Board of Trustees of the Leland Stanford Junior University v. Chinese University of Hong Kong

United States Court of Appeals
for the Federal Circuit
______________________
THE BOARD OF TRUSTEES OF THE LELAND
STANFORD JUNIOR UNIVERSITY,
Plaintiff-Appellant
v.
THE CHINESE UNIVERSITY OF HONG KONG,
Defendant-Appellee
______________________
2015-2011
______________________
Appeal from the United States District Court for the
Northern District of California in No. 3:12-cv-00865-SI,
Judge Susan Y. Illston.
______________________
Decided: June 27, 2017
______________________
EDWARD R. REINES, Weil, Gotshal & Manges LLP,
Redwood Shores, CA, argued for plaintiff-appellant. Also
represented by DEREK C. WALTER, MICHELE GAUGER.
CHARLES E. LIPSEY, Finnegan, Henderson,
Farabow, Garrett & Dunner, LLP, Reston, VA, argued for
defendant-appellee. Also represented by STEVEN
O’CONNOR; JENNIFER SWAN, ROBERT F. MCCAULEY,
JEFFREY DANIEL SMYTH, LILY LIM, Palo Alto, CA; HOWARD
WARREN LEVINE, Washington, DC.
______________________
2 STANFORD UNIV. v. THE CHINESE UNIV. OF HONG KONG
Before O’MALLEY, REYNA, and CHEN, Circuit Judges.
O’MALLEY, Circuit Judge.
The Board of Trustees of the Leland Stanford Junior
University (“Stanford”) appeals from orders of the Patent
Trial and Appeal Board (“Board”) in three interference
proceedings between Stanford and the Chinese University
of Hong Kong (“CUHK”). In all of these proceedings, the
Board found that Stanford’s claims were unpatentable for
lack of written description. See Quake v. Lo, No. 105,920
(P.T.A.B. Apr. 7, 2014); Lo v. Quake, No. 105,923
(P.T.A.B. Apr. 7, 2014); Lo v. Quake, No. 105,924
(P.T.A.B. Apr. 7, 2014). 1 Because we conclude that the
Board relied on improper evidence to support its key
findings and did not cite to other substantial evidence to
support its findings, we vacate the Board’s interference
decisions and remand for further proceedings.
I. BACKGROUND
A. Technology and Patents
This appeal concerns testing methods for fetal aneu-
ploidies, conditions in which a fetus either has an abnor-
mally high number of chromosomes (e.g., Down’s
1 Although Stanford has appealed the Board’s deci-
sion in all three of these interferences, the Board’s orders
in interferences 105,923 and 105,924, relating to Quake’s
application 12/393,833, contain largely the same findings
as those issued by the Board in interference 105,920,
between CUHK professor Dennis Lo’s application
13/070,275 and Stanford professor Stephen Quake’s U.S.
Patent No. 8,008,018 (“the ’018 patent”). We therefore
cite to the ’920 interference in this decision for clarity, but
our decision applies to the Board’s findings in all three
interferences.
STANFORD UNIV. v. THE CHINESE UNIV. OF HONG KONG 3
syndrome, a result of trisomy 21) or an abnormally low
number of chromosomes (e.g., Turner’s syndrome, a result
of a missing copy of an X chromosome). Prior to the
methods developed by the inventors involved in this
appeal, physicians typically diagnosed fetal aneuploidies
using invasive amniocentesis or chorionic villus sampling
procedures. Doctors used less invasive testing methods
for identifying aneuploidies, such as ultrasonography and
biochemical marker detection, but these methods had
suboptimal diagnostic accuracy.
The two competing inventors in the underlying inter-
ferences on appeal—Stanford professor Stephen Quake
and CUHK professor Dennis Lo—both developed methods
for diagnosing aneuploidies using cell-free fetal DNA (“cff-
DNA”) from maternal blood samples. In 1997, Lo and a
colleague discovered that cff-DNA circulates in maternal
blood in small amounts. This discovery made possible
new prenatal screening techniques for chromosomal and
other abnormalities, but researchers developing tech-
niques for assaying cff-DNA had to overcome interference
from maternal DNA in the maternal blood sample.
In 2006, Quake developed a “digital analysis” method
to detect small changes in the quantity of an aneuploid
chromosome relative to the quantity of one or more nor-
mal chromosomes, without distinguishing between ma-
ternal and fetal DNA. ’018 patent, col. 1, ll. 46–60; col. 2,
ll. 7–9; col. 7, ll. 46–61. Quake describes “a method of
differential detection of target sequences in a mixture of
maternal and fetal genetic material.” Id. col. 4, ll. 43–45.
The ’018 specification explains that the approach “in-
volves the separation of the extracted genomic material
into discrete units so that the detection of a target se-
quence (e.g., chromosome 21) may be simply quantified as
binary (0, 1) or simple multiples, 2, 3, etc.” Id. col. 1, ll.
49–52.
4 STANFORD UNIV. v. THE CHINESE UNIV. OF HONG KONG
Quake’s specification outlines the four steps in his
method: (1) obtaining a maternal tissue sample, prefera-
bly blood; (2) distributing single DNA molecules from this
sample to a number of discrete reaction samples;
(3) “[d]etecting the presence of the target in the DNA in a
large number of reaction samples”; and (4) performing
“[q]uantitative analysis of the detection of the maternal
and fetal target sequences.” Id. col. 8, l. 35–col. 9, l. 6.
The method requires a large number of samples, as only a
small amount of cff-DNA is present in a maternal sample.
The specification clarifies that the digital PCR technique,
in which a known target DNA sequence in a reaction well
is amplified by target-specific primers, is the preferred
embodiment for amplifying and detecting target sequenc-
es.
The capabilities of second-generation massively paral-
lel sequencing (“MPS”) are useful for performing Quake’s
method, as this method can process large numbers of
DNA samples simultaneously. Quake’s specification
discloses that second-generation MPS can be used for
counting chromosomes through DNA sequencing using
the Illumina sequencing platform. Id, col. 19, l. 59–col.
20, l. 3. MPS can be performed by “random” or “targeted”
methods. In the random format, all DNA in a sample is
linked to a leader sequence and amplified using a primer
complementary to the leader. Appellee Br. 10. In the
targeted format, the target sequence is specifically ampli-
fied, and then sequenced.
Quake claimed his method in an application filed on
February 2, 2007; this application issued as U.S. Patent
No. 7,888,017 (“the ’017 patent”). Quake filed continua-
tion application no. 12/393,803 (“the ’803 application”) in
February 2009. This continuation application issued as
the ’018 patent at issue in this appeal. The ’017 and ’018
patents share the same specification.
STANFORD UNIV. v. THE CHINESE UNIV. OF HONG KONG 5
The original claims of Quake’s ’803 application explic-
itly recited methods that required the detection of “target
sequences.” For example, claim 1 of the ’803 application
read:
1. A method of differential detection of target se-
quences in a mixture of maternal and fetal genetic
material, comprising the steps of:
a) obtaining maternal tissue containing both ma-
ternal and fetal genetic material;
b) distributing the genetic material into discrete
samples, each sample containing on average not
more than about one target sequence per sample;
c) measuring the presence of different target se-
quences in the discrete samples; and
d) analyzing a number of the discrete samples suf-
ficient to obtain results distinguishing different
target sequences.
J.A. 3253 (emphasis added).
In 2011, Quake cancelled all pending claims in the
application which later issued as the ’018 patent, and
added new claims. 2 A representative later-added claim
from the ’018 patent states:
1. A method for determining presence or absence
of fetal aneuploidy in a maternal tissue sample
comprising fetal and maternal genomic DNA,
wherein the method comprises:
2 Quake filed other applications on the same sub-
ject, including the 12/393,833 application at issue in the
’923 and ’924 interferences.
6 STANFORD UNIV. v. THE CHINESE UNIV. OF HONG KONG
a. obtaining a mixture of fetal and mater-
nal genomic DNA from said maternal tis-
sue sample;
b. conducting massively parallel DNA se-
quencing of DNA fragments randomly se-
lected from the mixture of fetal and
maternal genomic DNA of step a) to de-
termine the sequence of said DNA frag-
ments;
c. identifying chromosomes to which the
sequences obtained in step b) belong;
d. using the data of step c) to compare an
amount Stanfordof at least one first chro-
mosome in said mixture of maternal and
fetal genomic DNA to an amount of at
least one second chromosome in said mix-
ture of maternal and fetal genomic DNA,
wherein said at least one first chromosome
is presumed to be euploid in the fetus,
wherein said at least one second chromo-
some is suspected to be aneuploid in the
fetus, thereby determining the presence or
absence of said fetal aneuploidy.
’018 patent, col. 33, ll. 48–67 (emphasis added).
Lo’s “random sequencing” method uses random MPS
and does not require the detection of specific target se-
quences. The first step of Lo’s method is to obtain a
maternal blood sample, containing both maternal and cff-
DNA. The researcher then sequences the mixed maternal
and cff-DNA from the blood sample using random MPS.
The sequence fragments obtained from random MPS are
then aligned to a reference genome to determine a chro-
mosome or chromosomal region of origin for each se-
quence. Once the chromosome fragments have been
mapped to their respective chromosomes of origin, the
STANFORD UNIV. v. THE CHINESE UNIV. OF HONG KONG 7
researcher can compare the overall number of sequences
mapped to each chromosome. A disproportionate number
(e.g., greater frequency) of aligned sequences to chromo-
some 21 reveals the presence of a Down’s syndrome
trisomy.
Lo filed provisional application no. 60/951,438 describ-
ing the “random sequencing” method on July 23, 2007,
and subsequently filed application no. 12/178,181 on July
23, 2008. This application published in January 2009.
B. Interference History
CUHK claims that, in 2011, Quake realized that
CUHK had claimed the “random sequencing” method.
Quake then cancelled all pending claims in the applica-
tion that later issued as the ’018 patent, and added the
claims listed above that, for the first time, explicitly cover
random MPS methods. CUHK also claims that the ’833
application copied claims from Lo. Stanford contends that
random MPS is disclosed in the specification and supports
these later-filed claims.
Both Quake and Lo requested interferences to deter-
mine who invented the random sequencing method, and
when the method was invented. In early 2013, the PTO
declared three interferences between Quake’s patents and
applications and Lo’s patents and applications. 3 In each
proceeding, Lo attacked the Quake ’018 patent or the ’833
application as unpatentable for lack of written descrip-
tion. Supported by expert testimony from Dr. Stacey
Gabriel, CUHK claimed that Quake’s specification de-
3 The ’920 interference involved Lo application no.
13/070,275 and the ’018 patent. The ’923 interference
involved Lo applications nos. 12/178,181, 13/070,240,
12/614,350, and 13/070,251 and Quake’s ’833 application.
The ’924 interference involved Lo application no.
13/417,119 and Quake’s ’833 application.
8 STANFORD UNIV. v. THE CHINESE UNIV. OF HONG KONG
scribes the digital analysis of predetermined target se-
quences and is inconsistent with the random sequencing
method invented by Lo. Supported by expert testimony
from Dr. John Detter, Stanford claimed that Quake’s
specification clearly contemplated random MPS. Relying
primarily on the language of columns 19–20 of the ’018
patent, Stanford argued the ’018 patent discloses every
aspect needed to detect aneuploidy using random MPS
including random sequencing, step (b) of the claim;
alignment, step (c) of the claim; and a comparison step,
step (d) of the claim.
The Board granted CUHK’s written description mo-
tion in all three interferences and found Quake’s claims
were unpatentable. J.A. 23; J.A. 52; J.A. 81. The Board
found that the specification disclosed “targeted” rather
than “random” sequencing, and the specification would
not have indicated to one of ordinary skill in the art that
Quake was in possession of the claimed random MPS
method. J.A. 22.
In its decision, the Board repeatedly credited the tes-
timony of Dr. Gabriel, including in finding that (1) the
specification of the ’018 patent is directed to the use of
“digital analysis” of predetermined targeted sequences in
a sample, and (2) the language relied upon by Quake
could have related to either random or targeted sequenc-
ing but that, because “the main focus of the Quake ’018
patent [was] on diagnosing aneuploidy with digital PCR,
those of skill in the art would have understood the discus-
sion of massively parallel sequencing to refer to sequenc-
ing targeted, predetermined portions of the DNA in a
sample, not sequencing of random DNA.” J.A. 8–12; J.A.
20.
The Board also rejected “Quake’s characterization of
Dr. Gabriel’s testimony. Though Dr. Gabriel testified that
the Quake specification discloses massively parallel
sequencing, we do not find that she testified the applica-
STANFORD UNIV. v. THE CHINESE UNIV. OF HONG KONG 9
tion discloses massively parallel sequencing of random
DNA fragments.” J.A. 17 (emphasis in original). The
Board concluded that Dr. Gabriel’s statement that the
Illumina platform referenced in the specification could be
used for both random and targeted sequencing was not a
reference to random MPS, as used by Lo. According to the
Board, this reference to the Illumina platform could have
also supported targeted sequencing and, in the context of
the entirety of the specification, did in fact refer to the
targeted sequencing of DNA. J.A. 17–18.
Stanford argued that the references to “massively
parallel sequencing of millions of fragments using at-
tachment of randomly fragmented genomic DNA,” “ran-
dom sequence information,” “identify[ing] a sequence as
belonging to a specific human chromosome,” and “soft-
ware methods that can be used to identify a sequence in
comparison to the known genome sequence,” were all
indicative of the random method for carrying out MPS.
J.A. 11; J.A. 14–16. But the Board concluded that:
Though the Quake inventors may have possessed
parts of such a method, including massively paral-
lel sequencing, randomly fragmenting DNA, and
aligning sequences to genomic sequences, the
facts do not indicate that those of ordinary skill in
the art would have understood the inventors had
put these pieces together into a complete method
of sequencing random DNA fragments and identi-
fying the sequenced fragments to determine an-
euploidy.
J.A. 22.
C. District Court Proceedings
Stanford appealed the Board’s interference rulings to
the Northern District of California, pursuant to 35 U.S.C.
§ 146. Prior to the transfer of that appeal to this court,
the parties engaged in discovery, including full expert
10 STANFORD UNIV. v. THE CHINESE UNIV. OF HONG KONG
discovery, and CUHK filed a motion for summary judg-
ment seeking resolution of the interferences in its favor as
a matter of law. The district court conducted a hearing on
CUHK’s motion and thereafter denied CUHK’s request,
concluding that there were material issues of fact not
suitable for resolution on summary judgment. Two days
after the district court held the summary judgment hear-
ing, CUHK notified the district court of a potential juris-
dictional issue regarding § 146 in a District of
Massachusetts case, Biogen Idec MA, Inc. v. Japanese
Foundation for Cancer Research, 38 F. Supp. 3d 162 (D.
Mass. 2014). The district court in Biogen held that the
Leahy-Smith America Invents Act, Pub. L. No. 112-29,
125 Stat. 284 (2011), permitted the appeal of a Board
interference decision only to the Federal Circuit for inter-
ferences declared after September 15, 2012. 38 F. Supp.
3d at 168. Pending the Federal Circuit’s review in Bio-
gen, the Northern District of California stayed the § 146
action.
On May 7, 2015, we affirmed the lower court’s deci-
sion. Biogen MA, Inc. v. Japanese Found. for Cancer
Research, 785 F.3d 648 (Fed. Cir. 2015). After we denied
rehearing, the parties in this case jointly requested trans-
fer of this case from the Northern District of California to
the Federal Circuit. The district court granted the re-
quest and transferred the case here.
II. DISCUSSION
On appeal, Stanford briefs three questions. First,
though it consented to the transfer of its appeals to this
court, it asks that we rethink our decision in Biogen
regarding the continued right to seek relief in district
court after an unfavorable interference proceeding before
the Board. Second, Stanford contends that, even if it
cannot return to district court to complete the proceedings
begun there, we should either take into consideration the
record developed in that proceeding in reaching our
STANFORD UNIV. v. THE CHINESE UNIV. OF HONG KONG 11
decision or vacate the Board’s orders and instruct the
Board to take those matters into consideration. Finally,
Stanford argues that, if it is restricted to the record before
the Board, even on that record it is clear that the Board
improperly rejected its claims for lack of written descrip-
tion. We consider each issue in turn.
A. Availability of § 146 Proceedings
We held in Biogen that the AIA abolished the right of
parties to bring civil actions in district court under 35
U.S.C. § 146 for review of Board decisions in interferences
declared on or after September 16, 2012. See Biogen, 785
F.3d at 654. We concluded that we have exclusive juris-
diction over appeals from decisions of the Board in inter-
ferences declared after September 15, 2012, relying on the
version of 28 U.S.C. § 1295(a)(4)(A) that existed on Sep-
tember 15, 2012. We subsequently denied rehearing en
banc in Biogen. After the initial briefing in this case, the
Supreme Court also denied certiorari. Biogen MA v.
Japanese Found. for Cancer Research, 136 S. Ct. 1450
(Mar. 21, 2016).
While Stanford argued in its opening brief that Biogen
was wrongly decided and that we should rethink our
holding there, once the Supreme Court denied certiorari,
Stanford did not revisit that argument in its reply brief
and did not raise the point at oral argument. To the
extent Stanford has not abandoned its objection to Biogen,
we decline to accept Stanford’s invitation to criticize it.
Biogen is the law in this circuit and we, as a panel, will
not revisit it.
B. District Court Discovery
We next turn to the question of whether there is any
role the information elicited during discovery in the
district court can play in these proceedings. Stanford
relies heavily on that information in its appeal from the
Board’s decisions, contending that it materially alters
12 STANFORD UNIV. v. THE CHINESE UNIV. OF HONG KONG
what the Board understood in reaching its decisions.
CUHK contends that the material is not properly at issue
before this court and that the newly elicited facts, in any
event, actually support the Board’s conclusions and
CUHK’s arguments.
While the parties spend a great deal of their briefing
on the meaning and impact of this discovery, we agree
with CUHK’s threshold position that we may not consider
it and may not remand this matter to direct the Board to
do so. Given that the district court did not have subject
matter jurisdiction to review the Board’s interference
decisions, Stanford’s attempt to include evidence elicited
during proceedings there is inappropriate—the activities
in the district court are a nullity when the district court
lacks subject matter jurisdiction to consider a matter. See
Ruhrgas AG v. Marathon Oil Co., 526 U.S. 574, 577
(1999) (“The requirement that jurisdiction be established
as a threshold matter . . . is inflexible and without excep-
tion; for jurisdiction is power to declare the law, and
without jurisdiction the court cannot proceed at all in any
cause.” (quoting Steel Co. v. Citizens for a Better Env’t,
523 U.S. 83, 94–95 (1998)) (brackets, citations, and inter-
nal quotations marks omitted)). CUHK cannot waive the
district court’s lack of jurisdiction through its consent to
litigate pre-Biogen. See Ins. Corp. of Ir., Ltd. v. Com-
pagnie des Bauxites de Guinee, 456 U.S. 694, 702 (1982)
(“[N]o action of the parties can confer subject-matter
jurisdiction upon a federal court. Thus, the consent of the
parties is irrelevant . . . and a party does not waive the
requirement by failing to challenge jurisdiction early in
the proceedings.”) (citations omitted).
Our precedent makes clear that our review of a Board
interference decision must be confined to the “four cor-
ners” of the record before the Board. In re Gartside, 203
F.3d 1305, 1314 (Fed. Cir. 2000); 35 U.S.C. § 144 (2012).
CUHK correctly asks that we treat the district court
proceedings as if they never occurred. While we ultimate-
STANFORD UNIV. v. THE CHINESE UNIV. OF HONG KONG 13
ly vacate the Board’s decision for other reasons, moreover,
we do not do so because new evidence may have been
developed in the district court proceedings. It will be up
to the Board to decide whether it wishes to reopen the
record for that reason, or any other; we express no opinion
on whether it should do so.
C. Written Description
We now turn to the heart of Stanford’s appeal. We
review the Board’s legal conclusions de novo. In re Elsner,
381 F.3d 1125, 1127 (Fed. Cir. 2004). We review factual
findings of the Board for substantial evidence. In re
Gartside, 203 F.3d at 1313–15.
Whether a patent claim satisfies the written descrip-
tion requirement of 35 U.S.C. § 112, paragraph 1, depends
on whether the description “clearly allow[s] persons of
ordinary skill in the art to recognize that [the inventor]
invented what is claimed.” Vas-Cath Inc. v. Mahurkar,
935 F.2d 1555, 1562–63 (Fed. Cir. 1991) (internal quota-
tion marks omitted) (quoting In re Gosteli, 872 F.2d 1008,
1012 (Fed. Cir. 1989)).
[W]hatever the specific articulation, the test re-
quires an objective inquiry into the four corners of
the specification from the perspective of a person
of ordinary skill in the art. Based on that inquiry,
the specification must describe an invention un-
derstandable to that skilled artisan and show that
the inventor actually invented the invention
claimed.
Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351
(Fed. Cir. 2010) (en banc).
Substantial evidence supports a finding that the spec-
ification satisfies the written description requirement
when “the essence of the original disclosure” conveys the
necessary information—“regardless of how it” conveys
such information, and even when the disclosure’s “words
14 STANFORD UNIV. v. THE CHINESE UNIV. OF HONG KONG
[a]re open to different interpretation[s].” In re Wright,
866 F.2d 422, 424–25 (Fed. Cir. 1989) (citations and
internal quotation marks omitted, emphasis in original);
see also Falko-Gunter Falkner v. Inglis, 448 F.3d 1357,
1365–66 (Fed. Cir. 2006) (finding substantial evidence
supported written description based on “several passages
in the [patentee’s] application” and the unrebutted “tes-
timony of [the patentee’s] expert,” which showed that
skilled artisans would understand the invention); Novo-
zymes A/S v. DuPont Nutrition Biosciences APS, 723 F.3d
1336, 1346 (Fed. Cir. 2013) (discussing the metaphor from
In re Ruschig, 379 F.2d 990, 994–95 (CCPA 1967) that a
disclosure should “provide sufficient ‘blaze marks’ to guide
a reader through the forest of disclosed possibilities
toward the claimed compound”).
The parties dispute whether the Board correctly de-
termined that the ’018 patent does not disclose the ran-
dom massively parallel sequencing of nucleic acid
sequences claimed in the later-added claims such that a
person of skill in the art would have concluded that the
Quake inventors were in possession of the method
claimed. First, the parties disagree as to whether the
reference to Illumina products in the specification, quoted
below, adequately discloses random massively parallel
sequencing as the later-added claims require:
A methodology useful in the present invention
platform is based on massively parallel sequenc-
ing of millions of fragments using attachment of
randomly fragmented genomic DNA to a planar,
optically transparent surface and solid phase am-
plification to create a high density sequencing
flow cell with millions of clusters, each containing
~1,000 copies of template per sq. cm. These tem-
plates are sequenced using four-color DNA se-
quencing-by-synthesis technology. See, products
offered by Illumina, Inc., San Diego Calif. Also,
see US 2003/0022207 to Balasubramanian, et al.,
STANFORD UNIV. v. THE CHINESE UNIV. OF HONG KONG 15
published Jan. 30, 2003, entitled “Arrayed poly-
nucleotides and their use in genome analysis.”
’018 patent, col. 19, l. 59–col. 20, l. 3 (emphasis added).
On this issue, the Board had to determine what the
’018 specification’s reference to Illumina products meant
at the time of the invention, and whether such a reference
encompassed random and/or targeted sequencing. “Writ-
ten description is a question of fact, judged from the
perspective of one of ordinary skill in the art as of the
relevant filing date.” Falko-Gunter, 448 F.3d at 1363
(citing Vas-Cath, 935 F.2d at 1563–64). The parties do
not dispute the February 2007 priority date as it applies
to this issue.
The Board concluded that:
[G]iven that Dr. Gabriel supports her testimony
with published references and given that the lan-
guage of the Quake ’018 patent at 19:48-20:3 does
not preclude targeted massively parallel sequenc-
ing, we credit Dr. Gabriel’s testimony that those of
skill in the art could have considered the refer-
ences in the ’018 patent specification to Illumina
products to indicate targeted sequencing.
J.A. 19 (emphasis added). The Board relied on Dr. Gabri-
el’s testimony to conclude that the ’018 patent lacked
sufficient written support.
We must base our review on the analysis presented by
the Board. SEC v. Chenery Corp., 332 U.S. 194, 196
(1947) (“[A] reviewing court, in dealing with a determina-
tion or judgment which an administrative agency alone is
authorized to make, must judge the propriety of such
action solely by the grounds invoked by the agency. If
those grounds are inadequate or improper, the court is
powerless to affirm the administrative action by substi-
tuting what it considers to be a more adequate or proper
basis.”). The Board stated that it relied on Dr. Gabriel’s
16 STANFORD UNIV. v. THE CHINESE UNIV. OF HONG KONG
testimony, and further noted that Dr. Gabriel relied on
documents related to the Roche 454 sequencer and other
“published references.” We conclude that the Board erred
in its reliance on the portions of Dr. Gabriel’s testimony
that rely on these references.
Both Dr. Gabriel and the Board failed to cite any evi-
dence of targeted or random sequencing on the Illumina
platform prior to Quake’s filing date. Although Dr. Ga-
briel did point to two post-dated references (Porreca, Nat.
Methods 4:931 (2007) and Krishnakumar, Proc. Nat’l
Acad. Sci. USA 105:9296 (2008)) that discuss the use of
targeted sequencing methods on the Illumina GA and GS-
FLX platforms, the Board did not cite to or rely upon
these references to support its decision.
Dr. Gabriel also cited to several publications that do
not discuss the Illumina platform. These publications
describe targeted sequencing methods where a predeter-
mined target sequence can be selected by amplification
and then sequenced on an MPS platform. J.A. 4889–90
¶¶ 19–20. Dr. Gabriel cited to a November 2006 infor-
mation sheet for the Roche 454 Life Sciences Amplicon
Sequencing Template Preparation method, “which de-
scribes a targeted sequencing method in which a prede-
termined target sequence is selected by amplification and
then sequenced” on the Roche 454 massively parallel
sequencing platform. J.A. 4890 ¶ 20. Dr. Gabriel high-
lighted Thomas, a 2006 article, as one representative
example of a targeted sequencing approach using the
Roche 454 platform. J.A. 4890 ¶ 20. And Dr. Gabriel
noted two other related articles; one presents further
refinement of Thomas’s method (Binladen PLoS One
2:e197 (2007)), and the other discusses the use of human
target sequences on the Roche 454 platform (Dahl Proc.
Nat’l Acad. Sci. USA 104:9387 (2007)). Dr. Gabriel also
cited to a chapter in Metzker’s 2008 book “Advances in
Next-Generation DNA Sequencing Technologies” that
discusses a targeted approach for profiling sequence tags
STANFORD UNIV. v. THE CHINESE UNIV. OF HONG KONG 17
and using the Roche 454 platform to examine microbial
microenvironments and ancient DNA. J.A. 4889 ¶ 19.
The Board stated that it relied on Dr. Gabriel’s testi-
mony, at least in part, because of the “published refer-
ences” to which she cited. As discussed above, the
Illumina references post-date the 2007 priority date, and
the other references discuss a platform not referenced in
the ’018 patent. All of the published references on which
the Board relies focus on the Roche 454 platform, not the
Illumina platform actually referenced in the specification.
The Board did not cite evidence to connect targeted se-
quencing on the Roche 454 platform to targeted sequenc-
ing on the Illumina system, nor has the Board explained
what it found persuasive about the Roche 454 platform
references.
Indeed, Stanford offers evidence to show that the Il-
lumina sequencing platform—a second-generation MPS
platform first released in 2006—came after the Roche 454
platform—a first generation MPS platform first released
in 2005. And the systems operate differently: although
the Roche 454 system could apply targeting techniques
using its low-throughput PCR amplification reactions, the
Illumina platform could generate far more data using its
high-throughput system but had difficulties applying
simple PCR amplification procedures due to its scale. Yet
the Board never compared the difficulty of performing
targeted or random sequencing on an Illumina platform.
We further note that Dr. Gabriel and the Board failed to
cite to the Roche 454 references with specificity, leaving
us with no reviewable record to conclude that the dis-
closed methods or platform would have been applicable to
Illumina on Quake’s priority date.
Dr. Gabriel did testify that those of ordinary skill in
the art, both in 2006–07 and today, would consider the
Roche 454 platform to be an MPS platform; Stanford does
not dispute this point. J.A. 4888 ¶ 17; Appellant Br. 44,
18 STANFORD UNIV. v. THE CHINESE UNIV. OF HONG KONG
47–52. But both Dr. Gabriel’s testimony and the Board’s
discussion on this issue fail to explain why the Board
could properly rely on testimony focused on the Roche 454
platform for any purpose beyond its discussion of MPS
platforms in general, when the ’018 patent specifically
cites to the Illumina platform. Nor has Dr. Gabriel or the
Board explained why we should use conclusions about the
Roche 454 platform to conclude that Illumina teaches only
targeted sequencing.
Second, the Board found that a person of skill in the
art “would have understood the discussion of massively
parallel sequencing [in the ’018 patent] to refer to se-
quencing targeted, predetermined portions of the DNA in
a sample, not sequencing of random DNA.” J.A. 20. To
support this finding, the Board credits Dr. Gabriel’s
testimony that a person of skill in the art “could have
considered the references in the ’018 patent specification
to Illumina products to indicate targeted sequencing,” in
part because “the language of the Quake ’018 patent at
19:48-20:3 does not preclude targeted massively parallel
sequencing.” J.A. 19 (emphasis added). The Board’s
finding that the ’018 specification’s language does not
preclude targeted MPS ignores the fact that the same
description might be able to disclose both random and
targeted sequencing. Put another way, even if the ’018
specification could indicate targeted sequencing, it could
also disclose random sequencing, or it could disclose both
random and targeted sequencing. The Board frames its
finding in terms of an erroneous premise: the Board’s
task was to determine whether the ’018 patent’s written
description discloses random MPS sequencing, as recited
by the later-added claims, not whether the description
does not preclude targeted MPS sequencing. The Board’s
error on this issue is compounded by its failure to explain
the meaning of key sentences and phrases in the specifi-
cation’s discussion of the sequencing process, and its
failure to compare these statements to the claim limita-
STANFORD UNIV. v. THE CHINESE UNIV. OF HONG KONG 19
tions. For example, the Board failed to explain the mean-
ing of “using attachment of randomly fragmented genomic
DNA,” “solid phase amplification,” or “~1,000 copies of
template” in the context of this patent, nor did the Board
examine the meaning of “templates” or the specification’s
statement that “[t]hese templates are sequenced using
four-color DNA sequencing-by-synthesis technology.” See
’018 patent, col. 19, l. 48–col. 20, l. 3.
For these reasons, we vacate the interference deci-
sions and remand for the Board to reconsider whether
Quake’s relevant patents and applications satisfy the
written description requirement. In re Nuvasive, Inc., 842
F.3d 1376, 1382 (Fed. Cir. 2016) (finding that the Board
must “make the necessary findings and have an adequate
‘evidentiary basis for its findings’” (quoting In re Lee, 277
F.3d 1338, 1344 (Fed. Cir. 2002)); Ariosa Diagnostics v.
Verinata Health, Inc., 805 F.3d 1359, 1365 (Fed. Cir.
2015) (“[W]e must not ourselves make factual and discre-
tionary determinations that are for the agency to make.”)
(citing In re Lee, 277 F.3d at 1342, Interstate Commerce
Comm’n v. Bhd. of Locomotive Eng’rs, 482 U.S. 270, 283
(1987), and Chenery, 332 U.S. at 196–97).
On remand, the Board should examine whether a per-
son of ordinary skill in the art would have known, as of
the priority date, that the ’018 specification’s reference to
Illumina products meant random MPS sequencing as
recited in the claims, by examining the record evidence as
to pre-filing date art-related facts on Illumina products.
The Board’s inquiry may include an analysis of whether
the record contains testimony or evidence, relevant to this
written description analysis, showing that any post-filing
date publications contain art-related facts on random
MPS sequencing or Illumina products existing on the
filing date. See, e.g., In re Hogan, 559 F.2d 595, 605
(CCPA 1977) (in the enablement context, noting that the
CCPA permitted the use of “later publications as evidence
of the state of the art existing on the filing date of an
20 STANFORD UNIV. v. THE CHINESE UNIV. OF HONG KONG
application.” (citations omitted)); see also Plant Genetic
Sys., N.V. v. DeKalb Genetics Corp., 315 F.3d 1335, 1344
(Fed. Cir. 2003) (“[T]he district court looked into post–
1987 reports to determine whether monocot cells were
readily transformable in 1987 [the priority date] rather
than to show that monocot cells could be successfully
transformed in 1990. . . . Thus, the district court properly
used later reports as evidence of the state of the art
existing in 1987.”). The Board may not, however, use
post-dated references as a source for “later knowledge
about later art-related facts . . . which did not exist on the
filing date.” Hogan, 559 F.2d at 605; see also U.S. Steel
Corp. v. Phillips Petroleum Co., 865 F.2d 1247, 1251–52
(Fed. Cir. 1989) (“[T]he district court correctly held de-
fendants’ evidence immaterial to the section 112, first
paragraph inquiry. The central flaw in defendants’ evi-
dence, as recognized by the district court, is that it was
directed solely to a later state of the art,” and therefore,
“[d]efendants’ misdirected approach here is the same as
that improperly relied upon by the PTO in Hogan.”).
On remand, the Board also should examine whether a
person of ordinary skill would have understood that the
’018 patent’s specification disclosed random MPS sequenc-
ing, as opposed to whether the specification did not pre-
clude targeted MPS sequencing.
III. CONCLUSION
For the reasons stated above, we vacate and remand
the Board’s interference decisions for further proceedings
consistent with this opinion.
VACATED AND REMANDED
COSTS
No costs.