Illumina Vs Natera IPR2019-01201 Institution

Trials@uspto.
gov Paper 19
571-272-7822 Entered: December 18, 2019
UNITED STATES PATENT AND TRADEMARK OFFICE
____________
BEFORE THE PATENT TRIAL AND APPEAL BOARD

____________
ILLUMINA, INC.,
Petitioner,
v.
NATERA, INC.,
Patent Owner.
____________
IPR2019-01201
Patent 8,682,592 B2
____________
Before GRACE KARAFFA OBERMANN, SUSAN L. C. MITCHELL, and

CYNTHIA M. HARDMAN, Administrative Patent Judges.
HARDMAN, Administrative Patent Judge.
DECISION
Granting Institution of Inter Partes Review
35 U.S.C. § 314
Denying Without Prejudice Petitioner’s Motion to Seal
37 C.F.R. § 42.54
IPR2019-01201
Patent 8,682,592 B2
I. INTRODUCTION
Illumina, Inc. (“Petitioner”) filed a Petition for an inter partes review
of claims 1–27 of U.S. Patent No. 8,682,592 B2 (“the ’592 Patent,”
Ex. 1001). Paper 1 (“Pet.”). Natera, Inc. (“Patent Owner”) filed a
Preliminary Response to the Petition. Paper 7 (“Prelim. Resp.”). With our
authorization (Paper 11), Petitioner filed a Reply, and Patent Owner filed a
Sur-Reply. Paper 13 (“Reply”); Paper 18 (“Sur-Reply”). Under 37 C.F.R.
§ 42.4(a), we have authority to determine whether to institute review.
An inter partes review may not be instituted unless the information
presented in the Petition and the Preliminary Response shows “there is a
reasonable likelihood that the petitioner would prevail with respect to at
least 1 of the claims challenged in the petition.” 35 U.S.C. § 314(a) (2018).
Based on the information presented by the parties, for the reasons
explained below, we institute an inter partes review as to all challenged
claims and on all grounds raised in the Petition.
Real Parties-in-Interest
Petitioner and Patent Owner each identify themselves as the real
parties-in-interest. Pet. 69; Paper 6 (Patent Owner’s Updated Mandatory
Notices), 1.
Related Matters
According to the parties, the ’592 Patent is at issue in a co-pending
litigation entitled Illumina, Inc. v. Natera, Inc., United States District Court
for the Northern District of California, Case No. 18-cv-01662. Pet. 69;
Paper 6 (Patent Owner’s Updated Mandatory Notices), 1.
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The ’592 Patent and Illustrative Claim

The ’592 Patent, entitled “System and Method for Cleaning Noisy
Genetic Data from Target Individuals Using Genetic Data from Genetically
Related Individuals,” generally relates to
the field of acquiring, manipulating and using genetic data for
medically predictive purposes, and specifically to a system in
which imperfectly measured genetic data is made more precise
by using known genetic data of genetically related individuals,
thereby allowing more effective identification of genetic
irregularities that could result in various phenotypic outcomes.
Ex. 1001, 1:23–29. According to the Specification, “to make accurate
phenotypic predictions[,] high quality genetic data is critical.” Ex. 1001,
8:15–17. Yet, in the case of prenatal or pre-implantation genetic diagnoses,
“a complicating factor is the relative paucity of genetic material available.”
Ex. 1001, 8:17–19. The ’592 Patent discloses methods that
make use of imperfect knowledge of the genetic data of the
mother and the father, together with the knowledge of the
mechanism of meiosis and the imperfect measurement of the
embryonic DNA, in order to reconstruct, in silico, the
embryonic DNA at the location of key SNPs [single nucleotide
polymorphisms] with a high degree of confidence.
Ex. 1001, 8:45–50.
In one embodiment, once fetal or embryonic genetic data has been
measured, it “can be used to detect if the cell is aneuploid, that is, if fewer or
more than two of a particular chromosome is present in a cell.” Ex. 1001,
8:67–9:2. “A common example of this condition is trisomy-21, which gives
rise to Down syndrome.” Ex. 1001, 9:2–4. The Specification states that
“[t]his is done by creating a set of hypotheses about the potential states of
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the DNA, and testing to see which one has the highest probability of being
true given the measured data.” Ex. 1001, 9:7–10.
Claim 1, the only independent claim of the ’592 Patent, is illustrative
and is reproduced below:
1. An ex vivo method for determining a number of copies of a

chromosome or chromosome segment of interest in the genome
of an individual, the method comprising:
using a single nucleotide polymorphism (SNP)
genotyping array or high throughput DNA sequencing to
measure genetic material and produce genetic data for
some or all possible alleles at a plurality of at least 100
loci on the chromosome or chromosome segment of
interest in the individual, wherein the genetic data is
noisy due to a small amount of genetic material from the
individual; and wherein the small amount of genetic
material from the individual is from fifty or fewer of the
individual’s cells, 0.3 ng or less of the individual’s DNA,
extracellular DNA from the individual found in maternal
blood, or combinations thereof;
creating a set of one or more hypotheses specifying the
number of copies of the chromosome or chromosome
segment of interest in the genome of the individual;
determining, on a computer, the probability of each of
the hypotheses given the produced genetic data; and
using the probabilities associated with each hypothesis
to determine the most likely number of copies of the
chromosome or chromosome segment of interest in the
genome of the individual.
Ex. 1001, 62:39–62.
Asserted Prior Art and Grounds of Unpatentability
Petitioner challenges the patentability of claims 1–27 of the ’592
Patent on the following grounds:
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Claim(s) Challenged 35 U.S.C. § References

1–12, 15–17, 19–23, 27 1031 Dhallan 2
18 103 Dhallan, Bianchi3
24–26 103 Dhallan, Sham4
1–27 103 Rabinowitz5
Pet. 9. The Petition is supported by the declaration of David Peters, Ph.D.

Ex. 1004 (“Peters Decl.”).
II. ANALYSIS
Discretionary Denial
Institution of an inter partes review is discretionary, not mandatory.
See Cuozzo Speed Techs., LLC v. Lee, 136 S. Ct. 2131, 2140 (2016) (“[T]he
agency’s decision to deny a petition is a matter committed to the Patent
Office’s discretion.”); Harmonic Inc. v. Avid Tech., Inc., 815 F.3d 1356,
1367 (Fed. Cir. 2016) (“[T]he PTO is permitted, but never compelled, to
1
The Leahy-Smith America Invents Act, Pub. L. No. 112-29, 125 Stat. 284
(2011) (“AIA”), included revisions to 35 U.S.C. § 103 that became effective
after the filing of the application that led to the ’592 Patent. Therefore, we
apply the pre-AIA version of 35 U.S.C. § 103.
2
Dhallan, US 2004/0137470 A1, published July 15, 2004 (Ex. 1002).
3
Bianchi, Fetal Cells in the Maternal Circulation: Feasibility for
Prenatal Diagnosis, 105(3) BR. J. HAEMATOL. 574–83 (1999) (Ex. 1034).
4
Sham et al., DNA Pooling: A Tool for Large-Scale Association
Studies, 3(11) NAT. REV. GENET. 862–71 (2002) (Ex. 1021).
5
Rabinowitz et al., US 2007/0184467 A1, published Aug. 9, 2007 (Ex.
1003).
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institute an IPR proceeding.”). The parties briefed whether institution

should be denied due to duplication with the co-pending litigation, and/or
because the same or substantially the same prior art or arguments were
previously presented to the Office. See Reply 1–4; Sur-Reply 1–3; Prelim.
Resp. at, e.g., 37. We address these arguments in turn.
1. Discretionary Denial Under 35 U.S.C. § 314(a)
As noted above, the ’592 Patent is at issue in a co-pending district
court litigation. See supra Section I.B. Patent Owner argues that instituting
this IPR would be inefficient because the same invalidity issues presented
here will be presented to the district court, and because the district court
litigation will be resolved months prior to issuance of any final written
decision here. Sur-Reply 2–3. Petitioner argues that the IPR and litigation
are not co-extensive with respect to the claims and prior art at issue, and that
both the trial date and arguments that will be the subject of trial are
speculative at this stage. Reply 2–4.
The decision whether to exercise discretion to deny institution is
based on “a balanced assessment of all relevant circumstances in the case,
including the merits.” Patent Trial and Appeal Board Consolidated Trial
Practice Guide (Nov. 2019) (“Consolidated Trial Practice Guide”), available
at https://www.uspto.gov/sites/default/files/documents/tpgnov.pdf, at 58
(citing General Plastic Indus. Co. v. Canon Kabushiki Kaisha, IPR2016-
01357, Paper 19 at 15 (PTAB Sept. 6, 2017) (precedential)). Those
circumstances include “events in other proceedings related to the same
patent, either at the Office, in district courts, or the ITC.” Id. When
considering the impact of parallel litigation in a decision to institute, the
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Board seeks, among other things, to minimize the duplication of work by

two tribunals to resolve the same issue. See NHK Spring Co. v. Intri-Plex
Techs. Inc., IPR2018-00752, Paper 8 at 19–20 (PTAB Sept. 12, 2018)
(precedential).
We have considered the positions of the parties and find that, on this
record, considerations of efficiency, fairness, and the merits of the grounds
in the Petition do not weigh in favor of denying the Petition. See General
Plastic, at 18 (stating that discretionary denial factors should assess
efficiency and fundamental fairness).
As to efficiency, the claims at issue are not coextensive between this
IPR and the district court litigation. The Petition challenges the validity of
all 27 claims of the ’592 Patent, whereas claims 6, 10–14, 16, and 18 are not
at issue in district court. Reply 2; see also Facebook, Inc. v. Blackberry
Ltd., IPR2019-00899, Paper 15 at 12 (Oct. 8, 2019) (discretionary denial
disfavored where the petition challenged additional claims beyond those
reviewed by the district court); Huawei Device Co. v. Optis Wireless Tech.,
LLC, IPR2018-00653, Paper 27 at 11–12 (PTAB Mar. 13, 2019) (same);
Puma North Am., Inc. v. Nike, Inc., IPR2019-01043, Paper 8 at 9–10 (PTAB
Oct. 31, 2019) (same). Accordingly, even if the district court litigation goes
to trial prior to the Board reaching a final decision on this Petition, and the
trial addresses validity of the ’592 Patent claims, the trial would address only
a subset of the claims challenged in this Petition. Reply 2. We are
persuaded by Petitioner’s argument that denial of the Petition could cause
Petitioner harm because Patent Owner could later assert the additional
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claims against Petitioner or its customers, yet Petitioner would be time-

barred from bringing a later IPR on these claims. Reply 2.
Patent Owner responds that Petitioner’s “speculation as to potential
future harm” regarding potential assertion of the non-asserted claims does
not justify institution. Sur-Reply 3. We find, however, that the cases on
which Patent Owner relies to support this argument are inapposite. In both
cases, unlike here, the Board specifically noted that the petitioner had not
asserted any prejudice if an IPR were not instituted on the non-overlapping
claims. See Next Caller Inc. v. TRUSTID, Inc., IPR2019-00961, Paper 10 at
14 (PTAB Oct. 16, 2019) (“[N]or does Next Caller argue whether it would
be harmed if we do not institute on the non-overlapping claims.”); PayPal,
Inc. v. IOENGINE, LLC, IPR2019-00884, Paper 22 at 12 (PTAB Oct. 3,
2019) (“Petitioner has not argued that it will be prejudiced if trial is not
instituted on the non-overlapping claims.”).
Additionally, on this record, it is not clear that the invalidity
arguments at issue are coextensive between this IPR and the district court
litigation. Although it appears that the Dhallan reference is at issue in both
proceedings, Petitioner asserts that “the litigation contains no Rabinowitz
ground.” Reply 3. Patent Owner does not dispute this, but argues that the
Rabinowitz-based ground “depends entirely on a priority challenge—one
which [Illumina’s] invalidity contentions indicate it plans to raise at trial.”
Sur-Reply 3 (citing Ex. 2011, 3–4). On this record, however, we cannot
determine whether the priority challenges Illumina intends to raise in the
district court are the same as those it has raised here, because the cited pages
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of Illumina’s amended preliminary invalidity contentions do not detail the

basis for the priority challenge. See Ex. 2011, 3–4.
As to fairness, Petitioner was diligent in filing the present Petition,
doing so several months before the statutory deadline and in response to the
’592 Patent being added to the litigation in an Amended Complaint. Reply 3
(citing Ex. 1025 at 1). Patent Owner does not allege unfairness or assert that
Petitioner delayed filing its Petition to gain a strategic advantage. Sur-Reply
2–3.
As to the merits, as explained in detail below, we find the strength of
the merits on the present record outweighs relatively weaker countervailing
considerations of efficiency. See Comcast Cable Commc’ns, LLC v. Rovi
Guides, Inc., IPR2019-00231, Paper 14 at 11 (PTAB May 20, 2019) (finding
the merits sufficiently strong to weigh in favor of not denying institution
based on § 314(a)); see also Facebook, Inc. v. Blackberry Ltd., IPR2019-
00941, Paper 11 at 15 (PTAB Dec. 4, 2019) (same).
We acknowledge that pursuant to the current scheduling order in the
district court, a jury trial is scheduled to begin on July 7, 2020,
approximately five months before any final written decision is due in this
proceeding. See Reply 3; Sur-Reply 2. On this record, however, we find
that the other factors discussed above outweigh the timing issue. In contrast
to NHK, in which the panel found that the district court would conclude first
and would analyze the same issues as the Board (NHK, Paper 8 at 19–20),
here the district court litigation involves fewer claims and, at least in part,
different prior art. Further, as will be discussed below, unlike in NHK, the
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same prior art and arguments have not been previously presented to the
Office.
2. Discretionary Denial Under 35 U.S.C. § 325(d)
Under 35 U.S.C. § 325(d), in determining whether to institute inter
partes review, “the Director may take into account whether, and reject the
petition or request because, the same or substantially the same prior art or
arguments previously were presented to the Office.” 35 U.S.C. § 325(d)
(2018).
In evaluating whether to deny institution based on 35 U.S.C. § 325(d),
the Board considers the following non-exclusive factors: (a) the similarities
and material differences between the asserted art and the prior art involved
during examination; (b) the cumulative nature of the asserted art and the
prior art evaluated during examination; (c) the extent to which the asserted
art was evaluated during examination, including whether the prior art was
the basis for rejection; (d) the extent of the overlap between the arguments
made during examination and the manner in which Petitioner relies on the
prior art or Patent Owner distinguishes the prior art; (e) whether Petitioner
has pointed out sufficiently how the Examiner erred in its evaluation of the
asserted prior art; and (f) the extent to which additional evidence and facts
presented in the petition warrant reconsideration of prior art or arguments.
Becton, Dickinson & Co. v. B. Braun Melsungen AG, IPR2017-01586, Paper
8 at 17–18 (PTAB Dec. 15, 2017) (precedential).
Here, Petitioner contends that during prosecution, the Examiner did
not issue any rejections over Dhallan or Rabinowitz, the art asserted against
the challenged claims here. Reply 1. Patent Owner does not dispute this,
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but asserts that Becton, Dickinson factors (a), (b), and (d) favor denial
because “the Petition relies on art similar to and cumulative of that used in
examination.” Sur-Reply 1. Patent Owner asserts that, during prosecution,
the Examiner rejected the claims over a combination of two references, Zhao
and Findlay. See Prelim. Resp. 6–7. In response to that rejection, the
applicants argued that a skilled artisan would not have been motivated to
modify Zhao to use a small amount of genetic material, and “would not have
had a reasonable expectation of success from such a modification.” Ex.
2002 (Response to Non-Final Office Action), 17. The Examiner agreed,
concluding that “Applicants have shown that one of ordinary skill in the art
would not have had a reasonable expectation of success in combining the
prior art.” Ex. 2003 (Notice of Allowance), 2.
Patent Owner has not demonstrated how the combination of Zhao and
Findlay is similar to or cumulative of either Dhallan or Rabinowitz. Indeed,
in the Preliminary Response, Patent Owner acknowledges that Zhao “does
not disclose the use of a small amount of genetic material” as recited in the
claims, while conceding that Dhallan does “recite[] the possibility of using
extracellular or ‘free fetal DNA,’” which qualifies as a small amount of
genetic material. Prelim. Resp. 6, 39. Nor does the record suggest that
Findlay teaches this limitation as the Findlay reference was not made of
record in this proceeding. This distinction alone undercuts any argument
that Dhallan is cumulative of the combination of Zhao and Findlay
addressed during prosecution.
The thrust of Patent Owner’s § 325(d) argument is that “the Examiner
already decided a substantive contention essential to Illumina’s petition,”
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namely, “whether one of ordinary skill in the art would have had a
reasonable expectation of success in using a ‘small amount of genetic
material.’” Sur-Reply 1. We agree with Patent Owner that the Examiner
cited a lack of reasonable expectation of success in allowing the claims. See
Ex. 2003 (Notice of Allowance), 2. Nevertheless, on this record, we are
unable to conclude that the Petition presents the same question of reasonable
expectation of success already analyzed by the Examiner. As noted above,
Dhallan teaches that its method can be used with small amount of DNA—a
teaching that Patent Owner acknowledges was absent from Zhao. See, e.g.,
Ex. 1002 (Dhallan) ¶¶ 168–69. Additionally, in arguing reasonable
expectation of success, the Petition relies on arguments and evidence that
were not before the Examiner, including, for example, a disclosure in
Dhallan that states “a minimal amount of template DNA is not limiting for
the number of loci that can be detected.” Pet. 31 (quoting Ex. 1002 ¶ 270);
see also Pet. 31–33. Given the different records here and during
prosecution, we cannot conclude that the same or substantially the same
prior art or arguments previously were presented to the Office. Thus, we
disagree with Patent Owner that Becton, Dickinson factors (a), (b), and (d)
favor denial, because we are not persuaded that the Petition relies on art
similar to and cumulative of that used during prosecution.
Patent Owner additionally argues that Petitioner has not
demonstrated that the Examiner erred (factor (e)), or explained why its
“new evidence and arguments” warrant reconsideration of the Examiner’s
conclusion. Sur-Reply 1–2. We are not persuaded by these arguments,
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because as discussed above, we are not persuaded that the Petition seeks to
revisit the same issues already decided by the Examiner.
In sum, given that the co-pending litigation is not coextensive with the
claims or arguments presented in this IPR, and that the Examiner did not
analyze the same or substantially the same prior art or arguments used in the
Petition, we decline to exercise our discretion under 35 U.S.C. §§ 314(a) or
325(d) to deny institution.
Person of Ordinary Skill in the Art
In determining the level of skill in the art, we consider the type of
problems encountered in the art, prior art solutions to those problems, the
rapidity with which innovations are made, the sophistication of the
technology, and the educational level of active workers in the field. See
Custom Accessories, Inc. v. Jeffrey-Allan Indus., Inc., 807 F.2d 955, 962
(Fed. Cir. 1986).
Petitioner contends that a person of ordinary skill in the art as of the
relevant date would have
been a member of a team of scientists developing genetic
techniques to collect and analyze genetic data. The POSA
[person of ordinary skill in the art] would have had an M.D. or
master’s or Ph.D. in molecular biology, genetics,
bioinformatics, or a related field, and, through either education
or work experience, 2-3 years of experience with nucleic acid
sequencing, sample preparation, and prenatal diagnostics.
Pet. 6. Patent Owner “disputes the level of ordinary skill proposed in the
Petition,” but neither explains the basis for its dispute, nor advances a
different level of ordinary skill in the art. Prelim. Resp. 7. Nor does Patent
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Owner aver that adopting a different definition would alter the outcome of
this Decision.
Because Petitioner’s proposed definition is consistent with the cited
prior art, we apply it for purposes of this Decision. See also Okajima v.
Bourdeau, 261 F.3d 1350, 1355 (Fed. Cir. 2001) (explaining that specific
findings regarding ordinary skill level are not required “where the prior art
itself reflects an appropriate level and a need for testimony is not shown”
(quoting Litton Indus. Prods., Inc. v. Solid State Sys. Corp., 755 F.2d 158,
163 (Fed. Cir. 1985))). Any final determination pertaining to the level of
ordinary skill in the art will be made on the full trial record.
Claim Construction
We interpret a claim “using the same claim construction standard that
would be used to construe the claim in a civil action under 35 U.S.C.
282(b).” 37 C.F.R. § 42.100(b) (2018). Under this standard, we construe
the claim “in accordance with the ordinary and customary meaning of such
claim as understood by one of ordinary skill in the art and the prosecution
history pertaining to the patent.” Id.
Petitioner asserts that “[n]o term requires express construction in this
proceeding.” Pet. 5. Patent Owner does not address claim construction in
the Preliminary Response.
On this record, for purposes of this Decision, we agree with Petitioner
that no claim term requires express construction. See Nidec Motor Corp. v.
Zhongshan Broad Ocean Motor Co., 868 F.3d 1013, 1017 (Fed. Cir. 2017)
(“[W]e need only construe terms ‘that are in controversy, and only to the
extent necessary to resolve the controversy.’” (quoting Vivid Techs., Inc. v.
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Am. Sci. & Eng’g, Inc., 200 F.3d 795, 803 (Fed. Cir. 1999))). To the extent
any claim term requires discussion, however, we provide it in our analysis of
the asserted grounds of unpatentability.
Obviousness of Claims 1–12, 15–17, 19–23, and 27 Over Dhallan
“In an [inter partes review], the petitioner has the burden from the
onset to show with particularity why the patent it challenges is
unpatentable.” Harmonic Inc., 815 F.3d at 1363 (citing 35 U.S.C.
§ 312(a)(3) (requiring inter partes review petitions to identify “with
particularity . . . the evidence that supports the grounds for the challenge to
each claim”)). This burden of persuasion never shifts to the patent owner.
See Dynamic Drinkware, LLC v. Nat’l Graphics, Inc., 800 F.3d 1375, 1378
(Fed. Cir. 2015) (discussing the burden of proof in inter partes review).
A claim is unpatentable under 35 U.S.C. § 103(a) if the differences
between the subject matter sought to be patented and the prior art are such
that the subject matter as a whole would have been obvious at the time the
invention was made to a person having ordinary skill in the pertinent art.
KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 406 (2007). The question of
obviousness is resolved on the basis of underlying factual determinations
including: (1) the scope and content of the prior art; (2) any differences
between the claimed subject matter and the prior art; (3) the level of ordinary
skill in the art; and (4) objective evidence of nonobviousness. Graham v.
John Deere Co., 383 U.S. 1, 17–18 (1966). An obviousness determination
requires finding “a motivation to combine accompanied by a reasonable
expectation of achieving what is claimed in the patent-at-issue.” Intelligent
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Bio-Sys., Inc. v. Illumina Cambridge Ltd., 821 F.3d 1359, 1367 (Fed. Cir.
2016).
Petitioner asserts that claims 1–12, 15–17, 19–23, and 27 are
unpatentable as obvious over Dhallan. Pet. 11. Based on the current record,
we determine that Petitioner has established a reasonable likelihood that it
would prevail on this challenge with respect to the identified claims.
1. Overview of Dhallan (Exhibit 1002)
Dhallan, entitled “Methods for Detection of Genetic Disorders,”
discloses “a rapid, non-invasive method for determining the sequence of
DNA from a fetus,” which method “is especially useful for detection of
chromosomal abnormalities in a fetus,” including “monosomies, trisomies,
and other aneuploidies.” Ex. 1002 ¶ 3. Dhallan discloses that in one
embodiment, the method comprises
quantitating the relative amount of the alleles at a heterozygous
locus of interest, where the heterozygous locus of interest was
previously identified by determining the sequence of alleles at
a locus of interest from template DNA, wherein said relative
amount is expressed as a ratio, and wherein said ratio indicates
the presence or absence of a chromosomal abnormality.
Ex. 1002 ¶ 42. Dhallan states:
For example, this method is useful for detecting chromosomal
abnormalities. The ratio of alleles at a heterozygous site is
expected to be about 1:1 (one A allele and one G allele).
However, if an extra chromosome is present the ratio is
expected to be about 1:2 (one A allele and 2 G alleles or 2 A
alleles and 1 G allele).
Ex. 1002 ¶ 826.
Dhallan’s Example 14 reports an experiment that was designed to
“recapitulate the in vivo scenario of blood from a pregnant female.” Ex.
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1002 ¶ 2157. Dhallan discloses that maternal DNA was mixed with DNA
isolated from her child, who previously had been diagnosed with Trisomy
21, in various ratios to represent varying percentages of fetal DNA. Ex.
1002 ¶ 2157. Dhallan discloses that in each of the maternal and child blood
samples, a total of 768 SNPs on chromosome 13 and 768 SNPs on
chromosome 21 were genotyped. Ex. 1002 ¶¶ 2166–83, 2196–97. Dhallan
discloses that SNPs homozygous for the maternal DNA and heterozygous
for the child DNA were further analyzed using samples that contained
mixtures of maternal DNA and child DNA. Ex. 1002 ¶¶ 2198–2200.
Dhallan discloses that the allele ratio at each heterozygous SNP was
calculated by dividing the value obtained for allele 1 by the value obtained
for allele 2, e.g., “if SNP X can either be adenine (A) or guanine (G), the
ratio at SNP X was calculated by dividing the value obtained for adenine by
the value obtained for guanine.” Ex. 1002 ¶ 2201.
Dhallan discloses that samples containing 100% Down syndrome
DNA, 75% Down syndrome DNA, 50% Down syndrome DNA, and 40%
Down syndrome DNA were tested. Ex. 1002 ¶ 2200. Dhallan notes that for
the sample containing 100% Down syndrome DNA, 62 SNPs on
chromosome 13 and 49 SNPs on chromosome 21 were analyzed. Ex. 1002
¶¶ 2202–06. Dhallan reports that the average ratio of allele 1 to allele 2 on
chromosome 13 was approximately 1.0, whereas the average ratio for
chromosome 21 was found to be 0.531, in line with expectations. Id.
Dhallan states that “[s]tatistical analysis revealed a confidence value of
99.9% that the ratios obtained on chromosome 13 and on chromosome 21
represented true differences, rather than random numerical fluctuations in
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value.” Ex. 1002 ¶ 2206. Dhallan notes that the ratios obtained upon
analysis of the 75% Down syndrome DNA, 50% Down syndrome DNA, and
40% Down syndrome DNA samples similarly matched the expected ratios.
Ex. 1002 ¶¶ 2207–23.
Dhallan discloses that the method can be used with DNA obtained
from various sources, including from a single-cell of an embryo or from fetal
DNA obtained from maternal blood. Ex. 1002 ¶¶ 167–69. Dhallan teaches
use of commercially available SNP genotyping arrays for producing genetic
data. Ex. 1002 ¶ 43.
2. Claim 1
Petitioner argues that Dhallan is directed to a non-invasive method of
detecting chromosomal abnormalities. Pet. 11 (citing Ex. 1002, Abstract).
The method includes “determining alleles at a locus of interest and
quantitating a ratio for the alleles at the locus, where the ratio indicates the
presence or absence of a chromosomal abnormality.” Id. According to
Petitioner, Dhallan hypothesizes that an individual with a normal number of
chromosomes will have a balanced ratio of alleles, indicating an equal
number of copies of maternal and paternal chromosomes. Pet. 11.
However, where an individual has trisomy 21, Dhallan hypothesizes that an
imbalanced ratio of alleles is expected, reflecting an extra copy of the
chromosome. Pet. 11–13.
Petitioner argues that Dhallan’s Example 14 is a “proof-of-principle
experiment for detecting chromosome 21 trisomy in different samples.”
Pet. 12; see also supra Section II.D.1 (discussing Dhallan’s Example 14).
Petitioner asserts that following “[t]esting the DNA of a Down syndrome
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individual, Dhallan determined the average ratio for heterozygous SNPs

measured on chromosome 21 as 0.531, consistent with the hypothesis that
there is an extra copy of chromosome 21 in that individual.” Pet. 13 (citing
Ex. 1002 ¶ 2204). Petitioner further asserts that “Dhallan determined the
probability (confidence interval) that this hypothesis represents a true
aneuploidy, as opposed to ‘random numerical fluctuations in value,’” and
“concluded that the method accurately identified trisomy 21.” Pet. 13 (citing
Ex. 1002 ¶ 2206).
Although Dhallan reports that Example 14 used a SNP genotyping
technique that employed fluorescent labels (see Pet. 12), Petitioner argues
that “it would have been obvious to a POSA [person of ordinary skill in the
art] to use the same method with genetic data generated by one of the SNP
genotyping arrays disclosed in Dhallan,” as required by claim 1. Pet. 18; Ex.
1002 ¶ 97. Further, although Dhallan reports that Example 14 used DNA
from an already-born child, Petitioner argues that Dhallan teaches use of the
method with embryonic or fetal DNA, i.e., a “small amount of genetic
material” as recited in claim 1. Pet. 18–20. Petitioner also argues that
Dhallan teaches use of genetic data that is “noisy,” i.e., “incomplete” (see
Ex. 1001, 62:25–26), because Dhallan details various experimental errors
that can occur (such as poor PCR amplification). Pet. 20–21. Petitioner also
argues that Dhallan teaches use of its methodology with one embryo cell,
and “[t]he ’592 patent concedes that analysis of a single cell would
inherently result in noisy data.” Pet. 21 (citing Ex. 1001, 8:19–23; Ex. 1004
¶ 105); see also Reply 5 (arguing that in its infringement contentions, Patent
Owner equates use of cell-free fetal DNA with “noisy” genetic data).
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Petitioner argues that Dhallan discloses the claim limitations of

“determining, on a computer, the probability of each of the hypotheses given
the produced genetic data” and “using the probabilities associated with each
hypothesis to determine the most likely number of copies of the
chromosome or chromosome segment of interest in the genome of the
individual.” Pet. 23, 26. Specifically, Petitioner relies on Dhallan’s
calculation of confidence intervals as satisfying the “determining . . . the
probability” claim limitation, and argues that these confidence intervals were
used to determine the probability that the calculated ratio accurately reports
an actual difference in the number of chromosomes. Pet. 24; see also Reply
4–5 (arguing that pointing to Dhallan’s confidence intervals for the
“determining . . . the probability” claim limitation is consistent with Patent
Owner’s infringement contentions). Petitioner asserts that it would have
been “obvious to apply the statistical analysis used in Example 14 to genetic
data generated using other techniques,” such as SNP genotyping arrays.
Pet. 25 (citing Ex. 1004 ¶ 114).
On the present record, we conclude that Petitioner’s arguments and
evidence establish a reasonable likelihood that claim 1 is unpatentable as
obvious over Dhallan. Petitioner’s arguments are adequately supported for
institution purposes by, inter alia, disclosures in Dhallan and opinion
testimony explaining how a person of ordinary skill in the art would have
understood those disclosures and arrived at the subject matter of claim 1.
We address Patent Owner’s arguments below.
Patent Owner argues that “Dhallan does not disclose a method
‘wherein the genetic data is noisy due to a small amount of genetic material
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from the individual.’” Prelim. Resp. 13. According to Patent Owner,

Dhallan’s Example 14 uses blood samples from both the mother and her
already-born child, and, thus, to the extent this genetic data is “noisy,” it is
not noisy “due to” the fact that it came from a small amount of genetic
material. Prelim. Resp. 17–18. Patent Owner further argues that “Petitioner
identifies no instance where Dhallan actually produces (or uses) ‘genetic
data’ which is ‘noisy’ ‘due to’ the fact that a small amount of genetic
material was used.” Prelim. Resp. 16; see also Sur-Reply 5.
We are not persuaded by Patent Owner’s arguments. Although
Dhallan reports that Example 14 used more than a “small amount of genetic
material,” the experiment was designed “[t]o recapitulate the in vivo
scenario of blood from a pregnant female.” Ex. 1002 ¶ 2157. Dhallan
elsewhere teaches use of this method on small amounts of genetic data, e.g.,
DNA obtained from an embryo or from the blood of a pregnant female. Ex.
1002 at, e.g., ¶¶ 44, 167–69. Thus, Dhallan discloses use of the method with
genetic data that would be “noisy due to a small amount of genetic material
from the individual,” as recited in claim 1. That Dhallan does not present a
working example that actually produces (or uses) such noisy genetic data
does not diminish this express disclosure. See In re Mills, 470 F.2d 649, 651
(CCPA 1972) (“[A] reference is not limited to the disclosure of specific
working examples.”).
Patent Owner further argues that “Dhallan discards the unquantifiable
measurements, thereby teaching away from the use of noisy genetic data.”
Prelim. Resp. 19 (citing Ex. 1002 ¶ 2207); see also id. at 13. “A reference
may be said to teach away when a person of ordinary skill, upon reading the
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reference, would be discouraged from following the path set out in the
reference, or would be led in a direction divergent from the path that was
taken by the applicant.” Galderma Labs., L.P. v. Tolmar, Inc., 737 F.3d
731, 738 (Fed. Cir. 2013). The cited paragraph in Dhallan merely notes that
for some SNPs, insufficient data was generated and, thus, could not be
quantitated. See Ex. 1002 ¶ 2207 (“[N]ot all the SNPS could be quantitated
because the bands corresponding to certain SNPs were faint.”). Despite
noting this experimental error for some SNPs, Dhallan nevertheless
concludes that analysis of the remaining SNPs correctly identified the
presence of the chromosomal abnormality. Ex. 1002 ¶¶ 2208, 2211. And as
discussed above, Dhallan teaches use of this method with small amounts of
genetic data. Thus, in view of Dhallan’s disclosure as a whole, we disagree
that the cited passage teaches away from the use of genetic data that is
“noisy due to a small amount of genetic material from the individual.”
Patent Owner additionally argues that Dhallan does not teach or
suggest “a method in which a ‘probability’ of a ‘hypothesis’ ‘specifying the
number of copies of the chromosome or chromosome segment of interest in
the genome of the individual’ is ‘determin[ed]’ ‘given the produced genetic
data.’” Prelim. Resp. 21. Specifically, Patent Owner argues that “Dhallan
uses confidence intervals to assess the validity of its measured data; these
confidence intervals are not tied [to] the probability of any particular
hypotheses being true given that data.” Id.; see also Sur-Reply 4–5 (arguing
that Dhallan discloses “confidence values,” but nowhere explains how they
were obtained).
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On this record, we are not persuaded by Patent Owner’s arguments.

Claim 1 calls for “determining, on a computer, the probability of each of the
hypotheses given the produced genetic data.” Ex. 1001, 62:57–58. Patent
Owner variously contends that this step requires “assign[ing]” a probability
to each hypothesis, or “calculat[ing]” the probability of a hypothesis.
Prelim. Resp. 23. However, we see no such requirements in the claim
language. Rather, the claim merely requires that one “determin[e]” the
probability of each of the hypotheses, given the produced genetic data. See
also Ex. 1004 (Peters Decl.) ¶ 36 (“The claims do not require any of the
detailed and specific statistical manipulations that make up the vast majority
of the ’592 patent’s disclosure.”). On this record, we agree with Dr. Peters
that Dhallan’s confidence intervals are
a mathematical way to determine the probability that the
produced data accurately reflects the actual hypothesized
state—in other words, whether the calculated ratios for
heterozygous SNPs on chromosome 21, when compared to the
calculated ratio for chromosome 13, actually represent an extra
copy of chromosome 21, or whether the ratios are more likely
to reflect ‘random numerical fluctuations in value.’
Ex. 1004 (Peters Decl.) ¶ 113; see also id. ¶ 114 (“[I]n my experience, it is a
common and routine step for an artisan to use statistical analysis to
determine the probability that the observed, measured values accurately
reflect a hypothesized difference.”).
Patent Owner argues an additional reason why Dhallan does not
“determin[e] . . . the probability of each of the hypotheses given the
produced genetic data.” Prelim. Resp. 26. Specifically, Patent Owner
argues that in claim 1, “[t]he produced genetic data” refers to the claimed
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“genetic data for some or all possible alleles at a plurality of at least 100 loci
on the chromosome or chromosome segment of interest in the individual.”
Prelim. Resp. 26. Patent Owner asserts that, in Example 14, Dhallan does
not use genetic data from at least 100 loci in its computations. Prelim.
Resp. 26. Although Dhallan genotypes 768 SNPs on each of chromosomes
13 and 21, to calculate the ratios, Dhallan uses data from only 62 SNPs from
chromosome 13, and 49 SNPs from chromosome 21. Prelim. Resp. 26–27
(citing Ex. 1002 ¶¶ 2202–03). As such, Patent Owner argues that “Dhallan
uses data from fewer than 100 loci per chromosome.” Prelim. Resp. 27.
We are not persuaded by this argument, which narrowly focuses on
the number of loci actually measured in Dhallan’s Example 14, to the
exclusion of the broader teachings of Dhallan. Again, “a reference is not
limited to the disclosure of specific working examples.” In re Mills, 470
F.2d at 651. Dhallan elsewhere teaches that genetic data for “one to tens to
hundreds to thousands of loci of interest” can be determined. Ex. 1002 ¶ 45.
Patent Owner argues that Petitioner has not demonstrated “a
reasonable expectation of success in employing Dhallan’s methodology
using a small amount of genetic material obtained from a single cell in order
to make a determination regarding an individual’s chromosomal copy
number.” Prelim. Resp. 29–30; see also id. at 28–37. Patent Owner asserts
that Dhallan discloses no working examples using a small amount of
template DNA, and states only prophetically that a small amount of template
DNA is not limiting. Prelim. Resp. 28, 33–34, 36. Patent Owner further
argues that Petitioner’s reliance on references purporting to show that it was
routine to carry out genetic testing on a single embryonic cell is unavailing,
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including because the references do not first “produce genetic data for some
or all possible alleles at a plurality of at least 100 loci on the chromosome,”
then “determine the most likely number of copies of the chromosome.”
Prelim. Resp. 30; see also id. at 30–37.
We are not persuaded by Patent Owner’s arguments. Dhallan teaches
that, in view of known PCR and amplification techniques, “a minimal
amount of template DNA is not limiting for the number of loci that can be
detected.” Ex. 1002 ¶ 270. Dhallan teaches a number of techniques
designed to overcome “a low number of genomes, which is often seen with
fetal DNA obtained from the plasma of a pregnant female” and to increase
the copy number of loci of interest. Ex. 1002 ¶¶ 1160, 2334, 2380; see also
Ex. 1004 (Peters Decl.) ¶¶ 131–33. That Dhallan does not include working
examples using a small amount of genetic material (see, e.g., Prelim. Resp.
28) is not fatal to a reasonable expectation of success. Dr. Peters explains
that by 2004, it was routine to carry out genetic testing on a single cell from
an embryo, and that whole genome amplification on a single cell from an
embryo had been used to detect trisomy 21. Ex. 1004 (Peters Decl.) ¶ 131.
Further, Petitioner supported its arguments with general teachings in the
prior art regarding amplifying and genotyping small amounts of genetic
material. See Pet. 31–33; see also Ex. 1004 (Peters Decl.) ¶¶ 131–37. On
this record we find that these teachings support a reasonable expectation of
success even if, as Patent Owner suggests, they do not expressly address
whether the amplification product was of sufficient quality to produce
genetic data for at least 100 loci. See, e.g., In re Kubin, 561 F.3d 1351, 1360
(Fed. Cir. 2009) (“[O]bviousness does not require absolute predictability of
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success . . . all that is required is a reasonable expectation of success.”

(quotation omitted)).
Patent Owner also argues that several of Petitioner’s references
demonstrate problems that commonly arise when using DNA amplification
techniques, such as preferential amplification or biased allele amplification.
Prelim. Resp. 31–33 (discussing Ex. 1023 (Hellani), Ex. 1035 (Dietmaier),
and Ex. 1030 (Zhang)). Patent Owner argues that such problems would
undermine Dhallan’s method, because the method “relies on the ability to
accurately count copies of alleles.” Prelim. Resp. 31. At this stage of the
proceeding, we are not persuaded that the phenomenon of preferential
amplification would have prevented Dhallan’s method from being able to
accurately count copies of alleles. Both Petitioner and Dhallan acknowledge
preferential amplification. See Pet. 37; Ex. 1002 ¶¶ 1054, 1062. Dr. Peters
testifies that a person of ordinary skill in the art would have recognized that
Dhallan’s methodology is robust enough to account for errors such as
preferential amplification, and notes that Dhallan teaches increasing the
number of SNPs analyzed to mitigate the impact of such errors and increase
the accuracy of the analysis. Ex. 1004 (Peters Decl.) ¶¶ 91, 150; see also
Ex. 1002 ¶ 1054 (“This problem is eliminated by having a sufficient number
of genomes in the sample.”). At this stage of the proceeding, Patent Owner
directs us to no persuasive evidence (such as a counter declaration) that casts
doubt on that opinion testimony.
Finally, Patent Owner asserts that Petitioner “has previously argued to
the Board in connection with the defense of one of its own patents, as of a
time later than the priority date of the ’592 Patent, that automated SNP
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calling software (such as that used in commercial SNP arrays) is less reliable
in the face of imbalanced amplification between alleles.” Prelim. Resp. 36
(citing Ex. 2004 (Illumina Prelim. Resp. in IPR2018-01317), at 18). On this
record, we do not perceive Petitioner’s prior statements to be inconsistent
with Petitioner’s arguments here. The prior statements appear to
acknowledge the possibility of preferential amplification, which as noted
above, Petitioner also acknowledges here. See Pet. 37 (citing Dhallan
¶¶ 1054, 1062–63). Patent Owner will have the opportunity to further
address these statements at trial if desired.
Based on the record presently before us, we find Petitioner’s
arguments with respect to obviousness of claim 1 over Dhallan supported by
the evidence, and generally find persuasive Dr. Peter’s unopposed testimony
regarding the scope and content of the prior art. Accordingly, we find that
Petitioner satisfies the burden of showing that there is a reasonable
likelihood that at least claim 1 of the ’592 Patent would have been obvious
over Dhallan.
3. Dependent Claims 2–4
Claim 2 depends from claim 1 and recites: “wherein the small amount
of genetic material is from twenty or fewer of the individual’s cells.”
Ex. 1001, 62:63–65. Claim 3 depends from claim 2 and recites: “wherein
the small amount of genetic material is from one of the individual’s cell.”
Id. at 62:66–67. Claim 4 depends from claim 1 and recites: “wherein the
small amount of genetic material is from 0.3 ng or less of the individual’s
DNA.” Id. at 63:1–3.
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Petitioner argues that a person of ordinary skill in the art would have
been motivated to use Dhallan’s method to analyze genetic material from
one cell (which contains less than 0.3 ng of DNA), with a reasonable
expectation of success. Pet. 34 (citing, e.g., Ex. 1004 (Peters Decl.) ¶¶ 121–
24, 131–33, 141, 143).
At this stage, Patent Owner does not offer arguments specific to
claims 2–4 beyond those already discussed with respect to claim 1. See
Prelim. Resp. 38. Based on the current record, including the testimony of
Dr. Peters (ibid.), which we find generally persuasive and stands unopposed
at this juncture, we determine the Petition shows a reasonable likelihood that
Petitioner would prevail on its contentions that claims 2–4 would have been
obvious over Dhallan.
4. Dependent Claim 5
Claim 5 depends from claim 1 and recites “wherein the small amount
of genetic material is from extracellular DNA from the individual found in
maternal blood.” Ex. 1001, 55.
Petitioner argues that Dhallan teaches use of “free fetal DNA”
obtained from a maternal blood sample, and techniques for analyzing it.
Pet. 35 (citing, e.g., Ex. 1002 ¶¶ 39–40, 169, 176, 2152, 2157, 2223, 2273,
2346; Ex. 1004 (Peters Decl.) ¶¶ 145–46).
On the present record, including the unopposed testimony of
Dr. Peters (Ex. 1004 ¶¶ 145–46), we conclude that Petitioner’s arguments
and evidence establish a reasonable likelihood that claim 5 is unpatentable as
obvious over Dhallan. We address Patent Owner’s arguments below.
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Patent Owner argues a lack of reasonable expectation of success

because “Dhallan never uses extracellular DNA in Example 14 or anywhere
else” to generate genetic data. Prelim. Resp. 39; see also id. at 40, 41 n.10.
Again, we are not persuaded by this argument, because “a reference is not
limited to the disclosure of specific working examples.” In re Mills, 470
F.2d at 651. On this record, Petitioner shows sufficiently that a person of
ordinary skill in the art would have formed a reasonable expectation of
success in using Dhallan’s methodology with extracellular fetal DNA
obtained from a maternal blood sample, for reasons stated by Dr. Peters. See
supra Section II.D.2 (discussing reasonable expectation of success); see also
Ex. 1004 (Peters Decl.) ¶ 147.
Patent Owner further asserts that Petitioner’s arguments are
inconsistent with prior statements it made to the Board, in which it
purportedly asserted that cell-free fetal DNA presents many problems,
challenges, and practical difficulties when used in prenatal genetic testing.
Prelim. Resp. 39, 42–43 (citing Ex. 2004 (Illumina Prelim. Resp. in
IPR2018-01317), at 3–4, 9, 17, 18, 35). On this record it is not clear
whether, taken in context, the statements Patent Owner relies on are
irreconcilable with Petitioner’s present positions. Other than mentioning
amplification bias—which we addressed above, see supra Section II.D.2—
Patent Owner neither sufficiently elaborates on the purported problems,
challenges, and practical difficulties raised by Petitioner, nor explains how
they would have purportedly undermined Dhallan’s method. Patent Owner
will have the opportunity to further address these statements at trial if
desired.
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Based on the current record, we determine that the Petition shows a

reasonable likelihood that Petitioner would prevail on its contention that
claim 5 would have been obvious over Dhallan.
Claim 6 depends from claim 1 and recites: “wherein the noisy data
comprises allele drop out errors.” Ex. 1001, 63:7–8. According to
Petitioner, the ’592 Patent defines allele drop out (“ADO”) “as the failure to
amplify one of the two alleles in a heterozygous cell.” Pet. 36 (citing
Ex. 1001, 3:21–23).
Petitioner argues that Dhallan’s methodology is robust enough to
account for allele drop out (“ADO”) errors. Pet. 36–37 (citing Ex. 1002
¶¶ 1054, 1062, 2207; Ex. 1004 (Peters Decl.) ¶ 150). Patent Owner responds
that, although Dhallan does not specifically discuss ADOs, it accounts for
PCR amplification errors by simply discarding the unquantifiable data.
Prelim. Resp. 43–44. According to Patent Owner, this “illustrates the
problems when using Dhallan’s method when ADO is high.” Id. at 44.
obvious over Dhallan. At this stage, we are not persuaded that the presence
of ADOs would have prevented Dhallan’s method from accurately counting
the ratio of alleles. Dr. Peters testifies that a person of ordinary skill in the
art would have recognized that Dhallan’s methodology is robust enough to
account for such errors, and that increasing the number of SNPs analyzed
would have mitigated the impact of such errors. Ex. 1004 (Peters Decl.)
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¶¶ 91, 150. That testimony appears credible and stands unrebutted at this
stage of the proceeding.
6. Dependent Claims 7 and 8
Claim 7 depends from claim 1 and recites “wherein the noisy data
comprises measurement bias.” Ex. 1001, 63:9–10. Claim 8 depends from
claim 1 and recites “wherein the noisy data comprises incorrect
measurements.” Id. at 63:11–12.
Petitioner argues that Dhallan recognizes well-known sources of
measurement bias, and accounts for such bias by adjusting the data and
increasing the number of SNPs analyzed. Pet. 37–38 (citing, e.g., Ex. 1002
¶¶ 351, 704, 812, 870, 879, 1005, 1107–110, 1062, 1063, 1150–51, 2222,
2316; Ex. 1004 (Peters Decl.) ¶¶ 153, 155).
At this stage, Patent Owner does not offer arguments specific to
claims 7 and 8. Based on the current record, we determine that the Petition
shows a reasonable likelihood that Petitioner would prevail on its
contentions that claims 7 and 8 would have been obvious over Dhallan.
Claim 9 depends from claim 1 and recites “wherein a confidence is
computed for the determination of the number of copies of the chromosome
or chromosome segment of interest in the individual’s genome.” Ex. 1001,
63:13–16.
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Petitioner refers to its discussion of claim 1, which includes a

discussion of Dhallan’s use, in Example 14, of a confidence interval for
determining the number of copies of chromosome 21. Pet. 38–39 (citing
Ex. 1002 ¶¶ 2206, 2211, 2215, 2219, 2221, 2222; Ex. 1004 (Peters Decl.)
¶ 157). In response, Patent Owner asserts that Petitioner “does not and
cannot explain how Dhallan’s confidence intervals can be both ‘a confidence
. . . for the determination of the number of copies of the chromosome or
chromosome segment of interest in the individual’s genome’ as well as a
‘probability’ of a hypothesis[] given certain genetic data.” Pet. 45.
We previously addressed Dhallan’s use of confidence intervals and
how they read on claim 1. For similar reasons, we determine the Petition
shows a reasonable likelihood that Petitioner would prevail on its contention
that claim 9 would have been obvious over Dhallan.
Claim 10 depends from claim 1 and recites “wherein the plurality of
loci comprise SNPs.” Ex. 1001, 63:17–18. Claim 11 depends from claim
10 and recites “wherein the confidence that each SNP is correctly called is at
least 95%.” Id. at 63:19–20. Claim 12 depends from claim 11 and recites
“wherein the confidence that each SNP is correctly called is at least 99%.”
Id. at 63:21–22.
With respect to claim 10, Petitioner asserts that Dhallan discloses
measuring SNPs at a plurality of loci. Pet. 39. With respect to claims 11
and 12, Petitioner asserts that Dhallan teaches the benefit of using a
statistical confidence interval to analyze the data (Ex. 1002 ¶¶ 2205–06), and
a person of ordinary skill in the art would have been motivated to use
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commercially-available SNP genotyping arrays, which were known to call

SNPs at a high accuracy (>99%). Pet. 39–40 (citing, e.g., Ex. 1004 (Peters
Decl.) ¶¶ 162–63).
Patent Owner does not offer any arguments specific to claim 10. With
respect to claims 11 and 12, Patent Owner responds that Petitioner has not
demonstrated a reasonable expectation of success of achieving the claimed
confidence levels in SNP calls because “none of Petitioner’s citations
addresses the accuracy of such systems when using DNA that has been
obtained from a small amount of genetic material.” Prelim. Resp. 46.
evidence establish a reasonable likelihood that claims 10–12 are
unpatentable as obvious over Dhallan. At this stage, we are not persuaded
by Patent Owner’s arguments, because they do not provide specific reasons
why the claimed confidence limits would not have been reasonably achieved
when using the commercially-available SNP genotyping arrays with small
amount of genetic material. See Prelim. Resp. 45–46.
reasonable likelihood that Petitioner would prevail on its contentions that
claims 10–12 would have been obvious over Dhallan.
9. Dependent Claims 15 and 16
Claim 15 depends from claim 1 and recites “wherein the
determination of the number of copies of the chromosome or chromosome
segment of interest is used to make a clinical decision about the individual.”
Ex. 1001, 63:29–32. Claim 16 depends from claim 15 and recites “wherein
the individual(s) is one or more embryos, and wherein the method further
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comprises (i) using the determination of the number of copies of the

chromosome or chromosome segment of interest in the one or more embryos
to select an embryo for in vitro fertilization, and (ii) performing in vitro
fertilization with the selected embryo.” Id. at 63:33–39.
Petitioner argues that Dhallan’s method is useful for prenatal
diagnosis (Ex. 1002, Abstract), and can inform clinical decisions such as
managing pregnancy, planning for possible complications with the birth
process, preparing for problems that can occur in the newborn infant, finding
conditions that may affect future pregnancies, and selecting embryos for
implantation. Pet. 40–41 (citing, e.g., Ex. 1002 at Abstract, ¶¶ 11, 2157,
2200; Ex. 1004 (Peters Decl.) ¶¶ 164–71).
Patent Owner reiterates its arguments regarding lack of reasonable
expectation of success in using a small amount of genetic material. Prelim.
Resp. 46–47. With respect to claim 15, Patent Owner additionally points to
a prior statement presented to the Board by Verinata Health, Inc. (which
Patent Owner identifies as a wholly-owned subsidiary of Petitioner). Prelim.
Resp. 46–47. According to Patent Owner, Verinata previously stated that
“[a] method having an error rate above 10% would simply be unsuitable for
SNP detection . . . especially for use in clinical diagnostics where errors are
not tolerable.” Id. (quoting Ex. 2005 (Verinata Prelim. Resp. in IPR2013-
00276), 47). Patent Owner argues that Petitioner does not explain why a
person of ordinary skill in the art “should have expected to achieve error
rates in SNP detection below 10% here when starting with a single cell.”
Prelim. Resp. 47.
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We previously addressed Patent Owner’s arguments regarding lack of

reasonable expectation of success in using a small amount of genetic
material. We are not persuaded by Patent Owner’s reliance on Verinata’s
prior statement when read in light of the totality of the evidence of the
present record, including Dr. Peters’ testimony regarding Dhallan’s
methodology.
claims 15 and 16 would have been obvious over Dhallan.
Claim 17 depends from claim 1 and recites “wherein the individual is
a fetus, and wherein the sample is a maternal blood sample comprising DNA
from the fetus and DNA from the mother of the fetus.” Ex. 1001, 63:40–43.
Petitioner argues that Dhallan discloses a preferred embodiment in
which “fetal cells are isolated from maternal peripheral blood.” Pet. 42
(citing Ex. 1002 ¶¶ 187–88). Petitioner further argues that using standard
prior art techniques for isolating fetal cells from maternal blood and
producing genetic data, a person of ordinary skill in the art would have
reasonably expected success in performing the method exemplified in
Dhallan’s Example 14 on a fetal cell. Pet. 42–43 (citing, e.g., Ex. 1004
(Peters Decl.) ¶¶ 176–77).
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Patent Owner argues that Dhallan does not actually demonstrate use
of fetal DNA obtained from the mother’s blood to determine chromosomal
copy number, and argues that Petitioner has not explained why standard
prior art techniques for isolating fetal cells from maternal blood provide a
reasonable expectation of success, given that Dhallan’s method relies on
precise allele quantification. Prelim. Resp. 48. Again, that Dhallan does not
actually demonstrate use of fetal DNA is not determinative, because “a
reference is not limited to the disclosure of specific working examples.” In
re Mills, 470 F.2d at 651. As discussed above, we are persuaded that
Petitioner shows sufficiently a reasonable expectation of success in using
Dhallan’s methodology with fetal DNA. See supra Section II.D.2
(discussing reasonable expectation of success); see also Ex. 1004 (Peters
Decl.) ¶¶ 176–77.
Claim 19 depends from claim 1 and requires the genetic data to be
obtained by amplifying and/or measuring the individual’s genetic material
using one or more specified techniques, including PCR. Ex. 1001, 63:47–
56.
Petitioner asserts that Dhallan teaches use of at least PCR to amplify
loci of interest. Pet. 43–44 (citing, e.g., Ex. 1002 ¶¶ 168, 264–71, 2380,
2459; Ex. 1004 (Peters Decl.) ¶¶ 179, 124). At this stage, Patent Owner
does not offer any arguments specific to claim 19.
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Claim 20 depends from claim 1 and requires that “the individual’s
genetic data has been obtained by amplifying and/or measuring the
individual’s genetic material,” and wherein the genetic material is found in
one or more specifically-recited substances, including “cells from the
individual found in maternal blood,” or “genetic material known to have
originated from the individual.” Ex. 1001, 64:10–25.
Petitioner points back to its arguments for claims 1, 17, and 19, noting
that Dhallan discloses amplifying and measuring an individual’s genetic
material, and also discloses that the genetic material is preferably taken from
one embryonic cell (i.e., DNA known to have originated from the
individual), or fetal cell from maternal blood. Pet. 44 (citing Ex. 1004
(Peters Decl.) ¶ 182). At this stage, Patent Owner does not offer arguments
specific to claim 20.
Claim 21 depends from claim 1 and requires the chromosome of
interest be selected from a group that includes chromosome 21. Ex. 1001,
64:26–29. Claim 22 depends from claim 1 and requires the chromosomal
abnormality is selected from a group that includes trisomy. Id. at 64:30–34.
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Claim 23 depends from claim 1 and requires determining whether the

individual has one of a group of conditions that includes Down syndrome.
Id. at 64:35–37.
Petitioner points back to its arguments for claim 1, noting that Dhallan
applies its method to detect trisomy 21, which gives rise to Down syndrome.
Pet. 45 (citing, e.g., Ex. 1004 (Peters Decl.) ¶¶ 184–86). At this stage,
Patent Owner does not offer arguments specific to claims 21–23.
claims 21–23 would have been obvious over Dhallan.
Claim 27 depends from claim 1 and recites “wherein the probability
of each of the hypotheses is determined without use of a reference sample.”
Ex. 1001, 64:52–54.
Petitioner argues that Dhallan’s method does not use a reference
sample, noting that in Example 14, “a pure sample of an individual’s DNA
(100% child) is analyzed for a change in chromosome 21 number without a
reference sample.” Pet. 46 (citing Ex. 1004 (Peters Decl.) ¶ 187).
Patent Owner argues that Example 14 does use a reference sample,
i.e., genetic material obtained from the mother, which was necessary to
identify SNPs that are heterozygous in the child DNA, but homozygous in
the maternal DNA. Prelim. Resp. 49–50 (citing Ex. 1002 ¶ 2202). We are
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Patent 8,682,592 B2
not persuaded by this argument, because on this record, it is not clear how
Dhallan’s use of the maternal sample to identify heterozygous SNPs is
relevant to the pertinent limitation in claim 27. Claim 27 recites “wherein
the probability of each of the hypotheses is determined without use of a
reference sample.” Using the maternal sample to identify heterozygous
SNPs appears to be a distinct step from determining the probability of each
of the hypotheses. Further, as pointed out by Petitioner, the maternal DNA
is not used as a reference sample, but rather “a pure sample of an
individual’s DNA (100% child) is analyzed for a change in chromosome 21
number without a reference sample.” Pet. 46.
Obviousness of Claim 18 over Dhallan and Bianchi
Petitioner asserts that claim 18 is unpatentable as obvious over the
combination of Dhallan and Bianchi. Pet. 46. Based on the current record,
for reasons explained below, we determine that Petitioner has established a
reasonable likelihood that it would prevail on this challenge.
1. Overview of Bianchi (Exhibit 1034)
Bianchi, a review article entitled “Fetal Cells in the Maternal
Circulation: Feasibility for Prenatal Diagnosis,” discusses invasive and
non-invasive approaches to prenatal screening for chromosome
abnormalities such as trisomy 21. Ex. 1034, 574. Bianchi explains that
routine obstetric care incorporates second-trimester maternal serum
screening for certain protein markers indicating a Down syndrome risk, and
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Patent 8,682,592 B2
that “[w]omen who have a [serum screening] test result that indicates a fetal
Down syndrome risk of greater than 1 in 270 are offered amniocentesis.” Id.
Bianchi states that “to date there has been little impact upon the incidence of
trisomy 21, which is still close to 1 per 1000 live births.” Id. Accordingly,
Bianchi states that “over the past decade, increased attention has been paid
to noninvasive techniques of screening for fetal trisomy 21 that can be
offered to all pregnant woman.” Id.
Bianchi states that fetal chromosomes or DNA obtained non-
invasively by maternal venipuncture “could be used as a primary screen, a
secondary screen designed to be used in concert with the aforementioned
[serum] screening tests (to reduce the 5% false-positive rate) (Farina &
Bianchi, 1998), or, ultimately, as a diagnostic test.” Id. Bianchi goes on to
summarize “the clinical implications of this test for the clinical practice of
obstetrics and gynaecology, the surprising insights into the biology of
pregnancy that have come from the study of fetal cells in maternal blood,
and the technical challenges associated with rare event cell separation.” Id.
2. Analysis of Claim 18
Claim 18 depends from claim 1 and recites “wherein the individual is
a fetus, and wherein the method further comprises performing amniocentesis
or chorion villus biopsy.” Ex. 1001, 63:44–46. Petitioner asserts that a
person of ordinary skill in the art “would have been motivated to include a
further step of amniocentesis or CVS [chorion villus biopsy],” because as
Bianchi demonstrates, it was well known to use these techniques to confirm
a Down syndrome diagnosis following a suspect result from a non-invasive
screening. Pet. 46, 47.
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Patent 8,682,592 B2
Patent Owner responds that a person of ordinary skill in the art would
not have been motivated to employ a confirmatory amniocentesis or CVS,
because Bianchi “seeks [to] develop non-invasive approaches reliable
enough to reduce or eliminate the need for invasive testing,” and neither
“recommend[s]” nor “suggest[s] the desirability” of amniocentesis or CVS.
Prelim. Resp. 52, 53.
obvious over the combination of Dhallan and Bianchi. We are not
persuaded by Patent Owner’s argument, because Bianchi nowhere indicates
that testing of isolated fetal cells could supplant the use of a confirmatory
amniocentesis or CVS. At most, Bianchi states that isolated fetal cells may
“ultimately” be used as a diagnostic test (Ex. 1034, 574), while
acknowledging that the invasive tests are necessary for rooting out false
positive results from the non-invasive approaches available at that time.
In view of the above, we find that Petitioner has demonstrated a
reasonable likelihood of prevailing on its contention that claim 18 of
the ’592 Patent is unpatentable as obvious over Dhallan and Bianchi.
Obviousness of Claims 24–26 Over Dhallan and Sham
Petitioner asserts that claims 24–26 are unpatentable as obvious over
the combination of Dhallan and Sham. Pet. 47. Based on the current record,
for reasons explained below, we determine that Petitioner has established a
reasonable likelihood that it would prevail on these challenges.
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Patent 8,682,592 B2
1. Overview of Sham (Exhibit 1021)

Sham, a review article entitled “DNA Pooling: A Tool for Large-
Scale Association Studies,” addresses “recent developments in quantitative
genotyping assays.” Ex. 1021, Abstract. Sham indicates that “many SNPs
show differential amplification during PCR, which means that one allele is
more efficiently amplified than the other.” Id. at 865. Sham states that
“[r]egardless of the detection method, this causes the signal that represents
the more efficiently amplified allele to be higher than expected from its true
frequency in a pooled sample.” Id. Sham identifies additional factors that
can “distort allele frequency estimates,” including
allele-specific differences in the efficiency of the detection
assay (such as differential efficiency of nucleotide
incorporation in primer extension, differential efficiency of
hybridization in hybridization-based assays) and differential
detection efficiency of the allele-specific products by the
detector. Examples of the latter include differences in the
emission energies of different fluorescent dyes, and differences
in the UV light absorbance or in the mass of extension products
that are of equi-molar concentration but are of different mass
and/or size.
Id. Sham states that “[t]o obtain unbiased estimates of allele frequencies, the
strength of allele-specific signals should be corrected by a factor that is
obtained from reference samples of known allele frequencies.” Id.
2. Analysis of Claims 24–26
Claim 24 depends from claim 1 and recites “normalizing the genetic
data for differences in measurement efficiency between the loci.” Ex. 1001,
64:38–40. Claim 25 depends from claim 1 and recites “amplifying the
genetic material of the target individual; and normalizing the genetic data for
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Patent 8,682,592 B2
differences in amplification and/or measurement efficiency between the

loci.” Id. at 64:41–45. Claim 26 depends from claim 1 and recites
“amplifying the genetic material of the target individual; and normalizing
the genetic data for differences in amplification and/or measurement
efficiency between the loci, chromosome segments, or chromosomes.” Id. at
64:46–48.
Relying on Sham, Petitioner argues that “it was common practice to
normalize genetic data from an SNP genotyping array by adjusting the signal
measurements ‘by a factor that is obtained from reference samples of known
allele frequencies.’” Pet. 48 (citing Ex. 1021, 865). According to Petitioner,
Sham teaches normalization of the same sources of potential measurement
bias identified by Dhallan. Pet. 48–50 (citing Ex. 1002 ¶¶ 699, 812, 826,
1054, 1062–63, 2316). Petitioner concludes that a person of ordinary skill in
the art “would have been motivated to address known sources of bias in the
measurement of genetic data using SNP genotyping arrays, as identified in
both Dhallan and Sham, by normalizing the differences in measurement
efficiency to improve the quality of the data, as taught by Sham.” Pet. 49
(citing Ex. 1021, 865). Petitioner also notes that, with respect to the
amplification step recited in claims 25 and 26, Dhallan amplifies the genetic
material at the loci of interest, as discussed in connection with claim 1.
Pet. 50.
On the present record, Patent Owner does not present any additional
patentability arguments for claims 24–26 beyond those it presented for
claim 1. Prelim. Resp. 54. Our discussion above, pertaining to claim 1,
therefore, applies with equal force to claims 24–26. Based on the current
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Patent 8,682,592 B2
record, we determine that the Petition shows a reasonable likelihood that

Petitioner would prevail on its contention that claims 24–26 are unpatentable
as obvious over Dhallan and Sham.
Obviousness of Claims 1–27 Over Rabinowitz
Petitioner challenges claims 1–27 under 35 U.S.C. § 103 as obvious
over Rabinowitz (Ex. 1003). Pet. 51.
1. Whether Rabinowitz is Prior Art
Petitioner’s challenge is predicated on the assertion that Rabinowitz
qualifies as prior art because claims 1–27 are not entitled to a filing date
earlier than March 11, 2013 (i.e., the filing date of the application that led
directly to the ’592 Patent). Pet. 51. Specifically, Petitioner argues that the
priority applications fail to provide written description support for the
limitation “high throughput DNA sequencing” recited in claim 1. Pet. 4–5,
52–56.
A patent application is entitled to claim priority to the filing date of a
prior application only “for an invention disclosed [in the prior application] in
the manner provided by [35 U.S.C. §] 112(a).” 35 U.S.C. § 120 (2018).
“The priority date for later-added patent claims depends on when the
claimed subject matter first appeared in the chain of patent applications from
which the claims arose.” Paice LLC v. Ford Motor Co., 881 F.3d 894, 906
(Fed. Cir. 2018). “For claims to be entitled to a priority date of an earlier-
filed application, the application must provide adequate written description
support for the later-claimed limitations.” Id.
The test for sufficiency of a written description under 35 U.S.C. § 112
is whether the earlier application’s disclosure “reasonably conveys to those
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Patent 8,682,592 B2
skilled in the art that the inventor had possession of the claimed subject
matter as of the filing date.” Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d
1336, 1351 (Fed. Cir. 2010) (en banc). The written description “test requires
an objective inquiry into the four corners of the specification from the
perspective of a person of ordinary skill in the art.” Id. “Sufficient
description of a genus . . . requires the disclosure of either a representative
number of species falling within the scope of the genus or structural features
common to the members of the genus so that one of skill in the art can
‘visualize or recognize’ the members of the genus.” Id. at 1350. The
Federal Circuit has identified a number of factors to be considered in
evaluating the adequacy of disclosures supporting generic claims, including
“the existing knowledge in the particular field, the extent and content of the
prior art, the maturity of the science or technology, [and] the predictability
of the aspect at issue.” Id. at 1351 (quoting Capon v. Eshhar, 418 F.3d
1349, 1359 (Fed. Cir. 2005)) (alteration in original).
Petitioner asserts that “[h]igh throughput DNA sequencing is not
disclosed in the specification, nor is it described in any of the priority
applications.” Pet. 4. Petitioner contends that the sole sequencing technique
disclosed in the parent application (i.e., US App. 11/603,406, “the ’406
application”) is pyrosequencing, and the ’406 application expressly states
that this technique “is not currently conducive to high-throughput parallel
analysis.” Pet. 53–54 (citing Ex. 1026, 6:27–30). Accordingly, Petitioner
argues that “the parent ’406 application that published as Rabinowitz (Ex.
1003) makes clear that the named inventors did not consider any DNA
sequencing method to be suitable for high-throughput analysis.” Pet. 54.
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Patent 8,682,592 B2
Petitioner further argues that “[t]o the extent sequencing is mentioned in the
provisional applications, those applications also teach that the then-available
sequencing methods were not conducive to high-throughput applications.”
Pet. 55.
Patent Owner disagrees, arguing that the ’592 Patent claims are
supported by the written description of the ’406 application, and by at least
U.S. Provisional Application 60/817,741 (“the ’741 provisional”)
(Ex. 1039), which is incorporated by reference into the ’406 application.
See, e.g., Prelim. Resp. 54–55, 60. Patent Owner focuses on disclosure of
pyrosequencing, arguing that various prior art articles demonstrate that this
technique was in fact suitable to accomplish high-throughput genotyping and
SNP analysis as of the filing date of the ’406 application. Prelim. Resp. 57–
59 (citing Ex. 1011 (Jenkins), 60, 62; Ex. 2006 (Tsuchihashi), 103, 108;
Ex. 2007 (Meng), 3419; Ex. 2008 (Margulies), 376).
Patent Owner asserts that the discussion of pyrosequencing in the ’406
application must be read in conjunction with the discussion in the ’741
provisional, which provides:
Pyrosequencing. For a review of the method, see
http://www.pyrosequencing.com/. The main advantages to
pyrosequencing include an extremely fast turnaround and
unambiguous SNP calls, since you actually produce a
sequence. The disadvantage of pyrosequencing, as with
Taqman, is that the assay is not necessarily conducive to high-
throughput analysis (unless $1 million machines are
purchased). This may change as technology evolves.
Ex. 1039, 32 (emphasis added). Patent Owner argues that “[t]his disclosure
clearly teaches that pyrosequencing is conducive to high-throughput analysis
if $1 million machines are purchased.” Prelim. Resp. 61. Patent Owner
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Patent 8,682,592 B2
thus concludes that a person of ordinary skill in the art “reading these
disclosures would understand from them that the inventors believed that
pyrosequencing was a high-throughput method of DNA sequencing that
could be used to practice the claimed methods, but that it would be
expensive to do so.” Prelim. Resp. 62.
On this record, we agree with Patent Owner that the ’406 application,
when read together with the ’741 provisional, demonstrates to a person of
ordinary skill in the art that the inventors believed that pyrosequencing could
be used for high-throughput sequencing, if expensive machines were
purchased. In other words, we agree with Patent Owner that “‘[s]uitability’,
as the provisional makes clear, is a cost issue, rather than a technical one.”
Prelim. Resp. 61. We invite the parties to further address whether the
disclosure of pyrosequencing as a high-throughput technique is sufficient
support for the “high throughput DNA sequencing” recited in claim 1.
Although we agree with Patent Owner that Petitioner has not shown
that Rabinowitz qualifies as prior art on the present record, following SAS
and USPTO guidance, we institute review of all claims challenged under all
grounds in the Petition. See SAS Inst. Inc. v. Iancu, 138 S. Ct. 1348, 1355–
56 (2018) (stating that a decision to institute under 35 U.S.C. § 314(b) may
not institute review on fewer than all claims challenged in the petition); see
also Guidance on the Impact of SAS on AIA Trial Proceedings (April 26,
2018) (available at https://www.uspto.gov/patents-application-
process/patent-trial-and-appeal-board/trials/guidance-impact-sas-aia-trial)
(“[I]f the PTAB institutes a trial, the PTAB will institute on all challenges
46
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Patent 8,682,592 B2
raised in the petition.”). We consider the teachings of Rabinowitz below to

provide guidance to the parties.
2. Application of Rabinowitz to the ’592 Patent Claims
Petitioner contends that the ’592 Patent claims are unpatentable as
obvious over Rabinowitz, which is the publication of the ’406 application.
Pet. 56–68. The ’592 Patent is a continuation of the ’406 application, and
thus the ’592 Patent claims and Rabinowitz share a specification.
With respect to claim 1, Petitioner asserts that Rabinowitz discloses
using SNP genotyping arrays to measure the amount of genetic material at
more than 100 loci. Pet. 57 (citing Ex. 1003 ¶¶ 16–17, 33, 68, 93, 125, 129,
claims 30, 38). According to Petitioner, the measurements can be made
using “incomplete genetic data from a fetus . . . acquired from fetal cells, or
cell-free fetal DNA isolated from the mother’s blood,” which it argues is
“noisy genetic data.” Pet. 58–59 (citing Ex. 1003 Abstract, ¶¶ 29, 31, 39,
136, 393, claim 39). The measurements can be used to detect aneuploidy,
including by creating a set of hypotheses about the potential states of the
DNA, and testing (on a computer) to see which hypothesis has the highest
probability of being true given the measured data. Pet. 57, 59–60 (citing
Ex. 1003 ¶¶ 32, 33, 36, 68, 182, 294, claims 30, 31, 36, 43).
Based on the record before us, we find that Rabinowitz teaches or
suggests all of the limitations of claim 1. We have also reviewed
Petitioner’s contentions with respect to dependent claims 2–27, and
determine that the Petition demonstrates that Rabinowitz teaches or suggests
all of the limitations of these claims as well. See Pet. 61–68.
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Patent 8,682,592 B2
Thus, if it were established at trial that Rabinowitz qualifies as prior

art, we determine that Petitioner would likely prevail with respect to the
contention that claims 1–27 are unpatentable as obvious over Rabinowitz.
Motion to Seal
Concurrent with its Reply, Petitioner filed a Motion to Seal (Paper
15), which included a modified version of the Default Standing Protective
Order (Paper 15, Appendix A). Patent Owner did not file an opposition to
the motion. See 37 C.F.R. § 42.25(a)(1) (setting the default time limit for an
opposition at one month). For the reasons below, we deny Petitioner’s
Motion to Seal without prejudice.
Petitioner’s motion proposes entry of a modified version of the
Board’s Default Standing Protective Order (“Modified Protective Order”).
Paper 15 at 3, Appendix A. The proposed Modified Protective Order seeks
to add “a designation of ‘Outside Attorneys’ Eyes Only Information’ for
information containing sensitive technical information relating to the design,
development, research, testing and/or production of products.” Paper 15, 3.
Under the terms of the proposed Modified Protective Order, exhibits
designated “Outside Attorneys’ Eyes Only” would be available only to
outside counsel, experts, support personnel, and the Office, and would be
“subject to all provisions of the protective order directed to ‘OUTSIDE
ATTORNEYS’ EYES ONLY’ information in the related district court
proceeding.” Paper 15, 3–4 (citing Appendix B, District Court Protective
Order). Petitioner asserts that these modifications to the Default Standing
Protective Order “are necessary in order to protect a party’s sensitive
technical information relating to the design, development, research, testing
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IPR2019-01201
Patent 8,682,592 B2
and/or production of products from being disclosed to the opposing party’s

in-house counsel and to counsel who may participate in obtaining patent
claims on behalf of the opposing party.” Paper 15, 4.
As set forth in the Board’s Consolidated Trial Practice Guide, the
Board will generally accept proposed modifications to the Board’s Default
Protective Order, if the modifications are consistent with the integrity and
efficient administration of the proceeding. See Consolidated Trial Practice
Guide 115. The Consolidated Trial Practice Guide specifically provides that
parties may propose additional tiers or categories of confidential
information, such as “Attorneys’ Eyes Only.” See id. The Consolidated
Trial Practice Guide states, however, that the Board will not accept overly
inclusive definitions that encourage the parties to categorize all or most of
their discovery materials as “Attorneys’ Eyes Only.” See id. at 115–16.
The proposed Modified Protective Order runs afoul of this guidance.
It provides an “OUTSIDE ATTORNEYS’ EYES ONLY” category, but
nowhere defines what types of materials are to be included in this category.
Additionally, the proposed Modified Protective Order states that any
exhibit designated as “OUTSIDE ATTORNEYS’ EYES ONLY”
information “will be subject to all provisions of the protective order directed
to ‘OUTSIDE ATTORNEYS’ EYES ONLY’ information in the related
district court proceeding.” Paper 15, Appendix A, 2. The Board will not
undertake to review the district court protective order to identify which
provisions of that protective order Petitioner intends to have applied here.
Rather than attempting to incorporate select (and unidentified) portions of
the district court protective order into the Modified Protective Order by
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IPR2019-01201
Patent 8,682,592 B2
reference, Petitioner should prepare a modified version of the Board’s

default protective order that includes those provisions Petitioner expressly
intends to apply in this proceeding.
In preparing a modified version of the Board’s default protective
order, we direct Petitioner’s attention to the guidance in the Consolidated
Trial Practice Guide pertinent to district court protective orders. This
guidance states:
When a proceeding before the Board involves the same parties
and subject matter as a parallel district court proceeding, parties
may propose that a protective order entered by the district court
be adopted by the Board. The Board may enter such a
proposed protective order especially if certain provisions
commonly found in district court protective orders that are
unnecessary or inappropriate in proceedings before the
Board are removed before submitting the proposed protective
order to the Board. For example, provisions protecting
computer source code may be unnecessary because
proceedings before the Board rarely, if ever, require analysis of
computer source code. Likewise, prosecution bars are rarely
appropriate in proceedings before the Board because the
disadvantage caused by a prosecution bar to patent owners
wishing to make use of amendment or reissue processes in most
cases outweighs the risk that confidential technical information
about existing or future commercial products will be revealed
during a proceeding. Finally, all terms of district court
protective orders that conflict with Board procedures for
filing or otherwise handling confidential information should
be removed before the proposed order is submitted to the
Board.
Consolidated Trial Practice Guide 116 (emphasis added).
In view of the above, we deny the Motion to Seal without prejudice.
Although we have limited resources to deal with repeated motions, we
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IPR2019-01201
Patent 8,682,592 B2
authorize Petitioner to file a renewed motion to seal, with proposed

protective order, in compliance with our rules and the Consolidated Trial
Practice Guide. The renewed motion to seal shall be filed within ten days of
the entry of the below Order. The exhibit sought to be sealed in Petitioner’s
original Motion to Seal shall continue to be provisionally sealed until such
time as the Board resolves a second motion to seal, or should Petitioner not
file a renewed motion to seal, ten days after entry of the below Order. See
37 C.F.R. § 42.14 (discussing Board’s authority to provisionally seal
information).
We remind the parties that a movant to seal in this proceeding shall
assume the risk that its confidential information will become public if relied
upon in a final written decision. See Paper 11, 4.
III. CONCLUSION
On this record, for the reasons provided above, we determine that
Petitioner has shown a reasonable likelihood of prevailing on its assertion
that at least one of the challenged claims is unpatentable. Given our
determination, we institute trial on all challenged claims raised in the
Petition. See PGS Geophysical AS v. Iancu, 891 F.3d 1354, 1360 (Fed. Cir.
2018) (indicating that a decision whether to institute an inter partes review
“require[s] a simple yes-or-no institution choice respecting a petition,
embracing all challenges included in the petition”).
We emphasize that at this stage of the proceeding, we have not made a
final determination as to the patentability of the instituted claims. Our final
decision will be based on the full record developed during trial.
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Patent 8,682,592 B2
IV. ORDER
In consideration of the foregoing, it is hereby:
ORDERED that, pursuant to 35 U.S.C. § 314, an inter partes review
of claims 1–27 of U.S. Patent No. 8,682,592 B2 is instituted with respect to
all challenges set forth in the Petition;
FURTHER ORDERED that pursuant to 35 U.S.C. § 314(a), inter
partes review of the ʼ592 Patent is hereby instituted commencing on the
entry date of this Order, and pursuant to 35 U.S.C. § 314(c) and 37 C.F.R.
§ 42.4, notice is hereby given of the institution of a trial;
FURTHER ORDERED that Petitioner’s Motion to Seal is denied
without prejudice;
FURTHER ORDERED that Petitioner is hereby authorized to file a
renewed motion to seal consistent with our rules and guidance and any
additional guidance provided above, such a motion to be filed within 10 days
of entry of this Order; and
FURTHER ORDERED that the exhibit addressed by Petitioner’s
Motion to Seal shall be maintained as provisionally sealed, until we rule on
any renewed motion to seal, or should Petitioner not file a renewed motion
to seal, ten days after entry of the below Order.
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Patent 8,682,592 B2
PETITIONER:
Kerry S. Taylor
Michael L. Fuller
Nathanael R. Luman
William R. Zimmerman
KNOBBE, MARTENS, OLSON & BEAR, LLP
2kst@knobbe.com
2mlf@knobbe.com
2nrl@knobbe.com
boxillumina@knobbe.com
PATENT OWNER:
Matthew A. Smith
Andrew S. Baluch
Elizabeth Laughton
SMITH BALUCH LLP
smith@smithbaluch.com
baluch@smithbaluch.com
laughton@smithbaluch.com
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UNITED STATES PATENT AND TRADEMARK OFFICE

BEFORE THE PATENT TRIAL AND APPEAL BOARD

Before GRACE KARAFFA OBERMANN, SUSAN L. C. MITCHELL, and

HARDMAN, Administrative Patent Judge.

The ’592 Patent and Illustrative Claim

1. An ex vivo method for determining a number of copies of a

Claim(s) Challenged 35 U.S.C. § References

18 103 Dhallan, Bianchi3

24–26 103 Dhallan, Sham4

1–27 103 Rabinowitz5

Pet. 9. The Petition is supported by the declaration of David Peters, Ph.D.

institute an IPR proceeding.”). The parties briefed whether institution

Board seeks, among other things, to minimize the duplication of work by

claims against Petitioner or its customers, yet Petitioner would be time-

of Illumina’s amended preliminary invalidity contentions do not detail the

individual, Dhallan determined the average ratio for heterozygous SNPs

Petitioner argues that Dhallan discloses the claim limitations of

from the individual.’” Prelim. Resp. 13. According to Patent Owner,

On this record, we are not persuaded by Patent Owner’s arguments.

success . . . all that is required is a reasonable expectation of success.”

Patent Owner argues a lack of reasonable expectation of success

Based on the current record, we determine that the Petition shows a

Petitioner refers to its discussion of claim 1, which includes a

commercially-available SNP genotyping arrays, which were known to call

comprises (i) using the determination of the number of copies of the

We previously addressed Patent Owner’s arguments regarding lack of

Based on the current record, we determine that the Petition shows a

Claim 23 depends from claim 1 and requires determining whether the

1. Overview of Sham (Exhibit 1021)

differences in amplification and/or measurement efficiency between the

record, we determine that the Petition shows a reasonable likelihood that

raised in the petition.”). We consider the teachings of Rabinowitz below to

Thus, if it were established at trial that Rabinowitz qualifies as prior

and/or production of products from being disclosed to the opposing party’s

reference, Petitioner should prepare a modified version of the Board’s

authorize Petitioner to file a renewed motion to seal, with proposed

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