Pharma Patents & Environment

in Japan

Toshio Nakamura, Ph.D.

Fukami Patent Office, p.c.

February 2014
 Contents
1. Introduction

2. Japanese Patent System

3. Crystal inventions

4. Product by Process claim

5. Patent Term Extension

6. Combination Therapy

7. Pharmaceutical Regulations in Japan

2 Fukami Patent Office, p.c.

 1. Introduction
2012 was commemorated as the 60th anniversary
of the establishment of bilateral relations between
India and Japan.

Source: “Sankei News” on 5/1/2013

3 Fukami Patent Office, p.c.
 Dr. Singh:
Visited Japan for three days in May 2013 under “Look East” Policy.

Japanese Emperor Akihito & Empress Michiko:

2nd visit to India for seven days in November and December 2013.

Mr. Abe:
The chief guest at the Republic Day parade on January 26th.

Source: “Ministry of Foreign Affairs of Japan

4 Fukami Patent Office, p.c.

CEPA (Comprehensive Economic Partnership Agreement)
16/2/2011: was signed.
1/8/2011 : was enforced.
No tax will be laid on about 94% of the goods within 10 years.

Joint Declaration between the Leaders of India and Japan on 25/10/2010:

The India-Japan CEPA will develop areas of potential mutual

complementarity, further strengthen the bilateral economic
relationship, and promote economic development by increasing the
cross-border flows of goods, persons, investment and services.
It will also strengthen the foundation for the economic
development of India and Japan through closer cooperation
between the two countries in various fields.

The CEPA includes Article 54 “Cooperation on Generic Medicine”.

5 Fukami Patent Office, p.c.

 Japan is the world’s second biggest
market for pharmaceuticals,
with approximately 10% of global sales

6 Fukami Patent Office, p.c. Source: Wikimedia Commons

 2. Japanese Patent System

Golden Pavilion (Kyoto)

7 Fukami Patent Office, p.c. Source: kyoto-design.jp
 General Structure of Court System in Patent matters

Supreme Court Supreme Court

IP High Court IP High Court

Board of Appeal Board of Appeal Tokyo District Court Osaka District Court

Examiner
JPO

Patent application Request for revocation Infringement litigation

(IP High Court was established on 1/4/2005.)

8 Fukami Patent Office, p.c.
(1) Grand Panel Judgments of IP High Court
IP High Court picks up Grand Panel cases including “important legal issues”.

Not appealed
1 30/9/2005 2005(ne)10040 Indirect infringement (Flash memory)
(Final & binding)
Not appealed
2 11/11/2005 2005(gyo-ke)10042 Support requirement (Parameter claim)
(Final & binding)
Supreme Court
3 31/1/2006 2005(ne)10021 Patent exhaustion (Recycling Ink Cartridge) Judgment
(1/11/2007)
Not appealed
4 30/5/2008 2006(gyo-ke)10563 New matter (Disclaimer)
(Final & binding)
Construction of Product
5 27/1/2012 2010(ne)10043 (Pravastatin sodium) Appealed
by Process claim

6 1/2/2013 2012(ne)10015 Damage calculation (Waste storage device) Appealed

9 Fukami Patent Office, p.c.

(2) Supreme Court Judgments concerning Patents
Patent cases handed down
2010 － 1
2000 to 2009 15
1990 to 1999 18
1980 to 1989 15
1970 to 1979 19
1960 to 1969 37

< Important judgments >

(a) Parallel importation (Supreme Court, 1995(o)1988, 1/7/1997)

Parallel importation is generally allowable. However, it is not allowable if the
patent owner and the initial purchaser agree that the goods will not be sold in
Japan, and this geographic restriction is expressly stated on the goods.
(This judgment is similar to Section 107A(b) of the India Patent Act.)

10 Fukami Patent Office, p.c.

 (b) Doctrine of equivalents (Supreme Court, 1994(o)1083, 24/2/1998)
Doctrine of equivalents is affirmed if the five following requirements are
satisfied.
i) The difference is not an essential part of patent invention,
ii) Replaced product achieves the patent objectives and effects,
iii) Replacement was easily conceived by a person skilled in the art,
iv) Replaced product was not known or easily conceivable, and
v) The difference was not intentionally excluded from patent scope.

(c) Bolar exemption (Supreme Court, 1998(ju)153, 16/4/1999)

Bolar exemption is admitted.
(This judgment coincides with Section 107A(a) of the India Patent Act.)

(d) Unenforceability (Supreme Court, 1998(o)364, 11/4/2000)

Infringement court can declare unenforceability when the patent must be
invalid.

(e) Patent term extension (Supreme Court, H21(gyo hi)326, 28/4/2011)

Explain later
11 Fukami Patent Office, p.c.
 3. Crystal inventions

*) My article covering this topic

was published in “Chizai Kanri”
in January 2014

Mt. Fuji with its inverted image

12 Fukami Patent Office, p.c.
 Judgment of the Supreme Court of India
[Civil Appeal Nos. 2717-2727 of 2013, 1/4/2013]

The rejection of the invention of the b-crystal form of Imatinib

mesylate (Glivec) under Section 3(d) was finally affirmed.

Talked in this Section

The following judgments have been found in other jurisdictions,
concerning inventive step of crystal inventions of medicinal
compounds:
4 cases in Japan,
2 cases in the EPO,
2 cases in China,
4 cases in Korea.
Two criteria are deduced for assessment of inventive step from
these judgments.
13 Fukami Patent Office, p.c.
 JP case
<JP-1> Merck v JPO [IP High Court, 2006(gyo-ke)10270, 4/7/2007]
(a) Application
[Appl. No.] JP 1999-507368
[Claim 1] Form 1 crystal of “Aprepitant”.
[Effects]
Form 1 is non-hygroscopic and highly thermostable.
The ratio of the solubilities is 1.4, which indicates that Form 1 is
more stable than Form 2 by 0.2 kcal/mol.
[Example 21]
Form 1 was prepared by swirling Form 2 in isopropyl acetate,
ethanol, 2-propanol, water, aqueous methanol or acetonitrile at
25°C.

(b) Prior art (WO 95/23798)

Form 2 was prepared.

14 Fukami Patent Office, p.c.

(c) Decision
<Motivation>
It is well-known in the pharmaceutical field that many medical
compounds have polymorphs, and that polymorph-search must
usually be done.
<Production method>
Considering the solvents & conditions for recrystallization described
in the prior art, Form 1 could have been produced by a method &
condition which is normally tried when searching polymorphs.
<Effect>
Document 3 describes that the ratio of the solubilities of more than
half of 55 compounds are more than 1.4.
Thus, the ratio of the solubilities between Form 1 and Form 2 (1.4)
is not recognized as an unexpected remarkable effect.

[Conclusion] The appeal is dismissed (lack of inventive step)

15 Fukami Patent Office, p.c.

 EP case
<EP-1> T 777/08 (5/24/2011: “OJEPO 12/2011, p.633”)
[Patent] EP 1148049
[Claim 3] Form 4 of “Atrovastatin 1/2Ca 3/2H2O”.
[Effect] Shorter filtration & drying times, purity and stability.
[Prior art (WO 94/16693)] Amorphous form.
[History] The opposition division revoked the patent.
Warner-Lambert appealed.
[Decision]
At the priority date, it was well known to be advisable to screen for
polymorphs early in the drug development. Routine methods of
screening was also well known. In the absence of any technical
prejudice and in the absence of any unexpected property, mere
provision of a crystal form cannot be regarded as involving an
inventive step.
The effect against amorphous form would have been expected.

[Conclusion] The appeal is dismissed (lack of inventive step)

16
 KR case
<KR-1> Recordati v Ildong Pharmaceutical
[KR Supreme Court, 2010 fu 2865, 14/7/2011]

[Patent] KR 667687 (derived from WO 2003/014084)

[Claim 24] Form 1 of “Lercanidipine HCl”.
[Effect] Improved solubility and dissolution rate.
[Prior art] Another crystal form.
[History]
Ildong requested revocation. KIPO Board of Appeal revoked the patent.
Patent court dismissed the appeal. Recordati appealed to Supreme Ct.
[Decision]
It was well known in the pharmaceutical art that a compound can have
various crystal forms having different characteristics. Thus, screening
for polymorphs were normally done.
Therefore, without special circumstances, crystal inventions are
allowable only if they have different effects or same but remarkable
effects. This invention does not have such effects.
[Conclusion] The appeal is dismissed (lack of inventive step)
17
Summary of judgments
Special
Inventive Unexpected
Case No. Product production
step effect
method, etc.
IP High Court, 2006(gyo-ke)10270 Aprepitant
JP-1 No No No
4/7/2007 (Form 1)
Osaka District Court, 2009(wa)2208
JP-2 Cefcapene Pivoxyl HCl H 2O No No －
15/4/2010
IP High Court, 2011(gyo-ke)10445 Atrovastatin 1/2Ca 3/2H 2O
JP-3 No No No
5/12/2012 (Form 1)
IP High Court, 2011(gyo-ke)10340
JP-4 Alendronate Na 3H 2O No No (No)
30/1/2013
T 777/08 Atrovastatin 1/2Ca 3/2H 2O
EP-1 No － No
24/5/2011 (Form 4)
T1422/12
EP-2 Tigecycline Yes － Yes
11/4/2013
Supreme Court, 2011 tigyo 86
CN-1 Tiotropium Bromide H 2O No － No
6/12/2011
Beijing High Court, 2010 Kogyo 510
CN-2 Tetrabenzyl Voglibose No No No
8/11/2010
Supreme Court, 2010 fu 2865 Lercanidipine HCl
KR-1 No － No
14/7/2011 (Form 1)
Supreme Court, 2010 fu 3554
KR-2 Ibandronate Na No － No
8/9/2011
Patent Court, 2010 he 4168
KR-3 Docetaxel 3H 2O No Yes No
12/10/2011
Patent Court, 2011 he 8440
KR-4 Adefovir dipivoxil No － No
20/7/2012
 Most of the Judgments were decided by the following
two criteria for Inventive step on Crystal inventions

[Criteria 1] (Japan) Special production method.

(EPO) Technical prejudice.
(KR) Special circumstances.

[Criteria 2] Unexpected remarkable effects.

19 Fukami Patent Office, p.c.

 4. Product by Process claim

Itsukusima
Tokyo SKYTREEShrine
20 Fukami Patent Office, p.c.
 Typical Product by Process claim (PbP claim)
“Product X prepared by Process A”

In this case, any process of

Processes A to C prepare
exactly the same Product X.

How do you interpret the PbP claim in respect of “Novelty”

and “Infringement”?
21 Fukami Patent Office, p.c.
 Universal product theory Manufacturing process
limitation theory

The claim covers all of X1 to X3. The claim covers only X1.
Thus, X2 is novelty destroying. Thus, X2 is not novelty destroying.
X2 is infringing. X2 is not infringing.
22 Fukami Patent Office, p.c.
 < Comparison of PbP claim’s interpretation >

Novelty Infringment

UP MPL
US
(MPEP2113) (Abbott v. Sandoz, 2009)

UP1)
EP, UK, DE UP2)
(EP Guidelines, F, IV, 4.12)

JP UP
UP or MPL
previously (JP Guidelines, II, 2, 1.5.2(3))

1) PbP claim is acceptable, only in the case it is impossible or difficult

to directly specify the product by its structure or feature.
2) Thermoplastische Zusammensetzung, 2010 (DE);
Tetraploide Kamille, 1993 (DE)

23 Fukami Patent Office, p.c.

<Grand Panel Judgment>
Teva v. Kyowa Hakko Kirin [IP High court, 2010(Ne)10043, 27/1/2012]

(a) Claim 1 of JP 3737801

Pravastatin sodium containing less than 0.5 wt% of pravastatin lactone
and less than 0.2 wt% of epiprava,
prepared by a process comprising the steps of:
a) forming an enriched organic solution of pravastatin,
b) precipitating pravastatin as its ammonium salt,
c) purifying the ammonium salt by recrystallization,
d) transposing the ammonium salt to pravastatin sodium, and
e) isolating the pravastatin sodium. H CH 3
O CH3
O
H H
O
H CH3 HO O
H
O CH3
OH
H H H
H H O CH3
H
HO HO H H OH Pravastatin lactone
H
CO2Na H CH3
O CH3
H
CH3 HO H
O
H H HO H H OH
H
CO2Na
Pravastatin Na H

Fukami Patent Office, p.c.

CH3
24 H
Epiprava
(b) Summary of Judgment

(i) Classification of PbP claims

PbP claims are classified into two types of PbP claims, depending on
whether it is impossible or difficult to directly specify the product by its
structure or feature (“special circumstances”).
If yes, “authentic PbP claim” having a broad scope under UP theory.
If no, “unauthentic PbP claim” having a limited scope under MPL theory.

The PbP claims are interpreted similarly in assessment of both Novelty

and Infringement.

(ii) Burden of proving “special circumstances”

PbP claims are originally interpreted as “unauthentic PbP claims”.
Patentee (or applicant) shall bear the burden of proving “special
circumstances”. If he proves it, he will obtain a broader protection as an
“authentic PbP claim”.

25 Fukami Patent Office, p.c.

(c) Conclusion
The product in Claim 1 is specified sufficiently by the description of
impurities in Claim 1. Thus, it is possible to directly specify the product
by its feature.
Therefore, Claim 1 is an “unauthorized PbP claim” having a limited
scope.
Because the process is different, the patent is not infringed.

(d) Appeal to the Supreme Court

The case was appealed, and almost 2 years have passed since the
High Court judgment (27/1/2012).

Usually the Supreme Court decides within 6 months to 2 and a half

years after the High Court judgment.
We will see the Supreme Court judgment quite soon.

26 Fukami Patent Office, p.c.

 5. Patent Term Extension

Japanese monkeys in a hot spring

27 Fukami Patent Office, p.c. Source: Wikimedia Commons
 Article 67(2) of Japan Patent Law
(summarized)
Where there is a period during which the patented invention is
unable to be worked because of:
- Safety approvals prescribed by relevant Acts etc. necessary to
be obtained prior to the working of the patented invention,
the duration of the patent right may be extended, upon the filing of
a request, by a period not exceeding 5 years.

28 Fukami Patent Office, p.c.

 Japan Europe U.S.A.
Established day 1987 2.7.1992 & 23.7.1996 24.9.1984
Regulation Nos.469/2009＆1610/96
Law Article 67 (2) of Japan Patent Law 35 USC 156
(SPC, different from Patent Law)
(designated by the Cabinet Order)
Subject Medicine, Plant protection drug Medicine, Medical device, Food additive
Medicine, Plant protection drug
A patent which protects an active A patent which claims an active
A patent unable to be worked
Eligible patent ingredient etc., a method of production ingredient etc., a method of use or a
because authorization was necessary
or an application thereof method of manufacture thereof
Time limit for within 3 months within 6 months within 60 days
application from authorization from authorization etc. from authorization

[Ground of rejection of PTE] Patent term shall be extended, if

An SPC shall be granted if:
(1) the authorization was not (1) the patent term has not expired
(a) the active ingredient etc. is
necessary to work patent invention; before application of PTE;
protected by a basic patent;
(2) the patentee etc. did not obtain (2) the patent term has never been
(b) a valid authorization has been
the authorization; extended;
granted in accordance with Directive
Requirements (3) the requested period exceeds the (3) PTE application is submitted by the
2001/83 or 2001/82;
period when patnet invention was patent owner etc.;
(c) the active ingredient etc. has not
unable to be worked; (4) active ingredient etc. has been
already been the subject of an SPC;
(4) the applicant is not the patentee; subject to regulatory review period;
(d) the authorization in (b) is the first
(5) the application does not meet (5)(A) the authorization is the first
authorization.
requirement of Art. 67-2(4) authorization; (B) ... or (c) ...

One SPC for one patent owned by each

Multiple Multiple PTE available One PTE for one patent
patentee
applications for each authorization per an active ingredient
per an active ingredient
Former SPC covers the additional use
Additional use
New PTE applications available (New SPC available Former PTE covers the additional use
approved
for the second medical use patent）
Max. 5 years Max. 5 years + 0.5 year (Pediatric) Max. 5 years
Extended term
(Duration needed for authorization) (by different calculation) (by different calculation)
Authorized active ingredient etc.
Scope of Authorized product Any use authorized
for any medicinal uses authorized before
protection for authorized use for the active ingredient etc.
its expiry
(a) Supreme court, H21(gyo hi)326 (28/4/2011)(Takeda)
[History]
Board of Appeal (JPO) : Rejection under Art. 67-3(1)(i)
IP High Court : Dismissal of Rejection (PTE approved)
JPO appealed to the Supreme court

[Patented Invention]
A controlled release composition wherein a drug-containing core is
coated by a coating composition comprising:
(i) a water-insoluble substance,
(ii) a hydrophilic substance selected from … , and
(iii) a cross-linked acrylic polymer having …

[Present MA (September 2005)] [Former MA (March 2003)]

Active ingredient: Morphine HCl
Indications : Analgesia for moderate
or severe cancer pain
Formulation : Controlled-release
capsule
Active ingredient: Morphine HCl
Indications : Analgesia for moderate
or severe cancer pain
Formulation : Internal liquid

30 Fukami Patent Office, p.c.

 [Decision (relevant part)]
Even in the case where, prior to obtaining the authorization to
manufacture and sell, which was the reason for filing an application for
patent term extension, the authorization to manufacture and sell had
been granted for the former pharmaceutical product which has the Active
ingredient and Indications identical to those of the pharmaceutical
product for which the present authorization was rendered,
if the former pharmaceutical product does not fall within the technical
scope of the patented invention defined by any of the claims related to
the patent right for which an application for patent term extension was
filed, we cannot accept the position denying the argument that it was
necessary to receive the present authorization for the working of the
patented invention related to such patent right, on the grounds that the
former authorization had been already rendered.

[Conclusion] Dismissal of appeal (PTE approved)

31 Fukami Patent Office, p.c.

(b) Revision of the Examination Guidelines on 28/12/2011
The Guidelines were revised mainly regarding Art. 67-3(1)(i) as to
the necessity to obtain MA.

<Previous Guidelines>
(a) A PTE is allowable if the product (and use) approved by the present MA is
described in the claim (3.1.1(1)).
(b) When there are two or more MA in which the product (and use) is the same,
the latter MA is not necessary to work the patented invention because the
patented invention has been able to be worked by the former MA (3.1.1(1)).

<Revised Guidelines>
A ground of rejection under Art. 67-3(1)(i) arises in the following cases. (3.1.1(2))
(a) The act of manufacturing and marketing the authorized drug etc. does not
constitute an act of working the patented invention.
(b) The scope defined by the “matters falling under the matters defining the
invention (and the use)”*) of the authorized drug etc. has been able to be
worked by the former MA.
*) “Matters falling under the matters defining the invention (and the use)” is
explained in 3.1.1(1).
http://www.jpo.go.jp/tetuzuki_e/t_tokkyo_e/1312-002_e.htm
32 Fukami Patent Office, p.c.
 <Example 3>
[Patented Invention]
An analgesic injectable composition containing active ingredient A.

[Present MA]
Active ingredient: Compound a1 “Matters falling under the matters
Indications : Analgesia defining the invention”
Dosage form : Injection Compound a1, Analgesia, Injection
Dose : 10 mg
Authorized matters to be applied into the
matters defining patented invention

[Former MA 1] [Former MA 2]

No! Yes!
Active ingredient: Compound a1 Active ingredient: Compound a1
Indications : Analgesia Indications : Analgesia
Dosage form : Injection Dosage form : Tablets
Dose : 5 mg Dose : 10 mg

33 Fukami Patent Office, p.c.

 <Example 5>

[Patented Invention]
Cl. 1 An analgesic composition containing compound A as an active ingredient.
Cl. 2 The analgesic composition of claim 1, which is in the form of injection.

“Matters falling under the matters

[Present MA]
defining the invention” for Claim 1
Active ingredient: Compound a1
Compound a1, Analgesia
Indications : Analgesia
Dosage form : Injection
“Matters falling under the matters
defining the invention” for Claim 2
Compound a1, Analgesia, Injection

[Former MA] PTE will be rejected, because the above

Active ingredient: Compound a1 matters of Claim 2 are included in “the above
Indications : Analgesia matters of Claim 1 which have been able to
Dosage form : Tablets be worked by the former authorization”.
(PTE available if the invention of Claim 2 is
granted in a divisional application)
34 Fukami Patent Office, p.c.
 (c) Consideration

(1) The Examination Guidelines

i) Position of the Examination Guidelines
The Examination Guidelines do not fall under a “law norm”, and they
are the guidance describing fundamental applications of patent law
and related regulations.

ii) Comments in Judgments

[IP High Court 2009(gyo-ke)10345]
“Though Art. 67-3(1) is an important governing regulation, it includes
obscure wordings, and its interpretation is left to its relevant
enforcement ordinance, regulations, Q&A, etc.”
[IP High Court 2009(gyo-ke)10184]
“Art. 67-3(1) remains obscure wordings. Its clarification is desirable.”

Court judges do not follow the revised Examination Guidelines.

The Patent Law needs to be revised, probably in the near future.
35 Fukami Patent Office, p.c.
 (2) “Authorized product”
The scope of extended patent right is restricted by “authorized product” &
“authorized use” (Art. 68-2).
However, the Japan Patent Law does not explain what is “authorized product”,
and there have not been any actual decisions of infringement litigation in Japan.

Interpretation (a) [IP High court, No. 2006(gyo ke)10311, etc.]

“Authorized product” = Active ingredient
This was decided in consideration of legislation drafting documents for the PTE law.

Interpretation (b) [IP High court, No. 2008(gyo ke)10458, etc.]

“Authorized product” = Ingredients, dosage and structure of the medicine

Interpretation (c) [JPO’s Q&A No. 11&12 of the revised Guidelines]

“Authorized product” = Matters falling under the matters defining the invention

The scope of PTE is quite uncertain.

36 Fukami Patent Office, p.c.
(d) Decisions & Judgments after the Revision

- 59 Decisions by JPO Board of Appeal (based on 27 MAs).

- 2 Judgments by IP High Court.

There have been no decisions or judgments contradicting the Revision.

It is because all cases were appeals against rejection of PTE request,
and the JPO tends to allow PTEs broadly according to the revised
Examination Guidelines.

Once invalidation trials are requested, followed by appeals against them,

the IP High Court will decide legal acceptability of the Revision.

37 Fukami Patent Office, p.c.

 (e) “Omalizumab” case <Clerical errors>
Genentech v JPO [IP High Court, 2012(gyo-ke)10309, 30/9/2013]
(Genentech v JPO [IP High Court, 2012(gyo-ke)10268, 30/9/2013] “correction of patent”)

(1) Patent
[Patent] JP 3457962 (expired on 14/8/2012, but deemed to be extended)
[Claim 15]
An antibody comprising Fab heavy and light chain amino acid
sequences of humae11 ver.1 as set out in SEQ ID No. 8 and 9,
said heavy chain sequence being substituted at position 60 with
aspartic acid, at position 61 with proline and at position 67 with isoleucine.
[Clerical errors]
i) In SEQ ID No. 8, 125Lys and 126Gly should be deleted, and the length
“453” should be “451”.
ii) In Claim 15, 60Asp should be 60Asn.

(2) MA
“Omalizumab” for bronchial asthma, authorized on 21/1/2009.
38 Fukami Patent Office, p.c.
(3) Decision
[Error i)]
In view of the Kabat article and the common general knowledge,
Error i) could have been realized as a clerical error by a skilled person.
Thus, correction of Error i) is acceptable.
[Error ii)]
Though substitution by Asn is described many times in the specification,
“substitution by Asp at position 60” is exactly described once*).
Thus, the description of Claim 15 does not have any inconsistency, and
correction of Error ii) is not acceptable.
*) WO and EP publications do not describe Asp at all including this part.
[Conclusion]
Omalizumab is not covered by Claim 15.
PTE should be denied (remitted to the Board of Appeal)

(4) Situations in EU and USA

In EU, the corresponding EP 602126 has also Error i), but not Error ii).
SPC based on EP 602126 (Claim 7) was granted in UK.
In USA, the corresponding substance patent was not extended.
Instead, the formulation patent US 6267958 was extended.
39
 6. Combination Therapy

*) My article covering this topic

was published in “Chizai Kanri”
in December 2012

Kyoto
40 Fukami Patent Office, p.c.
Source: kyoto-design.jp
Measures for excluding doctor’s act from infringement
& its Consequences
[JP & EU]
Method of treatment is not patentable (Art. 29(1) JPL; Art. 53(c) EPC).
=> “Use-limited compound/product” is patentable.
[US]
Injunction or damages shall not apply against doctors (35 USC 287(c)).
=> “Method of treatment” is patentable.

41 Fukami Patent Office, p.c.

 In case of combination therapy?

The heart of combination therapy is “concerted action of two drugs”.

Thus, US claims directly cover the heart.
What do you claim for combination therapy under JP & EU systems?
There are three patterns of selling drugs:
(1) Tablet including two drugs
(2) Tablet including drug A (SmPC indicating combination therapy with drug B)
(3) In (2), drugs A and B are exchanged
42 Fukami Patent Office, p.c.
Approved claim in T09/81 (25/1/1983)
“Products containing an oxazaphosphorin cytostatic agent and
the sodium salt of 2-mercapto-ethane-sulphonic acid
as a combined preparation for simultaneous, separate or
sequential use in cytostatic therapy.”

Model claim in the Examination Guidelines in Japan

“A medicine for treating disease X containing active ingredients
A and B in combination.”

This kind of claims was believed in Japan as covering both

“combination drug” and “separate drugs for combination therapy” .

43 Fukami Patent Office, p.c.

Osaka District Court, No. H23 (wa) 7576 (27/9/2012)
Tokyo District Court, No. H23 (wa) 19435 (28/2/2013)
Patents : JP 3148973 & JP 3973280 (corresponding to EP 861666, etc.)
Claim 1 (JP 3148973) :
A medicine for the prophylaxis and treatment of diabetes or
diabetic complications, comprising pioglitazone and α-glucosidase
inhibitor in combination.
Accused infringers’ act :
Selling “pioglitazone” with SmPC indicating combination therapy.
Plaintiff’s argument:
They construct the claim as “A medicine containing two drugs”.
Their argument is that the accused infringers induced doctors to
produce the medicine.
Decision :
Not infringed by direct or indirect infringement.

44 Fukami Patent Office, p.c.

 Munich Appellate Court (6 U 3108/95, 1996, Germany)
Patented invention :
An oral combination drug comprising captopril and
hydrochlorothiazide or furosemide.
Accused infringers’ act :
Selling “captopril” with SmPC indicating combination therapy.

Decision :
Infringed by indirect infringement.

45 Fukami Patent Office, p.c.

 Düsseldorf District Court (4a O 12/03, 2/24/2004, Germany)
Patented invention :
Use of ribavirin for the manufacture of a pharmaceutical
composition for treating a patient having chronic Hepatitis C
infection … by a method comprising administering ribavirin
in association with interferon-α …
Accused infringers’ act :
Selling “ribavirin” with SmPC indicating combination therapy.

Decision :
Not infringed by direct or indirect infringement,
because SmPC does not describe specific patients determined in
the claim.

<My comment>
If SmPC described the specific patients, infringement would have
been acknowledged.

46 Fukami Patent Office, p.c.

CJEU judgment C-518/10 (25/11/2011)
<Art. 3(a) of Regulation No. 469/2009:“Product is protected by a basic patent”>

Patented invention (EP 667165) :

1. A therapeutic composition comprising:
(a) a monoclonal antibody …; and (b) an anti-neoplastic agent …
2. The therapeutic composition of claim 1 for separate administration
of the components.
1st MA :
[Product] “Cetuximab”
[Indication] treatment of cancer … in combination with Irinotecan.
Patentee’s argument :
Use by MA constitutes indirect or contributory infringement.

Decision :
The decision was made according to Medeva.
The SPC was denied under Art. 3(a).

47 Fukami Patent Office, p.c.

 There seems to be some confusion and ambiguity in
combination therapy patents in JP and the EU.

My recommendation
To prepare carefully claim wordings
so as to cover exactly your future product
(combination drugs, or separate drugs?).
To think about argument & claim construction
in litigation, so that the claimed invention is
divided into “product part” and “indication part”
corresponding to SmPC.
48 Fukami Patent Office, p.c.
 7. Pharmaceutical Regulations in Japan

Tokyo SKYTREE
49 Fukami Patent Office, p.c.
(1) Major Laws controlling Medicines

(a) Pharmaceutical Affairs Law

[Objectives] to improve public health
by assuring quality, efficacy and safety of drugs, etc. and
by measures to promote R&D of drugs, etc.
[Controlling] Clinical studies, Approvals, Sales, etc.

(b) Health Insurance Law

By this Law, “health insurance covers the entire population”.
Every citizen is required to join either:
i) One of the various industry-managed health insurance programs;
or
ii) the National Health Insurance.
<Reference>
“Information in English on Japanese Regulatory Affairs”, by JPMA
http://www.jpma.or.jp/english/parj/pdf/2012.pdf

50 Fukami Patent Office, p.c.

(2) Health Insurance System / Drug Pricing
(a) Universal Health Insurance

“Insurance charge” is determined depending on salary and is taken monthly.

National Health Insurance has a large deficit, so the government pays 16.4% of
all expenditures. Also the insurance charge rate is increasing.
51 Fukami Patent Office, p.c.
 (b) National Health Expenditure
¥1
兆円trillion ％
40 12.0

¥ 37.4 trillion in 2010. 35

ca. 25% cover drug costs. 10.0

(Rs.1=¥1.7)

Ratio per National Income & Ratio per GDP

30

National Health Expenditure

8.0 対
国
25 内
国 総
民 Ratio per National Income
対国民所得(NI)比率 生
医 産
比
Ministry of Health, Labour and 療 20
費
6.0 率
・
Welfare (MHLW) wants to 対
国
stop this increase of the 15 民
所
national health expenditure. 4.0 得
比
率
10
For this purpose they are
running a campaign for the Ratio per GDP
対国内総生産(GDP)比率 National Health
国民医療費 Expenditure 2.0
use of generic drugs. 5

0 0.0
1955
30 1960
35 1965
40 1970
45 1975
50 1980
55 1985
60 1990
2 19957 2000
12 200517 2010
22
52 Fukami Patent Office, p.c. 昭和・・年度 Source: website of MHLW
平成・年度
 (c) Generic Share in Japan

% (Volume)
% (Value)

Sep. 2005 Sep. 2007 Sep. 2009 Sep. 2011

Source: website of Ministry of Health, Labour and Welfare

The generic share in Japan is much lower than in the

US (approx. 70%) and EU (approx. 60%).
But, the share is steadily increasing.

53 Fukami Patent Office, p.c.

(d) Prescription drug pricing system

(i) Determination of drug prices when approved

Almost all prescription drugs are covered by Health Insurance.

MHLW determines the prices of such prescription drugs under a
reference system, based on comparison to similar marketed drugs,
safety, effectiveness, innovativeness, etc.

As an exception, there are a few drugs not covered by Health

Insurance (e.g. Viagra).
The prices for these drugs can be determined by the company itself.

54 Fukami Patent Office, p.c.

(ii) Re-evaluation (Reduction) of drug price

Normally every two years, MHLW reevaluates the

price. They reduce the price if there is a big
difference between the MHLW-determined price and
the market price. Average reduction
of drug prices
In 2010 and 2012, they focused on “creativity and 1990 -9.20%
patent”. Prices of creative patented drugs were 1992 -8.10%
maintained, but prices of patent-expired drugs were 1994 -6.60%
reduced in 2012: 1996 -6.80%
Actemra (tocilizumab) / Chugai : - 25% 1997 -3.00%
Aricept (donepezil) / Eisai : - 16.7% 1998 -9.70%
Pariet (rabeprazole) / Eisai : - 15.3% 2000 -7.00%
Lipitor (atorvastatin) / Asteras & Pfizer : - 11.3% 2002 -6.30%
2004 -4.20%
In April 2014, they will introduce an “exceptional reduction” 2006 -6.70%
for drugs for which more than 5 years have passed since
2008 -5.20%
generic entries, depending on generic shares:
2010 -5.75%
60% or less (1.5% down);
2012 -6.40%
40% or less (1.75% down);
Source: website of MHLW
20% or less (2% down)
55 Fukami Patent Office, p.c.
(3) Approval Procedures

a) Brand Name Drugs

(i) Timing
4 times per year, brand name drugs are approved and their prices
are listed (March, June, September & December).
(ii) Patent list
List of substance patents & use patents must be described in the
application for approval.
(Partially similar to “Orange Book”)

56 Fukami Patent Office, p.c.

b) Generic Drugs

(i) Timing
Twice per year, generic drugs are approved (February & August) and
their prices are listed (June & December).

(ii) Relation with patents

<Substance patents>
Generic drugs are not approved.
<Use patents>
In the case an indication is partially covered by a use patent, generic
drugs can be approved excluding the indication covered by the use
patent.
(changed by MHLW’s Notice on 5/6/2009)
<Crystal patents>
Generic drugs containing the ingredient in another crystal form can be
approved.
(changed by MHLW’s Notice on 16/6/2011)

57 Fukami Patent Office, p.c.

 (iii) Negotiation procedures between brand and generic companies

After approval of a generic drug, negotiation of patent matters, etc.

between the brand company and the generic company is required.
Both companies need to report the result to the MHLW prior to listing
the price of the generic drug, and then the price is listed.

Sometimes, both companies reach an agreement, but in most of the

cases, not. Even in such case, the MHLW provides permission
generally as far as both companies report in detail what and how they
discussed.

[Chugai’s announcement on 19/2/2013]

3 generic companies started to sell a maxacalcitol generic drug, though
negotiation on a method patent for manufacturing “maxacalcitol” was not
reached. So, Chugai initiated litigation for an injunction on 19/2/2013.

58 Fukami Patent Office, p.c.

(4) Drug re-examination system
Corresponding to “Data Exclusivity”

Under the drug re-examination system, the brand company must

continue to collect efficacies and side-effects data during a certain
period after launch.
Application for generic drugs can not be filed during such period.

10 years: Orphan drugs, Drugs requiring longer re-examination period.

8 years: Drug containing a new chemical ingredient.
6 years: New combination drug, Drug by new administration route.
4 years: Drug for new indication, Drug with new dosage/administration.

The re-examination period may be extended up to 10 years,

if clinical studies for pediatric use are planned.

59 Fukami Patent Office, p.c.

 Thank you for your attention.

Please contact me if you have questions.

E-mail: nakamura-to@fukamipat.gr.jp
http://www.fukamipat.gr.jp/english/

60 Fukami Patent Office, p.c.