising 1-4
heteroatoms selected from nitrogen, oxygen, or sulfur, and heteroaromatic is an aromatic
heterocyclylcomprising 1-4 heteroatoms selected from nitrogen, oxygen, or sulfur and at
least 1 carbon atom.
CLAIM 2: The pharmaceutical composition of claim 1, wherein Q-R7 is OH.

CLAIM 3: The pharmaceutical composition of claim 1, wherein R1 is
R8 is hydrogen, hydroxy, or benzyloxy, and

R9 is (C6-C22)alkyl.
CLAIM 4.
A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a
compound of formula IB,
4
Formula IB, or salts thereof, wherein
V is absent, O, NH, NR15, S, CH2, or CHR15;
Y is H, D, F, Cl, Br, I, CH3, CD3, CF3, (C1-C6)alkyl, acyl, (C2-C6)alkenyl, (C2-C6)alkynyl,
hydroxyl, formyl or SCH3;
R1
Monophosphate
ester,
diphosphate
ester
alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl,
carboxy, carbamoyl, carbanoyl, esteryl, alkoxy, (C1C22)alkylthio, (C1-C22)alkylamino, ((C1-
C22)alkyl)2amino,
(C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-
C12)aryl, or heterocyclyl, or phosphoramidyl,wherein R1 is optionally substituted with one
Y1 is O or S;
Y2 is OH, OR12, OAlkyl, or BH3-M+;
Y3 is OH or BH3-M+;
carbamoyl, , (C1-C22)alkoxy, (C1-
C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, , (C1-
C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl;
different, R20;
amino,mercapto, formyl, carboxy, carbamoyl, cycloalkyl, (C1-C22)alkoxy, (C1-C22)alkylthio,
(C1-C22)alkylamino,((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-
C12)arylsulfonyl, (C3-C6)carbocyclyl,(C6-C12)aryl,orheterocyclyl, wherein R9 is optionally
cyclohexyl, butyl, pentyl, hexyl, neopentyl, benzyl, halogen, nitro, cyano, hydroxy, amino,
mercapto, formyl, carboxy,carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-
C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6-
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R10 isoptionally
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R11 is optionally
5
R12 is hydrogen, (C1-C22)alkyl, (C6-C12)aryl, phenyl, 1-naphthyl, 2-naphthyl,aromatic,
or different, R20;
C22)alkoxy, (C1-C22)alkylthio,
C12)arylsulfonyl,(C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R13 is optionally
substituted with one or more, the
same or different, R20;
(C1-C22)alkylamino, ((C1-C22)alkyl)2amino, alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-
substituted with one or more, thesame or different, R20;
R15 is hydrogen, Lipid, -(C=O)Oalkyl(C1-C22), -(C=O)alkyl(C1-C22), -(C=O)NHalkyl(C1-C22), -
(C=O)N-dialkyl(C1-C22), -(C=O)Salkyl(C1-C22), hydroxy, (C1-C22)alkoxy, (C1-C22)alkyl,
halogen, nitro, cyano,amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, (C1-
C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-
C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; and
wherein the lipid comprises a C6-22 alkyl, (C6-C22)alkoxy, polyethylene glycol, or (C6-
C12)aryl substituted with an alkyl group,heterocyclylis acarbocyclylcomprising 1-4
CLAIM 5
The composition of claim 3, wherein the compound is selected from:
1-(3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-4((nonanoyloxy)amino)pyrimidin-
2-one,
1-(3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-4-
((((heptyloxy)carbonyl)oxy)amino)pyrimidin-2-one, and
isopropyl(((3,4-dihydroxy-5-(4-(hydroxyamino)-2-oxopyrimidin-1(2H)-yl)tetrahydrofuran-2-
yl)methoxy)(phenoxy)phosphoryl)alaninate.
CLAIM 6
A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a
compound of Formula IC,
6
or salts thereof, wherein
Y is H, D, F, Cl, Br, I, CH3, CD3, CF3, alkyl, acyl, alkenyl, alkynyl, hydroxyl, formyl or SCH3;
R1 is hydrogen, monophosphate, diphosphate, triphosphate,

carboxy, carbamoyl, carbanoyl, esteryl, alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-
C22)alkyl)2amino,
C12)aryl, or
heterocyclyl, or phosphoramidyl, or wherein R1 is optionally substituted with one or more,
the same or different, R20;
Y1 is O or S;
Y3 is OH or BH3-M+;
carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio,(C1-C22)alkylamino, ((C1-
C22)alkyl)2amino,(C1-C22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-
different, R20;
cyclohexyl,butyl, pentyl, hexyl, neopentyl, benzyl, halogen, nitro, cyano, hydroxy, amino,
7
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R10 isoptionally
C22)alkylamino, ((C1-C22)alkyl)2amino,(C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, orheterocyclyl, wherein R11 is optionally
R12 is hydrogen, (C1-C22)alkyl, (C6-C12)aryl, phenyl, 1-naphthyl, 2-
naphthyl,aromatic,heteroaromatic, 4-substituted phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-
bromophenyl, naphthyl, or heterocyclyl, wherein R12 is optionally substituted with one or
more, the same or different, R20;
cyano,
hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1-C22)alkoxy,
(C1-C22)alkylthio,
R15 is hydrogen, Lipid, -(C=O)Oalkyl(C1-C22), -(C=O)alkyl(C1-C22), -(C=O)NHalkyl(C1-C22), -
(C=O)N-dialkyl(C1-C22), -(C=O)Salkyl(C1-C22), hydroxy, (C1-C22)alkoxy, (C1-C22)alkyl,
halogen, nitro, cyano,amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, (C1-
C12)aryl substituted with an alkyl group,heterocyclylis acarbocyclylcomprising 1-4
CLAIM 7
7. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a
compound of Formula ID,
Formula ID,
8
or salt thereof, wherein
W is CH2, NH, S or O;
Y is N or CR”;
Z is N or CR”;
each R” is independently selected from is H, D, F, Cl, Br, I, CH3, CD3, CF3, alkyl, acyl, alkenyl,
alkynyl, hydroxyl, formyl or SCH3;
alkyl, halogen, nitro,
cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, carbanoyl, esteryl, alkoxy,
(C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-
C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, or
phosphoramidyl, or wherein R1 is optionally substituted with one or more, the same or
different, R20;
Y1 is O or S;
Y3 is OH or BH3-M+;
R2 is hydrogenor hydroxy;
R3 is hydrogen, hydroxy, alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl,
carboxy, carbamoyl, alkoxy, (C1-C22)alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl,
alkylsulfonyl, arylsulfonyl,carbocyclyl, aryl, or heterocyclyl;
hydroxymethyl,
halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (C1-
C22)alkoxy, (C1-
C22)alkylthio,(C1-C22)alkylamino, ((C1-C22)alkyl)2amino,(C1-C22)alkylsulfinyl,(C1-
C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl;
R6 is hydrogen, hydroxy, alkoxy, alkyl, ethynyl, allenyl, halogen, nitro, cyano, amino,
mercapto,formyl, carboxy, carbamoyl, alkoxy, (C1-C22)alkylthio, alkylamino, (alkyl)2amino,
alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl;
different, R20;
amino,mercapto, formyl, carboxy, carbamoyl, cycloalkyl, (C1-C22)alkoxy, (C1-C22)alkylthio,
C12)arylsulfonyl, (C3-C6)carbocyclyl,
(C6-C12)aryl,orheterocyclyl, wherein R9 is optionally substituted with one or more, the same
or different, R20;
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R10 is
optionally substituted with one or more, the same or different, R20;
9
mercapto,formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-
bromophenyl, naphthyl, or
heterocyclyl, wherein R12 is optionally substituted with one or more, the same or different,
R20;
C22)alkoxy, (C1-C22)alkylthio,(C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-
C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl,(C3-C6)carbocyclyl, (C6-
C12)aryl, or heterocyclyl, wherein R13 is optionally substituted with one or more, the same
or different, R20;
cyano,hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1-
C22)alkoxy, (C1-C22)alkylthio,(C1-C22)alkylamino, ((C1-C22)alkyl)2amino, alkylsulfinyl, (C1-
C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl,
R15 is hydrogen, -(C=O)Oalkyl(C1-C22), -(C=O)alkyl(C1-C22), -(C=O)NHalkyl(C1-C22), -
(C=O)Ndialkyl(C1-C22), -(C=O)Salkyl(C1-C22), hydroxy, (C1-C22)alkoxy, (C1-C22)alkyl,
halogen, nitro, cyano, amino,mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, (C1-
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl,wherein R15 is optionally
R15’ is hydrogen, -(C=O)Oalkyl(C1-C22), -(C=O)alkyl(C1-C22), -(C=O)NHalkyl(C1-C22), -
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl;
R15 and R15’ can form a ring that is optionally substituted with one or more, the same or
different, R20;
hydroxy,
amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1-
C22)alkylthio, (C1-
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; and
C12)aryl substituted with an (C1-C22)alkyl group heterocyclylis acarbocyclylcomprising 1-4
heteroatoms selected from nitrogen, oxygen, or sulfur,
and heteroaromatic is an aromatic heterocyclylcomprising 1-4 heteroatoms selected from
nitrogen,oxygen, or sulfur and at least 1 carbon atom.
CLAIM 8
8. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a
compound of Formula IE,
10
Formula IE,
Q is O, -O(C=O)-, -O(C=O)Lipid, -O(C=O)V-, NH, or NR7;
V is O, NH, NR7, S, CH2, or CHR7;
Y is N or CR”;
Z is N or CR”;
R2 is hydrogen, alkyl, alkenyl, alkynyl, ethynyl, fluoromethyl, difluoromethyl, trifluoromethyl,
chloromethyl, hydroxymethyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl,
carboxy, carbamoyl, alkoxy, (C1-C22)alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl,
alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, azido, or heterocyclyl;
carboxy, carbamoyl, alkoxy, (C1-C22)alkylthio, alkylamino, alkyl)2amino, alkylsulfinyl,
alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl;
carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio,(C1-22)alkylamino, ((C1-C22)alkyl)2amino,(C1-
C22)alkylsulfinyl,(C1-22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl,
or heterocyclyl;
R5 is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, alkynyl, ethynyl, fluoromethyl,
difluoromethyl,trifluoromethyl, hydroxymethyl, allenyl, halogen, nitro, cyano, amino,
mercapto, formyl, carboxy, carbamoyl,alkoxy, (C1-C22)alkylthio, alkylamino, (alkyl)2amino,
alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl,or heterocyclyl;
mercapto,formyl, carboxy, carbamoyl, alkoxy, (C1-C22)alkylthio, lkylamino, (alkyl)2amino,
alkylsulfinyl, alkylsulfonyl,arylsulfonyl, carbocyclyl, aryl, or heterocyclyl;
each R7 is independently selected from absent, hydrogen, -(C=O)Oalkyl, -(C=O)alkyl, -
(C=O)NHalkyl, -(C=O)N-dialkyl, -(C=O)Salkyl, hydroxy, alkoxy, alkyl, higher alkyl, (C6-
C16)alkyl, (C6-C22)alkyl, halogen, nitro, cyano, amino, mercapto, formyl, carboxy,
carbamoyl, alkoxy, (C1-C22)alkylthio,alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl,
arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, whereineach R7 is optionally substituted with
R15 is hydrogen, -(C=O)Oalkyl(C1-C22), -(C=O)alkyl(C1-C22), -C=O)NHalkyl(C1-C22), -
12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl,wherein R15 is optionally
R15’ is hydrogen, -(C=O)Oalkyl(C1-C22), -(C=O)alkyl(C1-C22), -C=O)NHalkyl(C1-C22), -
11
halogen, nitro, cyano, amino,
mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-
C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-
R15 and R15’ can form a ring that is optionally substituted with one or more, the same or
different,R20;
If Q = -O(C=O)V- and V = NR7 then the R7s can together form a ring that is optionally
substitutedwith one or more, the same or different, R20;
hydroxy,amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1-
C22)alkylthio, (C1-C22)alkylamino, ((C1-22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-
wherein lipid comprises a C6-22 alkyl, (C6-C22)alkoxy, polyethylene glycol, or (C6-C12)aryl
substituted with an (C1-C22)alkyl group, heterocyclylis carbocyclyl comprising 1-4
heteroatoms selected from nitrogen, oxygen, or sulfur,
and heteroaromatic is an aromatic heterocyclylcomprising 1-4 heteroatoms selected from
CLAIM 9 A pharmaceutical composition comprising a pharmaceutically acceptable excipient
and a compound of Formula II,

X is CH2 or O;
Y is N or CR”;
Z is N or CR”;
R1 is monophosphate, diphosphate, triphosphate,
12
Y1 is O or S;
Y3 is OH or BH3-M+;
R2 is hydrogen, alkyl, alkenyl, alkynyl, ethynyl, fluoromethyl, difluoromethyl,
trifluoromethyl,chloromethyl, hydroxymethyl, halogen, nitro, cyano, hydroxy, amino,
mercapto, formyl, carboxy, carbamoyl, alkoxy, (C1-C22)alkylthio, alkylamino, (alkyl)2amino,
alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl,azido, or heterocyclyl;
carboxy, carbamoyl, alkoxy, (C1-C22)alkylthio, alkylamino, alkyl)2amino, alkylsulfinyl,
alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl;
R4 is hydrogen, hydroxy,(C1-C22)alkyl, fluoromethyl, difluoromethyl, rifluoromethyl,
hydroxymethyl,halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy,
carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio,(C1-C22)alkylamino, ((C1-
C22)alkyl)2amino,(C1-C22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-
R5 is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, alkynyl, ethynyl, fluoromethyl,
difluoromethyl,trifluoromethyl, hydroxymethyl, allenyl, halogen, nitro, cyano, amino,
mercapto, formyl, carboxy, carbamoyl,alkoxy, (C1-C22)alkylthio, alkylamino, (alkyl)2amino,
alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl,or heterocyclyl;
mercapto,formyl, carboxy, carbamoyl, alkoxy, (C1-C22)alkylthio, alkylamino, (alkyl)2amino,
alkylsulfinyl, alkylsulfonyl,arylsulfonyl, carbocyclyl, aryl, or heterocyclyl;
each R7 is independently selected from absent, hydrogen, -(C=O)Oalkyl, -(C=O)alkyl, -
(C=O)NHalkyl, -(C=O)N-dialkyl, -(C=O)Salkyl, hydroxy, alkoxy, alkyl, higher alkyl, (C6-
C16)alkyl, (C6-C22)alkyl, halogen, nitro, cyano, amino, mercapto, formyl, carboxy,
carbamoyl, alkoxy, (C1-C22)alkylthio,alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl,
arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein each R7 is optionally substituted with
cyano,hydroxy, benzyloxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-
C22)alkylsulfinyl, (C1-22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-
12)aryl,orheterocyclyl, wherein R8 is optionally substituted with one or more, the same or
different, R20;
C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6-
13
mercapto,formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-
C22)alkylamino, ((C1-C22)alkyl)2amino,(C1-22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-
bromophenyl, naphthyl, or heterocyclyl, wherein R12 is optionally substituted with one or
cyano,hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1-
C22)alkoxy, (C1-C22)alkylthio,(C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-
C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl,(C3-C6)carbocyclyl, (C6-
C12)aryl, or heterocyclyl, wherein R13 is optionally substituted with one or more, the same
or different, R20;
cyano,hydroxy, amino, amido, mercapto, formyl, carboxy, arbamoyl, lipid, azido, (C1-
C22)alkoxy, (C1-C22)alkylthio,(C1-C22)alkylamino, ((C1-C22)alkyl)2amino, alkylsulfinyl, (C1-
C22)alkylsulfonyl, (C6-12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl,
If Q = -O(C=O)V- and V = NR7 then the R7s can together form a ring that is optionally
hydroxy,amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1-
C22)alkylthio, (C1-C22)alkylamino, ((C1-22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-
C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-
C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; and wherein lipid comprises a C6-22 alkyl, (C6-
C22)alkoxy, polyethylene glycol, or (C6-C12)aryl substituted
with an (C1-C22)alkyl group, heterocyclylis acarbocyclylcomprising 1-4 heteroatoms selected
from nitrogen, oxygen, or sulfur, and
heteroaromatic is an aromatic heterocyclylcomprising 1-4 heteroatoms selected from
CLAIM 10 The pharmaceutical composition of claim 1,further comprising a propellant.
CLAIM 11 The pharmaceutical composition of claim 10, wherein the propellant is

compressed air, ethanol, nitrogen, carbon dioxide, nitrous oxide, hydrofluoroalkanes (HFA),
1,1,1,2,-tetrafluoroethane, 1,1,1,2,3,3,3-heptafluoropropane or combinations thereof.
CLAIM 12 The composition of claim 1, wherein the compound has a structure according to
Formula IA

R7 is H,
X is CH2, CHMe, CMe2, CHF, CF2, or CD2;
Y is independently selected from is H, D, F, Cl, Br, I, CH3, CD3, CF3, alkyl, acyl, alkenyl,
14
R1 is
monophosphate
ester, diphosphate
ester
amino, mercapto, formyl, carboxy, carbanoyl, esteryl, alkoxy, (C1-

C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, or
phosphoramidyl, wherein R1 is optionally substituted with one or more, the same or
different, R20, Y1 is O or S;
Y3 is OH or BH3-M+;
R4 is hydrogen, hydroxy, (C1-C22)alkyl, fluoromethyl, difluoromethyl, trifluoromethyl,
carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino,
C12)aryl, or heterocyclyl, wherein R4 is optionally substituted with one or more, the same or
different, R20;
different, R20;
R12 is hydrogen, (C1-C22)alkyl, (C6-C12)aryl, phenyl, 1-naphthyl, 2-naphthyl, aromatic,
15
or different, R20;
CLAIM 13
The composition of claim 1, wherein R4 is hydrogen, hydroxy, alkyl, halogen, or fluoro.
CLAIM 14
The composition of claim 1, wherein R5 is hydrogen, hydroxy, alkoxy, alkyl, methyl, ethynyl,
or allenyl.
6. Background of the prior art: Molnupiravir (development codes MK-4482 and EIDD-
2801) is an experimental antiviral drug which is orally active and was developed for the
treatment of influenza. It is a prodrug of the synthetic nucleoside derivative N4-
hydroxycytidine, and exerts its antiviral action through introduction of copying errors
during viral RNA replication. Activity has also been demonstrated against corona viruses
including SARS, MERS and SARS-CoV-2. Molnupiravir is chemically is
((2R,3S,4R,5R)-3,4-dihydroxy-5-(hydroxyimino)-2-oxo-3,4 dihydropyrimidin-1(2H)-yl)
tetrahydro furan-2-yl)methyl isobutyrate having the chemical structure.
The drug was developed at Emory University by the university's drug innovation
company, Drug Innovation Ventures at Emory (DRIVE). First patent application
WO2002032920 covering the molecule was filed on Oct 18, 2001 by Pharmasset Limited.
Pharmasset was founded in 1998 by Raymond Schinazi and Dennis Liotta, scientists
at Emory University. The company's research and development concentrated
16
on nucleoside analogs. This information is freely available on
https://en.wikipedia.org/wiki/Molnupiravir .
This patent seems to be the foundation prior art for all further developments on antivirals
involving core N4-hydroxycytidine nucleoside moiety until now including
IN20717025098. The reasons to support the understanding shall be discussed in detail
further. WO2002032920 is included as D1 in this opposition representation.
7. Accordingly, the Opponent submits their opposition by way of representation under

Section 25(1) in respect of the said Indian Application No. 201717025098 on the
following amongst other grounds listed below, which are without prejudice and in the
alternative to each other:
a. 25(1)(b): that the invention so far as claimed in any claim of the complete
specification has been published before the priority date of the claim.
b. 25(1)(c): that the invention so far as claimed in any claim of the complete
specification is claimed in a claim of a complete specification published on
or after priority date of the applicant's claim and filed in pursuance of an
application for a patent in India, being a claim of which the priority date is
earlier than that of the applicant's claim;
c. 25(1)(e): that the invention so far as claimed in any claim of the complete
specification is obvious and clearly does not involve any inventive step,
having regard to the matter published as mentioned in clause (b) or having
regard to what was used in India before the priority date of the Applicant
’s claim;
d. 25(1)(f): that the subject of any claim of the complete specification is not
an invention within the meaning of this Act, or is not patentable under this
Act;
e. 25(1)(g): that the complete specification does not sufficiently and clearly
describe the invention or the method by which it is to be performed.
17
f. 25(1)(j): that the complete specification does not disclose or wrongly
mentions the source or geographical origin of biological material used for
the invention;
To oppose the application, Opponent relies on following documents:
D1: US 2003/0087873
D2: US20140235566A1
D3: WO2013142525A1
D4: EP2615101B1
GROUND I:
I) Section 25(1) (b)/(c): Lack of novelty:
CLAIMS 1-14: The invention as claimed in claims 1-14 lack novelty under Section 25(1)
(b)/(c) of the Patents Act, 1970 (as amended in 2005; hereinafter referred to as “The Act”).
i) Lack of novelty in view of US 2003/0087873 to Lieven Stuyver (D1)
A. US 2003/0087873 filed on Oct 18, 2001 having a priority date Oct 18, 2000 & April 6,
2001 is an admissible prior art for IN20717025098 having priority date of Dec 26, 2014.
US 2003/0087873 discloses a composition for and a method of treating

a Flaviviridae (including BVDV and HCV), Orthomyxoviridae (including Influenza A
and B) or Paramyxoviridae (including RSV) infection, or conditions related to abnormal
cellular proliferation, in a host, including animals, and especially humans, using a
nucleoside of general formula (I)-(XXIII) or its pharmaceutically acceptable salt or
prodrug. This invention also provides an effective process to quantify the viral load, and
in particular BVDV, HCV or West Nile Virus load, in a host, using real-time polymerase
chain reaction ('TR-PCR'). Additionally, the invention discloses probe molecules that can
fluoresce proportionally to the amount of virus present in a sample.
We shall discuss in further detail as to how the disclosure of US 2003/0087873

anticipates each claim of impugned patent application
18
Claim 1:
IN201717025098 D1: US 2003/0087873 A1
CLAIM 1: A pharmaceutical composition [0124]
In another embodiment of the invention, anti- virally or
comprising a pharmaceutically acceptable
anti proliferatively effective nucleoside is a B-L
excipient and a compound having Formula I nucleoside of the general formula (III)
[0114] each D is hydrogen, alkyl, acyl,

monophosphate, diphosphate, triphosphate,
Formula I, or salt thereof, wherein monophosphate ester, diphosphate ester,
Q is O, -O(C=O)-, -O(C=O)V-, or NR7; triphosphate ester, phospholipid or amino acid;
[0116] each X1 and X2 is independently hydrogen,
halogen (F, Cl, Br or I), NH, NHR4',
NR4'R4'',NHOR4, NR4'NR4’’R4", OH, OR, SH or
SR';
V is O, NH, NR7, CH2, or CHR7; [0117] each Y is O, S or Se;
[0119] each R1 and R1' is independently hydrogen,
W is O; lower alkyl, lower alkenyl, lower alkynyl, aryl,
X is CH2,CHMe, CMe2, CHF, CF2, or CD2; alkylaryl, halogen (F, Cl, Br or I), NH, NHR, NRR,
Y is CR”; NHOR, NRNHR, NRNRR", OH, OR, SH, SR5, NO,
Z is CR”; NO, CH-OH, CHOR, COH, COR, CONH, CONHR,
CONRR or CN:
each R” is independently selected from is H, D, [0120] each R2 and R2’ independently is hydrogen or
F, Cl, Br, I, CH3, CD3, CF3, C1-22alkyl, acyl, C2- halogen (F, Cl, Br or I), OH, SH, OCH3, SCH3,
22alkenyl, C2-22alkynyl, hydroxyl, formyl or NH2, NH2CH3, CH2=CH2, CN, CH2-NH, CH2-OH,
CO2H.
SCH3; Monophosphate ester, diphosphate [0121] each R3 and R3’ independently is hydrogen or
R1 is ester halogen (F, Cl, Br or I), OH, SH, OCH3, SCH3, NH,
NHCH3, CH3, C2H3, CH=CH, CN, CH-NH2,
CH2OH, CO2H.
[0122] each R4, R4', R4", R5, R5’ and R5"
independently is hydrogen, lower alkyl, lower alkenyl,
aryl, or arylalkyl Such as unsubstituted or Substituted
phenyl or benzyl,
[0123] such that for each nucleoside of the general
formula (1) or (II), at least one of R2 and R2’ is
alkyl, halogen, nitro, cyano, hydroxy, amino, hydrogen and at least one of R3 and R3’ is
mercapto, formyl, carboxy, carbamoyl, hydrogen.
carbanoyl, esteryl, alkoxy, (C1-C22)alkylthio,
Compound of impugned application also mentioned
(C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- in [0260] as compound IIIa
C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- [0341] In a preferred embodiment, the B-D and B-L
C12)aryl, or heterocyclyl, or nucleosides of general formula (I-a) and (III-a) are
represented by the non-limiting examples provided in
phosphoramidylwherein R1 is optionally Table 1.
substituted with one or more, the same or
different, R20;
Y1 is O or S;
Y2 is OH, OR12, OAlkyl, or BH3 - M+; Y3 is OH
or BH3 - M+;
R3 is hydrogen, hydroxy, (C1-C22)alkyl, X1 Y1 R1 R1 R2 R2’ R3 R3’
19
halogen, nitro, cyano, hydroxy, amino, BS NH- O H H H - H -
mercapto, formyl, carboxy, carbamoyl, , (C1- OH OH OH
BT NH- O F H H - H -
C22)alkoxy, (C1-C22)alkylthio, , (C1- OH OH OH
C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- BU NH- O BR H H - H -
C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- OH OH OH
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- BV NH- O I H H - H -
OH OH OH
C12)aryl, or heterocyclyl; BW NH- O H H OH -H H -
R4 is hydrogen, hydroxy,(C1-C22)alkyl, OH OH
fluoromethyl, difluoromethyl, trifluoromethyl,
hydroxymethyl, halogen, nitro, cyano, hydroxy,
amino, mercapto, formyl, carboxy, carbamoyl,
(C1-C22)alkoxy, (C1- C22)alkylthio, (C1-
C22)alkylamino, ((C1-C22)alkyl)2amino,(C1-
C22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6-
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-
C12)aryl, or heterocyclyl;
R6 is hydrogen, hydroxy, (C1-C22)alkoxy, (C1-
C22)alkyl, ethynyl, allenyl, halogen, nitro,
cyano, amino, mercapto, formyl, carboxy,
carbamoyl, (C1-C22)alkylthio, (C1-
C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-
C12)aryl,orheterocyclyl;
each R7 is independently selected from absent,
hydrogen, -(C=O)Oalkyl(C1-C22), -
(C=O)alkyl(C1- C22), -(C=O)NHalkyl(C1-C22), -
(C=O)N-dialkyl(C1-C22), -(C=O)Salkyl(C1-C22),
hydroxy, (C1-C22)alkoxy, (C1- C22)alkyl,
halogen, nitro, cyano, amino, mercapto, formyl,
carboxy, carbamoyl, (C1-C22)alkoxy, (C1- 127
C22)alkylthio, (C1-C22)alkylamino, ((C1-
C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-
C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-
C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl,
wherein each R7 is optionally substituted with
R8 is hydrogen, deuterium, (C1-C22)alkyl, (C2-
C22)alkenyl, (C2-C22)alkynyl, halogen, nitro,
cyano, hydroxy, benzyloxy, amino, amido,
mercapto, formyl, carboxy, carbamoyl, azido,
C12)aryl,orheterocyclyl, wherein R8 is
optionally substituted with one or more, the
R9 is hydrogen, methyl, ethyl, tert-butyl, (C1-
20
C22)alkyl, halogen, nitro, cyano, hydroxy,
cycloalkyl, (C1-C22)alkoxy, (C1-C22)alkylthio,
(C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-
R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, lipid,
methyl, ethyl, isopropyl, cyclopentyl,
cyclohexyl, butyl, pentyl, hexyl, neopentyl,
benzyl, halogen, nitro, cyano, hydroxy, amino,
mercapto, formyl, carboxy, carbamoyl, (C1-
C22)alkoxy, (C1-C22)alkylthio, (C1-
C12)aryl,orheterocyclyl,
wherein R10 is optionally substituted with one
R11 is hydrogen, deuterium, (C1-C22)alkyl,
methyl, halogen, nitro, cyano, hydroxy, amino,
R12 is hydrogen, (C1-C22)alkyl, (C6-C12)aryl,
phenyl, 1-naphthyl, 2-naphthyl,aromatic,
heteroaromatic, 4-substituted phenyl, 4-
fluorophenyl, 4-chlorophenyl, 4-bromophenyl,
naphthyl, or heterocyclyl, wherein R12 is
cyano, hydroxy, amino, amido, mercapto,
formyl, carboxy, carbamoyl, lipid, azido, (C1-
21
C22)alkylamino, ((C1-C22)alkyl)2amino,
alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-
C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-
C12)aryl, or heterocyclyl, wherein R14 is
R20 is deuterium, (C1-C22)alkyl, (C2-
formyl, carboxy, carbamoyl, azido, (C1-
C12)aryl, or heterocyclyl; and wherein the lipid
comprises a C6-22 alkyl, (C1-C22)alkoxy,
polyethylene glycol, or (C6-C12)aryl substituted
with an (C1-C22)alkyl group, heterocyclylis
acarbocyclylcomprising 1-4 heteroatoms
selected from nitrogen, oxygen, or sulfur, and
heteroaromatic is an aromatic
heterocyclylcomprising 1-4 heteroatoms
selected from nitrogen, oxygen, or sulfur and at
Thus, it is clear that all elements of claim 1 of IN201717025098 are covered in D1. The
features completely overlap with portions of D1 as detailed above. Therefore claim 1 and all
dependent claims 2, 3, 10, 12, 13 & 14 are not novel wrt to disclosure of D1 alone totally.
Other compounds claimed in claims 4, 6, 7, 9 framed as independent claims are carrying the
same chain skeleton and are covered under the markush of claim 1 so they are also novel for
the reasons for claim 1.
Therefore, claim 1 and all claims dependent on claim 1 lack novelty in view of D1.
Claim 2:
IN201717025098 D1: US 2003/0087873 A1
CLAIM 2: The pharmaceutical composition of claim 1, [0124]
wherein Q-R7 is OH. In another embodiment of the invention, anti- virally or anti
proliferatively effective nucleoside is a B-L nucleoside of the
general formula (III)
22
[0116] each X1 and X2 is independently hydrogen, halogen (F, Cl,
Br or I), NH, NHR4', NR4'R4'',NHOR4, NR4'NR4’’R4", OH, OR,
SH or SR';
[0122] each R4, R4', R4", R5, R5’ and R5" independently is
hydrogen, lower alkyl, lower alkenyl, aryl, or arylalkyl Such as
unsubstituted or Substituted phenyl or benzyl,
Claim 3:
IN201717025098 D1: US 2003/0087873 A1

CLAIM 3: The pharmaceutical composition of claim 1, [0124]
wherein R1 is In another embodiment of the invention, anti- virally or anti

[0114] each D is hydrogen, alkyl, acyl, monophosphate,

diphosphate, triphosphate, monophosphate ester, diphosphate
ester, triphosphate ester, phospholipid or amino acid;
Claim 4:
IN201717025098 D1: US 2003/0087873 A1

CLAIM 4. Compound of Formula I b is covered broadly under markush of
A pharmaceutical composition comprising a claim 1. Therefore, the compound is not novel for the arguments
pharmaceutically acceptable excipient and a compound of applicable for claim 1.
formula IB,
Further, the overlap is shown in following excerpts from D1.
[0124]
In another embodiment of the invention, anti- virally or anti

Y is H, D, F, Cl, Br, I, CH3, CD3, CF3, (C1-C6)alkyl,
acyl, (C2-C6)alkenyl, (C2-C6)alkynyl, hydroxyl, formyl or
SCH3;
[0114] each D is hydrogen, alkyl, acyl, monophosphate,

23
diphosphate, triphosphate, monophosphate ester, diphosphate
ester, triphosphate ester, phospholipid or amino acid;
[0116] each X1 and X2 is independently hydrogen, halogen (F,

Cl, Br or I), NH, NHR4', NR4'R4'',NHOR4, NR4'NR4’’R4",
OH, OR, SH or SR';
[0117] each Y is O, S or Se;
[0119] each R1 and R1' is independently hydrogen, lower alkyl,

lower alkenyl, lower alkynyl, aryl, alkylaryl, halogen (F, Cl, Br
or I), NH, NHR, NRR, NHOR, NRNHR, NRNRR", OH, OR,
SH, SR5, NO, NO, CH-OH, CHOR, COH, COR, CONH,
CONHR, CONRR or CN:
[0120] each R2 and R2’ independently is hydrogen or halogen
(F, Cl, Br or I), OH, SH, OCH3, SCH3, NH2, NH2CH3,
CH2=CH2, CN, CH2-NH, CH2-OH, CO2H.

alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, (F, Cl, Br or I), OH, SH, OCH3, SCH3, NH, NHCH3, CH3,
formyl, C2H3, CH=CH, CN, CH-NH2, CH2OH, CO2H.
carboxy, carbamoyl, carbanoyl, esteryl, alkoxy, [0122] each R4, R4', R4", R5, R5’ and R5" indepenently is
(C1C22)alkylthio, (C1-C22)alkylamino, ((C1- hydrogen, lower alkyl, lower alkenyl, aryl, or arylalkyl Such as
C22)alkyl)2amino, unsubstituted or Substituted phenyl or benzyl,
(C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- [0123] such that for each nucleoside of the general formula (1)
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or or (II), at least one of R2 and R2’ is hydrogen and at least one of
heterocyclyl, or phosphoramidyl,wherein R1 is optionally R3 and R3’ is hydrogen.
Y1 is O or S;
Y3 is OH or BH3-M+;
R4 is hydrogen, hydroxy,(C1-C22)alkyl, fluoromethyl,
difluoromethyl, trifluoromethyl, hydroxymethyl, halogen,
nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy,
C22)alkyl)2amino, (C1-C22)alkylsulfinyl, , (C1-
C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano,
hydroxy, benzyloxy, amino, amido, mercapto, formyl,
carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1-
C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R8
is optionally substituted with one or more, the same or
different, R20;
R9 is hydrogen, methyl, ethyl, tert-butyl, (C1-C22)alkyl,
halogen, nitro, cyano, hydroxy, amino,mercapto, formyl,
carboxy, carbamoyl, cycloalkyl, (C1-C22)alkoxy, (C1-
C22)alkylthio, (C1-C22)alkylamino,((C1-
C6)carbocyclyl,(C6-C12)aryl,orheterocyclyl, wherein R9
different, R20;
R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, lipid, methyl,
ethyl, isopropyl, cyclopentyl, cyclohexyl, butyl, pentyl,
hexyl, neopentyl, benzyl, halogen, nitro, cyano, hydroxy,
amino, mercapto, formyl, carboxy,carbamoyl, (C1-
C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino,
((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl,(C1-
isoptionally substituted with one or more, the same or
different, R20;
R11 is hydrogen, deuterium, (C1-C22)alkyl, methyl,
halogen, nitro, cyano, hydroxy, amino, mercapto, formyl,
24
carboxy, carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio,
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or
heterocyclyl, wherein R11 is optionally substituted with
R12 is hydrogen, (C1-C22)alkyl, (C6-C12)aryl, phenyl, 1-
naphthyl, 2-naphthyl,aromatic, heteroaromatic, 4-
substituted phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-
bromophenyl, naphthyl, or heterocyclyl, wherein R12 is
optionally substituted with one or more, the same or
different, R20;
hydroxy, amino, amido, mercapto, formyl, carboxy,
carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1-
C22)alkylthio,
C12)arylsulfonyl,(C3-C6)carbocyclyl, (C6-C12)aryl, or
one or more, the
C22)alkylthio,
(C1-C22)alkylamino, ((C1-C22)alkyl)2amino,
one or more, thesame or different, R20;
R15 is hydrogen, Lipid, -(C=O)Oalkyl(C1-C22), -
(C=O)alkyl(C1-C22), -(C=O)NHalkyl(C1-C22), -(C=O)N-
dialkyl(C1-C22), -(C=O)Salkyl(C1-C22), hydroxy, (C1-
C22)alkoxy, (C1-C22)alkyl, halogen, nitro, cyano,amino,
mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio,
R20 is deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2-
C22)alkynyl, halogen, nitro, cyano, hydroxy, amino,
amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-
((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-
C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; and
wherein the lipid comprises a C6-22 alkyl, (C6-
C22)alkoxy, polyethylene glycol, or (C6-C12)aryl
substituted with an alkyl group,heterocyclyl is a
carbocyclylcomprising 1-4 heteroatoms selected from
nitrogen, oxygen, or sulfur, and heteroaromatic is an
aromatic heterocyclylcomprising 1-4 heteroatoms selected
from nitrogen, oxygen, or sulfur and at least 1 carbon
atom.
Claim 5:
IN201717025098 D1: US 2003/0087873 A1
CLAIM 5 Claim 5 depends on claim 1, therefore the arguments
The composition of claim 3, wherein the compound is
applicable for claim 1 are applicable here as well
selected from:
1-(3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-
yl)4((nonanoyloxy)amino)pyrimidin- 2-one,1-(3,4-
dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-4
25
isopropyl(((3,4-dihydroxy-5-(4-(hydroxyamino)-2-
oxopyrimidin-1(2H)-yl)tetrahydrofuran-2-
Claim 6:
IN201717025098 D1: US 2003/0087873 A1

CLAIM 6 [0124]
A pharmaceutical composition comprising a In another embodiment of the invention, anti- virally or anti
pharmaceutically acceptable excipient and a compound proliferatively effective nucleoside is a B-L nucleoside of the
of Formula IC, general formula (III)

X is CH2,CHMe, CMe2, CHF, CF2, or CD2; [0114] each D is hydrogen, alkyl, acyl, monophosphate,
Y is H, D, F, Cl, Br, I, CH3, CD3, CF3, alkyl, acyl, diphosphate, triphosphate, monophosphate ester, diphosphate
alkenyl, alkynyl, hydroxyl, formyl or SCH3; ester, triphosphate ester, phospholipid or amino acid;
R1 is hydrogen, monophosphate, diphosphate,
triphosphate, [0116] each X1 and X2 is independently hydrogen, halogen (F, Cl,
Br or I), NH, NHR4', NR4'R4'',NHOR4, NR4'NR4’’R4", OH, OR,
SH or SR';
[0119] each R1 and R1' is independently hydrogen, lower alkyl,

lower alkenyl, lower alkynyl, aryl, alkylaryl, halogen (F, Cl, Br or
I), NH, NHR, NRR, NHOR, NRNHR, NRNRR", OH, OR, SH,
SR5, NO, NO, CH-OH, CHOR, COH, COR, CONH, CONHR,
CONRR or CN:
[0120] each R2 and R2’ independently is hydrogen or halogen (F,
Cl, Br or I), OH, SH, OCH3, SCH3, NH2, NH2CH3, CH2=CH2,
CN, CH2-NH, CH2-OH, CO2H.
(F, Cl, Br or I), OH, SH, OCH3, SCH3, NH, NHCH3, CH3,
C2H3, CH=CH, CN, CH-NH2, CH2OH, CO2H.
[0122] each R4, R4', R4", R5, R5’ and R5" indepenently is
hydrogen, lower alkyl, lower alkenyl, aryl, or arylalkyl Such as
unsubstituted or Substituted phenyl or benzyl,
[0123] such that for each nucleoside of the general formula (1) or
(II), at least one of R2 and R2’ is hydrogen and at least one of R3
and R3’ is hydrogen.
alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto,
formyl,
carboxy, carbamoyl, carbanoyl, esteryl, alkoxy, (C1-
C22)alkyl)2amino,
(C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-
heterocyclyl, or phosphoramidyl, or wherein R1 is
different, R20;
Y1 is O or S;
Y3 is OH or BH3-M+;
difluoromethyl, trifluoromethyl, hydroxymethyl,
carboxy, carbamoyl, (C1-C22)alkoxy, (C1-
C22)alkylthio,(C1-C22)alkylamino, ((C1-
C22)alkyl)2amino,(C1-C22)alkylsulfinyl,(C1-
26
C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein
R8 is optionally substituted with one or more, the same
or different, R20;
C6)carbocyclyl,(C6-C12)aryl,orheterocyclyl, wherein R9
different, R20;
methyl, ethyl, isopropyl, cyclopentyl, cyclohexyl,butyl,
pentyl, hexyl, neopentyl, benzyl, halogen, nitro, cyano,
hydroxy, amino, mercapto, formyl, carboxy,carbamoyl,
(C1-C22)alkoxy, (C1-C22)alkylthio, (C1-
C12)aryl,orheterocyclyl, wherein R10 isoptionally
C22)alkyl)2amino,(C1-C22)alkylsulfinyl, (C1-
C6)carbocyclyl, (C6-C12)aryl, orheterocyclyl, wherein
or different, R20;
R12 is hydrogen, (C1-C22)alkyl, (C6-C12)aryl, phenyl,
1-naphthyl, 2-naphthyl,aromatic,heteroaromatic, 4-
different, R20;
C22)alkylthio,
C22)alkylthio,
(C=O)alkyl(C1-C22), -(C=O)NHalkyl(C1-C22), -
(C=O)N-dialkyl(C1-C22), -(C=O)Salkyl(C1-C22),
hydroxy, (C1-C22)alkoxy, (C1-C22)alkyl, halogen,
27
nitro, cyano,amino, mercapto, formyl, carboxy,
carbamoyl, (C1-C22)alkylthio, (C1-C22)alkylamino,
((C1-C22)alkyl)2amino,(C1-C22)alkylsulfinyl, (C1-
C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein
or different, R20;
amido, mercapto, formyl, carboxy, carbamoyl, azido,
heterocyclyl; and
substituted with an alkyl group,heterocyclylis
acarbocyclylcomprising 1-4 heteroatoms selected from
aromatic heterocyclylcomprising 1-4 heteroatoms
selected from nitrogen, oxygen, or sulfur and at least 1
carbon atom.
Thus, clearly D1 anticipates the claimed subject matter.
Claim 7:
IN201717025098 D1: US 2003/0087873 A1
7. A pharmaceutical composition comprising a [0124]

pharmaceutically acceptable excipient and a compound In another embodiment of the invention, anti- virally or anti
of Formula ID, proliferatively effective nucleoside is a B-L nucleoside of the
Formula ID,
W is CH2, NH, S or O; [0114] each D is hydrogen, alkyl, acyl, monophosphate,
X is CH2,CHMe, CMe2, CHF, CF2, or CD2; diphosphate, triphosphate, monophosphate ester, diphosphate
Y is N or CR”; ester, triphosphate ester, phospholipid or amino acid;
Z is N or CR”; [0116] each X1 and X2 is independently hydrogen, halogen (F,
each R” is independently selected from is H, D, F, Cl, Cl, Br or I), NH, NHR4', NR4'R4'',NHOR4, NR4'NR4’’R4", OH,
Br, I, CH3, CD3, CF3, alkyl, acyl, alkenyl, alkynyl, OR, SH or SR';
hydroxyl, formyl or SCH3; [0117] each Y is O, S or Se;
R1 is hydrogen, monophosphate, diphosphate, [0119] each R1 and R1' is independently hydrogen, lower alkyl,
triphosphate, lower alkenyl, lower alkynyl, aryl, alkylaryl, halogen (F, Cl, Br or
alkyl, halogen, nitro, I), NH, NHR, NRR, NHOR, NRNHR, NRNRR", OH, OR, SH,
cyano, hydroxy, amino, mercapto, formyl, carboxy, SR5, NO, NO, CH-OH, CHOR, COH, COR, CONH, CONHR,
carbamoyl, carbanoyl, esteryl, alkoxy, (C1- CONRR or CN:
C22)alkylthio, (C1-C22)alkylamino, ((C1- [0120] each R2 and R2’ independently is hydrogen or halogen
C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- (F, Cl, Br or I), OH, SH, OCH3, SCH3, NH2, NH2CH3,
C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- CH2=CH2, CN, CH2-NH, CH2-OH, CO2H.
C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, or [0121] each R3 and R3’ independently is hydrogen or halogen
phosphoramidyl, or wherein R1 is optionally substituted (F, Cl, Br or I), OH, SH, OCH3, SCH3, NH, NHCH3, CH3,
with one or more, the same or different, R20; C2H3, CH=CH, CN, CH-NH2, CH2OH, CO2H.
Y1 is O or S; [0122] each R4, R4', R4", R5, R5’ and R5" indepenently is
Y2 is OH, OR12, OAlkyl, or BH3-M+; hydrogen, lower alkyl, lower alkenyl, aryl, or arylalkyl Such as
Y3 is OH or BH3-M+; unsubstituted or Substituted phenyl or benzyl,
R2 is hydrogenor hydroxy; [0123] such that for each nucleoside of the general formula (1) or
28
R3 is hydrogen, hydroxy, alkyl, halogen, nitro, cyano, (II), at least one of R2 and R2’ is hydrogen and at least one of R3
hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, and R3’ is hydrogen.
alkoxy, (C1-C22)alkylthio, alkylamino, (alkyl)2amino,
alkylsulfinyl, alkylsulfonyl, arylsulfonyl,carbocyclyl,
aryl, or heterocyclyl;
R6 is hydrogen, hydroxy, alkoxy, alkyl, ethynyl, allenyl,
halogen, nitro, cyano, amino, mercapto,formyl, carboxy,
carbamoyl, alkoxy, (C1-C22)alkylthio, alkylamino,
(alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl,
carbocyclyl, aryl, or heterocyclyl;
C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein
or different, R20;
C6)carbocyclyl,
(C6-C12)aryl,orheterocyclyl, wherein R9 is optionally
methyl, ethyl, isopropyl, cyclopentyl, cyclohexyl,butyl,
pentyl, hexyl, neopentyl, benzyl, halogen, nitro, cyano,
hydroxy, amino, mercapto, formyl, carboxy,carbamoyl,
different, R20;
halogen, nitro, cyano, hydroxy, amino, mercapto,formyl,
or different, R20;
R12 is hydrogen, (C1-C22)alkyl, (C6-C12)aryl, phenyl,
1-naphthyl, 2-naphthyl,aromatic,heteroaromatic, 4-
C22)alkylsulfonyl, (C6-C12)arylsulfonyl,(C3-
29
or different, R20;
cyano,hydroxy, amino, amido, mercapto, formyl,
carboxy, carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1-
C22)alkyl)2amino, alkylsulfinyl, (C1-C22)alkylsulfonyl,
(C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-
C12)aryl, or heterocyclyl, wherein R14 is optionally
R15 is hydrogen, -(C=O)Oalkyl(C1-C22), -
(C=O)Ndialkyl(C1-C22), -(C=O)Salkyl(C1-C22),
nitro, cyano, amino,mercapto, formyl, carboxy,
C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl,wherein
or different, R20;
R15’ is hydrogen, -(C=O)Oalkyl(C1-C22), -
R15 and R15’ can form a ring that is optionally
C22)alkynyl, halogen, nitro, cyano, hydroxy,
amino, amido, mercapto, formyl, carboxy, carbamoyl,
azido, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-
heterocyclyl; and
substituted with an (C1-C22)alkyl group heterocyclylis
nitrogen, oxygen, or sulfur,
and heteroaromatic is an aromatic
heterocyclylcomprising 1-4 heteroatoms selected from
Claim 8:
IN201717025098 D1: US 2003/0087873 A1
CLAIM 8
8. A pharmaceutical composition comprising a
[0124]
pharmaceutically acceptable excipient and a compound
In another embodiment of the invention, anti- virally or anti
of Formula IE,
30
Formula IE, [0114] each D is hydrogen, alkyl, acyl, monophosphate,
or salt thereof, wherein diphosphate, triphosphate, monophosphate ester, diphosphate ester,
Q is O, -O(C=O)-, -O(C=O)Lipid, -O(C=O)V-, NH, or triphosphate ester, phospholipid or amino acid;
NR7; [0116] each X1 and X2 is independently hydrogen, halogen (F, Cl,
V is O, NH, NR7, S, CH2, or CHR7; Br or I), NH, NHR4', NR4'R4'',NHOR4, NR4'NR4’’R4", OH, OR,
W is CH2, NH, S or O; SH or SR';
X is CH2,CHMe, CMe2, CHF, CF2, or CD2; [0117] each Y is O, S or Se;
Y is N or CR”; [0119] each R1 and R1' is independently hydrogen, lower alkyl,
Z is N or CR”; lower alkenyl, lower alkynyl, aryl, alkylaryl, halogen (F, Cl, Br or
each R” is independently selected from is H, D, F, Cl, I), NH, NHR, NRR, NHOR, NRNHR, NRNRR", OH, OR, SH,
Br, I, CH3, CD3, CF3, alkyl, acyl, alkenyl, alkynyl, SR5, NO, NO, CH-OH, CHOR, COH, COR, CONH, CONHR,
hydroxyl, formyl or SCH3; CONRR or CN:
R2 is hydrogen, alkyl, alkenyl, alkynyl, ethynyl, [0120] each R2 and R2’ independently is hydrogen or halogen (F,
fluoromethyl, difluoromethyl, trifluoromethyl, Cl, Br or I), OH, SH, OCH3, SCH3, NH2, NH2CH3, CH2=CH2,
chloromethyl, hydroxymethyl, halogen, nitro, cyano, CN, CH2-NH, CH2-OH, CO2H.
hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, [0121] each R3 and R3’ independently is hydrogen or halogen
alkoxy, (C1-C22)alkylthio, alkylamino, (alkyl)2amino, (F, Cl, Br or I), OH, SH, OCH3, SCH3, NH, NHCH3, CH3,
alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, C2H3, CH=CH, CN, CH-NH2, CH2OH, CO2H.
aryl, azido, or heterocyclyl; [0122] each R4, R4', R4", R5, R5’ and R5" indepenently is
R3 is hydrogen, hydroxy, alkyl, halogen, nitro, cyano, hydrogen, lower alkyl, lower alkenyl, aryl, or arylalkyl Such as
hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, unsubstituted or Substituted phenyl or benzyl,
alkoxy, (C1-C22)alkylthio, alkylamino, alkyl)2amino, [0123] such that for each nucleoside of the general formula (1) or
alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, (II), at least one of R2 and R2’ is hydrogen and at least one of R3
aryl, or heterocyclyl; and R3’ is hydrogen.
halogen, nitro, cyano, hydroxy, amino, mercapto,
formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1-
C22)alkylthio,(C1-22)alkylamino, ((C1-
22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-
R5 is hydrogen, hydroxy, alkoxy, alkyl, alkenyl,
alkynyl, ethynyl, fluoromethyl,
difluoromethyl,trifluoromethyl, hydroxymethyl, allenyl,
halogen, nitro, cyano, amino, mercapto, formyl,
carboxy, carbamoyl,alkoxy, (C1-C22)alkylthio,
alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl,
arylsulfonyl, carbocyclyl, aryl,or heterocyclyl;
halogen, nitro, cyano, amino, mercapto,formyl, carboxy,
carbamoyl, alkoxy, (C1-C22)alkylthio, lkylamino,
(alkyl)2amino, alkylsulfinyl, alkylsulfonyl,arylsulfonyl,
hydrogen, -(C=O)Oalkyl, -(C=O)alkyl, -(C=O)NHalkyl,
-(C=O)N-dialkyl, -(C=O)Salkyl, hydroxy, alkoxy, alkyl,
higher alkyl, (C6-C16)alkyl, (C6-C22)alkyl, halogen,
nitro, cyano, amino, mercapto, formyl, carboxy,
carbamoyl, alkoxy, (C1-C22)alkylthio,alkylamino,
carbocyclyl, aryl, or heterocyclyl, whereineach R7 is
different, R20;
R15 is hydrogen, -(C=O)Oalkyl(C1-C22), -
(C=O)alkyl(C1-C22), -C=O)NHalkyl(C1-C22), -
31
C22)alkylsulfonyl, (C6-12)arylsulfonyl, (C3-
C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl,wherein
or different, R20;
R15’ is hydrogen, -(C=O)Oalkyl(C1-C22), -
(C=O)alkyl(C1-C22), -C=O)NHalkyl(C1-C22), -
nitro, cyano, amino,
substituted with one or more, the same or different,R20;
If Q = -O(C=O)V- and V = NR7 then the R7s can
together form a ring that is optionally substitutedwith
R20 is deuterium, (C1-C22)alkyl, (C2-C22)alkenyl,
(C2-C22)alkynyl, halogen, nitro, cyano, hydroxy,amino,
amido, mercapto, formyl, carboxy, carbamoyl, azido,
C22)alkylamino, ((C1-22)alkyl)2amino, (C1-
heterocyclyl; and
wherein lipid comprises a C6-22 alkyl, (C6-C22)alkoxy,
polyethylene glycol, or (C6-C12)aryl substituted with an
(C1-C22)alkyl group, heterocyclylis carbocyclyl
comprising 1-4 heteroatoms selected from nitrogen,
oxygen, or sulfur,
Claim 9:
IN201717025098 D1: US 2003/0087873 A1

CLAIM 9 A pharmaceutical composition [0124]
comprising a pharmaceutically acceptable In another embodiment of the invention, anti- virally or anti proliferatively
excipient and a compound of Formula II, effective nucleoside is a B-L nucleoside of the general formula (III)
[0114] each D is hydrogen, alkyl, acyl, monophosphate, diphosphate,

or salt thereof, wherein triphosphate, monophosphate ester, diphosphate ester, triphosphate ester,
Q is O, -O(C=O)-, -O(C=O)Lipid, -O(C=O)V-, phospholipid or amino acid;
NH, or NR7; [0116] each X1 and X2 is independently hydrogen, halogen (F, Cl, Br or
V is O, NH, NR7, S, CH2, or CHR7; I), NH, NHR4', NR4'R4'',NHOR4, NR4'NR4’’R4", OH, OR, SH or SR';
W is CH2, NH, S or O; [0117] each Y is O, S or Se;
X is CH2 or O; [0119] each R1 and R1' is independently hydrogen, lower alkyl, lower
Y is N or CR”; alkenyl, lower alkynyl, aryl, alkylaryl, halogen (F, Cl, Br or I), NH,
Z is N or CR”; NHR, NRR, NHOR, NRNHR, NRNRR", OH, OR, SH, SR5, NO, NO,
each R” is independently selected from is H, D, CH-OH, CHOR, COH, COR, CONH, CONHR, CONRR or CN:
F, Cl, Br, I, CH3, CD3, CF3, alkyl, acyl, alkenyl, [0120] each R2 and R2’ independently is hydrogen or halogen (F, Cl, Br
alkynyl, hydroxyl, formyl or SCH3; or I), OH, SH, OCH3, SCH3, NH2, NH2CH3, CH2=CH2, CN, CH2-NH,
R1 is monophosphate, diphosphate, triphosphate, CH2-OH, CO2H.
[0121] each R3 and R3’ independently is hydrogen or halogen (F, Cl, Br
or I), OH, SH, OCH3, SCH3, NH, NHCH3, CH3, C2H3, CH=CH, CN,
CH-NH2, CH2OH, CO2H.
32
[0122] each R4, R4', R4", R5, R5’ and R5" indepenently is hydrogen,
lower alkyl, lower alkenyl, aryl, or arylalkyl Such as unsubstituted or
Substituted phenyl or benzyl,
[0123] such that for each nucleoside of the general formula (1) or (II), at
least one of R2 and R2’ is hydrogen and at least one of R3 and R3’ is
hydrogen.
Y1 is O or S;
Y3 is OH or BH3-M+;
R2 is hydrogen, alkyl, alkenyl, alkynyl, ethynyl,
fluoromethyl, difluoromethyl,
trifluoromethyl,chloromethyl, hydroxymethyl,
formyl, carboxy, carbamoyl, alkoxy, (C1-
C22)alkylthio, alkylamino, (alkyl)2amino,
alkylsulfinyl, alkylsulfonyl, arylsulfonyl,
carbocyclyl, aryl,azido, or heterocyclyl;
R3 is hydrogen, hydroxy, alkyl, halogen, nitro,
cyano, hydroxy, amino, mercapto, formyl,
carboxy, carbamoyl, alkoxy, (C1-C22)alkylthio,
alkylamino, alkyl)2amino, alkylsulfinyl,
alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or
heterocyclyl;
R4 is hydrogen, hydroxy,(C1-C22)alkyl,
fluoromethyl, difluoromethyl, rifluoromethyl,
hydroxymethyl,halogen, nitro, cyano, hydroxy,
(C1-C22)alkoxy, (C1-C22)alkylthio,(C1-
difluoromethyl,trifluoromethyl, hydroxymethyl,
allenyl, halogen, nitro, cyano, amino, mercapto,
formyl, carboxy, carbamoyl,alkoxy, (C1-
C22)alkylthio, alkylamino, (alkyl)2amino,
alkylsulfinyl, alkylsulfonyl, arylsulfonyl,
carbocyclyl, aryl,or heterocyclyl;
R6 is hydrogen, hydroxy, alkoxy, alkyl, ethynyl,
allenyl, halogen, nitro, cyano, amino,
mercapto,formyl, carboxy, carbamoyl, alkoxy,
(C1-C22)alkylthio, alkylamino, (alkyl)2amino,
alkylsulfinyl, alkylsulfonyl,arylsulfonyl,
hydrogen, -(C=O)Oalkyl, -(C=O)alkyl, -
(C=O)NHalkyl, -(C=O)N-dialkyl, -(C=O)Salkyl,
hydroxy, alkoxy, alkyl, higher alkyl, (C6-
C16)alkyl, (C6-C22)alkyl, halogen, nitro, cyano,
alkoxy, (C1-C22)alkylthio,alkylamino,
(alkyl)2amino, alkylsulfinyl, alkylsulfonyl,
arylsulfonyl, carbocyclyl, aryl, or heterocyclyl,
33
cyano,hydroxy, benzyloxy, amino, amido,
C22)alkylsulfinyl, (C1-22)alkylsulfonyl, (C6-
12)aryl,orheterocyclyl, wherein R8 is optionally
different, R20;
(C1-C22)alkylamino,((C1-C22)alkyl)2amino,
(C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl,
(C6-C12)arylsulfonyl, (C3-C6)carbocyclyl,(C6-
C12)aryl,orheterocyclyl, wherein R9 is optionally
different, R20;
R10 is hydrogen, (C1-C22)alkyl, cycloalkyl,
lipid, methyl, ethyl, isopropyl, cyclopentyl,
cyclohexyl,butyl, pentyl, hexyl, neopentyl,
mercapto, formyl, carboxy,carbamoyl, (C1-
22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6-
optionally substituted with one or more, the same
or different, R20;
mercapto,formyl, carboxy, carbamoyl, (C1-
22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-
or different, R20;
phenyl, 1-naphthyl, 2-
naphthyl,aromatic,heteroaromatic, 4-substituted
phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-
bromophenyl, naphthyl, or heterocyclyl, wherein
R12 is optionally substituted with one or more,
carboxy, carbamoyl, lipid, azido, (C1-
C22)alkoxy, (C1-C22)alkylthio,(C1-
C12)arylsulfonyl,(C3-C6)carbocyclyl, (C6-
or different, R20;
carboxy, arbamoyl, lipid, azido, (C1-C22)alkoxy,
(C1-C22)alkylthio,(C1-C22)alkylamino, ((C1-
C22)alkyl)2amino, alkylsulfinyl, (C1-
C22)alkylsulfonyl, (C6-12)arylsulfonyl, (C3-
C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl,
34
wherein R14 is optionally substituted with one or
together form a ring that is optionally substituted
with one or more, the same or different, R20;
cyano, hydroxy,amino, amido, mercapto, formyl,
22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-
and wherein lipid comprises a C6-22 alkyl, (C6-
C22)alkoxy, polyethylene glycol, or (C6-
C12)aryl substituted
with an (C1-C22)alkyl group, heterocyclylis
acarbocyclylcomprising 1-4 heteroatoms selected
from nitrogen, oxygen, or sulfur, and
heteroaromatic is an aromatic
heterocyclylcomprising 1-4 heteroatoms selected
from nitrogen,oxygen, or sulfur and at least 1
carbon atom.
Claim 10:
IN201717025098 D1: US 2003/0087873 A1

CLAIM 10 The pharmaceutical composition of Claim 10 is dependent on claim 1. Argument for claim 1
claim 1,further comprising a propellant.
applies as such here making claim 10 not novel. Propellant
itself is no invention.
Claim 11:
IN201717025098 D1: US 2003/0087873 A1

CLAIM 11 The pharmaceutical composition of Claim 10 is dependent on claim 1. Argument for claim 1
claim 10, wherein the propellant is compressed air,
applies as such here making claim 10 not novel. Propellant
ethanol, nitrogen, carbon dioxide, nitrous oxide,
hydrofluoroalkanes (HFA), 1,1,1,2,- itself is no invention.
tetrafluoroethane, 1,1,1,2,3,3,3-heptafluoropropane
or combinations thereof.
Claim 12:
IN201717025098 D1: US 2003/0087873 A1

CLAIM 12 The composition of claim 1, wherein [175] In a sub-embodiment of the present invention, the
the compound has a structure according to anti-virally or anti-proliferatively effective E-D or B-L
Formula IA nucleoside is of the formula (XX):

R7 is H,
Y is independently selected from is H, D, F, Cl,
Br, I, CH3, CD3, CF3, alkyl, acyl, alkenyl, [0185] or its pharmaceutically acceptable salt or prodrug
35
alkynyl, hydroxyl, formyl or SCH3; thereof, wherein:
R1 is [0186 ] each D, P1, P2, P3, R1, R4, R4’ and R9 is the Same as defined
monophosphate previously.
ester, diphosphate [0114] each D is hydrogen, alkyl, acyl, monophosphate, diphosphate,
ester triphosphate, monophosphate ester, diphosphate ester, triphosphate
ester, phospholipid or amino acid;
[0119] each R1 and R1' is independently hydrogen, lower alkyl, lower
alkenyl, lower alkynyl, aryl, alkylaryl, halogen (F, Cl, Br or I), NH,
NHR, NRR, NHOR, NRNHR, NRNRR", OH, OR, SH, SR5, NO, NO,
CH-OH, CHOR, COH, COR, CONH, CONHR, CONRR or CN:
[0178] each R9 is hydrogen, halogen (F, Cl, Br or I) or OP3;

[0179] each P1 is hydrogen, lower alkyl, lower alkenyl, aryl, arylalkyl
(such as an unsubstituted or substituted phenyl or benzyl), OH, OR, NH,
NHR' or NR'R'; and
[0180] each P2 and P3 is independently hydrogen, alkyl, acyl, -MS, -Ts,
monophosphate, diphosphate, triphosphate, mono-phosphate ester,
diphosphate ester, triphosphate ester, phospholipid or amino acid, though
preferably hydrogen
[0319] In another sub-embodiment of the present invention, the anti-

amino, mercapto, formyl, carboxy, carbanoyl, virally or anti-proliferatively effective ᵝ-D or ᵝ-L nucleoside is of the
esteryl, alkoxy, (C1- formula (XX):
C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, or
phosphoramidyl, wherein R1 is optionally
different, R20, Y1 is O or S;
Y3 is OH or BH3-M+;
R4 is hydrogen, hydroxy, (C1-C22)alkyl, [0320] or its pharmaceutically acceptable salt or prodrug
fluoromethyl, difluoromethyl, trifluoromethyl, thereof, wherein:
hydroxymethyl, halogen, nitro, cyano, hydroxy, [0321] each D, P', P, P, R, R', R"and R is the Same as defined previously.
(C1-C22)alkoxy, (C1-C22)alkylthio, (C1- [0341] In a preferred embodiment, the B-D and B-L nucleosides of
C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- general formula (I-a) and (III-a) are represented by the non-limiting
C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- examples provided in Table 1.
or different, R20;
mercapto, formyl, carboxy, carbamoyl, azido, X1 Y1 R1 R1 R2 R2’ R3
BS NH-OH O H H H -OH H
BT NH-OH O F H H -OH H
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- BU NH-OH O BR H H -OH H
C12)aryl,orheterocyclyl, wherein R8 is optionally BV NH-OH O I H H -OH H
substituted with one or more, the same or BW NH-OH O H H OH -H H
different, R20;
R9 is hydrogen, methyl, ethyl, tert-butyl, (C1- Claim 32
C22)alkyl, halogen, nitro, cyano, hydroxy, A method for the treatment or prophylaxis of host exhibiting a
amino, mercapto, formyl, carboxy, carbamoyl, Flaviviridae, Orthomyxoviridae or Paramyxoviridae viral infection or
cycloalkyl, (C1-C22)alkoxy, (C1-C22)alkylthio, abnormal cellular proliferation comprising administering an effective
(C1-C22)alkylamino,((C1-C22)alkyl)2amino, amount of a compound of the general formula (XX):
(C6-C12)arylsulfonyl, (C3-C6)carbocyclyl,(C6-
different, R20;
36
cyclohexyl,butyl, pentyl, hexyl, neopentyl,
mercapto, formyl, carboxy,carbamoyl, (C1-
or different, R20;
methyl, halogen, nitro, cyano, hydroxy, amino, its β-L enantiomer or its pharmaceutically acceptable salt thereof,
mercapto, formyl, carboxy, carbamoyl, (C1- wherein:
C22)alkoxy, (C1-C22)alkylthio, (C1- each D, P1, P2, P3, R1, R4, R4′ and R9 is the same as defined previously.
C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- Claim 33. A method for the treatment or prophylaxis of host exhibiting a
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- Flaviviridae, Orthomyxoviridae or Paramyxoviridae viral infection or
C12)aryl, or heterocyclyl, wherein R11 is abnormal cellular proliferation comprising administering an effective
optionally substituted with one or more, the same amount of a compound of the general formula (XXI):
or different, R20;
phenyl, 1-naphthyl, 2-naphthyl, aromatic,
or different, R20;
cyano, hydroxy, amino, amido, mercapto, formyl,
carboxy, carbamoyl, lipid, azido, (C1- its β-L enantiomer or its pharmaceutically acceptable salt thereof,
C22)alkoxy, (C1-C22)alkylthio, wherein: each D, P1, P2, P3, R1, R4 and R4′ is the same as defined
(C1-C22)alkylamino, ((C1-C22)alkyl)2amino, previously.
(C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, Claim 34. A method for the treatment or prophylaxis of host exhibiting a
(C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- Flaviviridae, Orthomyxoviridae or Paramyxoviridae viral infection or
C12)aryl, or heterocyclyl, wherein R13 is abnormal cellular proliferation comprising administering an effective
optionally substituted with one or more, the same amount of a compound of the general formula:
or different, R20;
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- its β-L enantiomer or its pharmaceutically acceptable salt thereof,
C12)aryl, or heterocyclyl, wherein R14 is wherein:
optionally substituted with one or more, the same each D, P2 and P3 is the same as defined previously.
or different, R20; Claim 37. A method for the treatment or prophylaxis of host exhibiting a
Flaviviridae, Orthomyxoviridae or Paramyxoviridae viral infection or
abnormal cellular proliferation comprising administering an effective
amount of a compound of the general formula (XXIII):
its β-L enantiomer or its pharmaceutically acceptable salt thereof,

wherein:
each D, P1, P2, P3, R1, R4 and R4′ is the same as defined previously.
44. A method for the treatment or prophylaxis of a hepatitis C virus
infection in a host comprising administering an effective treatment amount
of a compound according to any one of claims 1-29.
Claim 45. A method for the treatment or prophylaxis of a hepatitis C virus

of a β-D nucleoside of the formula (XIX):
37
wherein:
each D, R1, R4 and R4′ is the same as defined previously;
each R9 is hydrogen, halogen (F, Cl, Br or I) or OP3;
each P1 is hydrogen, lower alkyl, lower alkenyl, aryl, arylalkyl (such as an
unsubstituted or substituted phenyl or benzyl), OH, OR4, NH2, NHR4 or
NR4R4′; and
each P2 and P3 is independently hydrogen, alkyl, acyl, -Ms, -Ts,
monophosphate, diphosphate, triphosphate, mono-phosphate ester,
diphosphate ester, triphosphate ester, phospholipid or amino acid;
optionally in a pharmaceutically acceptable carrier.

of a 1-D nucleoside of the formula (XX):

wherein:
each D, P1, P2, P3, R1, R4, R4′ and R9 is the same as defined previously;
of a β-D nucleoside of the formula (XXI):
its 1-L enantiomer or its pharmaceutically acceptable salt thereof,

wherein:
each D, P1, P2, P3, R1, R4 and R4′ is the same as defined previously;
of a β-D nucleoside of the formula:
38
wherein:
each D, P2 and P3 is the same as defined previously;
Claim 55 A method for the treatment or prophylaxis of a hepatitis C virus

of a nucleoside of the formula:
or its pharmaceutically acceptable salt thereof; optionally in a

pharmaceutically acceptable carrier.
Claim 13:
IN201717025098 D1: US 2003/0087873 A1

CLAIM 13 [0124]
The composition of claim 1, wherein R4 is In another embodiment of the invention, anti- virally or anti proliferatively
hydrogen, hydroxy, alkyl, halogen, or fluoro. effective nucleoside is a B-L nucleoside of the general formula (III)

triphosphate, monophosphate ester, diphosphate ester, triphosphate
[0116] each X1 and X2 is independently hydrogen, halogen (F, Cl, Br or
I), NH, NHR4', NR4'R4'',NHOR4, NR4'NR4’’R4", OH, OR, SH or SR';
or I), OH, SH, OCH3, SCH3, NH2, NH2CH3, CH2=CH2, CN, CH2-NH,
CH2-OH, CO2H.
39
hydrogen.
Also mentioned in [0260] as compound IIIa
[0341] In a preferred embodiment, the B-D and B-L nucleosides of

general formula (I-a) and (III-a) are represented by the non-limiting
examples provided in Table 1.
Claim 14:
IN201717025098 D1: US 2003/0087873 A1

CLAIM 14 [0124]
The composition of claim 1, wherein R5 is In another embodiment of the invention, anti- virally or anti proliferatively
hydrogen, hydroxy, alkoxy, alkyl, methyl, effective nucleoside is a B-L nucleoside of the general formula (III)
ethynyl, or allenyl.

triphosphate, monophosphate ester, diphosphate ester, triphosphate
[0116] each X1 and X2 is independently hydrogen, halogen (F, Cl, Br or
I), NH, NHR4', NR4'R4'',NHOR4, NR4'NR4’’R4", OH, OR, SH or SR';
or I), OH, SH, OCH3, SCH3, NH2, NH2CH3, CH2=CH2, CN, CH2-NH,
CH2-OH, CO2H.
hydrogen.
Also mentioned in [0260] as compound IIIa
40
Without prejudice and in the alternative it is submitted that all the claims of the impugned
application are anticipated by the disclosure of D1.
Thus all claims of IN201717025098 lack novelty as per section 2(1)(l) of the Act. For this
reason alone the opposed application should not be granted a patent as per section 25(1)(b).
B. Opponent further introduces prior art US20140235566A1 (D2) to Franck Amblard

contest the novelty of the invention. US20140235566A1 to Franck Amblard of Emory
University, was filed on Oct 29, 2013 having priority dates of Oct 29, 2012 & Feb 12,
2013 is a permissible prior art for IN20717025098 having priority date of Dec 26, 2014.
ii) Lack of novelty in view of US20140235566A1 (D2) to Franck Amblard
D2 discloses compounds, compositions and methods for treating or preventing cancer and
viral infections, in particular, HIV, HCV, Norovirus, Saporovirus, cytomegalovirus (CMV),
herpes viruses (HSV-1, HSV-2), Dengue virus, Yellow fever, or HBV in human patients or
other animal hosts. The compounds are certain A-hydroxycytidine nucleosides derivatives,
modified monophosphate and phosphonates prodrugs analogs, and pharmaceutically
acceptable, salts, prodrugs, and other derivatives thereof. In particular, the compounds show
potent antiviral activity against HIV-1, HIV-2, HCV, Norovirus, Saporovirus,
cytomegalovirus (CMV), herpes viruses (HSV-1, HSV-2), Dengue virus, Yellow fever, and
HBV.
Petitioner discusses the reasons of anticipation of claims wrt to disclosure of D2.
Claim 1:
IN201717025098 D2: US20140235566A1

CLAIM 1: A pharmaceutical composition [0040] In one embodiment, the compound is a compound of Formula (I):
comprising a pharmaceutically acceptable
excipient and a compound having Formula I
[0041] or a pharmaceutically acceptable salt or prodrug thereof, wherein:

[0042] i) X1 is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6, alkoxy, C1-C6
alkenyl, C1-C6 alkynyl, COR', or COOR';
[0043] ii) X2 is hydrogen, COR', or COOR' wherein each R' is,
independently, CH2-O(CO)- X5, CH2- O(CO)O X5C1-20 alkyl, the
carbon chain derived from a fatty alcohol or C1-20 alkyl substituted with
41
W is O; a C1-C6, alkyl, alkoxy, di(C1-C6 alkyl)-amino, fluoro, C3-10 cycloalkyl,
X is CH2,CHMe, CMe2, CHF, CF2, or CD2; cycloalkyl alkyl, cycloheteroalkyl, aryl, heteroaryl, substituted aryl, or
Y is CR”; substituted heteroaryl; wherein the Substituents are C1-6 alkyl, or C1-6
Z is CR”; alkyl Substituted with a C1-C6 alkyl, C1—C6 alkoxy, di(C1-C6 alkyl)-
each R” is independently selected from is H, D, amino, fluoro, or C3-10 cycloalkyl
F, Cl, Br, I, CH3, CD3, CF3, C1-22alkyl, acyl, [0045] iii) Each X3 and X4 is independently H, C1-6, alkyl, C2-6alkenyl,
C2- 22alkenyl, C2-22alkynyl, hydroxyl, formyl C-alkynyl, aryl, alkylaryl, halogen (F, Cl,Br, I), NH2, OH, SH, CN, or
or SCH3; NO2.
R1 is [0046] In one embodiment, Sugar is ribose or a modified ribose of the
general Formula (II):
Monophosphate
ester, diphosphate
ester
[0047] wherein:
[048] D is H, C(O)R1, C(O)OR1, diphosphate ester, or triphosphate
ester;
[0049] R' is as defined above:
[0050] W is CL2 or CL2CL2, wherein L independently is selected from
the group consisting of H, C1-6 alkyl, C2-6 alkenyl, and C2-6alkynyl,
wherein C1-6 alkyl, C2-6alkenyl, and C2-6 alkynyl can each optionally
contain one or more heteroatoms;
alkyl, halogen, nitro, cyano, hydroxy, amino, [0051] A is O, S, CH, CHF, CF, C=CH, C=CHF, or C—CF;
mercapto, formyl, carboxy, carbamoyl, [0052] R4, R5, R5’ R6, R6’, and R7 are independently selected from the
carbanoyl, esteryl, alkoxy, (C1-C22)alkylthio, group consisting of H, F, Cl, Br, I, OH, SH, NH, NHOH, NHNH, N,
(C1-C22)alkylamino, ((C1-C22)alkyl)2amino, C(O)CH, CN, CHOH,
(C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, C(O)NH, C(S)NH, C(O)OR, R, OR, SR, SSR, NHR,and NR2;
(C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- [0173]
C12)aryl, or heterocyclyl, or
phosphoramidylwherein R1 is optionally
different, R20;
Y1 is O or S;
Y2 is OH, OR12, OAlkyl, or BH3 - M+; Y3 is
OH or BH3 - M+;
R3 is hydrogen, hydroxy, (C1-C22)alkyl,
halogen, nitro, cyano, hydroxy, amino,
C22)alkoxy, (C1-C22)alkylthio, , (C1-
[174] In one embodiment, at least one of R5 or R5’ is F, Cl, or Me.
[0177] In another embodiment, L is methyl.
[0178] In another embodiment, the base is a pyrimidine, and one of R5
and R 5’ is OH, Cl, or F.
[0179] The compounds described herein can be in the form of the ᵝL- or
R6 is hydrogen, hydroxy, (C1-C22)alkoxy, (C1-
ᵝD-configuration, or a mixture thereof, including a racemic mixture
C22)alkyl, ethynyl, allenyl, halogen, nitro,
thereof.
cyano, amino, mercapto, formyl, carboxy,
carbamoyl, (C1-C22)alkylthio, (C1-
1-((2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-
methyltetrahydrofuran-2-yl)-4-((octanoyloxy)amino)pyrimidin-2(1H)-one
40
0465.
C12)aryl,orheterocyclyl;
To a precooled (-20°C.) solution of 39 (0.06g, 0.23mmol) in 2 mL of
anhydrous pyridine was added octanoyl chloride (44 uL, 0.26 mmol).
hydrogen, -(C=O)Oalkyl(C1-C22), -
After stirring the mixture at 4C. for 16 h, the reaction was quenched with
(C=O)alkyl(C1- C22), -(C=O)NHalkyl(C1-C22),
MeOH (2 mL) and the Solution was concentrated under reduced pressure.
-(C=O)N-dialkyl(C1-C22), -(C=O)Salkyl(C1-
AcOEt (10 mL) was then added and the mixture was washed with water
C22), hydroxy, (C1-C22)alkoxy, (C1- C22)alkyl,
(3x5 mL). The organic layer was dried overn NaSO filtered and
42
halogen, nitro, cyano, amino, mercapto, formyl, concentrated under reduced pressure. The residue was purified by silica
carboxy, carbamoyl, (C1-C22)alkoxy, (C1- 127 gel column chromatogra
C22)alkylthio, (C1-C22)alkylamino, ((C1- phy (CH.Cl:MeOH=95:5 to 85:15 v/v) to give 40 (0.04 g, 0.09 mmol) in
C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- 37% yield. LCMS (ESI) Calcd for C.H.FNO. 401.4, observed (M+1)
C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3- 402.3
C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, Example 4
different, R20;
(C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-
different, R20;
cyclohexyl, butyl, pentyl, hexyl, neopentyl,
C12)aryl,orheterocyclyl,
R11 is hydrogen, deuterium, (C1-C22)alkyl, [0474]
phenyl, 1-naphthyl, 2-naphthyl,aromatic,
or different, R20;
43
or different, R20;
C22)alkylthio, (C1- C22)alkylamino, ((C1-
and wherein the lipid comprises a C6-22 alkyl,
(C1-C22)alkoxy, polyethylene glycol, or (C6-
C12)aryl substituted with an (C1-C22)alkyl
group, heterocyclylis acarbocyclylcomprising 1-4 [0487] HCV and toxicity data for MP prodrug 39 and the parent
heteroatoms selected from nitrogen, oxygen, or nucleoside 51 is shown below in Table 3.
sulfur, and heteroaromatic is an aromatic
from nitrogen, oxygen, or sulfur and at least 1
carbon atom.
[0534] The data on Vero, human PBM, and CEM (human

lymphoblastoid) cells is shown below in Table 5:
[0545]
44
Claim 1
1. A compound of Formula (I):
or a pharmaceutically acceptable salt or prodrug thereof,

wherein:
X1 is H, C1-C6 alkyl, C1-C6haloalkyl, C1-C6 alkoxy, C2-C6 alkenyl,
C2-C6 alkynyl, COR', or COOR';
X2 is hydrogen, COR1, or COOR1
wherein each R1 is, independently, CH2-O(CO)-X5, CH2-O(CO)O-X5,
C1-10 alkyl, the carbon chain derived from a fatty alcohol or C1-20 alkyl
substituted with a C1-C6 alkyl, alkoxy, di(C-C alkyl)-amino, fluoro, Co
cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aryl, heteroaryl, substituted
aryl, or substituted heteroaryl; wherein the Substituents are C1-6 alkyl, or
C1-6 alkyl substituted with a C-C alkyl, C1-C6 alkoxy, di(C-C alkyl)-
amino, fluoro, or C3-10 cycloalkyl
X5 is independently, C1-20 alkyl, the carbon chain derived from a fatty
alcohol or C1-20 alkyl Substituted with a C1-C6 alkyl, alkoxy, C1-6
cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aryl, heteroaryl, substituted
aryl, or substituted heteroaryl; wherein the substituents are C1-6alkyl, or
C1-6alkyl substituted with a C1-C6 alkyl, C1-C6,alkoxy, di(C-C alkyl)-
eachX3 and X4 is independently H, C1-6 alkyl, C2-6alkenyl, C2-
6alkynyl, aryl, alkylaryl, halogen, NH2, OH, SH, CN, or NO2.
Claim 2
The compound of claim 1, wherein each R' is, independently, Co alkyl,
the carbon chain derived from a fatty alcohol or C1-20 alkyl substituted
with a C1-C20 alkyl, alkoxy, di (C1-C6 alkyl)-amino, fluoro, C1-6
cycloalkyl, cycloalkyl, alkyl, cycloheteroalkyl, aryl, heteroaryl,
Substituted aryl, or substituted heteroaryl; wherein the substituents are
Calkyl, or C. alkyl Substituted with a C1-C6 alkyl, C1-C6 alkoxy, di (C1-
C6 alkyl)-amino, fluoro, or C3-10 cycloalkyl.
3. The compound of claim 1, wherein Sugar is ribose or a modified ribose
of the general Formula (II):
45
wherein:
[D is H, C(O)R1, C(O)OR1, diphosphate ester, or triphosphate ester;
R' is as defined above:
W is CL2 or CL2CL2, wherein L independently is selected from the
group consisting of H, C1-6 alkyl, C2-6 alkenyl, and C2-6alkynyl,
wherein C1-6 alkyl, C2-6alkenyl, and C2-6 alkynyl can each optionally
contain one or more heteroatoms;
A is O, S, CH, CHF, CF, C=CH, C=CHF, or C—CF;
R4, R5, R5’ R6, R6’, and R7 are independently selected from the group
consisting of H, F, Cl, Br, I, OH, SH, NH, NHOH, NHNH, N, C(O)CH,
CN, CHOH,
C(O)NH, C(S)NH, C(O)OR, R, OR, SR, SSR, NHR,and NR2;
5. The compound of claim3, wherein R7’ is independently selected from
the group consisting of H, F, Cl, Br, I, N,C(O)OH, CN, CH-OH, C(O)NH,
C(S)NH, C(O)OR, and R, and wherein R is independently a C-C alkyl,
C2-alkenyl, C-alkynyl, C. cycloalkyl, (C-C cycloalkyl) aryl, alkylaryl, or
arylalkyl, wherein the groups can be substituted with one or more
substituents as defined above in claim 1.
Thus, it is clear that all elements of claim 1of IN201717025098 are covered in D2.
Therefore, claim 1 and all dependent claims lacks novelty in view of D2 also.
Claim 2:
IN201717025098 D2: US20140235566A1

CLAIM 2: The pharmaceutical composition of [0040] In one embodiment, the compound is a compound of Formula
claim 1, wherein Q-R7 is OH. (I):
[0041] or a pharmaceutically acceptable salt or prodrug thereof,

wherein: [0043] ii) X2 is hydrogen, COR', or COOR'
Claim 1
1. A compound of Formula (I):

wherein:
X2 is hydrogen, COR1, or COOR1
46
Thus, all referred claims of IN201717025098 are anticipated by D2.
Claim 3
IN201717025098 D2: US20140235566A1

CLAIM 3: The pharmaceutical composition of 6. The compound of claim 1, wherein Sugar is ribose or modified ribose
claim 1, wherein R1 is of the general Formulas (III) or (IV):
wherein:
Y is O or S;
R9 is (C6-C22)alkyl. Z is selected from the group consisting of CL2, CL2CL2, CL2OCL2,
CL2SCL2, CL2O, OCL2 and CL2NHCL2, wherein L independently is
selected from the group consisting of H, F, C1-6 alkyl, C2-6 alkenyl, and C2-
6alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6alkynyl can each
optionally contain one or more heteroatoms;
A is O, S, CH2, CHF, CF2, C═CH2, C═CHF, or C═CF2;
R4′, R5, R5′, R6, R6′, and R7′ are independently selected from the group
consisting of H, F, Cl, Br, I, OH, SH, NH2, NHOH, NHNH2, N3, C(O)OH,
CN, CH2OH, C(O)NH2, C(S)NH2, C(O)OR, R, OR, SR, SSR, NHR, and
NR2;
R5′ and R6′ can come together to form a ring
wherein when A is O or S, R7′ cannot be OH, SH, NH2, NHOH, NHNH2,

OR, SR, SSR, NHR, or NR2, and
R is independently a C1-6 alkyl, C2-6 alkenyl, and C2-6alkynyl, C3-
C6 cycloalkyl, aryl, alkylaryl, or arylalkyl, wherein the groups can be
substituted with one or more substituents as defined above in claim 1,
R24 is selected from the group consisting of OR15,
and fatty alcohols,

R15 is selected from the group consisting of H, Li, Na, K, phenyl and
pyridinyl; wherein phenyl and pyridinyl are optionally substituted with
one to three substituents independently selected from the group consisting
of (CH2)0-6CO2R16 and (CH2)0-6CON(R16)2;
R17 is selected from those groups occurring in natural L-amino acids, C1-
6 alkyl, C2-6 alkenyl, C2-6alkynyl, C3-C6 cycloalkyl, aryl, alkylaryl, or
arylalkyl, wherein the groups can be substituted with one or more
substituents as defined above in claim 1,
R18 is H, C1-20 alkyl, the carbon chain derived from a fatty alcohol or C1-
20 alkyl substituted with a C1-C6 alkyl, C1-C6 alkoxy, di(C1-C6 alkyl)-
amino, fluoro, C3-10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aryl,
heteroaryl, substituted aryl, or substituted heteroaryl; wherein the
substituents are C1-5 alkyl, or C1-5 alkyl substituted with a C1-C6 alkyl, C1-
47
C6 alkoxy, di(C1-C6 alkyl)-amino, fluoro, C3-10 cycloalkyl, or cycloalkyl;
R2 and R3 are independently selected from the group consisting of:
(a) OR8 where R8 is H, Li, Na, K, C1-20 alkyl, C3-6 cycloalkyl, C1-
6 haloalkyl, aryl, or heteroaryl, optionally substituted with one to three
substituents independently selected from the group consisting of C1-
9a
6 alkyl, C2-6 alkenyl, C2-6alkynyl, C1-6 alkoxy, (CH2)0-6CO2R , halogen,
C1-6 haloalkyl, —N(R9a)2, C1-6 acylamino, —NHSO2C1-6 alkyl, —
SO2N(R9a)2, —SO2C1-6 alkyl, COR9b, nitro, cyano
Claim 4:
IN201717025098 D2: US20140235566A1

CLAIM 4. [0040] In one embodiment, the compound is a compound of Formula (I):
A pharmaceutical composition comprising a
pharmaceutically acceptable excipient and a
compound of formula IB,
Formula IB, or salts thereof, wherein [0041] or a pharmaceutically acceptable salt or prodrug thereof, wherein:
V is absent, O, NH, NR15, S, CH2, or CHR15; [0042] i) X1 is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6, alkoxy, C1-C6
X is CH2,CHMe, CMe2, CHF, CF2, or CD2; alkenyl, C1-C6 alkynyl, COR', or COOR';
Y is H, D, F, Cl, Br, I, CH3, CD3, CF3, (C1- [0043] ii) X2 is hydrogen, COR', or COOR' wherein each R' is,
C6)alkyl, acyl, (C2-C6)alkenyl, (C2- independently, CH2-O(CO)- X5, CH2- O(CO)O X5C1-20 alkyl, the
C6)alkynyl, hydroxyl, formyl or SCH3; carbon chain derived from a fatty alcohol or C1-20 alkyl substituted with
R1 a C1-C6, alkyl, alkoxy, di(C1-C6 alkyl)-amino, fluoro, C3-10 cycloalkyl,
cycloalkyl alkyl, cycloheteroalkyl, aryl, heteroaryl, substituted aryl, or
substituted heteroaryl; wherein the Substituents are C1-6 alkyl, or C1-6
alkyl Substituted with a C1-C6 alkyl, C1—C6 alkoxy, di(C1-C6 alkyl)-
[0045] iii) Each X3 and X4 is independently H, C1-6, alkyl, C2-6alkenyl,
C-alkynyl, aryl, alkylaryl, halogen (F, Cl,Br, I), NH2, OH, SH, CN, or
NO2.
[0046] In one embodiment, Sugar is ribose or a modified ribose of the
general Formula (II):
Monophosphate
ester,
diphosphate
[0047] wherein:
ester [048] D is H, C(O)R1, C(O)OR1, diphosphate ester, or triphosphate
ester;
alkyl, halogen, nitro, cyano, hydroxy, amino, [0049] R' is as defined above:
mercapto, formyl, [0050] W is CL2 or CL2CL2, wherein L independently is selected from
carboxy, carbamoyl, carbanoyl, esteryl, alkoxy, the group consisting of H, C1-6 alkyl, C2-6 alkenyl, and C2-6alkynyl,
(C1C22)alkylthio, (C1-C22)alkylamino, ((C1- wherein C1-6 alkyl, C2-6alkenyl, and C2-6 alkynyl can each optionally
C22)alkyl)2amino, contain one or more heteroatoms;
(C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, [0051] A is O, S, CH, CHF, CF, C=CH, C=CHF, or C—CF;
(C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- [0052] R4, R5, R5’ R6, R6’, and R7 are independently selected from the
C12)aryl, or heterocyclyl, or group consisting of H, F, Cl, Br, I, OH, SH, NH, NHOH, NHNH, N,
phosphoramidyl,wherein R1 is optionally C(O)CH, CN, CHOH,
substituted with one or more, the same or C(O)NH, C(S)NH, C(O)OR, R, OR, SR, SSR, NHR,and NR2;
different, R20;
Y1 is O or S; Claim 1
Y2 is OH, OR12, OAlkyl, or BH3-M+; 1. A compound of Formula (I):
Y3 is OH or BH3-M+;
48
amino, mercapto, formyl, carboxy, carbamoyl, ,
(C1-C22)alkoxy, (C1-
C12)aryl,orheterocyclyl, wherein R8 is optionally or a pharmaceutically acceptable salt or prodrug thereof,
substituted with one or more, the same or wherein:
different, R20; X1 is H, C1-C6 alkyl, C1-C6haloalkyl, C1-C6 alkoxy, C2-C6 alkenyl,
R9 is hydrogen, methyl, ethyl, tert-butyl, (C1- C2-C6 alkynyl, COR', or COOR';
C22)alkyl, halogen, nitro, cyano, hydroxy, X2 is hydrogen, COR1, or COOR1
amino,mercapto, formyl, carboxy, carbamoyl, wherein each R1 is, independently, CH2-O(CO)-X5, CH2-O(CO)O-X5,
cycloalkyl, (C1-C22)alkoxy, (C1-C22)alkylthio, C1-10 alkyl, the carbon chain derived from a fatty alcohol or C1-20 alkyl
(C1-C22)alkylamino,((C1-C22)alkyl)2amino, substituted with a C1-C6 alkyl, alkoxy, di(C-C alkyl)-amino, fluoro, Co
(C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aryl, heteroaryl, substituted
(C6-C12)arylsulfonyl, (C3-C6)carbocyclyl,(C6- aryl, or substituted heteroaryl; wherein the Substituents are C1-6 alkyl, or
C12)aryl,orheterocyclyl, wherein R9 is optionally C1-6 alkyl substituted with a C-C alkyl, C1-C6 alkoxy, di(C-C alkyl)-
substituted with one or more, the same or amino, fluoro, or C3-10 cycloalkyl
different, R20; X5 is independently, C1-20 alkyl, the carbon chain derived from a fatty
R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, alcohol or C1-20 alkyl Substituted with a C1-C6 alkyl, alkoxy, C1-6
lipid, methyl, ethyl, isopropyl, cyclopentyl, cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aryl, heteroaryl, substituted
cyclohexyl, butyl, pentyl, hexyl, neopentyl, aryl, or substituted heteroaryl; wherein the substituents are C1-6alkyl, or
benzyl, halogen, nitro, cyano, hydroxy, amino, C1-6alkyl substituted with a C1-C6 alkyl, C1-C6,alkoxy, di(C-C alkyl)-
mercapto, formyl, carboxy,carbamoyl, (C1- amino, fluoro, or C3-10 cycloalkyl
C22)alkoxy, (C1-C22)alkylthio, (C1- eachX3 and X4 is independently H, C1-6 alkyl, C2-6alkenyl, C2-
C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- 6alkynyl, aryl, alkylaryl, halogen, NH2, OH, SH, CN, or NO2.
C22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6- Claim 2
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- The compound of claim 1, wherein each R' is, independently, Co alkyl,
C12)aryl,orheterocyclyl, wherein R10 the carbon chain derived from a fatty alcohol or C1-20 alkyl substituted
isoptionally substituted with one or more, the with a C1-C20 alkyl, alkoxy, di (C1-C6 alkyl)-amino, fluoro, C1-6
same or different, R20; cycloalkyl, cycloalkyl, alkyl, cycloheteroalkyl, aryl, heteroaryl,
R11 is hydrogen, deuterium, (C1-C22)alkyl, Substituted aryl, or substituted heteroaryl; wherein the substituents are
methyl, halogen, nitro, cyano, hydroxy, amino, Calkyl, or C. alkyl Substituted with a C1-C6 alkyl, C1-C6 alkoxy, di (C1-
mercapto, formyl, carboxy, carbamoyl, (C1- C6 alkyl)-amino, fluoro, or C3-10 cycloalkyl.
C22)alkoxy, (C1-C22)alkylthio, (C1- 3. The compound of claim 1, wherein Sugar is ribose or a modified ribose
C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- of the general Formula (II):
or different, R20;
R12 is hydrogen, (C1-C22)alkyl, (C6-C12)aryl, wherein:
phenyl, 1-naphthyl, 2-naphthyl,aromatic, [D is H, C(O)R1, C(O)OR1, diphosphate ester, or triphosphate ester;
heteroaromatic, 4-substituted phenyl, 4- R' is as defined above:
fluorophenyl, 4-chlorophenyl, 4-bromophenyl, W is CL2 or CL2CL2, wherein L independently is selected from the
naphthyl, or heterocyclyl, wherein R12 is group consisting of H, C1-6 alkyl, C2-6 alkenyl, and C2-6alkynyl,
optionally substituted with one or more, the same wherein C1-6 alkyl, C2-6alkenyl, and C2-6 alkynyl can each optionally
or different, R20; contain one or more heteroatoms;
R13 is hydrogen, deuterium, (C1-C22)alkyl, (C2- A is O, S, CH, CHF, CF, C=CH, C=CHF, or C—CF;
C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, R4, R5, R5’ R6, R6’, and R7 are independently selected from the group
cyano, hydroxy, amino, amido, mercapto, formyl, consisting of H, F, Cl, Br, I, OH, SH, NH, NHOH, NHNH, N, C(O)CH,
carboxy, carbamoyl, lipid, azido, (C1- CN, CHOH,
C22)alkoxy, (C1-C22)alkylthio, C(O)NH, C(S)NH, C(O)OR, R, OR, SR, SSR, NHR,and NR2;
(C1-C22)alkylamino, ((C1-C22)alkyl)2amino, 5. The compound of claim3, wherein R7’ is independently selected from
(C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, the group consisting of H, F, Cl, Br, I, N,C(O)OH, CN, CH-OH, C(O)NH,
(C6-C12)arylsulfonyl,(C3-C6)carbocyclyl, (C6- C(S)NH, C(O)OR, and R, and wherein R is independently a C-C alkyl,
C12)aryl, or heterocyclyl, wherein R13 is C2-alkenyl, C-alkynyl, C. cycloalkyl, (C-C cycloalkyl) aryl, alkylaryl, or
optionally substituted with one or more, the arylalkyl, wherein the groups can be substituted with one or more
same or different, R20; substituents as defined above in claim 1.
49
optionally substituted with one or more, thesame
or different, R20;
R15 is hydrogen, Lipid, -(C=O)Oalkyl(C1-C22),
-(C=O)alkyl(C1-C22), -(C=O)NHalkyl(C1-C22),
-(C=O)N-dialkyl(C1-C22), -(C=O)Salkyl(C1-
C22), hydroxy, (C1-C22)alkoxy, (C1-C22)alkyl,
halogen, nitro, cyano,amino, mercapto, formyl,
carboxy, carbamoyl, (C1-C22)alkylthio, (C1-
or different, R20;
and
C12)aryl substituted with an alkyl
group,heterocyclylis acarbocyclylcomprising 1-4
heteroatoms selected from nitrogen, oxygen, or
sulfur, and heteroaromatic is an aromatic
from nitrogen, oxygen, or sulfur and at least 1
carbon atom.
Claim 5
IN201717025098 D2: US20140235566A1

CLAIM 5 Claim 5 is dependent on on claim 3 which is dependent on claim1.
The composition of claim 3, wherein the
compound is selected from: Arguments applicable for Claim 1 is applicable here as well
1-(3,4-dihydroxy-5-
(hydroxymethyl)tetrahydrofuran-2-yl)-
4((nonanoyloxy)amino)pyrimidin- 2-one,
1-(3,4-dihydroxy-5-
(hydroxymethyl)tetrahydrofuran-2-yl)-4-
((((heptyloxy)carbonyl)oxy)amino)pyrimidin-2-
one, and
isopropyl(((3,4-dihydroxy-5-(4-(hydroxyamino)-
2-oxopyrimidin-1(2H)-yl)tetrahydrofuran-2-
50
Claim 6
IN201717025098 D2: US20140235566A1

CLAIM 6 [0040]
A pharmaceutical composition comprising a In one embodiment, the compound is a compound of
pharmaceutically acceptable excipient and a compound Formula (I):
of Formula IC,
[0041]
wherein:
or salts thereof, wherein i) X1 is H, C1-C6alkyl, C1-C6haloalkyl, C1-C6 alkoxy,
X is CH2,CHMe, CMe2, CHF, CF2, or CD2; C2-C6 alkenyl, C2-C6 alkynyl, COR1, or COOR1;
Y is H, D, F, Cl, Br, I, CH3, CD3, CF3, alkyl, acyl, alkenyl, ii) X2 is hydrogen, COR1, or COOR1
alkynyl, hydroxyl, formyl or SCH3; wherein each R1 is, independently, CH2—O(CO)—X5;
R1 is hydrogen, monophosphate, diphosphate, CH2—O(CO)O—X5C1-20 alkyl, the carbon chain
derived from a fatty alcohol or C1-20 alkyl substituted
triphosphate,
with a C1-C6 alkyl, alkoxy, di(C1-C6 alkyl)-amino,
fluoro, C3-10 cycloalkyl, cycloalkyl alkyl,
cycloheteroalkyl, aryl, heteroaryl, substituted aryl, or
substituted heteroaryl; wherein the substituents are C1-6
alkyl, or C1-6 alkyl substituted with a C1-C6 alkyl, C1-
C6 alkoxy, di(C1-C6 alkyl)-amino, fluoro, or C3-10
cycloalkyl
[0044]
X5 is independently, C1-20 alkyl, the carbon chain
derived from a fatty alcohol or C1-20 alkyl substituted
with a C1-C6 alkyl, alkoxy, C3-10 cycloalkyl, cycloalkyl
alkyl, cycloheteroalkyl, aryl, heteroaryl, substituted aryl,
or substituted heteroaryl; wherein the substituents are C1-
6 alkyl, or C1-6 alkyl substituted with a C1-C6 alkyl, C1-
C6 alkoxy, di(C1-C6 alkyl)-amino, fluoro, or C3-10
cycloalkyl
iii) Each X3 and X4 is independently H, C1-6 alkyl, C2-
6 alkenyl, C2-6 alkynyl, aryl, alkylaryl, halogen (F, Cl,
Br, I), NH2, OH, SH, CN, or NO2.

formyl,
carboxy, carbamoyl, carbanoyl, esteryl, alkoxy, (C1-
C22)alkyl)2amino,
different, R20;
Y1 is O or S;
Y3 is OH or BH3-M+;
carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio,(C1-
heterocyclyl;
51
C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R8 is
different, R20;
C22)alkylthio, (C1-C22)alkylamino,((C1-C22)alkyl)2amino,
C12)arylsulfonyl, (C3-C6)carbocyclyl,(C6-
R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, lipid, methyl,
ethyl, isopropyl, cyclopentyl, cyclohexyl,butyl, pentyl,
hexyl, neopentyl, benzyl, halogen, nitro, cyano, hydroxy,
C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-
C22)alkyl)2amino, (C1-C22)alkylsulfinyl,(C1-
different, R20;
(C1-C22)alkylamino, ((C1-C22)alkyl)2amino,(C1-
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl,
orheterocyclyl, wherein R11 is optionally substituted
naphthyl, 2-naphthyl,aromatic,heteroaromatic, 4-
different, R20;
carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1-C22)alkylthio,
(C1-C22)alkylamino, ((C1-C22)alkyl)2amino, alkylsulfinyl,
(C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-
or different, R20;
(C=O)alkyl(C1-C22), -(C=O)NHalkyl(C1-C22), - (C=O)N-
dialkyl(C1-C22), -(C=O)Salkyl(C1-C22), hydroxy, (C1-
C22)alkoxy, (C1-C22)alkyl, halogen, nitro, cyano,amino,
mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio,
52
substituted with an alkyl group,heterocyclylis
aromatic heterocyclylcomprising 1-4 heteroatoms
selected from nitrogen, oxygen, or sulfur and at least 1
carbon atom.
Claim 7
IN201717025098 D2: US20140235566A1

CLAIM 7 1. A compound of Formula (I):
of Formula ID,

Formula ID, wherein:
or salt thereof, wherein X1 is H, C1-C6 alkyl, C1-C6haloalkyl, C1-C6 alkoxy, C2-
W is CH2, NH, S or O; C6 alkenyl, C2-C6 alkynyl, COR1, or COOR1;
X is CH2,CHMe, CMe2, CHF, CF2, or CD2; X2 is hydrogen, COR1, or COOR1
Y is N or CR”; wherein each R1 is, independently, CH2—O(CO)—X5;
Z is N or CR”; CH2—O(CO)O—X5, C1-20 alkyl, the carbon chain derived
each R” is independently selected from is H, D, F, Cl, Br, I, from a fatty alcohol or C1-20 alkyl substituted with a C1-
CH3, CD3, CF3, alkyl, acyl, alkenyl, alkynyl, hydroxyl, C6 alkyl, alkoxy, di(C1-C6 alkyl)-amino, fluoro, C3-
formyl or SCH3; 10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aryl,
R1 is hydrogen, monophosphate, diphosphate, heteroaryl, substituted aryl, or substituted heteroaryl;

triphosphate, wherein the substituents are C1-6 alkyl, or C1-6 alkyl
alkyl, halogen, nitro, substituted with a C1-C6 alkyl, C1-C6 alkoxy, di(C1-C6 alkyl)-
cyano, hydroxy, amino, mercapto, formyl, carboxy, amino, fluoro, or C3-10 cycloalkyl
carbamoyl, carbanoyl, esteryl, alkoxy, (C1-C22)alkylthio, X5 is independently, C1-20 alkyl, the carbon chain derived
(C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- from a fatty alcohol or C1-20 alkyl substituted with a C1-
C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C6 alkyl, alkoxy, C3-10 cycloalkyl, cycloalkyl alkyl,
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or cycloheteroalkyl, aryl, heteroaryl, substituted aryl, or
heterocyclyl, or phosphoramidyl, or wherein R1 is substituted heteroaryl; wherein the substituents are C1-
optionally substituted with one or more, the same or 6 alkyl, or C1-6 alkyl substituted with a C1-C6 alkyl, C1-
different, R20; C6 alkoxy, di(C1-C6 alkyl)-amino, fluoro, or C3-10 cycloalkyl

Y1 is O or S; each X3 and X4 is independently H, C1-6 alkyl, C2-6 alkenyl,
Y2 is OH, OR12, OAlkyl, or BH3-M+; C2-6alkynyl, aryl, alkylaryl, halogen, NH2, OH, SH, CN, or
Y3 is OH or BH3-M+; NO2.
R2 is hydrogenor hydroxy; 2. The compound of claim 1, wherein each R1 is,
R3 is hydrogen, hydroxy, alkyl, halogen, nitro, cyano, independently, C1-20 alkyl, the carbon chain derived from
hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, a fatty alcohol or C1-20 alkyl substituted with a C1-C6 alkyl,
alkoxy, (C1-C22)alkylthio, alkylamino, (alkyl)2amino, alkoxy, di(C1-C6 alkyl)-amino, fluoro, C3-10 cycloalkyl,
alkylsulfinyl, alkylsulfonyl, arylsulfonyl,carbocyclyl, aryl, cycloalkyl alkyl, cycloheteroalkyl, aryl, heteroaryl,
or heterocyclyl; substituted aryl, or substituted heteroaryl; wherein the
R4 is hydrogen, hydroxy,(C1-C22)alkyl, fluoromethyl, substituents are C1-6 alkyl, or C1-6 alkyl substituted with a
difluoromethyl, trifluoromethyl, hydroxymethyl, C1-C6 alkyl, C1-C6 alkoxy, di(C1-C6 alkyl)-amino, fluoro, or
C3-10 cycloalkyl.
53
halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, 3. The compound of claim 1, wherein Sugar is ribose or a
carboxy, carbamoyl, (C1-C22)alkoxy, (C1- modified ribose of the general Formula (II):
halogen, nitro, cyano, amino, mercapto,formyl, carboxy, wherein:
carbamoyl, alkoxy, (C1-C22)alkylthio, alkylamino, D is H, C(O)R1, C(O)OR1, diphosphate ester, or
(alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, triphosphate ester;
carbocyclyl, aryl, or heterocyclyl; R1 is as defined above;
R8 is hydrogen, deuterium, (C1-C22)alkyl, (C2- W is CL2 or CL2CL2, wherein L independently is selected
C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, from the group consisting of H, C1-6 alkyl, C2-6 alkenyl, and
hydroxy, benzyloxy, amino, amido, mercapto, formyl, C2-6alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6alkynyl
carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1- can each optionally contain one or more heteroatoms;
C22)alkylthio, (C1-C22)alkylamino, ((C1- A is O, S, CH2, CHF, CF2, C═CH2, C═CHF, or C═CF2;
C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- R4′, R5, R5′, R6, R6′, and R7′ are independently selected
C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- from the group consisting of H, F, Cl, Br, I, OH, SH, NH2,
C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R8 is NHOH, NHNH2, N3, C(O)OH, CN, CH2OH, C(O)NH2,
optionally substituted with one or more, the same or C(S)NH2, C(O)OR, R, OR, SR, SSR, NHR, and NR2;
different, R20; R5′ and R6′ can come together to form a ring
C22)alkylthio, (C1-C22)alkylamino,((C1-C22)alkyl)2amino,
(C6-C12)aryl,orheterocyclyl, wherein R9 is optionally wherein:
substituted with one or more, the same or different, R20; when A is O or CH2, D is H or acyl, W is CH2, R4′ and R7′ are
R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, lipid, methyl, H then, R5, R5′, R6, R6′ can not be H, halogen, OH, SH,
ethyl, isopropyl, cyclopentyl, cyclohexyl,butyl, pentyl, OCH3, SCH3, NH2, NHCH3, CH3, CH═CH2, CN, CH2NH2,
hexyl, neopentyl, benzyl, halogen, nitro, cyano, hydroxy, CH2OH, COOH
amino, mercapto, formyl, carboxy,carbamoyl, (C1- when A is O or S, R7′ cannot be OH, SH, NH2, NHOH,
C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1- NHNH2, OR, SR, SSR, NHR, or NR2, and
C22)alkyl)2amino, (C1-C22)alkylsulfinyl,(C1- R is independently a C1-C6 alkyl, C2-6 alkenyl, C2-6alkynyl,
C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C3-6 cycloalkyl, (C3-C6 cycloalkyl) aryl, alkylaryl, or arylalkyl,
C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R10 wherein the groups can be substituted with one or more
is substituents as defined above in claim 1.
different, R20;
halogen, nitro, cyano, hydroxy, amino, mercapto,formyl,
C22)alkylthio,(C1-C22)alkylamino, ((C1-C22)alkyl)2amino,
C12)arylsulfonyl,(C3-C6)carbocyclyl, (C6-C12)aryl, or
54
carboxy, carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1-
C22)alkylthio,(C1-C22)alkylamino, ((C1-C22)alkyl)2amino,
alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl,
(C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein
or different, R20;
R15 is hydrogen, -(C=O)Oalkyl(C1-C22), -(C=O)alkyl(C1-
C22), -(C=O)NHalkyl(C1-C22), -(C=O)Ndialkyl(C1-C22), -
(C=O)Salkyl(C1-C22), hydroxy, (C1-C22)alkoxy, (C1-
C22)alkyl, halogen, nitro, cyano, amino,mercapto, formyl,
heterocyclyl,wherein R15 is optionally substituted with
R15’ is hydrogen, -(C=O)Oalkyl(C1-C22), -(C=O)alkyl(C1-
C22), -(C=O)NHalkyl(C1-C22), -(C=O)Ndialkyl(C1-C22), -
heterocyclyl;
C22)alkynyl, halogen, nitro, cyano, hydroxy,
heterocyclyl; and
Claim 8
IN201717025098 D2: US20140235566A1

CLAIM 8 1. A compound of Formula (I):
of Formula IE,

wherein:
Formula IE, X1 is H, C1-C6 alkyl, C1-C6haloalkyl, C1-C6 alkoxy, C2-
or salt thereof, wherein C6 alkenyl, C2-C6 alkynyl, COR1, or COOR1;
Q is O, -O(C=O)-, -O(C=O)Lipid, -O(C=O)V-, NH, or NR7; X2 is hydrogen, COR1, or COOR1
V is O, NH, NR7, S, CH2, or CHR7; wherein each R1 is, independently, CH2—O(CO)—X5;
CH2—O(CO)O—X5, C1-20 alkyl, the carbon chain derived
55
W is CH2, NH, S or O; from a fatty alcohol or C1-20 alkyl substituted with a C1-
X is CH2,CHMe, CMe2, CHF, CF2, or CD2; C6 alkyl, alkoxy, di(C1-C6 alkyl)-amino, fluoro, C3-
Y is N or CR”; 10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aryl,
Z is N or CR”; heteroaryl, substituted aryl, or substituted heteroaryl;
each R” is independently selected from is H, D, F, Cl, Br, I, wherein the substituents are C1-6 alkyl, or C1-6 alkyl
CH3, CD3, CF3, alkyl, acyl, alkenyl, alkynyl, hydroxyl, substituted with a C1-C6 alkyl, C1-C6 alkoxy, di(C1-C6 alkyl)-
formyl or SCH3; amino, fluoro, or C3-10 cycloalkyl
R2 is hydrogen, alkyl, alkenyl, alkynyl, ethynyl, X5 is independently, C1-20 alkyl, the carbon chain derived
fluoromethyl, difluoromethyl, trifluoromethyl, from a fatty alcohol or C1-20 alkyl substituted with a C1-
chloromethyl, hydroxymethyl, halogen, nitro, cyano, C6 alkyl, alkoxy, C3-10 cycloalkyl, cycloalkyl alkyl,
hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, cycloheteroalkyl, aryl, heteroaryl, substituted aryl, or
alkoxy, (C1-C22)alkylthio, alkylamino, (alkyl)2amino, substituted heteroaryl; wherein the substituents are C1-
alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, 6 alkyl, or C1-6 alkyl substituted with a C1-C6 alkyl, C1-
azido, or heterocyclyl; C6 alkoxy, di(C1-C6 alkyl)-amino, fluoro, or C3-10 cycloalkyl
R3 is hydrogen, hydroxy, alkyl, halogen, nitro, cyano, each X3 and X4 is independently H, C1-6 alkyl, C2-6 alkenyl,
hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, C2-6alkynyl, aryl, alkylaryl, halogen, NH2, OH, SH, CN, or
alkoxy, (C1-C22)alkylthio, alkylamino, alkyl)2amino, NO2.
alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, 2. The compound of claim 1, wherein each R1 is,
or heterocyclyl; independently, C1-20 alkyl, the carbon chain derived from
R4 is hydrogen, hydroxy,(C1-C22)alkyl, fluoromethyl, a fatty alcohol or C1-20 alkyl substituted with a C1-C6 alkyl,
difluoromethyl, trifluoromethyl, hydroxymethyl, halogen, alkoxy, di(C1-C6 alkyl)-amino, fluoro, C3-10 cycloalkyl,
nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, cycloalkyl alkyl, cycloheteroalkyl, aryl, heteroaryl,
carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio,(C1- substituted aryl, or substituted heteroaryl; wherein the
22)alkylamino, ((C1-C22)alkyl)2amino,(C1- substituents are C1-6 alkyl, or C1-6 alkyl substituted with a
C22)alkylsulfinyl,(C1-22)alkylsulfonyl, (C6- C1-C6 alkyl, C1-C6 alkoxy, di(C1-C6 alkyl)-amino, fluoro, or
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or C3-10 cycloalkyl.
heterocyclyl; 3. The compound of claim 1, wherein Sugar is ribose or a
R5 is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, alkynyl, modified ribose of the general Formula (II):
ethynyl, fluoromethyl, difluoromethyl,trifluoromethyl,
hydroxymethyl, allenyl, halogen, nitro, cyano, amino,
mercapto, formyl, carboxy, carbamoyl,alkoxy, (C1-
C22)alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl,
alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl,or
heterocyclyl;
R6 is hydrogen, hydroxy, alkoxy, alkyl, ethynyl, allenyl, wherein:
halogen, nitro, cyano, amino, mercapto,formyl, carboxy, D is H, C(O)R1, C(O)OR1, diphosphate ester, or
carbamoyl, alkoxy, (C1-C22)alkylthio, lkylamino, triphosphate ester;
(alkyl)2amino, alkylsulfinyl, alkylsulfonyl,arylsulfonyl, R1 is as defined above;
carbocyclyl, aryl, or heterocyclyl; W is CL2 or CL2CL2, wherein L independently is selected
each R7 is independently selected from absent, from the group consisting of H, C1-6 alkyl, C2-6 alkenyl, and
hydrogen, -(C=O)Oalkyl, -(C=O)alkyl, -(C=O)NHalkyl, - C2-6alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6alkynyl
(C=O)N-dialkyl, -(C=O)Salkyl, hydroxy, alkoxy, alkyl, can each optionally contain one or more heteroatoms;
higher alkyl, (C6-C16)alkyl, (C6-C22)alkyl, halogen, nitro, A is O, S, CH2, CHF, CF2, C═CH2, C═CHF, or C═CF2;
cyano, amino, mercapto, formyl, carboxy, carbamoyl, R4′, R5, R5′, R6, R6′, and R7′ are independently selected
alkoxy, (C1-C22)alkylthio,alkylamino, (alkyl)2amino, from the group consisting of H, F, Cl, Br, I, OH, SH, NH2,
alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, NHOH, NHNH2, N3, C(O)OH, CN, CH2OH, C(O)NH2,
or heterocyclyl, whereineach R7 is optionally substituted C(S)NH2, C(O)OR, R, OR, SR, SSR, NHR, and NR2;
with one or more, the same or different, R20; R5′ and R6′ can come together to form a ring
R15 is hydrogen, -(C=O)Oalkyl(C1-C22), -(C=O)alkyl(C1-
C22), -C=O)NHalkyl(C1-C22), -(C=O)Ndialkyl(C1-C22), -
C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- wherein:
12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or when A is O or CH2, D is H or acyl, W is CH2, R4′ and R7′ are
heterocyclyl,wherein R15 is optionally substituted with 5 5′ 6 6′
H then, R , R , R , R can not be H, halogen, OH, SH,
one or more, the same or different, R20; OCH3, SCH3, NH2, NHCH3, CH3, CH═CH2, CN, CH2NH2,
R15’ is hydrogen, -(C=O)Oalkyl(C1-C22), -(C=O)alkyl(C1- CH2OH, COOH
C22), -C=O)NHalkyl(C1-C22), -(C=O)Ndialkyl(C1-C22), - when A is O or S, R7′ cannot be OH, SH, NH2, NHOH,
(C=O)Salkyl(C1-C22), hydroxy, (C1-C22)alkoxy, (C1- NHNH2, OR, SR, SSR, NHR, or NR2, and
C22)alkyl, halogen, nitro, cyano, amino, R is independently a C1-C6 alkyl, C2-6 alkenyl, C2-6alkynyl,
mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, C3-6 cycloalkyl, (C3-C6 cycloalkyl) aryl, alkylaryl, or arylalkyl,
(C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- wherein the groups can be substituted with one or more
C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- substituents as defined above in claim 1.
heterocyclyl;
56
substituted with one or more, the same or different,R20;
If Q = -O(C=O)V- and V = NR7 then the R7s can together
form a ring that is optionally substitutedwith one or
C22)alkynyl, halogen, nitro, cyano, hydroxy,amino,
wherein lipid comprises a C6-22 alkyl, (C6-C22)alkoxy,
polyethylene glycol, or (C6-C12)aryl substituted with an
(C1-C22)alkyl group, heterocyclylis carbocyclyl
comprising 1-4 heteroatoms selected from nitrogen,
oxygen, or sulfur,
Claim 9
IN201717025098 D2: US20140235566A1

CLAIM 9 A pharmaceutical composition Claim 1
comprising a pharmaceutically acceptable Use of an effective amount of a compound selected from Formula (I),
excipient and a compound of Formula II, Formula (II), and Formula (III), or a pharmaceutically acceptable salt of
the foregoing, for amelioring or treating a viral infection caused by a
virus selected from a henipavirus, a morbilli virus, a respirovirus, a
rubulavirus and a metapneumovirus, wherein the compound is selected
from Formula (I), Formula II), and Formula (III) has one of the following
structures:
or salt thereof, wherein (I) (Π)

Q is O, -O(C=O)-, -O(C=O)Lipid, -O(C=O)V-,
NH, or NR7;
X is CH2 or O;
Y is N or CR”; (HI)
Z is N or CR”; wherein:
each R” is independently selected from is H, D, B1A, B1B, and B1C are independently an optionally substituted
F, Cl, Br, I, CH3, CD3, CF3, alkyl, acyl, alkenyl, heterocyclic base or an optionally substituted heterocyclic base with a
alkynyl, hydroxyl, formyl or SCH3; protected amino group;
R1 is monophosphate, diphosphate, triphosphate, R1A is selected from the group consisting of hydrogen, an optionally
substituted
when the dashed line ( ) of Formula (I) is a single bond, R A is CH2, and
R is O (oxygen);
when the dashed line ( ) of Formula (I) is absent, RZA is selected from the
group consisting of an optionally substituted Ci_6 alkyl, an optionally
substituted C2_6 alkenyl, an optionally substituted C2_6 alkynyl, an
optionally substituted C3 cycloalkyl, an optionally substituted -O-C1-
6 alkyl, an optionally substituted -0-C3_6 alkenyl, an optionally
substituted -O-C3-6 alkynyl and cyano, and R3A is selected from the
group consistin of OH, -OC(=0)R"A and an optionally substituted O-
linked amino acid;
57
N-linked amino acid and an optionally substituted N-linked amino acid
ester derivative;
Y1 is O or S;
R1C and R2C are independently selected from the group consisting of
O-, OH, an
Y3 is OH or BH3-M+;
fluoromethyl, difluoromethyl,
trifluoromethyl,chloromethyl, hydroxymethyl,
formyl, carboxy, carbamoyl, alkoxy, (C1-
C22)alkylthio, alkylamino, (alkyl)2amino, , an optionally substituted N-linked amino acid and an optionally
alkylsulfinyl, alkylsulfonyl, arylsulfonyl, substituted N-linked amino acid ester derivative; or optionally
carbocyclyl, aryl,azido, or heterocyclyl; substituted C1-6 alkoxy
R3 is hydrogen, hydroxy, alkyl, halogen, nitro,
cyano, hydroxy, amino, mercapto, formyl,
alkylamino, alkyl)2amino, alkylsulfinyl,
alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or R2B and R3c are independently selected from the group consisting of an
heterocyclyl; optionally substituted Ci_6 alkyl, an optionally substituted C2-6 alkenyl,
R4 is hydrogen, hydroxy,(C1-C22)alkyl, an optionally substituted C2-6 alkynyl, an optionally substituted C3-6
fluoromethyl, difluoromethyl, rifluoromethyl, cycloalkyl, an optionally substituted -0-C1-6 alkyl, an optionally
hydroxymethyl,halogen, nitro, cyano, hydroxy, substituted -O-C3-6 alkenyl, an optionally substituted -0-C3-6 alkynyl and
amino, mercapto, formyl, carboxy, carbamoyl, cyano;
(C1-C22)alkoxy, (C1-C22)alkylthio,(C1- R4C is selected from the group consisting of OH, -OC(=0)R"c and an
C22)alkylamino, ((C1-C22)alkyl)2amino,(C1- optionally substituted O-linked amino acid;
C22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6- R4A, R3B and R5C are independently a halogen;
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- R5A, R4B and R6C are independently hydrogen or halogen;
C12)aryl, or heterocyclyl; R6A, R7A and R8A are independently selected from the group consisting of
R5 is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, absent, hydrogen, an optionally substituted Ci_24 alkyl, an optionally
alkynyl, ethynyl, fluoromethyl, substituted C2-24 alkenyl, an optionally substituted C2-24 alkynyl, an
difluoromethyl,trifluoromethyl, hydroxymethyl, optionally substituted C3-6 cycloalkyl, an optionally substituted C3-6
allenyl, halogen, nitro, cyano, amino, mercapto, cycloalkenyl, an optionally substituted aryl, an optionally substituted
formyl, carboxy, carbamoyl,alkoxy, (C1- heteroaryl, an optionally substituted aryl(Ci_6 alkyl), an optionally
C22)alkylthio, alkylamino, (alkyl)2amino, substituted *-(CR15AR16A)p-0-Ci_24 alkyl, an optionally substituted *-
alkylsulfinyl, alkylsulfonyl, arylsulfonyl, (CR17AR18A)q-0-Ci_24
carbocyclyl, aryl,or heterocyclyl;
allenyl, halogen, nitro, cyano, amino,
mercapto,formyl, carboxy, carbamoyl, alkoxy,
(C1-C22)alkylthio, alkylamino, (alkyl)2amino,
alkylsulfinyl, alkylsulfonyl,arylsulfonyl,
R6A is and R7 is absent or hydrogen; or
R and R , 7/AA are taken together to form a moiety selected from the
group
consisting of an optionally substituted
hydroxy, alkoxy, alkyl, higher alkyl, (C6-
C16)alkyl, (C6-C22)alkyl, halogen, nitro, cyano,
alkoxy, (C1-C22)alkylthio,alkylamino, and an optionally substituted
arylsulfonyl, carbocyclyl, aryl, or heterocyclyl,
one or more, the same or different, R20; wherein the oxygens connected to R6A and R7A, the phosphorus and the
R8 is hydrogen, deuterium, (C1-C22)alkyl, (C2- moiety form a six-membered to ten-membered ring system;.
C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, R9A is independently selected from the group consisting of an optionally
cyano,hydroxy, benzyloxy, amino, amido, substituted Ci_24 alkyl, an optionally substituted C2-24 alkenyl, an
mercapto, formyl, carboxy, carbamoyl, azido, optionally substituted C2-24 alkynyl, an optionally substituted
(C1-C22)alkoxy, (C1-C22)alkylthio, (C1- C3_6 cycloalkyl, an optionally substituted C3_6 cycloalkenyl, NR30AR31A,
C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- an optionally substituted N-linked amino acid and an optionally
C22)alkylsulfinyl, (C1-22)alkylsulfonyl, (C6- substituted N-linked amino acid ester derivative;
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- R10A and R11A are independently an optionally substituted N-linked
12)aryl,orheterocyclyl, wherein R8 is optionally amino acid or an optionally substituted N-linked amino acid ester
substituted with one or more, the same or derivative;
different, R20; R12A, R13A and R14A are independently absent or hydrogen;
R9 is hydrogen, methyl, ethyl, tert-butyl, (C1- each R15A, each R16A, each R17A and each R18A are independently
C22)alkyl, halogen, nitro, cyano, hydroxy, hydrogen, an optionally substituted Ci_24 alkyl or alkoxy; R19A, R20A,
amino, mercapto, formyl, carboxy, carbamoyl, R22A, R23A, R5B, R6B, R8B, R9B, R9C, R10C, R12C and R13C are
58
cycloalkyl, (C1-C22)alkoxy, (C1-C22)alkylthio, independently selected from the group consisting of hydrogen, an
(C1-C22)alkylamino,((C1-C22)alkyl)2amino, optionally substituted Ci_24 alkyl and an optionally substituted aryl;
(C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, R2iA R24A R7B^ Ri<m Rnc and Ri4C arg independently selected from the
(C6-C12)arylsulfonyl, (C3-C6)carbocyclyl,(C6- group consisting of hydrogen, an optionally substituted Ci_24 alkyl, an
C12)aryl,orheterocyclyl, wherein R9 is optionally substituted aryl, an optionally substituted -0-Ci_24 alkyl and
optionally substituted with one or more, the an optionally substituted -O-aryl;
same or different, R20; R25A R29A RHB and R15C are independently selected from the group
R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, consisting of hydrogen, an optionally substituted Ci_24 alkyl and an
lipid, methyl, ethyl, isopropyl, cyclopentyl, optionally substituted aryl;
cyclohexyl,butyl, pentyl, hexyl, neopentyl, R1U", R^ and R are independently absent or hydrogen;
benzyl, halogen, nitro, cyano, hydroxy, amino, R26A and R27A are independently -C≡N or an optionally substituted
mercapto, formyl, carboxy,carbamoyl, (C1- substituent selected from the group consisting of C2_8 organylcarbonyl,
C22)alkoxy, (C1-C22)alkylthio, (C1- C2_8 alkoxycarbonyl and C2_8 organylaminocarbonyl;
C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- R28A is selected from the group consisting of hydrogen, an optionally
22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6- substituted Ci_24-alkyl, an optionally substituted C2_24 alkenyl, an
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- optionally substituted C2-24 alkynyl, an optionally substituted
C12)aryl,orheterocyclyl, wherein R10 is C3_6 cycloalkyl and an optionally substituted C3_6 cycloalkenyl;
optionally substituted with one or more, the R30A and R31A are independently selected from the group consisting of
same or different, R20; hydrogen, an optionally substituted Ci_24-alkyl, an optionally substituted
R11 is hydrogen, deuterium, (C1-C22)alkyl, C2-24 alkenyl, an optionally substituted C2_24 alkynyl, an optionally
methyl, halogen, nitro, cyano, hydroxy, amino, substituted C3_6 cycloalkyl and an optionally substituted
mercapto,formyl, carboxy, carbamoyl, (C1- C3_6 cycloalkenyl;
C22)alkoxy, (C1-C22)alkylthio, (C1- for Formula (III), is a single bond or a double bond;
C22)alkylamino, ((C1-C22)alkyl)2amino,(C1- when is a single bond, each R and each R is independently hydrogen or
22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- halogen; and
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- when is a double bond, each R is absent and each R is independently
C12)aryl, or heterocyclyl, wherein R11 is hydrogen or halogen;
optionally substituted with one or more, the R"A and R"c are independently an optionally substituted Ci_24-alkyl;
same or different, R20; m and n are independently 0 or 1 ;
R12 is hydrogen, (C1-C22)alkyl, (C6-C12)aryl, p and q are independently selected from the group consisting of 1, 2 and
phenyl, 1-naphthyl, 2- 3;
naphthyl,aromatic,heteroaromatic, 4-substituted r is 1 or 2;
phenyl, 4-fluorophenyl, 4-chlorophenyl, 4- Z1A, Z2A, Z3A, Z4A, Z1B, Z2B and Z1C are independently O or S; and
bromophenyl, naphthyl, or heterocyclyl, wherein provided that when the dashed line ( ) of Formula (I) is absent; R1A is
R12 is optionally substituted with one or more,
(C2-C22)alkenyl, (C2-C22)alkynyl, halogen,
nitro, cyano,hydroxy, amino, amido, mercapto,
C22)alkoxy, (C1-C22)alkylthio,(C1-
C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- wherein R is an unsubstituted Ci_4 alkyl or phenyl optionally para-
C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- substituted with a halogen or methyl and R9A is methyl ester, ethyl ester,
C12)arylsulfonyl,(C3-C6)carbocyclyl, (C6- isopropyl ester, n-butyl ester, benzyl ester or phenyl ester of an amino
C12)aryl, or heterocyclyl, wherein R13 is acid selected from the group consisting of glycine, alanine, valine,
optionally substituted with one or more, the leucine, phenylalanine, tryptophan, methionine and proline; R3A is OH;
same or different, R20; R4A is fluoro; R5A is fluoro or hydrogen; and B1A is an unsubstituted
R14 is hydrogen, deuterium, (C1-C22)alkyl, uracil; then R2A cannot be -OCH3;
(C2-C22)alkenyl, (C12-C22)alkynyl, halogen, provided that when the dashed line ( ) of Formula (I) is absent; R1A is H;
nitro, cyano,hydroxy, amino, amido, mercapto, R3A is OH; R4A is fluoro; R5A is fluoro; and B1A is an unsubstituted
formyl, carboxy, arbamoyl, lipid, azido, (C1- cytosine; then R2A cannot be allenyl;
C22)alkoxy, (C1-C22)alkylthio,(C1- provided that when the dashed line ( ) of Formula (I) is absent; R1A is H;
C22)alkylamino, ((C1-C22)alkyl)2amino, R3A is OH; R4A is fluoro; R5A is hydrogen; and B1A is an unsubstituted
alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- thymine; then R2A cannot be Ci alkyl substituted with an N-amido; and
12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- provided that when the dashed line ( ) of Formula (I) is absent; R1A is H;
C12)aryl, or heterocyclyl, wherein R14 is R3A is OH; R4A is fluoro; R5A is fluoro; and B1A is an unsubstituted
optionally substituted with one or more, the cytosine; then R2A cannot be ethynyl.
If Q = -O(C=O)V- and V = NR7 then the R7s Claim 212.
can together form a ring that is optionally The use or method of any one of Claims 162-211, wherein B is selected
substituted with one or more, the same or from the group consisting of:
different, R20;
cyano, hydroxy,amino, amido, mercapto, formyl,
carboxy, carbamoyl, azido, (C1-C22)alkoxy,
(C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-
and wherein lipid comprises a C6-22 alkyl, (C6-
59
C12)aryl substituted wherein:
with an (C1-C22)alkyl group, heterocyclylis R is selected from the group consisting of hydrogen, halogen and NHR'
acarbocyclylcomprising 1-4 heteroatoms KC2 wherein R is selected from the group consisting of hydrogen, -
selected from nitrogen, oxygen, or sulfur, and C(=0)R U and
heteroaromatic is an aromatic C(=0)OR^ ;
heterocyclylcomprising 1-4 heteroatoms selected R is halogen or NHR , wherein R is selected from the group consisting of
from nitrogen,oxygen, or sulfur and at least 1 hydrogen, an optionally substituted Ci_6 alkyl, an optionally substituted
carbon atom. C2-6 alkenyl, an optionally substituted C3_8 cycloalkyl, -C(=0)RMC2 and -
C(=0)ORNC2;
RDC2 is hydrogen or NHR , wherein R is selected from the group
consisting of hydrogen, -C(=0)RPC2 and -C(=0)ORQC2; R is selected from
the group consisting of hydrogen, halogen, an optionally substituted
Ci_6 alkyl, an optionally substituted C2_6 alkenyl and an optionally
substituted C2_6 alkynyl;
R EC2 is selected from the group consisting of hydrogen, hydroxy, an
optionally substituted Ci_6 alkyl, an optionally substituted C3-8
cycloalkyl, -C(=0)R and - C(=0)ORSC2;
R is selected from the group consisting of hydrogen, halogen, an
optionally substituted Ci_6alkyl, an optionally substituted C2_6 alkenyl
and an optionally substituted C2_6 alkynyl;
Y2C and Y3C are independently N or CRIC2, wherein RIC2 is selected from
Ci_6-alkyl, an optionally substituted C2_6-alkenyl and an optionally
substituted C2_6-alkynyl;
R is an optionally substituted Ci_6 alkyl;
R is hydrogen or NHR , wherein R is independently selected from the
group consisting of hydrogen, -C(=0)RUC2 and -C(=0)ORVC2; and
RKC2, RLC2, RMC2, RNC2, RPC2, RQC2 RRC2, RSC2 RUC2 and RVC2 are
independently selected from the group consisting of Ci_6 alkyl,
C2_6 alkenyl, C2_6 alkynyl, C3-6 cycloalkyl, C3-6 cycloalkenyl, C6-1o
aryl, heteroaryl, heteroalicyclyl, aryl(Ci_6 alkyl), heteroaryl(Ci_6 alkyl)
and heteroalicyclyl(Ci_6 alkyl).
Claim 10
IN201717025098 D2: US20140235566A1

CLAIM 10 The pharmaceutical composition of claim Claim 10 is dependent on 1. Arguments applicable for Claim 1
1,further comprising a propellant. are applicable here as well. Including a propellant in
composition is no invention.
Claim 11
IN201717025098 D2: US20140235566A1

CLAIM 11 The pharmaceutical composition of claim 10, Claim 11 is dependent on 1o which depends on claim 1.
wherein the propellant is compressed air, ethanol, Arguments applicable for Claim 1 are applicable here as well.
nitrogen, carbon dioxide, nitrous oxide, Including a propellant in composition is no invention.
hydrofluoroalkanes (HFA), 1,1,1,2,-tetrafluoroethane,
1,1,1,2,3,3,3-heptafluoropropane or combinations thereof.
60
Claim 12
IN201717025098 D2: US20140235566A1

CLAIM 12 The composition of claim 1, wherein the Claim 25. A compound of the formula:
compound has a structure according to Formula IA

R7 is H,
Y is independently selected from is H, D, F, Cl, Br, pharmaceutically acceptable salts thereof.
I, CH3, CD3, CF3, alkyl, acyl, alkenyl, alkynyl,
R1 is
monophosphate
ester, diphosphate
ester
amino, mercapto, formyl, carboxy, carbanoyl,

esteryl, alkoxy, (C1-
substituted with one or more, the same or different,
R20, Y1 is O or S;
Y3 is OH or BH3-M+;
R4 is hydrogen, hydroxy, (C1-C22)alkyl,
amino, mercapto, formyl, carboxy, carbamoyl, (C1-
R20;
mercapto, formyl, carboxy, carbamoyl, azido, (C1-
61
R20;
C22)alkyl, halogen, nitro, cyano, hydroxy, amino,
mercapto, formyl, carboxy, carbamoyl, cycloalkyl,
C22)alkylamino,((C1-C22)alkyl)2amino, (C1-
C12)arylsulfonyl, (C3-C6)carbocyclyl,(C6-
R20;
cyclohexyl,butyl, pentyl, hexyl, neopentyl, benzyl,
formyl, carboxy,carbamoyl, (C1-C22)alkoxy, (C1-
phenyl, 1-naphthyl, 2-naphthyl, aromatic,
naphthyl, or heterocyclyl, wherein R12 is optionally
R20;
carboxy, carbamoyl, lipid, azido, (C1-C22)alkoxy,
(C1-C22)alkylthio,
R20;
carboxy, carbamoyl, lipid, azido, (C1-C22)alkoxy,
(C1-C22)alkylthio,
R20;
62
Claim 13
IN201717025098 D2: US20140235566A1

CLAIM 13 3. The compound of claim 1, wherein Sugar is ribose or a
The composition of claim 1, wherein R4 is hydrogen, modified ribose of the general Formula (II):
hydroxy, alkyl, halogen, or fluoro.
wherein:
[D is H, C(O)R1, C(O)OR1, diphosphate ester, or
triphosphate ester;
W is CL2 or CL2CL2, wherein L independently is
selected from the group consisting of H, C1-6 alkyl, C2-6
alkenyl, and C2-6alkynyl, wherein C1-6 alkyl, C2-
6alkenyl, and C2-6 alkynyl can each optionally contain
one or more heteroatoms;
R4, R5, R5’ R6, R6’, and R7 are independently selected
from the group consisting of H, F, Cl, Br, I, OH, SH,
NH, NHOH, NHNH, N, C(O)CH, CN, CHOH,
C(O)NH, C(S)NH, C(O)OR, R, OR, SR, SSR, NHR,and
NR2;
5. The compound of claim3, wherein R7’ is independently
selected from the
Claim 14
IN201717025098 D2: US20140235566A1

CLAIM 14 3. The compound of claim 1, wherein Sugar is ribose or a
The composition of claim 1, wherein R5 is hydrogen, modified ribose of the general Formula (II):
hydroxy, alkoxy, alkyl, methyl, ethynyl, or allenyl.
wherein:
[D is H, C(O)R1, C(O)OR1, diphosphate ester, or
triphosphate ester;
W is CL2 or CL2CL2, wherein L independently is
selected from the group consisting of H, C1-6 alkyl, C2-6
alkenyl, and C2-6alkynyl, wherein C1-6 alkyl, C2-
6alkenyl, and C2-6 alkynyl can each optionally contain
one or more heteroatoms;
R4, R5, R5’ R6, R6’, and R7 are independently selected
from the group consisting of H, F, Cl, Br, I, OH, SH, NH,
NHOH, NHNH, N, C(O)CH, CN, CHOH,
C(O)NH, C(S)NH, C(O)OR, R, OR, SR, SSR, NHR,and
NR2;
Therefore, it can be concluded that all claims of IN20717025098 lack novelty over D2 and
the patent to opposed application should be rejected on that ground alone as per section
25(1)(b) & (c).
63
C. Opponent further introduces prior art WO/2013/142525 (D3) to Wang, Guangi to
contest the novelty of the invention. WO/2013/142525 has priority dates of Dec 20, 2012 &
March 21, 2012 is a permissible prior art for IN20717025098 having priority date of Dec 26,
2014.
iii) Lack of novelty in view of WO/2013/142525 (D3) to Wang, Guangi
WO/2013/142525 (D3) discloses nucleosides, nucleotides and analogs thereof,
pharmaceutical compositions that include one or more of nucleosides, nucleotides and
analogs thereof, and methods of synthesizing the same. Also disclosed herein are methods of
ameliorating and/or treating a disease and/or a condition, including an infection from a
paramyxovirus and/or an orthomyxovirus, with a nucleoside, a nucleotide and an analog
thereof.
Lack of novelty in claims of 201717025098 is disussed in following tables
Claim 1:
IN201717025098 D3: WO2013142525A1

CLAIM 1: A pharmaceutical composition comprising a Claim 1
pharmaceutically acceptable excipient and a compound Use of an effective amount of a compound selected from Formula
having Formula I (I), Formula (II), and Formula (III), or a pharmaceutically
acceptable salt of the foregoing, for amelioring or treating a viral
infection caused by a virus selected from a henipavirus, a morbilli
virus, a respirovirus, a rubulavirus and a metapneumovirus,
wherein the compound is selected from Formula (I), Formula II),
and Formula (III) has one of the following structures:
(I) (Π)
W is O;
Y is CR”;
Z is CR”; (HI)
each R” is independently selected from is H, D, F, Cl, wherein:
Br, I, CH3, CD3, CF3, C1-22alkyl, acyl, C2- B1A, B1B, and B1C are independently an optionally substituted
22alkenyl, C2-22alkynyl, hydroxyl, formyl or SCH3; heterocyclic base or an optionally substituted heterocyclic base
R1 is with a protected amino group;
R1A is selected from the group consisting of hydrogen, an
optionally substituted
64
when the dashed line ( ) of Formula (I) is a single bond, R A is CH2,
Monophosphate and R is O (oxygen);
ester, diphosphate when the dashed line ( ) of Formula (I) is absent, RZA is selected
ester from the group consisting of an optionally substituted Ci_6 alkyl,
an optionally substituted C2_6 alkenyl, an optionally substituted
C2_6 alkynyl, an optionally substituted C3 cycloalkyl, an optionally
substituted -O-C1-6 alkyl, an optionally substituted -0-C3_6 alkenyl,
an optionally substituted -O-C3-6 alkynyl and cyano, and R3A is
selected from the group consistin of OH, -OC(=0)R"A and an
optionally substituted O-linked amino acid;

formyl, carboxy, carbamoyl, carbanoyl, esteryl, alkoxy,
(C1-C22)alkylthio, (C1-C22)alkylamino, ((C1- N-linked amino acid and an optionally substituted N-linked amino
C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- acid ester derivative;
C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- R1C and R2C are independently selected from the group
C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, or consisting of O-, OH, an
phosphoramidylwherein R1 is optionally substituted
Y1 is O or S;
Y2 is OH, OR12, OAlkyl, or BH3 - M+; Y3 is OH or
BH3 - M+;
, an optionally substituted N-linked amino acid and an optionally
R3 is hydrogen, hydroxy, (C1-C22)alkyl, halogen,
substituted N-linked amino acid ester derivative; or optionally
nitro, cyano, hydroxy, amino, mercapto, formyl,
substituted C1-6 alkoxy
C22)alkylthio, , (C1-C22)alkylamino, ((C1-
C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-
R4 is hydrogen, hydroxy,(C1-C22)alkyl, fluoromethyl, R2B and R are independently selected from the group consisting of
difluoromethyl, trifluoromethyl, hydroxymethyl, an optionally substituted Ci_6 alkyl, an optionally substituted C2-6
halogen, nitro, cyano, hydroxy, amino, mercapto, alkenyl, an optionally substituted C2-6 alkynyl, an optionally
formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1- substituted C3-6 cycloalkyl, an optionally substituted -0-C1-6 alkyl,
C22)alkylthio, (C1-C22)alkylamino, ((C1- an optionally substituted -O-C3-6 alkenyl, an optionally substituted
C22)alkyl)2amino,(C1-C22)alkylsulfinyl,(C1- -0-C3-6 alkynyl and cyano;
C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3- R4C is selected from the group consisting of OH, -OC(=0)R"c and
C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; an optionally substituted O-linked amino acid;
R5 is hydrogen, hydroxy, or halogen; R4A, R3B and R5C are independently a halogen;
R6 is hydrogen, hydroxy, (C1-C22)alkoxy, (C1- R5A, R4B and R6C are independently hydrogen or halogen;
C22)alkyl, ethynyl, allenyl, halogen, nitro, cyano, R6A, R7A and R8A are independently selected from the group
amino, mercapto, formyl, carboxy, carbamoyl, (C1- consisting of absent, hydrogen, an optionally substituted Ci_24
C22)alkylthio, (C1-C22)alkylamino, ((C1- alkyl, an optionally substituted C2-24 alkenyl, an optionally
C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- substituted C2-24 alkynyl, an optionally substituted C3-6
C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- cycloalkyl, an optionally substituted C3-6 cycloalkenyl, an
C6)carbocyclyl, (C6- C12)aryl,orheterocyclyl; optionally substituted aryl, an optionally substituted heteroaryl, an
each R7 is independently selected from absent, optionally substituted aryl(Ci_6 alkyl), an optionally substituted *-
hydrogen, -(C=O)Oalkyl(C1-C22), -(C=O)alkyl(C1- (CR15AR16A)p-0-Ci_24 alkyl, an optionally substituted *-
C22), -(C=O)NHalkyl(C1-C22), -(C=O)N-dialkyl(C1- (CR17AR18A)q-0-Ci_24
C22), -(C=O)Salkyl(C1-C22), hydroxy, (C1-
C22)alkoxy, (C1- C22)alkyl, halogen, nitro, cyano,
C22)alkoxy, (C1- 127 C22)alkylthio, (C1-
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- R6A is and R7 is absent or hydrogen; or
C12)aryl,orheterocyclyl, wherein each R7 is optionally R and R , 7/AA are taken together to form a moiety selected from
substituted with one or more, the same or different, R20; the group
R8 is hydrogen, deuterium, (C1-C22)alkyl, (C2- consisting of an optionally substituted
C22)alkylthio, (C1-C22)alkylamino, ((C1- and an optionally substituted
C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-
65
C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein wherein the oxygens connected to R6A and R7A, the phosphorus and
R8 is optionally substituted with one or more, the same the moiety form a six-membered to ten-membered ring system;.
or different, R20; R9A is independently selected from the group consisting of an
R9 is hydrogen, methyl, ethyl, tert-butyl, (C1-C22)alkyl, optionally substituted Ci_24 alkyl, an optionally substituted C2-
halogen, nitro, cyano, hydroxy, amino, mercapto, 24 alkenyl, an optionally substituted C2-24 alkynyl, an optionally
formyl, carboxy, carbamoyl, cycloalkyl, (C1- substituted C3_6 cycloalkyl, an optionally substituted
C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, C3_6 cycloalkenyl, NR30AR31A, an optionally substituted N-linked
((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- amino acid and an optionally substituted N-linked amino acid ester
C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- derivative;
C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R10A and R11A are independently an optionally substituted N-linked
R9 is optionally substituted with one or more, the same amino acid or an optionally substituted N-linked amino acid ester
or different, R20; derivative;
R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, lipid, R12A, R13A and R14A are independently absent or hydrogen;
methyl, ethyl, isopropyl, cyclopentyl, cyclohexyl, butyl, each R15A, each R16A, each R17A and each R18A are independently
pentyl, hexyl, neopentyl, benzyl, halogen, nitro, cyano, hydrogen, an optionally substituted Ci_24 alkyl or alkoxy; R19A,
hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, R20A, R22A, R23A, R5B, R6B, R8B, R9B, R9C, R10C, R12C and R13C are
(C1-C22)alkoxy, (C1-C22)alkylthio, (C1- independently selected from the group consisting of hydrogen, an
C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- optionally substituted Ci_24 alkyl and an optionally substituted
C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- aryl;
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- R2iA R24A R7B^ Ri<m Rnc and Ri4C arg independently selected from
C12)aryl,orheterocyclyl, the group consisting of hydrogen, an optionally substituted Ci_24
wherein R10 is optionally substituted with one or more, alkyl, an optionally substituted aryl, an optionally substituted -0-
the same or different, R20; Ci_24 alkyl and an optionally substituted -O-aryl;
R11 is hydrogen, deuterium, (C1-C22)alkyl, methyl, R25A R29A RHB and R15C are independently selected from the
halogen, nitro, cyano, hydroxy, amino, mercapto, group consisting of hydrogen, an optionally substituted Ci_24 alkyl
formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1- and an optionally substituted aryl;
C22)alkylthio, (C1-C22)alkylamino, ((C1- R1U", R^ and R are independently absent or hydrogen;
C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- R26A and R27A are independently -C≡N or an optionally substituted
C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- substituent selected from the group consisting of C2_8
C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, organylcarbonyl, C2_8 alkoxycarbonyl and C2_8
wherein R11 is optionally substituted with one or more, organylaminocarbonyl;
the same or different, R20; R28A is selected from the group consisting of hydrogen, an
R12 is hydrogen, (C1-C22)alkyl, (C6-C12)aryl, phenyl, optionally substituted Ci_24-alkyl, an optionally substituted C2_24
1-naphthyl, 2-naphthyl,aromatic, heteroaromatic, 4- alkenyl, an optionally substituted C2-24 alkynyl, an optionally
substituted phenyl, 4-fluorophenyl, 4-chlorophenyl, 4- substituted C3_6 cycloalkyl and an optionally substituted
bromophenyl, naphthyl, or heterocyclyl, wherein R12 is C3_6 cycloalkenyl;
optionally substituted with one or more, the same or R30A and R31A are independently selected from the group consisting
different, R20; of hydrogen, an optionally substituted Ci_24-alkyl, an optionally
R13 is hydrogen, deuterium, (C1-C22)alkyl, (C2- substituted C2-24 alkenyl, an optionally substituted C2_24 alkynyl,
C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, an optionally substituted C3_6 cycloalkyl and an optionally
hydroxy, amino, amido, mercapto, formyl, carboxy, substituted C3_6 cycloalkenyl;
carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1- for Formula (III), is a single bond or a double bond;
C22)alkylthio, (C1-C22)alkylamino, ((C1- when is a single bond, each R and each R is independently
C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- hydrogen or halogen; and
C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- when is a double bond, each R is absent and each R is
C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, independently hydrogen or halogen;
wherein R13 is optionally substituted with one or more, R"A and R"c are independently an optionally substituted Ci_24-
the same or different, R20; alkyl;
R14 is hydrogen, deuterium, (C1-C22)alkyl, (C2- m and n are independently 0 or 1 ;
C22)alkenyl, (C12-C22)alkynyl, halogen, nitro, cyano, p and q are independently selected from the group consisting of 1,
hydroxy, amino, amido, mercapto, formyl, carboxy, 2 and 3;
carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1- r is 1 or 2;
C22)alkylthio, (C1-C22)alkylamino, ((C1- Z1A, Z2A, Z3A, Z4A, Z1B, Z2B and Z1C are independently O or S; and
C22)alkyl)2amino, alkylsulfinyl, (C1-C22)alkylsulfonyl, provided that when the dashed line ( ) of Formula (I) is absent;
(C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6- R1A is
(C2-C22)alkynyl, halogen, nitro, cyano, hydroxy,
C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- wherein R is an unsubstituted Ci_4 alkyl or phenyl optionally para-
C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, substituted with a halogen or methyl and R9A is methyl ester, ethyl
or heterocyclyl; and wherein the lipid comprises a C6- ester, isopropyl ester, n-butyl ester, benzyl ester or phenyl ester of
22 alkyl, (C1-C22)alkoxy, polyethylene glycol, or (C6- an amino acid selected from the group consisting of glycine,
C12)aryl substituted with an (C1-C22)alkyl group, alanine, valine, leucine, phenylalanine, tryptophan, methionine and
heterocyclylis acarbocyclylcomprising 1-4 heteroatoms proline; R3A is OH; R4A is fluoro; R5A is fluoro or hydrogen; and
selected from nitrogen, oxygen, or sulfur, and B1A is an unsubstituted uracil; then R2A cannot be -OCH3;
heteroaromatic is an aromatic heterocyclylcomprising 1- provided that when the dashed line ( ) of Formula (I) is absent;
4 heteroatoms selected from nitrogen, oxygen, or sulfur R1A is H; R3A is OH; R4A is fluoro; R5A is fluoro; and B1A is an
66
and at least 1 carbon atom. unsubstituted cytosine; then R2A cannot be allenyl;
provided that when the dashed line ( ) of Formula (I) is absent;
R1A is H; R3A is OH; R4A is fluoro; R5A is hydrogen; and B1A is an
unsubstituted thymine; then R2A cannot be Ci alkyl substituted with
an N-amido; and
R1A is H; R3A is OH; R4A is fluoro; R5A is fluoro; and B1A is an
unsubstituted cytosine; then R2A cannot be ethynyl.
Claim 2
2. A method for ameliorating or treating a viral infection caused by
a virus comprising administering to or contacting a cell in a subject
with an effective amount of a compound selected from Formula (I),
Formula (II), and Formula (III), or a pharmaceutically acceptable
salt of the foregoing, wherein the virus is selected from a
henipavirus, a morbiUivirus, a respirovirus, a rubulavirus and a
metapneumo virus, and wherein the compound is selected from
Formula (I), Formula (II), and Formula (III) has one of the
following structures:
(I) (Π)
(HI)
wherein:
B1A B1B and B1C are independently an optionally substituted
heterocyclic base or an optionally substituted heterocyclic base
with a protected amino group; R , ΙΑ is selected from the group
consisting of hydrogen, an optionally substituted
acyl, an optionally substituted O-linked amino acid,
when the dashed line ( ) of Formula (I) is a single bond, R2A is CH2,
and R3A is O (oxygen);
when the dashed line ( ) of Formula (I) is absent, R2A is selected
from the group consisting of an optionally substituted Ci_6 alkyl,
C2_6 alkynyl, an optionally substituted C3_6 cycloalkyl, an
optionally substituted -0-Ci_6 alkyl, an optionally substituted -0-
C3_6 alkenyl, an optionally substituted -0-C3_6 alkynyl and cyano,
and R3A is selected from the group consisting of OH, -
OC(=O)R"A and an optionally substituted O-linked amino acid;
R2Cselected from the group consisting of O", OH,
, an optionally substituted N-linked amino acid and an

optionally substituted N-linked amino acid ester derivative;
R^ and R^ are independently selected from the group consisting of
O", OH, an
optionally substituted Ci_, alkoxy,
67
substituted N-linked amino acid ester derivative; or
RZB and RJ are independently selected from the group consisting of

an optionally substituted Ci_6 alkyl, an optionally substituted
C2_6 alkenyl, an optionally substituted C2_6 alkynyl, an optionally
substituted C3-6 cycloalkyl, an optionally substituted -0-C1-6 alkyl,
an optionally substituted -0-C3-6 alkenyl, an optionally substituted -
0-C3-6 alkynyl and cyano;
R is selected from the group consisting of OH, -OC(=0)R" and an
optionally substituted 0-linked amino acid;
R4A, R3B and R5C are independently a halogen;
R , R and R , R6C are independently hydrogen or halogen;
R6A, R7A and R8A are independently selected from the group
consisting of absent, hydrogen, an optionally substituted
Ci_24 alkyl, an optionally substituted C2_24 alkenyl, an optionally
substituted C2_24 alkynyl, an optionally substituted C3-6 cycloalkyl,
an optionally substituted C3-6 cycloalkenyl, an optionally
substituted aryl, an optionally substituted heteroaryl, an optionally
substituted aryl(Ci_6 alkyl), an optionally substituted
*- 15AR16A)p-0-Ci_24 alkyl, an optionally substituted *-
(CR17AR18A)q-0-Ci. 24
R6A is and R is absent or hydrogen; or R6A and R7A are taken

together to form a moiety selected from the group
and an optionally substituted
, wherein the oxygens connected to R6A and R7A, the phosphorus

and the moiety form a six-membered to ten-membered ring
system;.
R9A is independently selected from the group consisting of an
68
optionally substituted Ci_24 alkyl, an optionally substituted C2_24
alkenyl, an optionally substituted C2-24 alkynyl, an optionally
substituted C3-6 cycloalkyl, an optionally substituted C3-6
cycloalkenyl, NR30AR31A, an optionally substituted N-linked amino
acid and an optionally substituted N-linked amino acid ester
derivative;
R10A and R11A are independently an optionally substituted N-linked
amino acid or an optionally substituted N-linked amino acid ester
derivative;
R12A, R13A and R14A are independently absent or hydrogen;
each R15A, each R16A, each R17A and each R18A are independently
hydrogen, an optionally substituted Ci_24 alkyl or alkoxy;
R19A, R20A, R22A, R23A, R5B, R6B, R8B, R9B, R9C, R10C, R12C and
R13C are independently selected from the group consisting of
hydrogen, an optionally substituted Ci_24 alkyl and an optionally
substituted aryl;
i
R2IA R24A r7B^ R <m RI IC AND Ri4C arg ndependently selected from
the group consisting of hydrogen, an optionally substituted Ci_24
alkyl, an optionally substituted aryl, an optionally substituted -0-
Ci_24 alkyl and an optionally substituted -O-aryl;
R25A R29A RHB AND R15C are independently selected from the
group consisting of hydrogen, an optionally substituted Ci_24 alkyl
and an optionally substituted aryl;
R1U", R^ and R are independently absent or hydrogen;
R26A and R27A are independently -C≡N or an optionally substituted
substituent selected from the group consisting of C2-8
organylcarbonyl, C2-8 alkoxycarbonyl and C2-8
organylaminocarbonyl;
optionally substituted Ci_24-alkyl, an optionally substituted C2_24
alkenyl, an optionally substituted C2_24 alkynyl, an optionally
substituted C3-6 cycloalkyl and an optionally substituted C3-6
cycloalkenyl; R30A and R31A are independently selected from the
group consisting of hydrogen, an optionally substituted Ci_24-alkyl,
C2_24 alkynyl, an optionally substituted C3-6 cycloalkyl and an
optionally substituted C3-6 cycloalkenyl;
for Formula (III), is a single bond or a double bond;
when is a single bond, each R and each R is independently
hydrogen or halogen; and
when is a double bond, each R is absent and each R is
independently hydrogen or halogen;
R"A and R"c are independently an optionally substituted Ci_24-alkyl;
m and n are independently 0 or 1 ;
p and q are independently selected from the group consisting of 1 ,
2 and 3;
r is 1 or 2;
Z1A, Z2A, Z3A, Z4A, Z1B, Z2B and Z1C are independently O or S; and
R1A is
wherein R5A is an unsubstituted Ci_4 alkyl or phenyl optionally

para- substituted with a halogen or methyl and R9A is methyl ester,
ethyl ester, isopropyl ester, n-butyl ester, benzyl ester or phenyl
ester of an amino acid selected from the group consisting of
glycine, alanine, valine, leucine, phenylalanine, tryptophan,
methionine and proline; R3A is OH; R4A is fluoro; R5A is fluoro or
hydrogen; and B1A is an unsubstituted uracil; then R2A cannot be -
OCH3;
unsubstituted cytosine; then R2A cannot be allenyl;
R1A is H; R3A is OH; R4A is fluoro; R5A is hydrogen; and B1A is an
an N-amido; and
69
Claim 163.
The use or method of Claim 162, wherein R1c is O" or OH.
Claim 168.
The use or method of Claim 162, wherein R1c i s an optionally
substituted N - linked amino acid.
Claim 169.
The use or method of Claim 162, wherein R1c i s an optionally
substituted N- linked amino acid ester derivative.
Claim 170.
The use or method of any one of Claims 162-169, wherein R2c i s
O or OH.
Claim 171.
The use or method of any one of Claims 162-169, wherein R2c i s
an optionally substituted C1-6 alkoxy.
Claim 192.
The use or method of any one of Claims 162-191, wherein R4C i s
OH.
Claim 193.
The use or method of any one of Claims 162- 191 , wherein R4C is
-OC(=0)R"C
Claim 194.
The use or method of Claim 193, wherein R4c is an optionally
substituted C 1-8 alkyl.
Claim 201 .
The use or method of any one of Claims 162-200, wherein R6C is
halogen.
Claim 202.
The use or method of any one of Claims 162-200, wherein R6C is
hydrogen.
Claim 203.
The use or method of any one of Claims 162-202, wherein R6c is
fluoro.
Claim 205.
The use or method of Claim 204, wherein the R7C and the R8C
groups are all hydrogen.
Claim 206.
The use or method of Claim 204, wherein one R7C is halogen, one
R8C is hydrogen and both R groups are all hydrogen.
Claim 207.
The use or method of Claim 204, wherein one R 7C is halogen,
one R8C is hydrogen, one R is halogen and one R is hydrogen.
Claim 212.
The use or method of any one of Claims 162-211, wherein B is
selected from the group consisting of:
wherein:
R is selected from the group consisting of hydrogen, halogen and
NHR'
KC2 wherein R is selected from the group consisting of hydrogen, -
C(=0)R U and
C(=0)OR^ ;
R is halogen or NHR , wherein R is selected from the group
consisting of hydrogen, an optionally substituted Ci_6 alkyl, an
optionally substituted C2-6 alkenyl, an optionally substituted
C3_8 cycloalkyl, -C(=0)RMC2 and -C(=0)ORNC2;
consisting of hydrogen, -C(=0)RPC2 and -C(=0)ORQC2; R is selected
70
from the group consisting of hydrogen, halogen, an optionally
substituted Ci_6 alkyl, an optionally substituted C2_6 alkenyl
R EC2 is selected from the group consisting of hydrogen, hydroxy,
an optionally substituted Ci_6 alkyl, an optionally substituted C3-8
optionally substituted Ci_6alkyl, an optionally substituted
C2_6 alkenyl and an optionally substituted C2_6 alkynyl;
Y2C and Y3C are independently N or CRIC2, wherein RIC2 is selected
substituted Ci_6-alkyl, an optionally substituted C2_6-alkenyl and
an optionally substituted C2_6-alkynyl;
R is hydrogen or NHR , wherein R is independently selected from
the group consisting of hydrogen, -C(=0)RUC2 and -C(=0)ORVC2;
and
C2_6 alkenyl, C2_6 alkynyl, C3-6 cycloalkyl, C3-6 cycloalkenyl,
C6-1o aryl, heteroaryl, heteroalicyclyl, aryl(Ci_6 alkyl),
heteroaryl(Ci_6 alkyl) and heteroalicyclyl(Ci_6 alkyl).
Thus, it is clear that all elements of claim 1, IN201717025098 are covered in D2.
Therefore, claim 1 and all dependent claims lack novelty in view of D2 also.
Claim 2:
IN201717025098 D3: WO2013142525A1

CLAIM 2: The pharmaceutical composition of claim Claim 212.
1, wherein Q-R7 is OH. The use or method of any one of Claims 162-211, wherein B is
wherein:
NHR'
C(=0)R U and
C(=0)OR^ ;
R is halogen or NHR , wherein R is selected from the group consisting
of hydrogen, an optionally substituted Ci_6 alkyl, an optionally
substituted C2-6 alkenyl, an optionally substituted C3_8 cycloalkyl, -
C(=0)RMC2 and -C(=0)ORNC2;
consisting of hydrogen, -C(=0)RPC2 and -C(=0)ORQC2; R is selected
substituted Ci_6 alkyl, an optionally substituted C2_6 alkenyl and an
optionally substituted C2_6 alkynyl;
71
Y2C and Y3C are independently N or CRIC2, wherein RIC2 is selected
substituted Ci_6-alkyl, an optionally substituted C2_6-alkenyl and an
optionally substituted C2_6-alkynyl;
aryl, heteroaryl, heteroalicyclyl, aryl(Ci_6 alkyl), heteroaryl(Ci_6
alkyl) and heteroalicyclyl(Ci_6 alkyl).
Claim 1
Use of an effective amount of a compound selected from Formula (I),
Formula (II), and Formula (III), or a pharmaceutically acceptable salt
of the foregoing, for amelioring or treating a viral infection caused by
a virus selected from a henipavirus, a morbilli virus, a respirovirus, a
from Formula (I), Formula II), and Formula (III) has one of the
(I) (Π)
(HI)
wherein:
B1A, B1B, and B1C are independently an optionally substituted
heterocyclic base or an optionally substituted heterocyclic base with a
protected amino group;
R1A is selected from the group consisting of hydrogen, an optionally
substituted

and R is O (oxygen);
when the dashed line ( ) of Formula (I) is absent, RZA is selected from
the group consisting of an optionally substituted Ci_6 alkyl, an
optionally substituted C2_6 alkenyl, an optionally substituted
substituted -O-C1-6 alkyl, an optionally substituted -0-C3_6 alkenyl, an
optionally substituted -O-C3-6 alkynyl and cyano, and R3A is selected
from the group consistin of OH, -OC(=0)R"A and an optionally
substituted O-linked amino acid;
N-linked amino acid and an optionally substituted N-linked amino acid

ester derivative;
R1C and R2C are independently selected from the group consisting
of O-, OH, an
72
R2B and R are independently selected from the group consisting of an

substituted C3-6 cycloalkyl, an optionally substituted -0-C1-6 alkyl, an
optionally substituted -O-C3-6 alkenyl, an optionally substituted -0-C3-
6 alkynyl and cyano;
R4C is selected from the group consisting of OH, -OC(=0)R"c and an
R5A, R4B and R6C are independently hydrogen or halogen;
R6A, R7A and R8A are independently selected from the group consisting
of absent, hydrogen, an optionally substituted Ci_24 alkyl, an
optionally substituted C2-24 alkenyl, an optionally substituted C2-24
alkynyl, an optionally substituted C3-6 cycloalkyl, an optionally
substituted C3-6 cycloalkenyl, an optionally substituted aryl, an
optionally substituted heteroaryl, an optionally substituted aryl(Ci_6
alkyl), an optionally substituted *-(CR15AR16A)p-0-Ci_24 alkyl, an
optionally substituted *-(CR17AR18A)q-0-Ci_24

group
wherein the oxygens connected to R6A and R7A, the phosphorus and
the moiety form a six-membered to ten-membered ring system;.
optionally substituted Ci_24 alkyl, an optionally substituted C2-
24 alkenyl, an optionally substituted C2-24 alkynyl, an optionally
substituted C3_6 cycloalkyl, an optionally substituted
C3_6 cycloalkenyl, NR30AR31A, an optionally substituted N-linked
amino acid and an optionally substituted N-linked amino acid ester
derivative;
derivative;
hydrogen, an optionally substituted Ci_24 alkyl or alkoxy; R19A, R20A,
R22A, R23A, R5B, R6B, R8B, R9B, R9C, R10C, R12C and R13C are
independently selected from the group consisting of hydrogen, an
optionally substituted Ci_24 alkyl and an optionally substituted aryl;
R2iA R24A R7B^ Ri<m Rnc and Ri4C arg independently selected from the
group consisting of hydrogen, an optionally substituted Ci_24 alkyl, an
optionally substituted aryl, an optionally substituted -0-Ci_24 alkyl and
an optionally substituted -O-aryl;
R25A R29A RHB and R15C are independently selected from the group
consisting of hydrogen, an optionally substituted Ci_24 alkyl and an
73
optionally substituted aryl;
substituent selected from the group consisting of C2_8
organylcarbonyl, C2_8 alkoxycarbonyl and C2_8
substituted Ci_24-alkyl, an optionally substituted C2_24 alkenyl, an
optionally substituted C2-24 alkynyl, an optionally substituted
C3_6 cycloalkyl and an optionally substituted C3_6 cycloalkenyl;
R30A and R31A are independently selected from the group consisting of
hydrogen, an optionally substituted Ci_24-alkyl, an optionally
substituted C2-24 alkenyl, an optionally substituted C2_24 alkynyl, an
optionally substituted C3_6 cycloalkyl and an optionally substituted
C3_6 cycloalkenyl;
when is a single bond, each R and each R is independently hydrogen
or halogen; and
when is a double bond, each R is absent and each R is independently
hydrogen or halogen;
p and q are independently selected from the group consisting of 1, 2
and 3;
r is 1 or 2;
provided that when the dashed line ( ) of Formula (I) is absent; R1A is
wherein R is an unsubstituted Ci_4 alkyl or phenyl optionally para-

substituted with a halogen or methyl and R9A is methyl ester, ethyl
ester, isopropyl ester, n-butyl ester, benzyl ester or phenyl ester of an
amino acid selected from the group consisting of glycine, alanine,
valine, leucine, phenylalanine, tryptophan, methionine and proline;
R3A is OH; R4A is fluoro; R5A is fluoro or hydrogen; and B1A is an
unsubstituted uracil; then R2A cannot be -OCH3;
H; R3A is OH; R4A is fluoro; R5A is fluoro; and B1A is an unsubstituted
cytosine; then R2A cannot be allenyl;
H; R3A is OH; R4A is fluoro; R5A is hydrogen; and B1A is an
unsubstituted thymine; then R2A cannot be Ci alkyl substituted with an
N-amido; and
H; R3A is OH; R4A is fluoro; R5A is fluoro; and B1A is an unsubstituted
cytosine; then R2A cannot be ethynyl.
Similar arguments are applicable to other independent claims 8 & 14.
Thus, all claims of IN201717025098 are anticipated by D3.
74
Claim 3
IN201717025098 D3: WO2013142525A1

CLAIM 3: The pharmaceutical composition of claim Claim 1
1, wherein R1 is Use of an effective amount of a compound selected from Formula (I),
Formula (II), and Formula (III), or a pharmaceutically acceptable salt
of the foregoing, for amelioring or treating a viral infection caused by
a virus selected from a henipavirus, a morbilli virus, a respirovirus, a
rubulavirus and a metapneumovirus, wherein the compound is
selected from Formula (I), Formula II), and Formula (III) has one of
the following structures:

(I) (Π)
(HI)
wherein:
substituted

and R is O (oxygen);
when the dashed line ( ) of Formula (I) is absent, RZA is selected from
the group consisting of an optionally substituted Ci_6 alkyl, an
optionally substituted C2_6 alkenyl, an optionally substituted
substituted -O-C1-6 alkyl, an optionally substituted -0-C3_6 alkenyl,
an optionally substituted -O-C3-6 alkynyl and cyano, and R3A is
selected from the group consistin of OH, -OC(=0)R"A and an
N-linked amino acid and an optionally substituted N-linked amino

acid ester derivative;
R1C and R2C are independently selected from the group consisting
of O-, OH, an

R2B and R are independently selected from the group consisting of an

substituted C3-6 cycloalkyl, an optionally substituted -0-C1-6 alkyl,
75
an optionally substituted -O-C3-6 alkenyl, an optionally substituted -
0-C3-6 alkynyl and cyano;
R4C is selected from the group consisting of OH, -OC(=0)R"c and an
consisting of absent, hydrogen, an optionally substituted Ci_24 alkyl,
an optionally substituted C2-24 alkenyl, an optionally substituted C2-
24 alkynyl, an optionally substituted C3-6 cycloalkyl, an optionally
substituted C3-6 cycloalkenyl, an optionally substituted aryl, an
optionally substituted heteroaryl, an optionally substituted aryl(Ci_6
alkyl), an optionally substituted *-(CR15AR16A)p-0-Ci_24 alkyl, an
optionally substituted *-(CR17AR18A)q-0-Ci_24

group
wherein the oxygens connected to R6A and R7A, the phosphorus and
the moiety form a six-membered to ten-membered ring system;.
optionally substituted Ci_24 alkyl, an optionally substituted C2-
24 alkenyl, an optionally substituted C2-24 alkynyl, an optionally
substituted C3_6 cycloalkyl, an optionally substituted
C3_6 cycloalkenyl, NR30AR31A, an optionally substituted N-linked
amino acid and an optionally substituted N-linked amino acid ester
derivative;
derivative;
hydrogen, an optionally substituted Ci_24 alkyl or alkoxy; R19A, R20A,
R22A, R23A, R5B, R6B, R8B, R9B, R9C, R10C, R12C and R13C are
optionally substituted Ci_24 alkyl and an optionally substituted aryl;
R2iA R24A R7B^ Ri<m Rnc and Ri4C arg independently selected from
the group consisting of hydrogen, an optionally substituted Ci_24
alkyl, an optionally substituted aryl, an optionally substituted -0-
Ci_24 alkyl and an optionally substituted -O-aryl;
R25A R29A RHB and R15C are independently selected from the group
consisting of hydrogen, an optionally substituted Ci_24 alkyl and an
optionally substituted aryl;
substituent selected from the group consisting of C2_8
R30A and R31A are independently selected from the group consisting
of hydrogen, an optionally substituted Ci_24-alkyl, an optionally
substituted C2-24 alkenyl, an optionally substituted C2_24 alkynyl, an
optionally substituted C3_6 cycloalkyl and an optionally substituted
C3_6 cycloalkenyl;
76
when is a single bond, each R and each R is independently hydrogen
or halogen; and
p and q are independently selected from the group consisting of 1, 2
and 3;
r is 1 or 2;

substituted with a halogen or methyl and R9A is methyl ester, ethyl
ester, isopropyl ester, n-butyl ester, benzyl ester or phenyl ester of an
amino acid selected from the group consisting of glycine, alanine,
valine, leucine, phenylalanine, tryptophan, methionine and proline;
R3A is OH; R4A is fluoro; R5A is fluoro or hydrogen; and B1A is an
unsubstituted uracil; then R2A cannot be -OCH3;
H; R3A is OH; R4A is fluoro; R5A is fluoro; and B1A is an
H; R3A is OH; R4A is fluoro; R5A is hydrogen; and B1A is an
an N-amido; and
H; R3A is OH; R4A is fluoro; R5A is fluoro; and B1A is an
Claim 4:
IN201717025098 D3: WO2013142525A1

CLAIM 4.
A pharmaceutical composition comprising a Claim 1
pharmaceutically acceptable excipient and a compound of Use of an effective amount of a compound selected from
formula IB, Formula (I), Formula (II), and Formula (III), or a
pharmaceutically acceptable salt of the foregoing, for
amelioring or treating a viral infection caused by a virus
selected from a henipavirus, a morbilli virus, a respirovirus, a
selected from Formula (I), Formula II), and Formula (III) has
one of the following structures:

Y is H, D, F, Cl, Br, I, CH3, CD3, CF3, (C1-C6)alkyl,
(I) (Π)
acyl, (C2-C6)alkenyl, (C2-C6)alkynyl, hydroxyl, formyl or
SCH3;
R1
(HI)
wherein:
Monophosphate ester, B1A, B1B, and B1C are independently an optionally
diphosphate ester substituted heterocyclic base or an optionally substituted
heterocyclic base with a protected amino group;
77
when the dashed line ( ) of Formula (I) is a single bond, R A is

CH2, and R is O (oxygen);
when the dashed line ( ) of Formula (I) is absent, RZA is
selected from the group consisting of an optionally substituted
alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, Ci_6 alkyl, an optionally substituted C2_6 alkenyl, an optionally
formyl, substituted C2_6 alkynyl, an optionally substituted C3
carboxy, carbamoyl, carbanoyl, esteryl, alkoxy, cycloalkyl, an optionally substituted -O-C1-6 alkyl, an
(C1C22)alkylthio, (C1-C22)alkylamino, ((C1- optionally substituted -0-C3_6 alkenyl, an optionally substituted
C22)alkyl)2amino, -O-C3-6 alkynyl and cyano, and R3A is selected from the group
(C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- consistin of OH, -OC(=0)R"A and an optionally substituted O-
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or linked amino acid;
heterocyclyl, or phosphoramidyl,wherein R1 is optionally
Y1 is O or S;
Y3 is OH or BH3-M+; N-linked amino acid and an optionally substituted N-linked
R4 is hydrogen, hydroxy,(C1-C22)alkyl, fluoromethyl, amino acid ester derivative;
difluoromethyl, trifluoromethyl, hydroxymethyl, halogen, R1C and R2C are independently selected from the group
nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, consisting of O-, OH, an
, an optionally substituted N-linked amino acid and an
or optionally substituted C1-6 alkoxy
R2B and R are independently selected from the group consisting
optionally substituted with one or more, the same or of an optionally substituted Ci_6 alkyl, an optionally
substituted C2-6 alkenyl, an optionally substituted C2-6 alkynyl,
different, R20;
R9 is hydrogen, methyl, ethyl, tert-butyl, (C1-C22)alkyl, an optionally substituted C3-6 cycloalkyl, an optionally
halogen, nitro, cyano, hydroxy, amino,mercapto, formyl, substituted -0-C1-6 alkyl, an optionally substituted -O-C3-6
carboxy, carbamoyl, cycloalkyl, (C1-C22)alkoxy, (C1- alkenyl, an optionally substituted -0-C3-6 alkynyl and cyano;
R4C is selected from the group consisting of OH, -
C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- OC(=0)R"c and an optionally substituted O-linked amino acid;
C6)carbocyclyl,(C6-C12)aryl,orheterocyclyl, wherein R9 is R5A, R4B and R6C are independently hydrogen or halogen;
different, R20; consisting of absent, hydrogen, an optionally substituted Ci_24
R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, lipid, methyl, alkyl, an optionally substituted C2-24 alkenyl, an optionally
substituted C2-24 alkynyl, an optionally substituted C3-6
ethyl, isopropyl, cyclopentyl, cyclohexyl, butyl, pentyl,
hexyl, neopentyl, benzyl, halogen, nitro, cyano, hydroxy, cycloalkyl, an optionally substituted C3-6 cycloalkenyl, an
optionally substituted aryl, an optionally substituted heteroaryl,
C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1- an optionally substituted aryl(Ci_6 alkyl), an optionally
substituted *-(CR15AR16A)p-0-Ci_24 alkyl, an optionally
C22)alkyl)2amino, (C1-C22)alkylsulfinyl,(C1-
C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- substituted *-(CR17AR18A)q-0-Ci_24
different, R20;
(C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- R6A is and R7 is absent or hydrogen; or
C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- R and R , 7/AA are taken together to form a moiety selected
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or from the group
heterocyclyl, wherein R11 is optionally substituted with one consisting of an optionally substituted
naphthyl, 2-naphthyl,aromatic, heteroaromatic, 4-substituted
phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, and an optionally substituted
78
naphthyl, or heterocyclyl, wherein R12 is optionally
C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, wherein the oxygens connected to R6A and R7A, the phosphorus
hydroxy, amino, amido, mercapto, formyl, carboxy, and the moiety form a six-membered to ten-membered ring
carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1- system;.
C22)alkylthio, R9A is independently selected from the group consisting of an
(C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- optionally substituted Ci_24 alkyl, an optionally substituted C2-
C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- 24 alkenyl, an optionally substituted C2-24 alkynyl, an
C12)arylsulfonyl,(C3-C6)carbocyclyl, (C6-C12)aryl, or optionally substituted C3_6 cycloalkyl, an optionally substituted
heterocyclyl, wherein R13 is optionally substituted with one C3_6 cycloalkenyl, NR30AR31A, an optionally substituted N-
or more, the linked amino acid and an optionally substituted N-linked amino
same or different, R20; acid ester derivative;
R14 is hydrogen, deuterium, (C1-C22)alkyl, (C2- R10A and R11A are independently an optionally substituted N-
C22)alkenyl, (C12-C22)alkynyl, halogen, nitro, cyano, linked amino acid or an optionally substituted N-linked amino
hydroxy, amino, amido, mercapto, formyl, carboxy, acid ester derivative;
carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1- R12A, R13A and R14A are independently absent or hydrogen;
C22)alkylthio, each R15A, each R16A, each R17A and each R18A are
(C1-C22)alkylamino, ((C1-C22)alkyl)2amino, alkylsulfinyl, independently hydrogen, an optionally substituted Ci_24 alkyl
(C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- or alkoxy; R19A, R20A, R22A, R23A, R5B, R6B, R8B, R9B, R9C, R10C,
C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R14 R12C and R13C are independently selected from the group
is optionally substituted with one or more, thesame or consisting of hydrogen, an optionally substituted Ci_24 alkyl
different, R20; and an optionally substituted aryl;
R15 is hydrogen, Lipid, -(C=O)Oalkyl(C1-C22), - R2iA R24A R7B^ Ri<m Rnc and Ri4C arg independently selected
(C=O)alkyl(C1-C22), -(C=O)NHalkyl(C1-C22), -(C=O)N- from the group consisting of hydrogen, an optionally
dialkyl(C1-C22), -(C=O)Salkyl(C1-C22), hydroxy, (C1- substituted Ci_24 alkyl, an optionally substituted aryl, an
C22)alkoxy, (C1-C22)alkyl, halogen, nitro, cyano,amino, optionally substituted -0-Ci_24 alkyl and an optionally
mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, substituted -O-aryl;
(C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- R25A R29A RHB and R15C are independently selected from the
C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- group consisting of hydrogen, an optionally substituted Ci_24
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or alkyl and an optionally substituted aryl;
heterocyclyl, wherein R15 is optionally substituted with one R1U", R^ and R are independently absent or hydrogen;
or more, the same or different, R20; R26A and R27A are independently -C≡N or an optionally
R20 is deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2- substituted substituent selected from the group consisting of
C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, C2_8 organylcarbonyl, C2_8 alkoxycarbonyl and C2_8
mercapto, formyl, carboxy, carbamoyl, azido, (C1- organylaminocarbonyl;
C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1- R28A is selected from the group consisting of hydrogen, an
C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- optionally substituted Ci_24-alkyl, an optionally substituted
C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C2_24 alkenyl, an optionally substituted C2-24 alkynyl, an
C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; and optionally substituted C3_6 cycloalkyl and an optionally
wherein the lipid comprises a C6-22 alkyl, (C6-C22)alkoxy, substituted C3_6 cycloalkenyl;
polyethylene glycol, or (C6-C12)aryl substituted with an R30A and R31A are independently selected from the group
alkyl group,heterocyclylis acarbocyclylcomprising 1-4 consisting of hydrogen, an optionally substituted Ci_24-alkyl,
heteroatoms selected from nitrogen, oxygen, or sulfur, and an optionally substituted C2-24 alkenyl, an optionally
heteroaromatic is an aromatic heterocyclylcomprising 1-4 substituted C2_24 alkynyl, an optionally substituted
heteroatoms selected from nitrogen, oxygen, or sulfur and at C3_6 cycloalkyl and an optionally substituted
least 1 carbon atom. C3_6 cycloalkenyl;
R"A and R"c are independently an optionally substituted Ci_24-
alkyl;
p and q are independently selected from the group consisting of
1, 2 and 3;
r is 1 or 2;
Z1A, Z2A, Z3A, Z4A, Z1B, Z2B and Z1C are independently O or S;
and
R1A is
wherein R is an unsubstituted Ci_4 alkyl or phenyl optionally

para- substituted with a halogen or methyl and R9A is methyl
79
ester, ethyl ester, isopropyl ester, n-butyl ester, benzyl ester or
phenyl ester of an amino acid selected from the group
consisting of glycine, alanine, valine, leucine, phenylalanine,
tryptophan, methionine and proline; R3A is OH; R4A is fluoro;
R5A is fluoro or hydrogen; and B1A is an unsubstituted uracil;
then R2A cannot be -OCH3;
R1A is H; R3A is OH; R4A is fluoro; R5A is hydrogen; and B1A is
an unsubstituted thymine; then R2A cannot be Ci alkyl
substituted with an N-amido; and
Claim 212.
wherein:
R is selected from the group consisting of hydrogen, halogen
and NHR'
KC2 wherein R is selected from the group consisting of
hydrogen, -C(=0)R U and
C(=0)OR^ ;
RDC2 is hydrogen or NHR , wherein R is selected from the
group consisting of hydrogen, -C(=0)RPC2 and -C(=0)ORQC2; R
is selected from the group consisting of hydrogen, halogen, an
optionally substituted Ci_6 alkyl, an optionally substituted
R EC2 is selected from the group consisting of hydrogen,
hydroxy, an optionally substituted Ci_6 alkyl, an optionally
substituted C3-8 cycloalkyl, -C(=0)R and - C(=0)ORSC2;
R is selected from the group consisting of hydrogen, halogen,
an optionally substituted Ci_6alkyl, an optionally substituted
Y2C and Y3C are independently N or CRIC2, wherein RIC2 is
selected from the group consisting of hydrogen, halogen, an
optionally substituted Ci_6-alkyl, an optionally substituted
C2_6-alkenyl and an optionally substituted C2_6-alkynyl;
R is hydrogen or NHR , wherein R is independently selected
from the group consisting of hydrogen, -C(=0)RUC2 and -
C(=0)ORVC2; and
RKC2, RLC2, RMC2, RNC2, RPC2, RQC2 RRC2, RSC2 RUC2 and
RVC2 are independently selected from the group consisting of
Ci_6 alkyl, C2_6 alkenyl, C2_6 alkynyl, C3-6 cycloalkyl, C3-6
cycloalkenyl, C6-1o aryl, heteroaryl, heteroalicyclyl,
aryl(Ci_6 alkyl), heteroaryl(Ci_6 alkyl) and
heteroalicyclyl(Ci_6 alkyl).
80
Claim 5
IN201717025098 D3: WO2013142525A1

CLAIM 5 Claim 5 is dependent on claim 3 which is dependent on
The composition of claim 3, wherein the compound is
selected from: claim 1. Hence arguments of claim 1 apply here as such.
1-(3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-
4-((((heptyloxy)carbonyl)oxy)amino)pyrimidin-2-one, and
isopropyl(((3,4-dihydroxy-5-(4-(hydroxyamino)-2-
oxopyrimidin-1(2H)-yl)tetrahydrofuran-2-
Claim 6
IN201717025098 D3: WO2013142525A1

CLAIM 6 Claim 1
A pharmaceutical composition comprising a Use of an effective amount of a compound selected from
pharmaceutically acceptable excipient and a compound of Formula (I), Formula (II), and Formula (III), or a
Formula IC, pharmaceutically acceptable salt of the foregoing, for
rubulavirus and a metapneumovirus, wherein the compound
is selected from Formula (I), Formula II), and Formula (III)
has one of the following structures:

X is CH2,CHMe, CMe2, CHF, CF2, or CD2; (I) (Π)
Y is H, D, F, Cl, Br, I, CH3, CD3, CF3, alkyl, acyl, alkenyl,
R1 is hydrogen, monophosphate, diphosphate,
triphosphate,
(HI)
wherein:
B1A, B1B, and B1C are independently an optionally
substituted heterocyclic base or an optionally substituted
heterocyclic base with a protected amino group;

selected from the group consisting of an optionally
substituted Ci_6 alkyl, an optionally substituted C2_6 alkenyl,
an optionally substituted C2_6 alkynyl, an optionally
substituted C3 cycloalkyl, an optionally substituted -O-C1-
6 alkyl, an optionally substituted -0-C3_6 alkenyl, an
alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, optionally substituted -O-C3-6 alkynyl and cyano, and R3A is
formyl, selected from the group consistin of OH, -OC(=0)R"A and an
carboxy, carbamoyl, carbanoyl, esteryl, alkoxy, (C1- optionally substituted O-linked amino acid;
C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino,
81
different, R20; N-linked amino acid and an optionally substituted N-linked
Y1 is O or S; amino acid ester derivative;
Y2 is OH, OR12, OAlkyl, or BH3-M+; R1C and R2C are independently selected from the group
Y3 is OH or BH3-M+; consisting of O-, OH, an
carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio,(C1-
C22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6- , an optionally substituted N-linked amino acid and an
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or optionally substituted N-linked amino acid ester derivative;
heterocyclyl; or optionally substituted C1-6 alkoxy
R8 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl,
(C2-C22)alkynyl, halogen, nitro, cyano, hydroxy,
benzyloxy, amino, amido, mercapto, formyl, carboxy,
carbamoyl, azido, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1- R2B and R are independently selected from the group
C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- consisting of an optionally substituted Ci_6 alkyl, an
C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- optionally substituted C2-6 alkenyl, an optionally substituted
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- C2-6 alkynyl, an optionally substituted C3-6 cycloalkyl, an
C12)aryl,orheterocyclyl, wherein R8 is optionally optionally substituted -0-C1-6 alkyl, an optionally substituted
substituted with one or more, the same or different, R20; -O-C3-6 alkenyl, an optionally substituted -0-C3-6 alkynyl and
R9 is hydrogen, methyl, ethyl, tert-butyl, (C1-C22)alkyl, cyano;
halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, R4C is selected from the group consisting of OH, -
carboxy, carbamoyl, cycloalkyl, (C1-C22)alkoxy, (C1- OC(=0)R"c and an optionally substituted O-linked amino acid;
C22)alkylthio, (C1-C22)alkylamino,((C1-C22)alkyl)2amino, R4A, R3B and R5C are independently a halogen;
(C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- R5A, R4B and R6C are independently hydrogen or halogen;
C12)arylsulfonyl, (C3-C6)carbocyclyl,(C6- R6A, R7A and R8A are independently selected from the group
C12)aryl,orheterocyclyl, wherein R9 is optionally consisting of absent, hydrogen, an optionally substituted
substituted with one or more, the same or different, R20; Ci_24 alkyl, an optionally substituted C2-24 alkenyl, an
R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, lipid, methyl, optionally substituted C2-24 alkynyl, an optionally
ethyl, isopropyl, cyclopentyl, cyclohexyl,butyl, pentyl, substituted C3-6 cycloalkyl, an optionally substituted C3-6
hexyl, neopentyl, benzyl, halogen, nitro, cyano, hydroxy, cycloalkenyl, an optionally substituted aryl, an optionally
amino, mercapto, formyl, carboxy,carbamoyl, (C1- substituted heteroaryl, an optionally substituted aryl(Ci_6
C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1- alkyl), an optionally substituted *-(CR15AR16A)p-0-Ci_24 alkyl,
C22)alkyl)2amino, (C1-C22)alkylsulfinyl,(C1- an optionally substituted *-(CR17AR18A)q-0-Ci_24
C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl,
(C6-C12)aryl,orheterocyclyl, wherein R10 isoptionally
(C1-C22)alkylamino, ((C1-C22)alkyl)2amino,(C1- R6A is and R7 is absent or hydrogen; or
C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- R and R , 7/AA are taken together to form a moiety selected
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, from the group
orheterocyclyl, wherein R11 is optionally substituted with consisting of an optionally substituted
substituted phenyl, 4-fluorophenyl, 4-chlorophenyl, 4- and an optionally substituted
different, R20; 6A 7A
wherein the oxygens connected to R and R , the
phosphorus and the moiety form a six-membered to ten-
membered ring system;.
R9A is independently selected from the group consisting of
an optionally substituted Ci_24 alkyl, an optionally
substituted C2-24 alkenyl, an optionally substituted C2-24
alkynyl, an optionally substituted C3_6 cycloalkyl, an
optionally substituted C3_6 cycloalkenyl, NR30AR31A, an
optionally substituted N-linked amino acid and an optionally
substituted N-linked amino acid ester derivative;
82
C22)alkenyl, (C12-C22)alkynyl, halogen, nitro, cyano, R10A and R11A are independently an optionally substituted N-
hydroxy, amino, amido, mercapto, formyl, carboxy, linked amino acid or an optionally substituted N-linked
carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1-C22)alkylthio, amino acid ester derivative;
(C1-C22)alkylamino, ((C1-C22)alkyl)2amino, alkylsulfinyl, R12A, R13A and R14A are independently absent or hydrogen;
(C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- each R15A, each R16A, each R17A and each R18A are
C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R14 independently hydrogen, an optionally substituted
is optionally substituted with one or more, the same or Ci_24 alkyl or alkoxy; R19A, R20A, R22A, R23A, R5B, R6B, R8B, R9B,
different, R20; R9C, R10C, R12C and R13C are independently selected from the
R15 is hydrogen, Lipid, -(C=O)Oalkyl(C1-C22), - group consisting of hydrogen, an optionally substituted
(C=O)alkyl(C1-C22), -(C=O)NHalkyl(C1-C22), - (C=O)N- Ci_24 alkyl and an optionally substituted aryl;
dialkyl(C1-C22), -(C=O)Salkyl(C1-C22), hydroxy, (C1- R2iA R24A R7B^ Ri<m Rnc and Ri4C arg independently selected
C22)alkoxy, (C1-C22)alkyl, halogen, nitro, cyano,amino, from the group consisting of hydrogen, an optionally
mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, substituted Ci_24 alkyl, an optionally substituted aryl, an
(C1-C22)alkylamino, ((C1-C22)alkyl)2amino,(C1- optionally substituted -0-Ci_24 alkyl and an optionally
C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- substituted -O-aryl;
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or R25A R29A RHB and R15C are independently selected from the
heterocyclyl, wherein R15 is optionally substituted with group consisting of hydrogen, an optionally substituted Ci_24
one or more, the same or different, R20; alkyl and an optionally substituted aryl;
R20 is deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2- R1U", R^ and R are independently absent or hydrogen;
C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, R26A and R27A are independently -C≡N or an optionally
mercapto, formyl, carboxy, carbamoyl, azido, (C1- substituted substituent selected from the group consisting
C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1- of C2_8 organylcarbonyl, C2_8 alkoxycarbonyl and C2_8
C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- organylaminocarbonyl;
C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, R28A is selected from the group consisting of hydrogen, an
(C6-C12)aryl, or heterocyclyl; and optionally substituted Ci_24-alkyl, an optionally substituted
wherein the lipid comprises a C6-22 alkyl, (C6-C22)alkoxy, C2_24 alkenyl, an optionally substituted C2-24 alkynyl, an
polyethylene glycol, or (C6-C12)aryl substituted with an optionally substituted C3_6 cycloalkyl and an optionally
alkyl group,heterocyclylis acarbocyclylcomprising 1-4 substituted C3_6 cycloalkenyl;
heteroatoms selected from nitrogen, oxygen, or sulfur, R30A and R31A are independently selected from the group
and heteroaromatic is an aromatic heterocyclylcomprising consisting of hydrogen, an optionally substituted Ci_24-alkyl,
1-4 heteroatoms selected from nitrogen, oxygen, or sulfur an optionally substituted C2-24 alkenyl, an optionally
and at least 1 carbon atom. substituted C2_24 alkynyl, an optionally substituted
C3_6 cycloalkyl and an optionally substituted
C3_6 cycloalkenyl;
R"A and R"c are independently an optionally substituted
Ci_24-alkyl;
p and q are independently selected from the group
consisting of 1, 2 and 3;
r is 1 or 2;
and
provided that when the dashed line ( ) of Formula (I) is
absent; R1A is

ester, ethyl ester, isopropyl ester, n-butyl ester, benzyl ester
or phenyl ester of an amino acid selected from the group
consisting of glycine, alanine, valine, leucine, phenylalanine,
tryptophan, methionine and proline; R3A is OH; R4A is fluoro;
R5A is fluoro or hydrogen; and B1A is an unsubstituted uracil;
then R2A cannot be -OCH3;
absent; R1A is H; R3A is OH; R4A is fluoro; R5A is fluoro; and
B1A is an unsubstituted cytosine; then R2A cannot be allenyl;
83
absent; R1A is H; R3A is OH; R4A is fluoro; R5A is hydrogen; and
B1A is an unsubstituted thymine; then R2A cannot be Ci alkyl
absent; R1A is H; R3A is OH; R4A is fluoro; R5A is fluoro; and
1A 2A
B is an unsubstituted cytosine; then R cannot be ethynyl.
Claim 212.
The use or method of any one of Claims 162-211, wherein B
is selected from the group consisting of:
wherein:
and NHR'
C(=0)OR^ ;
consisting of hydrogen, an optionally substituted Ci_6 alkyl,
an optionally substituted C2-6 alkenyl, an optionally
substituted C3_8 cycloalkyl, -C(=0)RMC2 and -C(=0)ORNC2;
is selected from the group consisting of hydrogen, halogen,
an optionally substituted Ci_6 alkyl, an optionally
substituted C2_6 alkenyl and an optionally substituted C2_6
alkynyl;
R is selected from the group consisting of hydrogen,
halogen, an optionally substituted Ci_6alkyl, an optionally
substituted C2_6 alkenyl and an optionally substituted C2_6
alkynyl;
2C 3C IC2 IC2
Y and Y are independently N or CR , wherein R is
C(=0)ORVC2; and
independently selected from the group consisting of
84
Claim 7
IN201717025098 D3: WO2013142525A1

CLAIM 7 Claim 1
7. A pharmaceutical composition comprising a Use of an effective amount of a compound selected from
pharmaceutically acceptable excipient and a compound Formula (I), Formula (II), and Formula (III), or a
of Formula ID, pharmaceutically acceptable salt of the foregoing, for amelioring
or treating a viral infection caused by a virus selected from a
henipavirus, a morbilli virus, a respirovirus, a rubulavirus and a
metapneumovirus, wherein the compound is selected from
Formula (I), Formula II), and Formula (III) has one of the
Formula ID,
W is CH2, NH, S or O; (I) (Π)
Y is N or CR”;
Z is N or CR”;
each R” is independently selected from is H, D, F, Cl,
Br, I, CH3, CD3, CF3, alkyl, acyl, alkenyl, alkynyl,
R1 is hydrogen, monophosphate, diphosphate, (HI)
triphosphate, wherein:
alkyl, halogen, nitro, B1A, B1B, and B1C are independently an optionally
cyano, hydroxy, amino, mercapto, formyl, carboxy, substituted heterocyclic base or an optionally substituted
carbamoyl, carbanoyl, esteryl, alkoxy, (C1- heterocyclic base with a protected amino group;
C22)alkylthio, (C1-C22)alkylamino, ((C1- R1A is selected from the group consisting of hydrogen, an
C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- optionally substituted
phosphoramidyl, or wherein R1 is optionally
R20; when the dashed line ( ) of Formula (I) is a single bond, R A is
Y1 is O or S; CH2, and R is O (oxygen);
Y2 is OH, OR12, OAlkyl, or BH3-M+; when the dashed line ( ) of Formula (I) is absent, RZA is selected
Y3 is OH or BH3-M+; from the group consisting of an optionally substituted Ci_6 alkyl,
R2 is hydrogenor hydroxy; an optionally substituted C2_6 alkenyl, an optionally substituted
R3 is hydrogen, hydroxy, alkyl, halogen, nitro, cyano, C2_6 alkynyl, an optionally substituted C3 cycloalkyl, an
hydroxy, amino, mercapto, formyl, carboxy, optionally substituted -O-C1-6 alkyl, an optionally substituted -0-
carbamoyl, alkoxy, (C1-C22)alkylthio, alkylamino, C3_6 alkenyl, an optionally substituted -O-C3-6 alkynyl and
(alkyl)2amino, alkylsulfinyl, alkylsulfonyl, cyano, and R3A is selected from the group consistin of OH, -
arylsulfonyl,carbocyclyl, aryl, or heterocyclyl; OC(=0)R"A and an optionally substituted O-linked amino acid;
C22)alkyl)2amino,(C1-C22)alkylsulfinyl,(C1- N-linked amino acid and an optionally substituted N-linked
C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- amino acid ester derivative;
C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; R1C and R2C are independently selected from the group
R5 is hydrogen, hydroxy, or halogen; consisting of O-, OH, an
allenyl, halogen, nitro, cyano, amino, mercapto,formyl,
alkylamino, (alkyl)2amino, alkylsulfinyl,
alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or
heterocyclyl; , an optionally substituted N-linked amino acid and an optionally
R8 is hydrogen, deuterium, (C1-C22)alkyl, (C2- substituted N-linked amino acid ester derivative; or
C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, optionally substituted C1-6 alkoxy
C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- R2B and R are independently selected from the group consisting
C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein of an optionally substituted Ci_6 alkyl, an optionally substituted
R8 is optionally substituted with one or more, the same C2-6 alkenyl, an optionally substituted C2-6 alkynyl, an
85
or different, R20; optionally substituted C3-6 cycloalkyl, an optionally substituted -
R9 is hydrogen, methyl, ethyl, tert-butyl, (C1- 0-C1-6 alkyl, an optionally substituted -O-C3-6 alkenyl, an
C22)alkyl, halogen, nitro, cyano, hydroxy, optionally substituted -0-C3-6 alkynyl and cyano;
amino,mercapto, formyl, carboxy, carbamoyl, R4C is selected from the group consisting of OH, -
cycloalkyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1- OC(=0)R"c and an optionally substituted O-linked amino acid;
C22)alkylamino,((C1-C22)alkyl)2amino, (C1- R4A, R3B and R5C are independently a halogen;
C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- R5A, R4B and R6C are independently hydrogen or halogen;
C12)arylsulfonyl, (C3-C6)carbocyclyl, R6A, R7A and R8A are independently selected from the group
(C6-C12)aryl,orheterocyclyl, wherein R9 is optionally consisting of absent, hydrogen, an optionally substituted Ci_24
substituted with one or more, the same or different, alkyl, an optionally substituted C2-24 alkenyl, an optionally
R20; substituted C2-24 alkynyl, an optionally substituted C3-6
R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, lipid, cycloalkyl, an optionally substituted C3-6 cycloalkenyl, an
methyl, ethyl, isopropyl, cyclopentyl, cyclohexyl,butyl, optionally substituted aryl, an optionally substituted heteroaryl,
pentyl, hexyl, neopentyl, benzyl, halogen, nitro, cyano, an optionally substituted aryl(Ci_6 alkyl), an optionally
hydroxy, amino, mercapto, formyl, carboxy,carbamoyl, substituted *-(CR15AR16A)p-0-Ci_24 alkyl, an optionally
(C1-C22)alkoxy, (C1-C22)alkylthio, (C1- substituted *-(CR17AR18A)q-0-Ci_24
different, R20;
halogen, nitro, cyano, hydroxy, amino, R6A is and R7 is absent or hydrogen; or
mercapto,formyl, carboxy, carbamoyl, (C1- R and R , 7/AA are taken together to form a moiety selected from
C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, the group
((C1-C22)alkyl)2amino,(C1-C22)alkylsulfinyl, (C1- consisting of an optionally substituted
wherein R11 is optionally substituted with one or and an optionally substituted
phenyl, 1-naphthyl, 2-
naphthyl,aromatic,heteroaromatic, 4-substituted wherein the oxygens connected to R6A and R7A, the phosphorus
phenyl, 4-fluorophenyl, 4-chlorophenyl, 4- and the moiety form a six-membered to ten-membered ring
bromophenyl, naphthyl, or system;.
heterocyclyl, wherein R12 is optionally substituted R9A is independently selected from the group consisting of an
with one or more, the same or different, R20; optionally substituted Ci_24 alkyl, an optionally substituted C2-
R13 is hydrogen, deuterium, (C1-C22)alkyl, (C2- 24 alkenyl, an optionally substituted C2-24 alkynyl, an optionally
C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, substituted C3_6 cycloalkyl, an optionally substituted
hydroxy, amino, amido, mercapto, formyl, carboxy, C3_6 cycloalkenyl, NR30AR31A, an optionally substituted N-linked
carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1- amino acid and an optionally substituted N-linked amino acid
C22)alkylthio,(C1-C22)alkylamino, ((C1- ester derivative;
C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- R10A and R11A are independently an optionally substituted N-
C22)alkylsulfonyl, (C6-C12)arylsulfonyl,(C3- linked amino acid or an optionally substituted N-linked amino
C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, acid ester derivative;
wherein R13 is optionally substituted with one or R12A, R13A and R14A are independently absent or hydrogen;
more, the same or different, R20; each R15A, each R16A, each R17A and each R18A are independently
R14 is hydrogen, deuterium, (C1-C22)alkyl, (C2- hydrogen, an optionally substituted Ci_24 alkyl or alkoxy; R19A,
C22)alkenyl, (C12-C22)alkynyl, halogen, nitro, R20A, R22A, R23A, R5B, R6B, R8B, R9B, R9C, R10C, R12C and R13C are
cyano,hydroxy, amino, amido, mercapto, formyl, independently selected from the group consisting of hydrogen, an
carboxy, carbamoyl, lipid, azido, (C1-C22)alkoxy, optionally substituted Ci_24 alkyl and an optionally substituted
(C1-C22)alkylthio,(C1-C22)alkylamino, ((C1- aryl;
C22)alkyl)2amino, alkylsulfinyl, (C1- R2iA R24A R7B^ Ri<m Rnc and Ri4C arg independently selected
C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- from the group consisting of hydrogen, an optionally substituted
C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, Ci_24 alkyl, an optionally substituted aryl, an optionally
wherein R14 is optionally substituted with one or substituted -0-Ci_24 alkyl and an optionally substituted -O-aryl;
more, the same or different, R20; R25A R29A RHB and R15C are independently selected from the
R15 is hydrogen, -(C=O)Oalkyl(C1-C22), - group consisting of hydrogen, an optionally substituted Ci_24
(C=O)alkyl(C1-C22), -(C=O)NHalkyl(C1-C22), - alkyl and an optionally substituted aryl;
(C=O)Ndialkyl(C1-C22), -(C=O)Salkyl(C1-C22), R1U", R^ and R are independently absent or hydrogen;
hydroxy, (C1-C22)alkoxy, (C1-C22)alkyl, halogen, R26A and R27A are independently -C≡N or an optionally
nitro, cyano, amino,mercapto, formyl, carboxy, substituted substituent selected from the group consisting of C2_8
carbamoyl, (C1-C22)alkylthio, (C1-C22)alkylamino, organylcarbonyl, C2_8 alkoxycarbonyl and C2_8
((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- organylaminocarbonyl;
C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- R28A is selected from the group consisting of hydrogen, an
C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl,wherein optionally substituted Ci_24-alkyl, an optionally substituted
R15 is optionally substituted with one or more, the C2_24 alkenyl, an optionally substituted C2-24 alkynyl, an
same or different, R20; optionally substituted C3_6 cycloalkyl and an optionally
R15’ is hydrogen, -(C=O)Oalkyl(C1-C22), - substituted C3_6 cycloalkenyl;
(C=O)alkyl(C1-C22), -(C=O)NHalkyl(C1-C22), - R30A and R31A are independently selected from the group
86
(C=O)Ndialkyl(C1-C22), -(C=O)Salkyl(C1-C22), consisting of hydrogen, an optionally substituted Ci_24-alkyl, an
hydroxy, (C1-C22)alkoxy, (C1-C22)alkyl, halogen, optionally substituted C2-24 alkenyl, an optionally substituted
nitro, cyano, amino,mercapto, formyl, carboxy, C2_24 alkynyl, an optionally substituted C3_6 cycloalkyl and an
carbamoyl, (C1-C22)alkylthio, (C1-C22)alkylamino, optionally substituted C3_6 cycloalkenyl;
((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- for Formula (III), is a single bond or a double bond;
C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- when is a single bond, each R and each R is independently
C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; hydrogen or halogen; and
R15 and R15’ can form a ring that is optionally when is a double bond, each R is absent and each R is
substituted with one or more, the same or different, independently hydrogen or halogen;
R20; R"A and R"c are independently an optionally substituted Ci_24-
R20 is deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, alkyl;
(C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, m and n are independently 0 or 1 ;
amino, amido, mercapto, formyl, carboxy, carbamoyl, p and q are independently selected from the group consisting of
azido, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1- 1, 2 and 3;
C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- r is 1 or 2;
C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- Z1A, Z2A, Z3A, Z4A, Z1B, Z2B and Z1C are independently O or S;
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, and
or heterocyclyl; and provided that when the dashed line ( ) of Formula (I) is absent;
wherein the lipid comprises a C6-22 alkyl, (C6- R1A is
phenyl ester of an amino acid selected from the group consisting
of glycine, alanine, valine, leucine, phenylalanine, tryptophan,
hydrogen; and B1A is an unsubstituted uracil; then R2A cannot be
-OCH3;
an unsubstituted thymine; then R2A cannot be Ci alkyl substituted
with an N-amido; and
Claim 212.
wherein:
NHR'
C(=0)OR^ ;
87
consisting of hydrogen, -C(=0)RPC2 and -C(=0)ORQC2; R is
optionally substituted Ci_6-alkyl, an optionally substituted C2_6-
alkenyl and an optionally substituted C2_6-alkynyl;
C(=0)ORVC2; and
Claim 8
IN201717025098 D3: WO2013142525A1

CLAIM 8 Claim 1
8. A pharmaceutical composition comprising a Use of an effective amount of a compound selected from
pharmaceutically acceptable excipient and a compound Formula (I), Formula (II), and Formula (III), or a
of Formula IE, pharmaceutically acceptable salt of the foregoing, for amelioring
or treating a viral infection caused by a virus selected from a
henipavirus, a morbilli virus, a respirovirus, a rubulavirus and a
metapneumovirus, wherein the compound is selected from
Formula (I), Formula II), and Formula (III) has one of the
Formula IE,
or salt thereof, wherein (I) (Π)
Q is O, -O(C=O)-, -O(C=O)Lipid, -O(C=O)V-, NH, or
NR7;
Y is N or CR”;
Z is N or CR”; (HI)
each R” is independently selected from is H, D, F, Cl, wherein:
Br, I, CH3, CD3, CF3, alkyl, acyl, alkenyl, alkynyl, B1A, B1B, and B1C are independently an optionally
hydroxyl, formyl or SCH3; substituted heterocyclic base or an optionally substituted
R2 is hydrogen, alkyl, alkenyl, alkynyl, ethynyl, heterocyclic base with a protected amino group;
fluoromethyl, difluoromethyl, trifluoromethyl, R1A is selected from the group consisting of hydrogen, an
chloromethyl, hydroxymethyl, halogen, nitro, cyano, optionally substituted
hydroxy, amino, mercapto, formyl, carboxy,
arylsulfonyl, carbocyclyl, aryl, azido, or heterocyclyl;
R3 is hydrogen, hydroxy, alkyl, halogen, nitro, cyano, when the dashed line ( ) of Formula (I) is a single bond, R A is
hydroxy, amino, mercapto, formyl, carboxy, CH2, and R is O (oxygen);
carbamoyl, alkoxy, (C1-C22)alkylthio, alkylamino, when the dashed line ( ) of Formula (I) is absent, RZA is selected
alkyl)2amino, alkylsulfinyl, alkylsulfonyl, from the group consisting of an optionally substituted Ci_6 alkyl,
arylsulfonyl, carbocyclyl, aryl, or heterocyclyl; an optionally substituted C2_6 alkenyl, an optionally substituted
88
difluoromethyl, trifluoromethyl, hydroxymethyl, C2_6 alkynyl, an optionally substituted C3 cycloalkyl, an
halogen, nitro, cyano, hydroxy, amino, mercapto, optionally substituted -O-C1-6 alkyl, an optionally substituted -0-
formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1- C3_6 alkenyl, an optionally substituted -O-C3-6 alkynyl and
C22)alkylthio,(C1-22)alkylamino, ((C1- cyano, and R3A is selected from the group consistin of OH, -
C22)alkyl)2amino,(C1-C22)alkylsulfinyl,(C1- OC(=0)R"A and an optionally substituted O-linked amino acid;
22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-
difluoromethyl,trifluoromethyl, hydroxymethyl,
allenyl, halogen, nitro, cyano, amino, mercapto, N-linked amino acid and an optionally substituted N-linked
formyl, carboxy, carbamoyl,alkoxy, (C1- amino acid ester derivative;
C22)alkylthio, alkylamino, (alkyl)2amino, R1C and R2C are independently selected from the group
alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, consisting of O-, OH, an
aryl,or heterocyclyl;
allenyl, halogen, nitro, cyano, amino, mercapto,formyl,
lkylamino, (alkyl)2amino, alkylsulfinyl,
alkylsulfonyl,arylsulfonyl, carbocyclyl, aryl, or , an optionally substituted N-linked amino acid and an optionally
heterocyclyl; substituted N-linked amino acid ester derivative; or
each R7 is independently selected from absent, optionally substituted C1-6 alkoxy
hydroxy, alkoxy, alkyl, higher alkyl, (C6-C16)alkyl,
(C6-C22)alkyl, halogen, nitro, cyano, amino,
mercapto, formyl, carboxy, carbamoyl, alkoxy, (C1- R2B and R3c are independently selected from the group consisting
C22)alkylthio,alkylamino, (alkyl)2amino, of an optionally substituted Ci_6 alkyl, an optionally substituted
alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, C2-6 alkenyl, an optionally substituted C2-6 alkynyl, an
aryl, or heterocyclyl, whereineach R7 is optionally optionally substituted C3-6 cycloalkyl, an optionally substituted -
substituted with one or more, the same or different, 0-C1-6 alkyl, an optionally substituted -O-C3-6 alkenyl, an
R20; optionally substituted -0-C3-6 alkynyl and cyano;
R15 is hydrogen, -(C=O)Oalkyl(C1-C22), - R4C is selected from the group consisting of OH, -
(C=O)alkyl(C1-C22), -C=O)NHalkyl(C1-C22), - OC(=0)R"c and an optionally substituted O-linked amino acid;
(C=O)Ndialkyl(C1-C22), -(C=O)Salkyl(C1-C22), R4A, R3B and R5C are independently a halogen;
hydroxy, (C1-C22)alkoxy, (C1-C22)alkyl, halogen, R5A, R4B and R6C are independently hydrogen or halogen;
nitro, cyano, amino,mercapto, formyl, carboxy, R6A, R7A and R8A are independently selected from the group
carbamoyl, (C1-C22)alkylthio, (C1-C22)alkylamino, consisting of absent, hydrogen, an optionally substituted Ci_24
((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- alkyl, an optionally substituted C2-24 alkenyl, an optionally
C22)alkylsulfonyl, (C6-12)arylsulfonyl, (C3- substituted C2-24 alkynyl, an optionally substituted C3-6
C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl,wherein cycloalkyl, an optionally substituted C3-6 cycloalkenyl, an
R15 is optionally substituted with one or more, the optionally substituted aryl, an optionally substituted heteroaryl,
same or different, R20; an optionally substituted aryl(Ci_6 alkyl), an optionally
R15’ is hydrogen, -(C=O)Oalkyl(C1-C22), - substituted *-(CR15AR16A)p-0-Ci_24 alkyl, an optionally
(C=O)alkyl(C1-C22), -C=O)NHalkyl(C1-C22), - substituted *-(CR17AR18A)q-0-Ci_24
nitro, cyano, amino,
C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; R6A is and R7 is absent or hydrogen; or
R15 and R15’ can form a ring that is optionally R and R , 7/AA are taken together to form a moiety selected from
substituted with one or more, the same or the group
different,R20; consisting of an optionally substituted
together form a ring that is optionally substitutedwith
one or more, the same or different, R20; and an optionally substituted
(C2-C22)alkynyl, halogen, nitro, cyano,
hydroxy,amino, amido, mercapto, formyl, carboxy,
carbamoyl, azido, (C1-C22)alkoxy, (C1-C22)alkylthio, wherein the oxygens connected to R6A and R7A, the phosphorus
(C1-C22)alkylamino, ((C1-22)alkyl)2amino, (C1- and the moiety form a six-membered to ten-membered ring
C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- system;.
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, R9A is independently selected from the group consisting of an
or heterocyclyl; and optionally substituted Ci_24 alkyl, an optionally substituted C2-
wherein lipid comprises a C6-22 alkyl, (C6- 24 alkenyl, an optionally substituted C2-24 alkynyl, an optionally
C22)alkoxy, polyethylene glycol, or (C6-C12)aryl substituted C3_6 cycloalkyl, an optionally substituted
substituted with an (C1-C22)alkyl group, C3_6 cycloalkenyl, NR30AR31A, an optionally substituted N-linked
heterocyclylis carbocyclyl comprising 1-4 heteroatoms amino acid and an optionally substituted N-linked amino acid
89
selected from nitrogen, oxygen, or sulfur, ester derivative;
and heteroaromatic is an aromatic R10A and R11A are independently an optionally substituted N-
heterocyclylcomprising 1-4 heteroatoms selected from linked amino acid or an optionally substituted N-linked amino
nitrogen,oxygen, or sulfur and at least 1 carbon atom. acid ester derivative;
hydrogen, an optionally substituted Ci_24 alkyl or alkoxy; R19A,
R20A, R22A, R23A, R5B, R6B, R8B, R9B, R9C, R10C, R12C and R13C are
optionally substituted Ci_24 alkyl and an optionally substituted
aryl;
R2iA R24A R7B^ Ri<m Rnc and Ri4C arg independently selected
from the group consisting of hydrogen, an optionally substituted
Ci_24 alkyl, an optionally substituted aryl, an optionally
substituted -0-Ci_24 alkyl and an optionally substituted -O-aryl;
R25A R29A RHB and R15C are independently selected from the
group consisting of hydrogen, an optionally substituted Ci_24
alkyl and an optionally substituted aryl;
R26A and R27A are independently -C≡N or an optionally
substituted substituent selected from the group consisting of C2_8
C2_24 alkenyl, an optionally substituted C2-24 alkynyl, an
optionally substituted C3_6 cycloalkyl and an optionally
substituted C3_6 cycloalkenyl;
R30A and R31A are independently selected from the group
consisting of hydrogen, an optionally substituted Ci_24-alkyl, an
C2_24 alkynyl, an optionally substituted C3_6 cycloalkyl and an
optionally substituted C3_6 cycloalkenyl;
R"A and R"c are independently an optionally substituted Ci_24-
alkyl;
p and q are independently selected from the group consisting of
1, 2 and 3;
r is 1 or 2;
and
R1A is

phenyl ester of an amino acid selected from the group consisting
of glycine, alanine, valine, leucine, phenylalanine, tryptophan,
hydrogen; and B1A is an unsubstituted uracil; then R2A cannot be
-OCH3;
an unsubstituted thymine; then R2A cannot be Ci alkyl substituted
with an N-amido; and
90
Claim 212.
wherein:
NHR'
C(=0)OR^ ;
consisting of hydrogen, -C(=0)RPC2 and -C(=0)ORQC2; R is
optionally substituted Ci_6-alkyl, an optionally substituted C2_6-
alkenyl and an optionally substituted C2_6-alkynyl;
C(=0)ORVC2; and
Claim 9
IN201717025098 D3: WO2013142525A1

CLAIM 9 A pharmaceutical composition comprising a Claim 1
pharmaceutically acceptable excipient and a compound of Use of an effective amount of a compound selected from
Formula II, Formula (I), Formula (II), and Formula (III), or a
pharmaceutically acceptable salt of the foregoing, for
selected from Formula (I), Formula II), and Formula (III) has
one of the following structures:
91
(I) (Π)

Q is O, -O(C=O)-, -O(C=O)Lipid, -O(C=O)V-, NH, or (HI)
NR7; wherein:
V is O, NH, NR7, S, CH2, or CHR7; B1A, B1B, and B1C are independently an optionally
W is CH2, NH, S or O; substituted heterocyclic base or an optionally substituted
X is CH2 or O; heterocyclic base with a protected amino group;
Y is N or CR”; R1A is selected from the group consisting of hydrogen, an
Z is N or CR”; optionally substituted
each R” is independently selected from is H, D, F, Cl, Br,
I, CH3, CD3, CF3, alkyl, acyl, alkenyl, alkynyl, hydroxyl,
formyl or SCH3;
R1 is monophosphate, diphosphate, triphosphate,

selected from the group consisting of an optionally substituted
Ci_6 alkyl, an optionally substituted C2_6 alkenyl, an optionally
substituted C2_6 alkynyl, an optionally substituted C3
cycloalkyl, an optionally substituted -O-C1-6 alkyl, an
optionally substituted -0-C3_6 alkenyl, an optionally substituted
-O-C3-6 alkynyl and cyano, and R3A is selected from the group
consistin of OH, -OC(=0)R"A and an optionally substituted O-
linked amino acid;
N-linked amino acid and an optionally substituted N-linked

amino acid ester derivative;
R1C and R2C are independently selected from the group
consisting of O-, OH, an
Y1 is O or S;
Y3 is OH or BH3-M+;
fluoromethyl, difluoromethyl, , an optionally substituted N-linked amino acid and an
trifluoromethyl,chloromethyl, hydroxymethyl, halogen, optionally substituted N-linked amino acid ester derivative;
nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, or optionally substituted C1-6 alkoxy
carbocyclyl, aryl,azido, or heterocyclyl;
R3 is hydrogen, hydroxy, alkyl, halogen, nitro, cyano,
hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, R2B and R3c are independently selected from the group
alkoxy, (C1-C22)alkylthio, alkylamino, alkyl)2amino, consisting of an optionally substituted Ci_6 alkyl, an
alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, optionally substituted C2-6 alkenyl, an optionally substituted
or heterocyclyl; C2-6 alkynyl, an optionally substituted C3-6 cycloalkyl, an
R4 is hydrogen, hydroxy,(C1-C22)alkyl, fluoromethyl, optionally substituted -0-C1-6 alkyl, an optionally substituted -
difluoromethyl, rifluoromethyl, hydroxymethyl,halogen, O-C3-6 alkenyl, an optionally substituted -0-C3-6 alkynyl and
nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, cyano;
carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio,(C1- R4C is selected from the group consisting of OH, -
C22)alkylamino, ((C1-C22)alkyl)2amino,(C1- OC(=0)R"c and an optionally substituted O-linked amino
C22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6- acid;
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or R4A, R3B and R5C are independently a halogen;
heterocyclyl; R5A, R4B and R6C are independently hydrogen or halogen;
R5 is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, alkynyl, R6A, R7A and R8A are independently selected from the group
ethynyl, fluoromethyl, difluoromethyl,trifluoromethyl, consisting of absent, hydrogen, an optionally substituted Ci_24
hydroxymethyl, allenyl, halogen, nitro, cyano, amino, alkyl, an optionally substituted C2-24 alkenyl, an optionally
92
mercapto, formyl, carboxy, carbamoyl,alkoxy, (C1- substituted C2-24 alkynyl, an optionally substituted C3-6
C22)alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, cycloalkyl, an optionally substituted C3-6 cycloalkenyl, an
alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl,or optionally substituted aryl, an optionally substituted heteroaryl,
heterocyclyl; an optionally substituted aryl(Ci_6 alkyl), an optionally
R6 is hydrogen, hydroxy, alkoxy, alkyl, ethynyl, allenyl, substituted *-(CR15AR16A)p-0-Ci_24 alkyl, an optionally
halogen, nitro, cyano, amino, mercapto,formyl, carboxy, substituted *-(CR17AR18A)q-0-Ci_24
(alkyl)2amino, alkylsulfinyl, alkylsulfonyl,arylsulfonyl,
each R7 is independently selected from absent, hydrogen,
-(C=O)Oalkyl, -(C=O)alkyl, - (C=O)NHalkyl, -(C=O)N-
dialkyl, -(C=O)Salkyl, hydroxy, alkoxy, alkyl, higher
alkyl, (C6-C16)alkyl, (C6-C22)alkyl, halogen, nitro,
cyano, amino, mercapto, formyl, carboxy, carbamoyl, R6A is and R7 is absent or hydrogen; or
alkoxy, (C1-C22)alkylthio,alkylamino, (alkyl)2amino, R and R , 7/AA are taken together to form a moiety selected
alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, from the group
or heterocyclyl, wherein each R7 is optionally substituted consisting of an optionally substituted
C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, and an optionally substituted
cyano,hydroxy, benzyloxy, amino, amido, mercapto,
formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1-
C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- wherein the oxygens connected to R6A and R7A, the phosphorus
22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- and the moiety form a six-membered to ten-membered ring
C6)carbocyclyl, (C6-12)aryl,orheterocyclyl, wherein R8 is system;.
optionally substituted with one or more, the same or R9A is independently selected from the group consisting of an
different, R20; optionally substituted Ci_24 alkyl, an optionally substituted C2-
R9 is hydrogen, methyl, ethyl, tert-butyl, (C1-C22)alkyl, 24 alkenyl, an optionally substituted C2-24 alkynyl, an
halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, optionally substituted C3_6 cycloalkyl, an optionally
carboxy, carbamoyl, cycloalkyl, (C1-C22)alkoxy, (C1- substituted C3_6 cycloalkenyl, NR30AR31A, an optionally
C22)alkylthio, (C1-C22)alkylamino,((C1- substituted N-linked amino acid and an optionally substituted
C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- N-linked amino acid ester derivative;
C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- R10A and R11A are independently an optionally substituted N-
C6)carbocyclyl,(C6-C12)aryl,orheterocyclyl, wherein R9 linked amino acid or an optionally substituted N-linked amino
is optionally substituted with one or more, the same or acid ester derivative;
different, R20; R12A, R13A and R14A are independently absent or hydrogen;
R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, lipid, methyl, each R15A, each R16A, each R17A and each R18A are
ethyl, isopropyl, cyclopentyl, cyclohexyl,butyl, pentyl, independently hydrogen, an optionally substituted Ci_24 alkyl
hexyl, neopentyl, benzyl, halogen, nitro, cyano, hydroxy, or alkoxy; R19A, R20A, R22A, R23A, R5B, R6B, R8B, R9B, R9C, R10C,
amino, mercapto, formyl, carboxy,carbamoyl, (C1- R12C and R13C are independently selected from the group
C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, consisting of hydrogen, an optionally substituted Ci_24 alkyl
((C1-C22)alkyl)2amino, (C1-22)alkylsulfinyl,(C1- and an optionally substituted aryl;
C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- R2iA R24A R7B^ Ri<m Rnc and Ri4C arg independently selected
C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R10 from the group consisting of hydrogen, an optionally
is optionally substituted with one or more, the same or substituted Ci_24 alkyl, an optionally substituted aryl, an
different, R20; optionally substituted -0-Ci_24 alkyl and an optionally
R11 is hydrogen, deuterium, (C1-C22)alkyl, methyl, substituted -O-aryl;
halogen, nitro, cyano, hydroxy, amino, mercapto,formyl, R25A R29A RHB and R15C are independently selected from the
carboxy, carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio, group consisting of hydrogen, an optionally substituted Ci_24
(C1-C22)alkylamino, ((C1-C22)alkyl)2amino,(C1- alkyl and an optionally substituted aryl;
22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- R1U", R^ and R are independently absent or hydrogen;
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or R26A and R27A are independently -C≡N or an optionally
heterocyclyl, wherein R11 is optionally substituted with substituted substituent selected from the group consisting of
one or more, the same or different, R20; C2_8 organylcarbonyl, C2_8 alkoxycarbonyl and C2_8
R12 is hydrogen, (C1-C22)alkyl, (C6-C12)aryl, phenyl, 1- organylaminocarbonyl;
naphthyl, 2-naphthyl,aromatic,heteroaromatic, 4- R28A is selected from the group consisting of hydrogen, an
substituted phenyl, 4-fluorophenyl, 4-chlorophenyl, 4- optionally substituted Ci_24-alkyl, an optionally substituted
bromophenyl, naphthyl, or heterocyclyl, wherein R12 is C2_24 alkenyl, an optionally substituted C2-24 alkynyl, an
optionally substituted with one or more, the same or optionally substituted C3_6 cycloalkyl and an optionally
different, R20; substituted C3_6 cycloalkenyl;
R13 is hydrogen, deuterium, (C1-C22)alkyl, (C2- R30A and R31A are independently selected from the group
C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, consisting of hydrogen, an optionally substituted Ci_24-alkyl,
cyano,hydroxy, amino, amido, mercapto, formyl, carboxy, an optionally substituted C2-24 alkenyl, an optionally
carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1- substituted C2_24 alkynyl, an optionally substituted
C22)alkylthio,(C1-C22)alkylamino, ((C1- C3_6 cycloalkyl and an optionally substituted
C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C3_6 cycloalkenyl;
C22)alkylsulfonyl, (C6-C12)arylsulfonyl,(C3- for Formula (III), is a single bond or a double bond;
C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein when is a single bond, each R and each R is independently
R13 is optionally substituted with one or more, the same or hydrogen or halogen; and
different, R20; when is a double bond, each R is absent and each R is
93
R14 is hydrogen, deuterium, (C1-C22)alkyl, (C2- independently hydrogen or halogen;
C22)alkenyl, (C12-C22)alkynyl, halogen, nitro, R"A and R"c are independently an optionally substituted Ci_24-
cyano,hydroxy, amino, amido, mercapto, formyl, carboxy, alkyl;
arbamoyl, lipid, azido, (C1-C22)alkoxy, (C1- m and n are independently 0 or 1 ;
C22)alkylthio,(C1-C22)alkylamino, ((C1- p and q are independently selected from the group consisting
C22)alkyl)2amino, alkylsulfinyl, (C1-C22)alkylsulfonyl, of 1, 2 and 3;
(C6-12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or r is 1 or 2;
heterocyclyl, wherein R14 is optionally substituted with Z1A, Z2A, Z3A, Z4A, Z1B, Z2B and Z1C are independently O or S;
one or more, the same or different, R20; and
If Q = -O(C=O)V- and V = NR7 then the R7s can together provided that when the dashed line ( ) of Formula (I) is absent;
form a ring that is optionally substituted with one or more, R1A is
C22)alkynyl, halogen, nitro, cyano, hydroxy,amino, amido,
mercapto, formyl, carboxy, carbamoyl, azido, (C1-
((C1-22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-
C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; and wherein R is an unsubstituted Ci_4 alkyl or phenyl optionally
wherein lipid comprises a C6-22 alkyl, (C6-C22)alkoxy, para- substituted with a halogen or methyl and R9A is methyl
polyethylene glycol, or (C6-C12)aryl substituted ester, ethyl ester, isopropyl ester, n-butyl ester, benzyl ester or
with an (C1-C22)alkyl group, heterocyclylis phenyl ester of an amino acid selected from the group
acarbocyclylcomprising 1-4 heteroatoms selected from consisting of glycine, alanine, valine, leucine, phenylalanine,
nitrogen, oxygen, or sulfur, and tryptophan, methionine and proline; R3A is OH; R4A is fluoro;
heteroaromatic is an aromatic heterocyclylcomprising 1-4 R5A is fluoro or hydrogen; and B1A is an unsubstituted uracil;
heteroatoms selected from nitrogen,oxygen, or sulfur and then R2A cannot be -OCH3;
at least 1 carbon atom. provided that when the dashed line ( ) of Formula (I) is absent;
an unsubstituted thymine; then R2A cannot be Ci alkyl
Claim 212.
wherein:
and NHR'
C(=0)OR^ ;
is selected from the group consisting of hydrogen, halogen, an
94
R is selected from the group consisting of hydrogen, halogen,
an optionally substituted Ci_6alkyl, an optionally substituted
C(=0)ORVC2; and
RKC2, RLC2, RMC2, RNC2, RPC2, RQC2 RRC2, RSC2 RUC2 and
RVC2 are independently selected from the group consisting of
Claim 10
IN201717025098 D3: WO2013142525A1

CLAIM 10 The pharmaceutical composition of claim Claim 10 is dependent on claim 3 which is dependent on claim 1.
1,further comprising a propellant. Hence, the arguments applicable for claim 1are applicable here
too. Propellant as such is no new invention.
Claim 11
IN201717025098 D3: WO2013142525A1

CLAIM 11 The pharmaceutical composition of claim 10, Claim 11 is dependent on claim 10 which is dependent on claim 1.
wherein the propellant is compressed air, ethanol, Hence, the arguments applicable for claim 1 & 10 are applicable
nitrogen, carbon dioxide, nitrous oxide, here too. Propellant as such is no new invention.
hydrofluoroalkanes (HFA), 1,1,1,2,-tetrafluoroethane,
1,1,1,2,3,3,3-heptafluoropropane or combinations thereof.
Claim 12
IN201717025098 D3: WO2013142525A1

CLAIM 12 The composition of claim 1, wherein the Claim 1
compound has a structure according to Formula IA Use of an effective amount of a compound selected from Formula (I),
Formula (II), and Formula (III), or a pharmaceutically acceptable salt of
the foregoing, for amelioring or treating a viral infection caused by a
virus selected from a henipavirus, a morbilli virus, a respirovirus, a
from Formula (I), Formula II), and Formula (III) has one of the following
structures:
R7 is H,
Y is independently selected from is H, D, F, Cl, Br,
I, CH3, CD3, CF3, alkyl, acyl, alkenyl, alkynyl,
hydroxyl, formyl or SCH3; (I) (Π)
R1 is
95
monophosphate
ester, diphosphate
ester
(HI)
wherein:
substituted
when the dashed line ( ) of Formula (I) is a single bond, R A is CH2, and
R is O (oxygen);
when the dashed line ( ) of Formula (I) is absent, RZA is selected from the
group consisting of an optionally substituted Ci_6 alkyl, an optionally
substituted C2_6 alkenyl, an optionally substituted C2_6 alkynyl, an
optionally substituted C3 cycloalkyl, an optionally substituted -O-C1-
amino, mercapto, formyl, carboxy, carbanoyl,
6 alkyl, an optionally substituted -0-C3_6 alkenyl, an optionally
esteryl, alkoxy, (C1- substituted -O-C3-6 alkynyl and cyano, and R3A is selected from the
C22)alkylthio, (C1-C22)alkylamino, ((C1- group consistin of OH, -OC(=0)R"A and an optionally substituted O-
C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- linked amino acid;
R20, Y1 is O or S;
Y2 is OH, OR12, OAlkyl, or BH3-M+; N-linked amino acid and an optionally substituted N-linked amino acid
Y3 is OH or BH3-M+; ester derivative;
R4 is hydrogen, hydroxy, (C1-C22)alkyl, R1C and R2C are independently selected from the group consisting of
fluoromethyl, difluoromethyl, trifluoromethyl, O-, OH, an
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- , an optionally substituted N-linked amino acid and an optionally
C12)aryl, or heterocyclyl, wherein R4 is optionally substituted N-linked amino acid ester derivative; or optionally
substituted with one or more, the same or different, substituted C1-6 alkoxy
R20;
cyano, hydroxy, benzyloxy, amino, amido, R2B and R3c are independently selected from the group consisting of an
mercapto, formyl, carboxy, carbamoyl, azido, (C1- optionally substituted Ci_6 alkyl, an optionally substituted C2-6 alkenyl,
C22)alkoxy, (C1-C22)alkylthio, (C1- an optionally substituted C2-6 alkynyl, an optionally substituted C3-6
C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- cycloalkyl, an optionally substituted -0-C1-6 alkyl, an optionally
C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- substituted -O-C3-6 alkenyl, an optionally substituted -0-C3-6 alkynyl and
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- cyano;
C12)aryl,orheterocyclyl, wherein R8 is optionally R4C is selected from the group consisting of OH, -OC(=0)R"c and an
substituted with one or more, the same or different, optionally substituted O-linked amino acid;
R20; R4A, R3B and R5C are independently a halogen;
R9 is hydrogen, methyl, ethyl, tert-butyl, (C1- R5A, R4B and R6C are independently hydrogen or halogen;
C22)alkyl, halogen, nitro, cyano, hydroxy, amino, R6A, R7A and R8A are independently selected from the group consisting of
mercapto, formyl, carboxy, carbamoyl, cycloalkyl, absent, hydrogen, an optionally substituted Ci_24 alkyl, an optionally
(C1-C22)alkoxy, (C1-C22)alkylthio, (C1- substituted C2-24 alkenyl, an optionally substituted C2-24 alkynyl, an
C22)alkylamino,((C1-C22)alkyl)2amino, (C1- optionally substituted C3-6 cycloalkyl, an optionally substituted C3-6
C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- cycloalkenyl, an optionally substituted aryl, an optionally substituted
C12)arylsulfonyl, (C3-C6)carbocyclyl,(C6- heteroaryl, an optionally substituted aryl(Ci_6 alkyl), an optionally
C12)aryl,orheterocyclyl, wherein R9 is optionally substituted *-(CR15AR16A)p-0-Ci_24 alkyl, an optionally substituted *-
substituted with one or more, the same or different, (CR17AR18A)q-0-Ci_24
R20;
cyclohexyl,butyl, pentyl, hexyl, neopentyl, benzyl,
96
formyl, carboxy,carbamoyl, (C1-C22)alkoxy, (C1-
R11 is hydrogen, deuterium, (C1-C22)alkyl, methyl, R6A is and R7 is absent or hydrogen; or
halogen, nitro, cyano, hydroxy, amino, mercapto, R and R , 7/AA are taken together to form a moiety selected from the
formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1- group
C22)alkylthio, (C1-C22)alkylamino, ((C1- consisting of an optionally substituted
C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, and an optionally substituted
phenyl, 1-naphthyl, 2-naphthyl, aromatic, wherein the oxygens connected to R6A and R7A, the phosphorus and the
heteroaromatic, 4-substituted phenyl, 4- moiety form a six-membered to ten-membered ring system;.
fluorophenyl, 4-chlorophenyl, 4-bromophenyl, R9A is independently selected from the group consisting of an optionally
naphthyl, or heterocyclyl, wherein R12 is optionally substituted Ci_24 alkyl, an optionally substituted C2-24 alkenyl, an
substituted with one or more, the same or different, optionally substituted C2-24 alkynyl, an optionally substituted
R20; C3_6 cycloalkyl, an optionally substituted C3_6 cycloalkenyl, NR30AR31A,
R13 is hydrogen, deuterium, (C1-C22)alkyl, (C2- an optionally substituted N-linked amino acid and an optionally
C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, substituted N-linked amino acid ester derivative;
cyano, hydroxy, amino, amido, mercapto, formyl, R10A and R11A are independently an optionally substituted N-linked
carboxy, carbamoyl, lipid, azido, (C1-C22)alkoxy, amino acid or an optionally substituted N-linked amino acid ester
(C1-C22)alkylthio, derivative;
(C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- R12A, R13A and R14A are independently absent or hydrogen;
C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- each R15A, each R16A, each R17A and each R18A are independently
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- hydrogen, an optionally substituted Ci_24 alkyl or alkoxy; R19A, R20A,
C12)aryl, or heterocyclyl, wherein R13 is optionally R22A, R23A, R5B, R6B, R8B, R9B, R9C, R10C, R12C and R13C are
substituted with one or more, the same or different, independently selected from the group consisting of hydrogen, an
R20; optionally substituted Ci_24 alkyl and an optionally substituted aryl;
R14 is hydrogen, deuterium, (C1-C22)alkyl, (C2- R2iA R24A R7B^ Ri<m Rnc and Ri4C arg independently selected from the
C22)alkenyl, (C12-C22)alkynyl, halogen, nitro, group consisting of hydrogen, an optionally substituted Ci_24 alkyl, an
cyano, hydroxy, amino, amido, mercapto, formyl, optionally substituted aryl, an optionally substituted -0-Ci_24 alkyl and
carboxy, carbamoyl, lipid, azido, (C1-C22)alkoxy, an optionally substituted -O-aryl;
(C1-C22)alkylthio, R25A R29A RHB and R15C are independently selected from the group
(C1-C22)alkylamino, ((C1-C22)alkyl)2amino, consisting of hydrogen, an optionally substituted Ci_24 alkyl and an
alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- optionally substituted aryl;
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- R1U", R^ and R are independently absent or hydrogen;
C12)aryl, or heterocyclyl, wherein R14 is optionally R26A and R27A are independently -C≡N or an optionally substituted
substituted with one or more, the same or different, substituent selected from the group consisting of C2_8 organylcarbonyl,
R20; C2_8 alkoxycarbonyl and C2_8 organylaminocarbonyl;
R30A and R31A are independently selected from the group consisting of
hydrogen, an optionally substituted Ci_24-alkyl, an optionally substituted
C2-24 alkenyl, an optionally substituted C2_24 alkynyl, an optionally
substituted C3_6 cycloalkyl and an optionally substituted
C3_6 cycloalkenyl;
when is a single bond, each R and each R is independently hydrogen or
halogen; and
p and q are independently selected from the group consisting of 1, 2 and
3;
r is 1 or 2;
97
substituted with a halogen or methyl and R9A is methyl ester, ethyl ester,
isopropyl ester, n-butyl ester, benzyl ester or phenyl ester of an amino
acid selected from the group consisting of glycine, alanine, valine,
leucine, phenylalanine, tryptophan, methionine and proline; R3A is OH;
R4A is fluoro; R5A is fluoro or hydrogen; and B1A is an unsubstituted
uracil; then R2A cannot be -OCH3;
provided that when the dashed line ( ) of Formula (I) is absent; R1A is H;
R3A is OH; R4A is fluoro; R5A is fluoro; and B1A is an unsubstituted
cytosine; then R2A cannot be allenyl;
R3A is OH; R4A is fluoro; R5A is hydrogen; and B1A is an unsubstituted
thymine; then R2A cannot be Ci alkyl substituted with an N-amido; and
R3A is OH; R4A is fluoro; R5A is fluoro; and B1A is an unsubstituted
cytosine; then R2A cannot be ethynyl.
Claim 212.
The use or method of any one of Claims 162-211, wherein B is selected
from the group consisting of:
wherein:
R is selected from the group consisting of hydrogen, halogen and NHR'
C(=0)R U and
C(=0)OR^ ;
R is halogen or NHR , wherein R is selected from the group consisting of
hydrogen, an optionally substituted Ci_6 alkyl, an optionally substituted
C2-6 alkenyl, an optionally substituted C3_8 cycloalkyl, -C(=0)RMC2 and -
C(=0)ORNC2;
consisting of hydrogen, -C(=0)RPC2 and -C(=0)ORQC2; R is selected from
Ci_6 alkyl, an optionally substituted C2_6 alkenyl and an optionally
substituted C2_6 alkynyl;
Y2C and Y3C are independently N or CRIC2, wherein RIC2 is selected from
Ci_6-alkyl, an optionally substituted C2_6-alkenyl and an optionally
substituted C2_6-alkynyl;
aryl, heteroaryl, heteroalicyclyl, aryl(Ci_6 alkyl), heteroaryl(Ci_6 alkyl)
and heteroalicyclyl(Ci_6 alkyl).
98
Claim 13
IN201717025098 D3: WO2013142525A1

CLAIM 13 Claim 13 is dependent on claim 1 so the arguments applicable for
The composition of claim 1, wherein R4 is hydrogen, claim 1are applicable here too
hydroxy, alkyl, halogen, or fluoro.
Claim 14
IN201717025098 D3: WO2013142525A1

CLAIM 14 Claim 13 is dependent on claim 1 so the arguments applicable for
The composition of claim 1, wherein R5 is hydrogen, claim 1are applicable here too
hydroxy, alkoxy, alkyl, methyl, ethynyl, or allenyl.
D. Opponent further introduces prior art EP2615101B1 (D4) to Junbiao Chang to contest the
novelty of the invention. EP2615101B1 having priority date of Sept 7, 2010 is a
permissible prior art for IN20717025098 having priority date of Dec 26, 2014.
iv. Lack of novelty in view of EP2615101B1 (D4) to Junbiao Chang
D4 discloses fluorinated and azido-substituted pyrimidine nucleoside derivatives, and

preparation methods and uses thereof. The structural formula is as shown (I). These
compounds can be used for preparing medicaments for treating diseases such as tumors and
viral infections, and can be used separately or in combination with other medicaments. The
compounds also have effective activity against diseases such as tumors and viral infections.
IN201717025098 D4: EP2615101B1

CLAIM 1: A pharmaceutical composition comprising a pharmaceutically acceptable [0001] The present invention relates to 4’-azido-2’-deoxy-2’-
excipient and a compound having Formula I β-fluoropyrimidine nucleoside derivatives, preparation
methods thereof, and uses thereof for preparing anti-tumor
and anti-virus medicaments.
[030]
Monophosphate
Q is O, -O(C=O)-, -O(C=O)V-, or NR7; ester,
V is O, NH, NR7, CH2, or CHR7; diphosphate [031] 5-07 R1=NHOCH3, 5-08 R1=NHOEt, 5-17 R1= NHOH,
W is O;
ester
Y is CR”;
Z is CR”; 5-30 R1= , 5-31 R1=CH3NHNH
each R” is independently selected from is H, D, F, Cl, Br, I, CH3, CD3, CF3, C1-22alkyl,
acyl, C2- 22alkenyl, C2-22alkynyl, hydroxyl, formyl or SCH3; [032] Compound 5-07: HRMS(ESI) calcd for C10H13FN6O5Na
R1 is [M + Na]+ 339.0829, found 339.0831.
Compound 5-08: HRMS(ESI) calcd for C11H15FN6O5Na [M +
Na]+ 353.0986, found 353.0986
Compound 5-30: 1H NMR (300 MHz, CD4O): δ 3.85 (2H, s, 5’-
CH2), 4.49 (1H, dd, J = 21.8 and 4.7, 3’-H), 5.21 (1H,d, J = 53.6,
2’-H), 5.93 (1H, s, 5-H), 6.47 (1H, dd, J = 11.9 and 4.9, 1’-H),
99
7.61 (1H, s, 6-H); 13C NMR (75 MHz, CD4O): δ 63.4 (5’-CH2),
76.4 (3’-CH, d, J 24.9), 84.6 (1’-CH), 92.6 (5-CH), 96.2 (2’-CH,
d, JFC 192.4), 98.6 (4’-C),144.1 (6-CH), 156.7 (4-C), 161.9
(CO); HRMS (ESI) calcd for C10H13FN8O5Na [M + Na]+
367.0891, found 367.0912 (calcd for C13H20FN6O6 [M + H]+
345.1071, found 345.1103).
Claim 4
The 4'-azido-2'-deoxy-2'-β-fluoropyrimidine nucleoside
derivative of
alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, claim 1, wherein when
carbanoyl, esteryl, alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-
C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl,
(C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, or phosphoramidyl wherein R1 is
Y1 is O or S; the following compounds in which R2 =H and
Y2 is OH, OR12, OAlkyl, or BH3 - M+; Y3 is OH or BH3 - M+; R1 is one of the following groups are preferred, entry R1 5-01
R2 is hydrogen or hydroxy; EtNH 5-02 NHCH2CH2NH2 5-03
R3 is hydrogen, hydroxy, (C1-C22)alkyl, halogen, nitro, cyano, hydroxy, amino, Figure imgb0164
mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio, , (C1- 5-04 NEt2 5-05
C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, Figure imgb0165
(C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; 5-06
R4 is hydrogen, hydroxy,(C1-C22)alkyl, fluoromethyl, difluoromethyl, Figure imgb0166
trifluoromethyl, hydroxymethyl, halogen, nitro, cyano, hydroxy, amino, mercapto, 5-07 NHOCH3 5-08 NHOEt 5-09
formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino, Figure imgb0167
((C1-C22)alkyl)2amino,(C1-C22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6- 5-10
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; Figure imgb0168
R5 is hydrogen, hydroxy, or halogen; 5-11
R6 is hydrogen, hydroxy, (C1-C22)alkoxy, (C1-C22)alkyl, ethynyl, allenyl, halogen, Figure imgb0169
nitro, cyano, amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, (C1- 5-12
C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, Figure imgb0170
(C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- C12)aryl,orheterocyclyl; 5-13
each R7 is independently selected from absent, hydrogen, -(C=O)Oalkyl(C1-C22), - Figure imgb0171
(C=O)alkyl(C1- C22), -(C=O)NHalkyl(C1-C22), -(C=O)N-dialkyl(C1-C22), - 5-14
(C=O)Salkyl(C1-C22), hydroxy, (C1-C22)alkoxy, (C1- C22)alkyl, halogen, nitro, cyano, Figure imgb0172
amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1- 127 5-15
C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- Figure imgb0173
C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- 5-16
C12)aryl,orheterocyclyl, wherein each R7 is optionally substituted with one or more, Figure imgb0174
the same or different, R20; 5-17 NHOH 5-18
R8 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2-C22)alkynyl, halogen, Figure imgb0175
nitro, cyano, hydroxy, benzyloxy, amino, amido, mercapto, formyl, carboxy, 5-19
carbamoyl, azido, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino, ((C1- Figure imgb0176
C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, 5-20
(C3-C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R8 is optionally substituted Figure imgb0177
with one or more, the same or different, R20; 5-21 N(CH3)2 5-22
R9 is hydrogen, methyl, ethyl, tert-butyl, (C1-C22)alkyl, halogen, nitro, cyano, Figure imgb0178
hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, cycloalkyl, (C1-C22)alkoxy, 5-23
(C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, Figure imgb0179
(C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- 5-24 NH(CH2)4CH3 5-25 NH(CH2)5CH3 5-26 NH(CH2)6CH3 5-
C12)aryl,orheterocyclyl, wherein R9 is optionally substituted with one or more, the 27 NH(CH2)7CH3 5-28 NHCH3 5-29
same or different, R20; Figure imgb01=
R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, lipid, methyl, ethyl, isopropyl, 5-30
cyclopentyl, cyclohexyl, butyl, pentyl, hexyl, neopentyl, benzyl, halogen, nitro,
cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1-
C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-
C12)aryl,orheterocyclyl, 5-31 CH3NHNH
R11 is hydrogen, deuterium, (C1-C22)alkyl, methyl, halogen, nitro, cyano, hydroxy,
amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio,
(C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-
C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or
heterocyclyl,
naphthyl,aromatic, heteroaromatic, 4-substituted phenyl, 4-fluorophenyl, 4-
chlorophenyl, 4-bromophenyl, naphthyl, or heterocyclyl, wherein R12 is optionally
R13 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2-C22)alkynyl,
halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy,
carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-
C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl,
(C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl,
R14 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C12-C22)alkynyl,
100
halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy,
carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-
C22)alkyl)2amino, alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-
C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R14 is optionally substituted
R20 is deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2-C22)alkynyl, halogen, nitro,
cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-
C22)alkoxy, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-
C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl,
(C6-C12)aryl, or heterocyclyl; and wherein the lipid comprises a C6-22 alkyl, (C1-
C22)alkoxy, polyethylene glycol, or (C6-C12)aryl substituted with an (C1-C22)alkyl
group, heterocyclylis acarbocyclylcomprising 1-4 heteroatoms selected from
nitrogen, oxygen, or sulfur, and heteroaromatic is an aromatic
heterocyclylcomprising 1-4 heteroatoms selected from nitrogen, oxygen, or sulfur
and at least 1 carbon atom.
CLAIM 2: The pharmaceutical composition of claim 1, wherein Q-R7 is [031] 5-07 R1=NHOCH3, 5-08 R1=NHOEt, 5-17 R1=
OH. NHOH,
5-30 R1= , 5-31 R1=CH3NHNH
CLAIM 3: The pharmaceutical composition of claim 1, wherein R1 is Claim dependent on claim 1 so the arguments of claim
1 apply as such

CLAIM 4. [0001] The present invention relates to 4’-azido-2’-
A pharmaceutical composition comprising a pharmaceutically acceptable deoxy-2’-β-fluoropyrimidine nucleoside derivatives,
excipient and a compound of formula IB, preparation methods thereof, and uses thereof for
preparing anti-tumor and anti-virus medicaments.

Y is H, D, F, Cl, Br, I, CH3, CD3, CF3, (C1-C6)alkyl, acyl, (C2-C6)alkenyl, (C2-
C6)alkynyl, hydroxyl, formyl or SCH3;
R1
Monophosphate
ester,
diphosphate
ester

carboxy, carbamoyl, carbanoyl, esteryl, alkoxy, (C1C22)alkylthio, (C1-
101
(C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-
C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, or phosphoramidyl,wherein
R1 is optionally substituted with one or more, the same or different, R20;
Y1 is O or S;
Y3 is OH or BH3-M+;
R4 is hydrogen, hydroxy,(C1-C22)alkyl, fluoromethyl, difluoromethyl,
trifluoromethyl, hydroxymethyl, halogen, nitro, cyano, hydroxy, amino,
mercapto, formyl, carboxy, carbamoyl, , (C1-C22)alkoxy, (C1-
C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-
C22)alkylsulfinyl, , (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-
R8 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2-
C22)alkynyl, halogen, nitro, cyano, hydroxy, benzyloxy, amino, amido,
mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1-
C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-
C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R8 is optionally
R9 is hydrogen, methyl, ethyl, tert-butyl, (C1-C22)alkyl, halogen, nitro,
cyano, hydroxy, amino,mercapto, formyl, carboxy, carbamoyl, cycloalkyl,
(C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino,((C1-
C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-
C12)arylsulfonyl, (C3-C6)carbocyclyl,(C6-C12)aryl,orheterocyclyl, wherein
R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, lipid, methyl, ethyl, isopropyl,
cyclopentyl, cyclohexyl, butyl, pentyl, hexyl, neopentyl, benzyl, halogen,
nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy,carbamoyl, (C1-
C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino,
(C1-C22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-
C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R10 isoptionally
R11 is hydrogen, deuterium, (C1-C22)alkyl, methyl, halogen, nitro, cyano,
hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy,
(C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-
C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R11 is optionally
naphthyl,aromatic, heteroaromatic, 4-substituted phenyl, 4-fluorophenyl,
4-chlorophenyl, 4-bromophenyl, naphthyl, or heterocyclyl, wherein R12 is
C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto,
formyl, carboxy, carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1-C22)alkylthio,
C22)alkylsulfonyl, (C6-C12)arylsulfonyl,(C3-C6)carbocyclyl, (C6-C12)aryl, or
heterocyclyl, wherein R13 is optionally substituted with one or more, the
(C1-C22)alkylamino, ((C1-C22)alkyl)2amino, alkylsulfinyl, (C1-
heterocyclyl, wherein R14 is optionally substituted with one or more,
thesame or different, R20;
R15 is hydrogen, Lipid, -(C=O)Oalkyl(C1-C22), -(C=O)alkyl(C1-C22), -
(C=O)NHalkyl(C1-C22), -(C=O)N-dialkyl(C1-C22), -(C=O)Salkyl(C1-C22),
hydroxy, (C1-C22)alkoxy, (C1-C22)alkyl, halogen, nitro, cyano,amino,
mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, (C1-
C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-
R20 is deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2-C22)alkynyl, halogen,
102
nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy,
carbamoyl, azido, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino,
((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-
wherein the lipid comprises a C6-22 alkyl, (C6-C22)alkoxy, polyethylene
glycol, or (C6-C12)aryl substituted with an alkyl group,heterocyclylis
acarbocyclylcomprising 1-4 heteroatoms selected from nitrogen, oxygen,
or sulfur, and heteroaromatic is an aromatic heterocyclylcomprising 1-4
heteroatoms selected from nitrogen, oxygen, or sulfur and at least 1
carbon atom.
CLAIM 5 Claim dependent on claim 3 which depends on claim 1,
The composition of claim 3, wherein the compound is selected from: so the arguments of claim 1 apply as such here.
1-(3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-4-
isopropyl(((3,4-dihydroxy-5-(4-(hydroxyamino)-2-oxopyrimidin-1(2H)-
yl)tetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)alaninate.
CLAIM 6 [0001] The present invention relates to 4’-azido-2’-
A pharmaceutical composition comprising a pharmaceutically acceptable deoxy-2’-β-fluoropyrimidine nucleoside derivatives,
excipient and a compound of Formula IC, preparation methods thereof, and uses thereof for

Y is H, D, F, Cl, Br, I, CH3, CD3, CF3, alkyl, acyl, alkenyl, alkynyl, hydroxyl,
formyl or SCH3;

carboxy, carbamoyl, carbanoyl, esteryl, alkoxy, (C1-C22)alkylthio, (C1-
(C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-
C6)carbocyclyl, (C6-C12)aryl, or
heterocyclyl, or phosphoramidyl, or wherein R1 is optionally substituted
Y1 is O or S;
Y3 is OH or BH3-M+;
103
mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1-
C22)alkylthio,(C1-C22)alkylamino, ((C1-C22)alkyl)2amino,(C1-
C22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-
cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, cycloalkyl,
cyclopentyl, cyclohexyl,butyl, pentyl, hexyl, neopentyl, benzyl, halogen,
C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R10 isoptionally
hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy,
(C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino,(C1-
C6)carbocyclyl, (C6-C12)aryl, orheterocyclyl, wherein R11 is optionally
naphthyl,aromatic,heteroaromatic, 4-substituted phenyl, 4-fluorophenyl,
C22)alkynyl, halogen, nitro, cyano,
hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido,
(C1-C22)alkoxy, (C1-C22)alkylthio,
R15 is hydrogen, Lipid, -(C=O)Oalkyl(C1-C22), -(C=O)alkyl(C1-C22), -
(C=O)NHalkyl(C1-C22), - (C=O)N-dialkyl(C1-C22), -(C=O)Salkyl(C1-C22),
hydroxy, (C1-C22)alkoxy, (C1-C22)alkyl, halogen, nitro, cyano,amino,
mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, (C1-
C22)alkylamino, ((C1-C22)alkyl)2amino,(C1-C22)alkylsulfinyl, (C1-
nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy,
((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-
glycol, or (C6-C12)aryl substituted with an alkyl group,heterocyclylis
acarbocyclylcomprising 1-4 heteroatoms selected from nitrogen, oxygen,
104
or sulfur, and heteroaromatic is an aromatic heterocyclylcomprising 1-4
heteroatoms selected from nitrogen, oxygen, or sulfur and at least 1
carbon atom.
7. A pharmaceutical composition comprising a pharmaceutically deoxy-2’-β-fluoropyrimidine nucleoside derivatives,
acceptable excipient and a compound of Formula ID, preparation methods thereof, and uses thereof for
Formula ID,
Y is N or CR”;
Z is N or CR”;
each R” is independently selected from is H, D, F, Cl, Br, I, CH3, CD3, CF3,
alkyl, acyl, alkenyl, alkynyl, hydroxyl, formyl or SCH3;
alkyl, halogen, nitro,
cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, carbanoyl,
esteryl, alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, or
phosphoramidyl, or wherein R1 is optionally substituted with one or more,
Y1 is O or S;
Y3 is OH or BH3-M+;
R2 is hydrogenor hydroxy;
R3 is hydrogen, hydroxy, alkyl, halogen, nitro, cyano, hydroxy, amino,
mercapto, formyl, carboxy, carbamoyl, alkoxy, (C1-C22)alkylthio,
alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl,
arylsulfonyl,carbocyclyl, aryl, or heterocyclyl;
trifluoromethyl, hydroxymethyl,
halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy,
carbamoyl, (C1-C22)alkoxy, (C1-
C22)alkylthio,(C1-C22)alkylamino, ((C1-C22)alkyl)2amino,(C1-
C22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-
R6 is hydrogen, hydroxy, alkoxy, alkyl, ethynyl, allenyl, halogen, nitro,
cyano, amino, mercapto,formyl, carboxy, carbamoyl, alkoxy, (C1-
C22)alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl,
arylsulfonyl, carbocyclyl, aryl, or heterocyclyl;
cyano, hydroxy, amino,mercapto, formyl, carboxy, carbamoyl, cycloalkyl,
(C6-C12)aryl,orheterocyclyl, wherein R9 is optionally substituted with one
105
hydroxy, amino, mercapto,formyl, carboxy, carbamoyl, (C1-C22)alkoxy,
4-chlorophenyl, 4-bromophenyl, naphthyl, or
formyl, carboxy, carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1-
C22)alkylthio,(C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-
C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl,(C3-
C22)alkynyl, halogen, nitro, cyano,hydroxy, amino, amido, mercapto,
C22)alkylthio,(C1-C22)alkylamino, ((C1-C22)alkyl)2amino, alkylsulfinyl, (C1-
R15 is hydrogen, -(C=O)Oalkyl(C1-C22), -(C=O)alkyl(C1-C22), -
(C=O)NHalkyl(C1-C22), -(C=O)Ndialkyl(C1-C22), -(C=O)Salkyl(C1-C22),
hydroxy, (C1-C22)alkoxy, (C1-C22)alkyl, halogen, nitro, cyano,
amino,mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, (C1-
heterocyclyl,wherein R15 is optionally substituted with one or more, the
R15’ is hydrogen, -(C=O)Oalkyl(C1-C22), -(C=O)alkyl(C1-C22), -
(C=O)NHalkyl(C1-C22), -(C=O)Ndialkyl(C1-C22), -(C=O)Salkyl(C1-C22),
hydroxy, (C1-C22)alkoxy, (C1-C22)alkyl, halogen, nitro, cyano,
amino,mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, (C1-
heterocyclyl;
R15 and R15’ can form a ring that is optionally substituted with one or
nitro, cyano, hydroxy,
amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-
heterocyclyl; and
glycol, or (C6-C12)aryl substituted with an (C1-C22)alkyl group
heterocyclylis acarbocyclylcomprising 1-4 heteroatoms selected from
and heteroaromatic is an aromatic heterocyclylcomprising 1-4
heteroatoms selected from nitrogen,oxygen, or sulfur and at least 1
carbon atom.
8. A pharmaceutical composition comprising a pharmaceutically deoxy-2’-β-fluoropyrimidine nucleoside derivatives,
acceptable excipient and a compound of Formula IE, preparation methods thereof, and uses thereof for
[030]
106
Formula IE, [031] 5-07 R1=NHOCH3, 5-08 R1=NHOEt, 5-17 R1=
or salt thereof, wherein NHOH,
W is CH2, NH, S or O; 5-30 R1= , 5-31 R1=CH3NHNH
Y is N or CR”; [032] Compound 5-07: HRMS(ESI) calcd for
Z is N or CR”; C10H13FN6O5Na [M + Na]+ 339.0829, found
each R” is independently selected from is H, D, F, Cl, Br, I, CH3, CD3, CF3, 339.0831.
alkyl, acyl, alkenyl, alkynyl, hydroxyl, formyl or SCH3; Compound 5-08: HRMS(ESI) calcd for
R2 is hydrogen, alkyl, alkenyl, alkynyl, ethynyl, fluoromethyl, C11H15FN6O5Na [M + Na]+ 353.0986, found 353.0986
difluoromethyl, trifluoromethyl, chloromethyl, hydroxymethyl, halogen, Compound 5-30: 1H NMR (300 MHz, CD4O): δ 3.85
nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (2H, s, 5’-CH2), 4.49 (1H, dd, J = 21.8 and 4.7, 3’-H),
alkoxy, (C1-C22)alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, 5.21 (1H,d, J = 53.6, 2’-H), 5.93 (1H, s, 5-H), 6.47 (1H,
alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, azido, or heterocyclyl; dd, J = 11.9 and 4.9, 1’-H), 7.61 (1H, s, 6-H); 13C NMR
R3 is hydrogen, hydroxy, alkyl, halogen, nitro, cyano, hydroxy, amino, (75 MHz, CD4O): δ 63.4 (5’-CH2), 76.4 (3’-CH, d, J
mercapto, formyl, carboxy, carbamoyl, alkoxy, (C1-C22)alkylthio, 24.9), 84.6 (1’-CH), 92.6 (5-CH), 96.2 (2’-CH, d, JFC
alkylamino, alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, 192.4), 98.6 (4’-C),144.1 (6-CH), 156.7 (4-C), 161.9
carbocyclyl, aryl, or heterocyclyl; (CO); HRMS (ESI) calcd for C10H13FN8O5Na [M + Na]+
R4 is hydrogen, hydroxy,(C1-C22)alkyl, fluoromethyl, difluoromethyl, 367.0891, found 367.0912 (calcd for C13H20FN6O6
trifluoromethyl, hydroxymethyl, halogen, nitro, cyano, hydroxy, amino, [M + H]+ 345.1071, found 345.1103).
mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1- Claim 4
C22)alkylthio,(C1-22)alkylamino, ((C1-C22)alkyl)2amino,(C1- The 4'-azido-2'-deoxy-2'-β-fluoropyrimidine nucleoside
C22)alkylsulfinyl,(C1-22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- derivative of
C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; claim 1, wherein when
R5 is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, alkynyl, ethynyl,
fluoromethyl, difluoromethyl,trifluoromethyl, hydroxymethyl, allenyl,
halogen, nitro, cyano, amino, mercapto, formyl, carboxy,
carbamoyl,alkoxy, (C1-C22)alkylthio, alkylamino, (alkyl)2amino,
alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl,or heterocyclyl; the following compounds in which R2 =H
R6 is hydrogen, hydroxy, alkoxy, alkyl, ethynyl, allenyl, halogen, nitro, and R1 is one of the following groups are preferred,
cyano, amino, mercapto,formyl, carboxy, carbamoyl, alkoxy, (C1- entry R1 5-01 EtNH 5-02 NHCH2CH2NH2 5-03
C22)alkylthio, lkylamino, (alkyl)2amino, alkylsulfinyl, Figure imgb0164
alkylsulfonyl,arylsulfonyl, carbocyclyl, aryl, or heterocyclyl; 5-04 NEt2 5-05
each R7 is independently selected from absent, hydrogen, -(C=O)Oalkyl, - Figure imgb0165
(C=O)alkyl, -(C=O)NHalkyl, -(C=O)N-dialkyl, -(C=O)Salkyl, hydroxy, alkoxy, 5-06
alkyl, higher alkyl, (C6-C16)alkyl, (C6-C22)alkyl, halogen, nitro, cyano, Figure imgb0166
amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, (C1- 5-07 NHOCH3 5-08 NHOEt 5-09
C22)alkylthio,alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, Figure imgb0167
arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, whereineach R7 is optionally 5-10
substituted with one or more, the same or different, R20; Figure imgb0168
R15 is hydrogen, -(C=O)Oalkyl(C1-C22), -(C=O)alkyl(C1-C22), - 5-11
C=O)NHalkyl(C1-C22), -(C=O)Ndialkyl(C1-C22), -(C=O)Salkyl(C1-C22), Figure imgb0169
hydroxy, (C1-C22)alkoxy, (C1-C22)alkyl, halogen, nitro, cyano, 5-12
amino,mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, (C1- Figure imgb0170
C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- 5-13
C22)alkylsulfonyl, (C6-12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or Figure imgb0171
heterocyclyl,wherein R15 is optionally substituted with one or more, the 5-14
same or different, R20; Figure imgb0172
R15’ is hydrogen, -(C=O)Oalkyl(C1-C22), -(C=O)alkyl(C1-C22), - 5-15
C=O)NHalkyl(C1-C22), -(C=O)Ndialkyl(C1-C22), -(C=O)Salkyl(C1-C22), Figure imgb0173
hydroxy, (C1-C22)alkoxy, (C1-C22)alkyl, halogen, nitro, cyano, amino, 5-16
mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, (C1- Figure imgb0174
C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- 5-17 NHOH 5-18
C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or Figure imgb0175
heterocyclyl; 5-19
R15 and R15’ can form a ring that is optionally substituted with one or Figure imgb0176
more, the same or different,R20; 5-20
107
If Q = -O(C=O)V- and V = NR7 then the R7s can together form a ring that is Figure imgb0177
optionally substitutedwith one or more, the same or different, R20; 5-21 N(CH3)2 5-22
R20 is deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2-C22)alkynyl, halogen, Figure imgb0178
nitro, cyano, hydroxy,amino, amido, mercapto, formyl, carboxy, 5-23
carbamoyl, azido, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, Figure imgb0179
((C1-22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- 5-24 NH(CH2)4CH3 5-25 NH(CH2)5CH3 5-26
C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; and NH(CH2)6CH3 5-27 NH(CH2)7CH3 5-28 NHCH3 5-29
wherein lipid comprises a C6-22 alkyl, (C6-C22)alkoxy, polyethylene glycol, Figure imgb0180
or (C6-C12)aryl substituted with an (C1-C22)alkyl group, heterocyclylis 5-30
carbocyclyl comprising 1-4 heteroatoms selected from nitrogen, oxygen,
or sulfur,
and heteroaromatic is an aromatic heterocyclylcomprising 1-4
heteroatoms selected from nitrogen,oxygen, or sulfur and at least 1 5-31 CH3NHNH
carbon atom.
CLAIM 9 A pharmaceutical composition comprising a pharmaceutically [0001] The present invention relates to 4’-azido-2’-
acceptable excipient and a compound of Formula II, deoxy-2’-β-fluoropyrimidine nucleoside derivatives,
preparation methods thereof, and uses thereof for
[030]

[031] 5-07 R1=NHOCH3, 5-08 R1=NHOEt, 5-17 R1=
NHOH,
X is CH2 or O;
Y is N or CR”;
Z is N or CR”;
each R” is independently selected from is H, D, F, Cl, Br, I, CH3, CD3, CF3, 5-30 R1= , 5-31 R1=CH3NHNH
alkyl, acyl, alkenyl, alkynyl, hydroxyl, formyl or SCH3;
R1 is monophosphate, diphosphate, triphosphate, [032] Compound 5-07: HRMS(ESI) calcd for
C10H13FN6O5Na [M + Na]+ 339.0829, found
339.0831.
Compound 5-08: HRMS(ESI) calcd for
C11H15FN6O5Na [M + Na]+ 353.0986, found 353.0986
Compound 5-30: 1H NMR (300 MHz, CD4O): δ 3.85
(2H, s, 5’-CH2), 4.49 (1H, dd, J = 21.8 and 4.7, 3’-H),
5.21 (1H,d, J = 53.6, 2’-H), 5.93 (1H, s, 5-H), 6.47 (1H,
dd, J = 11.9 and 4.9, 1’-H), 7.61 (1H, s, 6-H); 13C NMR
(75 MHz, CD4O): δ 63.4 (5’-CH2), 76.4 (3’-CH, d, J
24.9), 84.6 (1’-CH), 92.6 (5-CH), 96.2 (2’-CH, d, JFC
192.4), 98.6 (4’-C),144.1 (6-CH), 156.7 (4-C), 161.9
367.0891, found 367.0912 (calcd for C13H20FN6O6
[M + H]+ 345.1071, found 345.1103).
Claim 4
derivative of
claim 1, wherein when
Y1 is O or S;
Y2 is OH, OR12, OAlkyl, or BH3-M+; the following compounds in which R2 =H
Y3 is OH or BH3-M+; and R1 is one of the following groups are preferred,
R2 is hydrogen, alkyl, alkenyl, alkynyl, ethynyl, fluoromethyl, entry R1 5-01 EtNH 5-02 NHCH2CH2NH2 5-03
difluoromethyl, trifluoromethyl,chloromethyl, hydroxymethyl, halogen, Figure imgb0164
nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, 5-04 NEt2 5-05
alkoxy, (C1-C22)alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, Figure imgb0165
alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl,azido, or heterocyclyl; 5-06
R3 is hydrogen, hydroxy, alkyl, halogen, nitro, cyano, hydroxy, amino, Figure imgb0166
mercapto, formyl, carboxy, carbamoyl, alkoxy, (C1-C22)alkylthio, 5-07 NHOCH3 5-08 NHOEt 5-09
108
alkylamino, alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, Figure imgb0167
carbocyclyl, aryl, or heterocyclyl; 5-10
R4 is hydrogen, hydroxy,(C1-C22)alkyl, fluoromethyl, difluoromethyl, Figure imgb0168
rifluoromethyl, hydroxymethyl,halogen, nitro, cyano, hydroxy, amino, 5-11
mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1- Figure imgb0169
C22)alkylthio,(C1-C22)alkylamino, ((C1-C22)alkyl)2amino,(C1- 5-12
C22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- Figure imgb0170
C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; 5-13
R5 is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, alkynyl, ethynyl, Figure imgb0171
fluoromethyl, difluoromethyl,trifluoromethyl, hydroxymethyl, allenyl, 5-14
halogen, nitro, cyano, amino, mercapto, formyl, carboxy, Figure imgb0172
carbamoyl,alkoxy, (C1-C22)alkylthio, alkylamino, (alkyl)2amino, 5-15
alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl,or heterocyclyl; Figure imgb0173
R6 is hydrogen, hydroxy, alkoxy, alkyl, ethynyl, allenyl, halogen, nitro, 5-16
cyano, amino, mercapto,formyl, carboxy, carbamoyl, alkoxy, (C1- Figure imgb0174
C22)alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, 5-17 NHOH 5-18
alkylsulfonyl,arylsulfonyl, carbocyclyl, aryl, or heterocyclyl; Figure imgb0175
each R7 is independently selected from absent, hydrogen, -(C=O)Oalkyl, - 5-19
(C=O)alkyl, - (C=O)NHalkyl, -(C=O)N-dialkyl, -(C=O)Salkyl, hydroxy, alkoxy, Figure imgb0176
alkyl, higher alkyl, (C6-C16)alkyl, (C6-C22)alkyl, halogen, nitro, cyano, 5-20
amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, (C1- Figure imgb0177
C22)alkylthio,alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, 5-21 N(CH3)2 5-22
arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein each R7 is Figure imgb0178
optionally substituted with one or more, the same or different, R20; 5-23
R8 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2- Figure imgb0179
C22)alkynyl, halogen, nitro, cyano,hydroxy, benzyloxy, amino, amido, 5-24 NH(CH2)4CH3 5-25 NH(CH2)5CH3 5-26
mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1- NH(CH2)6CH3 5-27 NH(CH2)7CH3 5-28 NHCH3 5-29
C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- Figure imgb0180
C22)alkylsulfinyl, (C1-22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- 5-30
C6)carbocyclyl, (C6-12)aryl,orheterocyclyl, wherein R8 is optionally
cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, cycloalkyl, 5-31 CH3NHNH
(C1-22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-
hydroxy, amino, mercapto,formyl, carboxy, carbamoyl, (C1-C22)alkoxy,
22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-
C22)alkylthio,(C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-
C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl,(C3-
formyl, carboxy, arbamoyl, lipid, azido, (C1-C22)alkoxy, (C1-
C22)alkylthio,(C1-C22)alkylamino, ((C1-C22)alkyl)2amino, alkylsulfinyl, (C1-
C22)alkylsulfonyl, (C6-12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or
109
If Q = -O(C=O)V- and V = NR7 then the R7s can together form a ring that is
nitro, cyano, hydroxy,amino, amido, mercapto, formyl, carboxy,
((C1-22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-
C12)arylsulfonyl, (C3-
C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; and wherein lipid comprises
a C6-22 alkyl, (C6-C22)alkoxy, polyethylene glycol, or (C6-C12)aryl
substituted
with an (C1-C22)alkyl group, heterocyclylis acarbocyclylcomprising 1-4
heteroatoms selected from nitrogen, oxygen, or sulfur, and
heteroaromatic is an aromatic heterocyclylcomprising 1-4 heteroatoms
selected from nitrogen,oxygen, or sulfur and at least 1 carbon atom.
CLAIM 10 The pharmaceutical composition of claim 1,further comprising a Claim 10 is dependent on claim 1 so the arguments of
propellant. claim 1 apply as such here. Propellant as such no
invention
CLAIM 11 The pharmaceutical composition of claim 10, wherein the Claim 10 is dependent on claim 1 so the arguments of
propellant is compressed air, ethanol, nitrogen, carbon dioxide, nitrous claim 1 apply as such here. Propellant as such no
oxide, hydrofluoroalkanes (HFA), 1,1,1,2,-tetrafluoroethane, 1,1,1,2,3,3,3- invention
heptafluoropropane or combinations thereof.
CLAIM 12 The composition of claim 1, wherein the compound has a [0001] The present invention relates to 4’-azido-2’-
structure according to Formula IA deoxy-2’-β-fluoropyrimidine nucleoside derivatives,
preparation methods thereof, and uses thereof for
[030]

R7 is H,
Y is independently selected from is H, D, F, Cl, Br, I, CH3, CD3, CF3, alkyl,
acyl, alkenyl, alkynyl, hydroxyl, formyl or SCH3;
R1 is
[031] 5-07 R1=NHOCH3, 5-08 R1=NHOEt, 5-17 R1=
NHOH,
monophosphate
ester, diphosphate
ester 5-30 R1= , 5-31 R1=CH3NHNH
[032] Compound 5-07: HRMS(ESI) calcd for

C10H13FN6O5Na [M + Na]+ 339.0829, found
339.0831.
Compound 5-08: HRMS(ESI) calcd for
C11H15FN6O5Na [M + Na]+ 353.0986, found 353.0986
Compound 5-30: 1H NMR (300 MHz, CD4O): δ 3.85
(2H, s, 5’-CH2), 4.49 (1H, dd, J = 21.8 and 4.7, 3’-H),
5.21 (1H,d, J = 53.6, 2’-H), 5.93 (1H, s, 5-H), 6.47 (1H,
dd, J = 11.9 and 4.9, 1’-H), 7.61 (1H, s, 6-H); 13C NMR
(75 MHz, CD4O): δ 63.4 (5’-CH2), 76.4 (3’-CH, d, J
24.9), 84.6 (1’-CH), 92.6 (5-CH), 96.2 (2’-CH, d, JFC
192.4), 98.6 (4’-C),144.1 (6-CH), 156.7 (4-C), 161.9
367.0891, found 367.0912 (calcd for C13H20FN6O6
[M + H]+ 345.1071, found 345.1103).
amino, mercapto, formyl, carboxy, carbanoyl, esteryl, alkoxy, (C1-
Claim 4
derivative of
C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, or phosphoramidyl, wherein
claim 1, wherein when
R1 is optionally substituted with one or more, the same or different, R20,
Y1 is O or S;
Y3 is OH or BH3-M+;
110
R4 is hydrogen, hydroxy, (C1-C22)alkyl, fluoromethyl, difluoromethyl,
mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio,
C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or the following compounds in which R2 =H
heterocyclyl, wherein R4 is optionally substituted with one or more, the and R1 is one of the following groups are preferred,
same or different, R20; entry R1 5-01 EtNH 5-02 NHCH2CH2NH2 5-03
R5 is hydrogen, hydroxy, or halogen; Figure imgb0164
R8 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2- 5-04 NEt2 5-05
C22)alkynyl, halogen, nitro, cyano, hydroxy, benzyloxy, amino, amido, Figure imgb0165
mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1- 5-06
C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- Figure imgb0166
C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- 5-07 NHOCH3 5-08 NHOEt 5-09
C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R8 is optionally Figure imgb0167
substituted with one or more, the same or different, R20; 5-10
R9 is hydrogen, methyl, ethyl, tert-butyl, (C1-C22)alkyl, halogen, nitro, Figure imgb0168
cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, cycloalkyl, 5-11
(C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino,((C1- Figure imgb0169
C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- 5-12
C12)arylsulfonyl, (C3-C6)carbocyclyl,(C6-C12)aryl,orheterocyclyl, wherein Figure imgb0170
R9 is optionally substituted with one or more, the same or different, R20; 5-13
R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, lipid, methyl, ethyl, isopropyl, Figure imgb0171
cyclopentyl, cyclohexyl,butyl, pentyl, hexyl, neopentyl, benzyl, halogen, 5-14
nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy,carbamoyl, (C1- Figure imgb0172
C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, 5-15
(C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- Figure imgb0173
C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R10 is optionally 5-16
R11 is hydrogen, deuterium, (C1-C22)alkyl, methyl, halogen, nitro, cyano, 5-17 NHOH 5-18
hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, Figure imgb0175
(C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino,(C1- 5-19
C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- Figure imgb0176
C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R11 is optionally 5-20
R12 is hydrogen, (C1-C22)alkyl, (C6-C12)aryl, phenyl, 1-naphthyl, 2- 5-21 N(CH3)2 5-22
naphthyl, aromatic, heteroaromatic, 4-substituted phenyl, 4-fluorophenyl, Figure imgb0178
4-chlorophenyl, 4-bromophenyl, naphthyl, or heterocyclyl, wherein R12 is 5-23
optionally substituted with one or more, the same or different, R20; Figure imgb0179
R13 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2- 5-24 NH(CH2)4CH3 5-25 NH(CH2)5CH3 5-26
C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, NH(CH2)6CH3 5-27 NH(CH2)7CH3 5-28 NHCH3 5-29
formyl, carboxy, carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1-C22)alkylthio, Figure imgb0180
(C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- 5-30
R14 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C12- 5-31 CH3NHNH
CLAIM 13 Claim dependent on claim 1 so the arguments of claim

The composition of claim 1, wherein R4 is hydrogen, hydroxy, alkyl, 1 apply as such
halogen, or fluoro.
CLAIM 14 Claim dependent on claim 1 so the arguments of claim
The composition of claim 1, wherein R5 is hydrogen, hydroxy, alkoxy, alkyl, 1 apply as such
methyl, ethynyl, or allenyl.
Therefore, it may be concluded that all claims of IN201717025098 are anticpated by contents
of D4 as well apart from D1-D3.
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From the above comparison it is amply clear that none of the claims of opposed application
are novel wrt to D1-D4 independently as per Section 2(1)(l) of the IPA.
Therefore, Learned Examiner is request to reject the case on grounds of Section 25(1)(b)&
(c) and not allow any claim on grounds of lack of novelty alone.
GROUND II:
II) Section 25(1)(e): Lack of inventive step
The invention so far as claimed in any claim of the complete specification is obvious and
clearly does not involve any inventive step, having regard to the matter published as
mentioned in clause (b) or having regard to what was used in India before the priority date of
the claim.
It is submitted that the invention lacks any inventive step and on this ground alone should be
rejected.
As such, when none of the claims 1-14 as submitted by Applicant in response to FER
(Annexure 2) are novel for the reasons as aforesaid, claims lack inventive step without a
doubt. However for sake of clarity, Applicant has discussed lack of inventive step wrt to
each citation.
Applicant shall rely on following prior art while discussing lack of inventive step in the
impugned application:
D1: US 2003/0087873
D2: US20140235566A1
D3: WO2013142525A1
D4: EP2615101B1
D5: US2004/0171860A1
D6: US 2014/0273023
D7: WO 2009/143011A1
D8: US5349947A1
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Opponent shall consider the problem solution approach to clarify his stand as following:
The problem in the prior art as anticipated by opponent (as there is no mention of the same in
the specification of impugned application) could be the need of new antiviral drugs and
antivirals with broader coverage.
Considering both D1 & D2 are from Emory University only, its very obvious for a person to
use the background technology available with their institute and find new uses of the existing
compounds known to be having antiviral properties. That is clearly what the Applicant has
done in the current case. Completely overlapping compounds of impugned application with
compounds of D1 & D2 alone or combined for same usage proves opponent’s point.
Further discussing the lack of inventive step in the impugned application, wrt to Graham’s
factors of inventive step as laid in Graham v. John Deere Co.
Graham’s Factors Facts

The scope and content of the prior art; D1-D4 and are clearly identified prior art
The level of ordinary skill in the art; Ordinary skilled in the art has access to
information available in public domain to
make the β-D or β-L nucleosides to be used as
antivirals. Applicant being from the same
institute as of D1, D2 had the privilege of
readily available background technology to
work on.
The differences between the claimed invention and Contents of impugned application seem to be
the prior art. completely anticipating the consent of the
opposed application. Applicant seems to be
claiming the prior art as no improvements over
existing prior art are reported.
Further, there have been no multiple failed efforts to answer the need of the prior art. Even
Emory University, the Applicant in this application and of D1 & D2, has been working in the
area and filing patents in the same set of compounds for past 15 years.
Thus, the invention lacks novelty in view of D1, D2, D3, and D4 independently and so the
fact obviously renders invention not having inventive alone or when combined.
i) Obviousness of the invention wrt to D1 US 2003/0087873
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D1 discloses a β-D or β-L nucleosides or its pharmaceutically acceptable salt or prodrug for
the treatment of a host infected with a virus belonging to the Flaviviridae infection including
all members of the Hepacivirus genus (HCV), Pestivirus genus (BVDV, CSFV, BDV), or
Flavivirus genus (Dengue virus, Japanese encephalitis virus group (including West Nile
Virus), and Yellow Fever virus); Orthomyxoviridae including all members of the Influenza
A, B genus, in particular influenza A and all relevant subtypes - including H1N1 and H3N2 -
and Influenza B; and Paramyxoviridae family including Respiratory Syncytial Virus (RSV)
infection or for the treatment of abnormal cellular proliferation including malignant tumors.
All claims of IN201717025098 are clearly anticipated by D1 as described above in context of
novelty. Thus IN201717025098 offers no technical advancement over D1 and is clearly
obvious over D1 alone.
ii) Obviousness of the invention wrt to D2 2014/23556
D2 discloses compounds and compositions for treating and preventing cancer and viral
infections such as HIV, HCV, Norovirus, Saporovirus, cytomegalovirus (CMV), herpes
viruses (HSV-1, HSV-2), Dengue virus, Yellow fever, or HBV in human patients or other
animal hosts, using N4-hydroxycytidine nucleosides derivatives, modified monophosphate
and phosphonates prodrugs analogs, and pharmaceutically acceptable, salts, prodrugs, and
other derivatives thereof of the Formula (I),
X1 is H, C1-C6 alkyl, C1-C6haloalkyl, C1-C6alkoxy, C2-C 6 alkenyl, C2-C6alkynyl,

COR1, or COOR1; X2 is hydrogen, COR1, or COOR1 wherein each R1 is, independently,
CH2-O(CO)-X5; CH2-O(CO)O-X5, C1-20alkyl, the carbon chain derived from a fatty
114
alcohol or C1-20alkyl substituted with a C1-C6alkyl, alkoxy, di(C1- C6alkyl)-amino, fluoro,
C3-C10cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aryl, heteroaryl, substituted aryl, or
substituted heteroaryl; wherein the substituents are C1-6 alkyl, or C1-6 alkyl substituted with
a C1-C6 alkyl, C1 –C6alkoxy, di(C1-C6alkyl)-amino, fluoro, or C3-10cycloalkyl;
X5 is independently, C1-20 alkyl, the carbon chain derived from a fatty alcohol or C alkyl
substituted with a C1–C6 alkyl, alkoxy, C3-10cycloalkyl, cycloalkyl alkyl,
cycloheteroalkyl, aryl, heteroaryl, substituted aryl, or substituted heteroaryl; wherein the
substituents are C1-6alkyl, or C1-6alkyl substituted with a C1-C6alkyl, C1-C6alkoxy, di(C1-
C6alkyl)-amino, fluoro, or C cycloalkyl each X3 and X4 is independently H, C1-6alkyl, C2-
C6 alkenyl, C2-C6alkynyl, aryl, alkylaryl, halogen, NH2, OH, SH, CN, or NO2;
Wherein the sugar moiety is ribose or modified ribose of the general Formula (II),
wherein:
D is H, C(O)R1, C(O)OR1, diphosphate ester, or triphosphate
ester; R1 is as defined above;
W is CL2 or CL2CL2, wherein L independently is selected from the group consisting
of H, C1-6alkyl, C2-6alkenyl, and C2-6 alkynyl, wherein C1-C6 alkyl, C2-6 alkenyl,
and C2-6alkynyl can each optionally contain one or more heteroatoms; A is O, S,
CH2, CHF, CF2, C=CH2, C=CHF, or C=CF2;
R4', R5, R5', R6, R6', and R7 are independently selected from the group consisting of
H, F, CI, Br, I, OH, SH, NH2, NHOH, NHNH2, N3, C(O)OH, CN, CH2OH,
C(O)NH2, C(S)NH2, C(O)OR, R, OR, SR,SSRNHR,andNR2;
R5’andR6’ can come together to form a ring;

wherein: when A is O or CH2, D is H or acyl, W is CH2, R4' and R7’are H then, R5,
R5', R6, R6' cannot be H, halogen, OH, SH, OCH3 , SCH3, NH2, NHCH3, CH3,
CH=CH2, CN, CH2NH2, CH2OH, COOH when A is O or S, R7cannot be OH, SH,
NH2, NHOH,
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NHNH2, OR, SR, SSR, NHR, or NR2, and R is independently a C1-C6alkyl, C2-
6alkenyl, C2-6alkynyl, C3-6 cycloalkyl, (C3-C6cycloalkyl) aryl, alkylaryl, or
arylalkyl, wherein the groups can be substituted with one or more substituents as
defined above.
The Opponent states that the antiviral compounds having the core N4-hydroxycytidine
nucleoside moiety covered under the Markush structure in pharmaceutical composition of
independent claim(s) 1, 4, 6, 7, 8 and 9 of the impugned Patent Application wherein the
variables are as defined in the amended claims with identical properties and functions are
prior disclosed in D2.
Therefore all the claims of the impugned application are obvious and lack any inventive
feature over D2 alone.
iii) Obviousness of the invention wrt to D3 WO2013142525A1 to etal
D3 discloses Formula (I), Formula (II), and Formula (III), or a pharmaceutically acceptable
salt of the foregoing, for ameliorating or treating a viral infection caused by a virus selected
from a henipavirus, a morbilli virus, a respirovirus, a rubulavirus and a metapneumovirus,
wherein the compound is selected from Formula (I), Formula II), and Formula (III) has one
of the following structures:
(I) (Π)
(HI)
wherein:
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B B and B are independently an optionally substituted heterocyclic base or an optionally substituted heterocyclic
base with a protected amino group;
R1A is selected from the group consisting of hydrogen, an optionally substituted
when the dashed line ( ) of Formula (I) is a single bond, R A is CH2, and R is O (oxygen);
when the dashed line ( ) of Formula (I) is absent, RZA is selected from the group consisting of an optionally
substituted Ci_6 alkyl, an optionally substituted C2_6 alkenyl, an optionally substituted C2_6 alkynyl, an
optionally substituted C3 cycloalkyl, an optionally substituted -O-C1-6 alkyl, an optionally substituted -0-
C3_6 alkenyl, an optionally substituted -O-C3-6 alkynyl and cyano, and R3A is selected from the group consistin
of OH, -OC(=0)R"A and an optionally substituted O-linked amino acid;
N-linked amino acid and an optionally substituted N-linked amino acid ester derivative;
R1C and R2C are independently selected from the group consisting of O", OH, an
, an optionally substituted N-linked amino acid and an optionally substituted N-linked amino acid ester
derivative; or
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R2B and R are independently selected from the group consisting of an optionally substituted Ci_6 alkyl, an
optionally substituted C2-6 alkenyl, an optionally substituted C2-6 alkynyl, an optionally substituted C3-6
cycloalkyl, an optionally substituted -0-C1-6 alkyl, an optionally substituted -O-C3-6 alkenyl, an optionally
substituted -0-C3-6 alkynyl and cyano;
R4C is selected from the group consisting of OH, -OC(=0)R"c and an optionally substituted O-linked amino acid;
R6A, R7A and R8A are independently selected from the group consisting of absent, hydrogen, an optionally
substituted Ci_24 alkyl, an optionally substituted C2-24 alkenyl, an optionally substituted C2-24 alkynyl, an
optionally substituted C3-6 cycloalkyl, an optionally substituted C3-6 cycloalkenyl, an optionally substituted
aryl, an optionally substituted heteroaryl, an optionally substituted aryl(Ci_6 alkyl), an optionally substituted *-
(CR15AR16A)p-0-Ci_24 alkyl, an optionally substituted *-(CR17AR18A)q-0-
Ci_24
R6A is and R7 is absent or hydrogen; or R and R , 7/AA are taken together to form a moiety selected from the
group consisting of an optionally substituted
wherein the oxygens connected to R6A and R7A, the phosphorus and the moiety form a six-membered to ten-
membered ring system;.
R9A is independently selected from the group consisting of an optionally substituted Ci_24 alkyl, an optionally
substituted C2-24 alkenyl, an optionally substituted C2-24 alkynyl, an optionally substituted C3_6 cycloalkyl, an
optionally substituted C3_6 cycloalkenyl, NR30AR31A, an optionally substituted N-linked amino acid and an
R10A and R11A are independently an optionally substituted N-linked amino acid or an optionally substituted N-
linked amino acid ester derivative;
each R15A, each R16A, each R17A and each R18A are independently hydrogen, an optionally substituted Ci_24 alkyl
or alkoxy; R19A, R20A, R22A, R23A, R5B, R6B, R8B, R9B, R9C, R10C, R12C and R13C are independently selected from
the group consisting of hydrogen, an optionally substituted Ci_24 alkyl and an optionally substituted aryl;
R2iA R24A R7B^ Ri<m Rnc and Ri4C arg independently selected from the group consisting of hydrogen, an
optionally substituted Ci_24 alkyl, an optionally substituted aryl, an optionally substituted -0-Ci_24 alkyl and an
optionally substituted -O-aryl;
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R25A R29A RHB and R15C are independently selected from the group consisting of hydrogen, an optionally
substituted Ci_24 alkyl and an optionally substituted aryl;
R26A and R27A are independently -C≡N or an optionally substituted substituent selected from the group
consisting of C2_8 organylcarbonyl, C2_8 alkoxycarbonyl and C2_8 organylaminocarbonyl;
R28A is selected from the group consisting of hydrogen, an optionally substituted Ci_24-alkyl, an optionally
substituted C2_24 alkenyl, an optionally substituted C2-24 alkynyl, an optionally substituted C3_6 cycloalkyl and
an optionally substituted C3_6 cycloalkenyl;
R30A and R31A are independently selected from the group consisting of hydrogen, an optionally substituted
Ci_24-alkyl, an optionally substituted C2-24 alkenyl, an optionally substituted C2_24 alkynyl, an optionally
substituted C3_6 cycloalkyl and an optionally substituted C3_6 cycloalkenyl;
when is a single bond, each R and each R is independently hydrogen or halogen; and
when is a double bond, each R is absent and each R is independently hydrogen or halogen;
p and q are independently selected from the group consisting of 1, 2 and 3;

r is 1 or 2;
wherein R is an unsubstituted Ci_4 alkyl or phenyl optionally para- substituted with a halogen or methyl and
R9A is methyl ester, ethyl ester, isopropyl ester, n-butyl ester, benzyl ester or phenyl ester of an amino acid
selected from the group consisting of glycine, alanine, valine, leucine, phenylalanine, tryptophan, methionine
and proline; R3A is OH; R4A is fluoro; R5A is fluoro or hydrogen; and B1A is an unsubstituted uracil; then
R2A cannot be -OCH3;
provided that when the dashed line ( ) of Formula (I) is absent; R1A is H; R3A is OH; R4A is fluoro; R5A is fluoro;
and B1A is an unsubstituted cytosine; then R2A cannot be allenyl;
provided that when the dashed line ( ) of Formula (I) is absent; R1A is H; R3A is OH; R4A is fluoro; R5A is
hydrogen; and B1A is an unsubstituted thymine; then R2A cannot be Ci alkyl substituted with an N-amido; and
provided that when the dashed line ( ) of Formula (I) is absent; R1A is H; R3A is OH; R4A is fluoro; R5A is fluoro;
and B1A is an unsubstituted cytosine; then R2A cannot be ethynyl.
Therefore, all the claims of IN201717025098 do not offer any technological advancement
over D3 alone rendering it obvious.
iv) Obviousness of the invention wrt to D4 EP2615101B1 to Junbiao Chang
D4 discloses fluorinated and azido-substituted pyrimidine nucleoside derivatives, particularly

compounds of the formula shown below:
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Also disclosed are methods of preparation and uses for these compounds. The compounds
can be used for preparing medicaments for treating diseases such as tumors and viral
infections, and can be used separately or in combination with other medicaments. The
compounds also have effective activity against diseases such as tumors and viral infections,
while having few side effects, and thus have potential application value.
Thus, it is clear from aforesaid discussion about novelty that that D4 not only affects novelty
of the invention it also makes the invention obvious over it.
Therefore, it may be concluded that opposed application was obvious to a person practicing
in the field on its priority date given the teachings of D1,D2, D3, D4 and other cited prior art
when each is considered even alone.
The mosaicism of the prior art renders all the features of IN201717025098 completely
overlapping with the prior art not involving any inventive step and not offering any technical
advancement over existing prior art.
IN201717025098 merely reclaims the prior art, offering yet another way of producing
antivirals without any technical advancement over the prior art.
120
N4 hydroxycytidine nucleoside compound(s) and derivatives thereof covered under the
Markush claims of the impugned Patent Application being pertinently prior disclosed in D1
and D2 with a similar core structure and with broad spectrum anti-viral activity, a person of
ordinary skill in art will easily be motivated to use a pharmaceutical composition comprising
the N4 hydroxycytidine nucleoside against viral infections.
Hence, there seems to be enough motivation to the Applicant to try out activity of existing
compounds against new virus groups, with teachings available within the organization (not
even suggestions).
Further when teachings of D1, D2, D3 or D4 alone or combined, there is no burden over a
person skilled in the art to come up with invention as disclosed in IN201717025098.
Opponent further refers to D5-D8 as relevant document rendering contents of opposed

application as obvious. Since arguments using D1-D4 are enough to prove the fact that the
invention is not involving an inventive step, D5-D8 have been not discussed again for sake of
brevity and not being repetitive.
Further, attention of Learned Examiner is sought towards response to FER filed by Applicant
Annexure 1, on Sept 18, 2020 page 6, first para reading “The Applicant submits herewith
amended set of claims wherein claims have been amended to exclude compounds that are
recited in D1-D8 and are therefore believed to be novel and inventive as submitted in above
paragraph under head “Novelty and Inventive step”. Effectively, Applicant himself confesses
overlap of his invention with standing prior art in FER. Even after the amendments, which
include only removal of few variables from the main compound of the impugned invention,
the main compound still is the same which lacks novelty and inventive step as admitted by
the Applicant in response to FER. It is also obvious that adding few variables in the existing
compounds without any proved advantage of doing the same cannot make the invention
novel or inventive.
As such Opponent has proved the point of lack of novelty and inventive step wrt D1-D4 in
above paragraphs.
Therefore, the claims of impugned applications lack inventive step as per section 2(1)(ja) of
the Act and renders it non patentable. Hence the application should be rejected being obvious
121
and lacking in inventive step under Section 25(1)(e) apart from lacking novelty totally as per
Section 2(1)(l) of the IPA.
GROUND III
III) Section 25(1)(f): The subject of any claim of the complete specification is not an
invention within the meaning of this Act, or is not patentable under this Act.
It is submitted that considering all the aforesaid arguments contesting novelty of the
invention under Ground I, the invention lacks novelty as per section 2(1)(l) of the Act.
Further, considering the obviousness arguments, under Ground the invention does not involve
an inventive step as per section 2(1)(ja) of the Act, hence renders it unpatentable.
Therefore the invention does not qualify to be an invention under section 2(1)(j) of the Act
and is therefore not patentable.
Further, Opponent pleads that the contents of the opposed application attract the provisions of
Section 3 of the Indian Patents Act, 1970 and hence are non-patentable. The reasons are as
following:
a. Section 3(d):
Section 3(d) of 'the Act reads as “the mere discovery of a new form of a known
substance which does not result in the enhancement of the known efficacy of that
substance or the mere discovery of any new property or new use for a known
substance or of the mere use at a known process, machine or apparatus unless such
known process results in a new product or employs at least one new reactant’ is not
patentable under the Act.
Explanation:- For the purpose of this clause, salts, esters, ethers, polymorphs,
metabolites, pure form, particle size, isomers, mixtures of isomers, complexes,
combinations and other derivatives of known substance shall be considered to be
the same substance, unless they differ significantly in properties with regard to
efficacy.”
122
It is clear from aforesaid arguments that the compounds disclosed in opposed application are
not novel, inventive and merely an attempt to reclaim the prior art. Further, Opponent states
that the alleged Applicant has failed to demonstrate enhancement in the therapeutic efficacy
of the plethora of compounds, covered under the Markush structure, as broad spectrum
antivirals in the as filed impugned patent application over the known compounds disclosed in
said prior art documents.
D1 has disclosed the antiviral effect of the N4 hydroxycytidine nucleoside compounds on
various cell lines at active concentration of low-micromolar range on pages 184-201.
D2 has disclosed the antiviral activity of the N4 hydroxycytidine nucleoside compounds
in low micromolar range against HCV on page 131.
Learned Controller’s attention is sought to following points in the reply to FER filed by
Applicant on Sept 18, 2020:
i. Applicant has disclaimed the compounds covered under the Markush structure
of Formula (I) and in Formula IA (newly added claim 12) in the as filed
complete specification by virtue of deletion of the group ‘H’ atom from the
variable R1 in the amended claims as on record attached as Annexure 2.
Hence, the claim to compound(s) covered under the Markush structure of
Formula I or Formula IA, wherein R1 is hydrogen and provided in the
examples (shown below) as antiviral agents now stand invalid. Therefore, the
data provided by the Applicant to support the claim of improved efficacy does
not hold good.
ii. The Opponent further submits that the anti-viral activity efficacy data
provided by the alleged Applicant in the FER response pages 6 to 10
attached as Annexure 1 for the compound EIDD-1931 is confusing since
123
the Applicant has disclaimed the compound by deletion of the group ‘H’
atom from the R1 variable of Formula I (claim 1) and Formula (IA) in
newly added Claim 12.
iii. Applicant on page 6 of the FER response filed on Sept 18, 2020 first para
mentions “The Applicant submits herewith amended set of claims wherein
claims have been amended to exclude compounds that are recited in D1-
D8 and are therefore believed to be novel and inventive as submitted in
above paragraph under head “Novelty and Inventive step”. Therefore,
Applicant himself confesses that the deleted variables of the markush were
not novel and hence any data related to the same cannot be used to
establish enhance efficacy over the prior art.
iv. Applicant on page 10, first para of the response to FER refers to
“PCT/US2018/064503 (Example 33) demonstrates the efficacy of EIDD-
1931 against Togaviridae, particularly against CHIKV, EEEV, VEEV, and
WEEV.” To support its arguments of improved efficacy.
PCT/US2018/064503 by Emory University has an Indian counterpart
202017019418 published on Aug 14, 2020. Applicant is citing support
from data of application filed in 2020 during prosecution of his application
claiming priority of 2014. This is clear evidence to believe that Applicant
is trying to keep molecules of potential value always under patent
protection thus evergreening the molecule for around 10 yrs or so. This
itself defeats the purpose of inclusion of Section 3(d) of the IPA and
should be the ground alone to reject the opposed Application.
v. Applicant mentions “It is therefore incorrect to assume that because D1
compounds (as an example) treat Flaviviridae virus infection, then the
124
same compounds would be effective against other RNA virus infections,
such as those caused by MERS coronavirus, Eastern equine encephalitis
virus, and the like. Even more, it is unseemly to assume that after
structural modifications to a known antiviral compound, the modified
compound would still possess any or similar antiviral activity.”on page 4
second last para of the response Annexure 1. Applicant seems to be
contradicting his own statement when he cites his 202017019418 data to
support this application against Section 3(d) objections. This actually
opens up a question as to compounds of 202017019418 & currently
opposed application are same that the Applicant expects results of one to
be used for other or else his quoted statement is not valid. If the statement
of extrapolating results of 202017019418 is meant to be true, then same
logic applies to D1-D4 and these results could be applicable to compounds
therein, thus anticipating antiviral properties against all viral families as
attempted by Applicant. If this is the case, then compounds of D1-D4
render markush of currently opposed application as not novel only, as per
his own admission.
vi. Applicant may be tempted to revive his interest in antiviral compounds of
currently opposed application, given the pandemic, but can the data being
cited to support the claims be treated as part of specification as per section
10(4) (a) of the Indian Patent Act is left to Learned Examiner’s wise
judgement.
vii. This could be a case of double patenting by Applicant’s own admission so
either of the application should be dropped by the Applicant on his own.
125
Section 3(e):
The Opponent submits that the impugned claims 1 to 14 (as amended) fall within the ambit of
section 3(e) and hence are not patentable.
The Opponent submits that the alleged Applicant has failed to demonstrate the synergy of the
pharmaceutical composition containing the compounds covered under the Markush structure
in the amended claims. Hence, the provision of section 3(e) of the Patents Act is also
attracted. The complete specification and the claims of the impugned patent application
indicate that the pharmaceutical compounds are obtained by mere admixture resulting only in
the aggregation of the properties of the component thereof or a process of producing the
substance. There is no synergism as reflected by absence of any supporting data in the patent
application and it ought to be rejected.
Opponent humbly submits that the Applicant is merely attempting to reclaim the prior art
without establishing any efficacy or synergy over the prior art. Therefore, it should be
rejected as being under the provision of Section 3 (e) of the IPA, 1970.
Further, the Opponent has come to know that there have been concerns about similar drugs
having mutagenic (DNA damaging) properties. A previous company, Pharmasset, that had
investigated the drug's active ingredient had abandoned it. Source:
https://en.wikipedia.org/wiki/Molnupiravir . Negishi K, Harada C, Ohara Y, Oohara K, Nitta
N, Hayatsu H. 1983. N4-aminocytidine, a nucleoside analog that has an exceptionally high
mutagenic activity. Nucleic Acids Res 11:5223–5233. doi:10.1093/nar/11.15.522
In this context, Opponent has as humble submission that Applicant should be asked to submit
the safety data available else the application may attract the provisions of Section 3(b) of the
IPA, reading “an invention the primary or intended use or commercial exploitation of
126
which could be contrary public order or morality or which causes serious prejudice to
human” . While opponent is not bringing this objection right now but reserves the right to
recall this objection during the opposition proceedings while looking at the data made
available by the Applicant.
GROUND IV
IV) Section 25(1)(g): The complete specification does not sufficiently and clearly
describe the invention or the method by which it is to be performed:
It is submitted that the complete specification of the impugned patent application
contains a plurality of possibilities and no clarity as to what exactly is claimed.
It is further submitted that the alleged Applicant has failed to describe the plethora of
compounds covered under the Markush structure of the impugned claims 1 to 14 and
the anti-viral activity in the as filed complete specification.
Claims mention “pharmaceutical composition comprising a pharmaceutically
acceptable excipient” however what is actual composition and what are the excipients,
dosage etc. are not defined.
There is no supporting antiviral activity data for the kind of the breadth of antiviral
activity claimed by Applicant.
Therefore, it is submitted that the impugned claims are not sufficiently enabled by
way of description as per the requirement of section 25(1)(g) read with section 10(4)
of the Patent Act, 1970 and hence be rejected on this ground alone.
127
GROUND V
V. Section 25 (1)(i): The complete specification does not disclose or wrongly

mentions the source or geographical origin of biological material used for the
invention
The specification does not state that the source and geographical origin of the
biological materials hydrogenated castor oil or hydrogenated vegetable oil, or
mixtures used in the invention.
In view of the above serious defects in the claims and specification, all the claims are liable to
be rejected.
PRAYER
In the facts and circumstances of the case the Petitioner prays as follows:
(i) That the Patent Application No. IN201717025098 filed by the Applicant
be rejected in toto and the grant of Patent to the Applicant is refused;
(ii) That the Opponent be granted a hearing under section 25(1) read with Rule
55(1) and the Opponent be informed immediately of any response filed by
the Applicant to this Opposition;
(iii) That the Opponent be provided the Reply Statement along with evidence,
if any, filed by the Patent Applicant under Rule 55(4);
(iv) That the Opponent be granted leave to file further arguments and evidence
(rejoinder) against the impugned application of the Applicant;
(v) That the Opponent be allowed to oppose with documents and further
evidence any amendments or changes that the Applicant may make to the
Complete Specifications or claims;
(vi) For costs;
(vii) Such other and further relief/s be granted to the Opponent, as the Ld.
Controller may deem fit in the facts and circumstances of this case.
128
All communications relating to these proceedings may be sent to the
following address in India:-
Poorvashree Joshi
100, NCL Innovation Park,
Dr Homi Bhabha Rd,
Pune, Maharashtra 411008
E-mail address: poorvashree@ipface.org
Dated this 31st day of March 2021
Poorvashree Joshi
IN/PA- 4071
On behalf of Opponent
The Controller of Patents
The Patent Office, DELHI
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Molnupiravir March 31, 2021 Opposition by Entrepreneurship Development Center

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Molnupiravir March 31, 2021 Opposition by Entrepreneurship Development Center

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IN THE MATTER OF:

THE PATENTS ACT 1970,

IN THE MATTER of a Pre-grant Opposition

IN THE MATTER OF:

IN201717025098 filed on 14/07/2017, by EMORY UNIVERSITY

In the matter of:

Entrepreneurship Development Center

STATEMENT OF CASE OF THE OPPONENT

1. The Opponent herein is on behalf of Entrepreneurship Development Center, a not for

Entrepreneurship Development Center (aka Venture Center) is a DSIR

including the National Biopharma mission.

2. Entrepreneurship Development Center serves as the Nerve Center supporting the

Petitioner has real and substantial interest in the matter at hand.

HYDROXYCYTIDINE AND DERIVATIVES AND ANTI VIRAL USES RELATED

THERETO” filed by Emory University (hereinafter referred to as “Applicant”).

Formula I, or salt thereof, wherein

CLAIM 2: The pharmaceutical composition of claim 1, wherein Q-R7 is OH.

R8 is hydrogen, hydroxy, or benzyloxy, and

alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl,

or salt thereof, wherein

CLAIM 10 The pharmaceutical composition of claim 1,further comprising a propellant.

CLAIM 11 The pharmaceutical composition of claim 10, wherein the propellant is

or salt thereof, wherein

amino, mercapto, formyl, carboxy, carbanoyl, esteryl, alkoxy, (C1-

7. Accordingly, the Opponent submits their opposition by way of representation under

specification is claimed in a claim of a complete specification published on

or after priority date of the applicant's claim and filed in pursuance of an

earlier than that of the applicant's claim;

having regard to the matter published as mentioned in clause (b) or having

describe the invention or the method by which it is to be performed.

mentions the source or geographical origin of biological material used for

To oppose the application, Opponent relies on following documents:

I) Section 25(1) (b)/(c): Lack of novelty:

i) Lack of novelty in view of US 2003/0087873 to Lieven Stuyver (D1)

US 2003/0087873 discloses a composition for and a method of treating

We shall discuss in further detail as to how the disclosure of US 2003/0087873

[0114] each D is hydrogen, alkyl, acyl,

IN201717025098 D1: US 2003/0087873 A1

R8 is hydrogen, hydroxy, or benzyloxy, and

[0114] each D is hydrogen, alkyl, acyl, monophosphate,

IN201717025098 D1: US 2003/0087873 A1

Formula IB, or salts thereof, wherein

[0114] each D is hydrogen, alkyl, acyl, monophosphate,

[0116] each X1 and X2 is independently hydrogen, halogen (F,

[0117] each Y is O, S or Se;

[0119] each R1 and R1' is independently hydrogen, lower alkyl,

[0121] each R3 and R3’ independently is hydrogen or halogen

IN201717025098 D1: US 2003/0087873 A1

or salts thereof, wherein

[0117] each Y is O, S or Se;

[0119] each R1 and R1' is independently hydrogen, lower alkyl,

Thus, clearly D1 anticipates the claimed subject matter.

IN201717025098 D1: US 2003/0087873 A1

7. A pharmaceutical composition comprising a [0124]

IN201717025098 D1: US 2003/0087873 A1

IN201717025098 D1: US 2003/0087873 A1

[0114] each D is hydrogen, alkyl, acyl, monophosphate, diphosphate,

IN201717025098 D1: US 2003/0087873 A1

IN201717025098 D1: US 2003/0087873 A1

IN201717025098 D1: US 2003/0087873 A1

or salt thereof, wherein

[0178] each R9 is hydrogen, halogen (F, Cl, Br or I) or OP3;

[0319] In another sub-embodiment of the present invention, the anti-

its β-L enantiomer or its pharmaceutically acceptable salt thereof,