Court Opinion

ID: 4310945
Source: CourtListenerOpinion
Date Created: 2018-09-10 15:00:50.669018+00
Date Added: 2024-06-11T14:44:25.471395
License: Public Domain

United States Court of Appeals
      for the Federal Circuit
                ______________________

REGENTS OF THE UNIVERSITY OF CALIFORNIA,
   UNIVERSITY OF VIENNA, EMMANUELLE
             CHARPENTIER,
                Appellants

                          v.

  BROAD INSTITUTE, INC., MASSACHUSETTS
INSTITUTE OF TECHNOLOGY, PRESIDENT AND
     FELLOWS OF HARVARD COLLEGE,
                  Appellees
           ______________________

                      2017-1907
                ______________________

    Appeal from the United States Patent and Trademark
Office, Patent Trial and Appeal Board in No. 106,048.
                  ______________________

             Decided: September 10, 2018
               ______________________

   DONALD B. VERRILLI, JR., Munger, Tolles & Olson
LLP, Washington, DC, argued for appellants. Appellants
Regents of the University of California, University of
Vienna also represented by GINGER ANDERS; EDWARD
GEORGE DANE, ADAM R. LAWTON, Los Angeles, CA.

    RAYMOND N. NIMROD, Quinn Emanuel Urquhart &
Sullivan, LLP, New York, NY, argued for appellees. Also
2            UNIVERSITY OF CALIFORNIA   v. BROAD INSTITUTE, INC.

represented by MATTHEW D. ROBSON; STEVEN R. TRYBUS,
HARRY J. ROPER, Jenner & Block LLP, Chicago, IL.

    LI-HSIEN RIN-LAURES, RinLaures LLC, Chicago, IL,
for appellant Emmanuelle Charpentier. Also represented
by SANDIP PATEL, Marshall, Gerstein & Borun LLP,
Chicago, IL.
                ______________________

        Before PROST, Chief Judge, SCHALL and MOORE, Cir-
                         cuit Judges.
MOORE, Circuit Judge.
    The University of California, the University of Vien-
na, and Emmanuelle Charpentier, (collectively “UC”),
appeal a decision of the Patent Trial and Appeal Board
determining there was no interference-in-fact between
UC’s Application No. 13/842,859, and the claims of twelve
patents and one application owned by the Broad Institute,
Inc., Massachusetts Institute of Technology, and the
President and Fellows of Harvard College, (collectively
“Broad”). Because the Board’s underlying factual findings
are supported by substantial evidence and the Board did
not err in concluding that Broad’s claims would not have
been obvious over UC’s claims, we affirm.
                        BACKGROUND
    The involved claims relate to the use of a
CRISPR-Cas9 1 system for the targeted cutting of DNA
molecules. The system includes three components: (1) a
“crRNA”; (2) a “tracrRNA”; and (3) the Cas9 protein.
J.A. 4803. The crRNA is an RNA molecule with a
variable portion that targets a particular DNA sequence.
J.A. 4799–803.    The nucleotides that make up the

    1  “CRISPR” is an acronym for “Clustered Regularly
Interspaced Short Palindromic Repeats.” J.A. 4682.
UNIVERSITY OF CALIFORNIA   v. BROAD INSTITUTE, INC.       3

variable portion complement the target sequence in the
DNA and hybridize with the target DNA. J.A. 4801.
Another portion of the crRNA consists of nucleotides that
complement and bind to a portion of the tracrRNA.
J.A. 4801. The Cas9 protein interacts with the crRNA
and tracrRNA and cuts both strands of DNA at the target
location. J.A. 4799.
     In August 2012, UC researchers published an article
(“Jinek 2012”) demonstrating that the isolated elements
of the CRISPR-Cas9 system could be used in vitro in a
non-cellular experimental environment. J.A. 4799–804.
In February 2013, Broad researchers published an article
describing the use of CRISPR-Cas9 in a human cell line.
J.A. 4682–86. Both parties sought patent protection.
CRISPR-Cas systems occur naturally in prokaryotes such
as bacteria, J.A. 4799, but have not been found to natural-
ly exist in eukaryotes, such as plants and animals,
J.A. 5488; see also J.A. 5006, 5029. It is undisputed that
the Jinek 2012 article did not report the results of exper-
iments using CRISPR-Cas9 in a eukaryotic cell, and the
claims in UC’s ’859 application do not refer to a particular
cell type or environment. J.A. 13, 9665–66. Claim 165 of
the ’859 application is representative:
   165. A method of cleaving a nucleic acid compris-
   ing
   contacting a target DNA molecule having a target
   sequence with an engineered and/or non-
   naturally-occurring Type II Clustered Regularly
   Interspaced     Short   Palindromic     Repeats
   (CRISPR)— CRISPR associated (Cas) (CRISPR-
   Cas) system comprising
       a) a Cas9 protein; and
       b) a single molecule DNA-targeting RNA
       comprising
4         UNIVERSITY OF CALIFORNIA   v. BROAD INSTITUTE, INC.

           i) a targeter-RNA that hybridizes
           with the target sequence, and
           ii) an activator-RNA that hybrid-
           izes with the targeter-RNA to form
           a double-stranded RNA duplex of
           a protein-binding segment,
       wherein the activator-RNA and the tar-
       geter-RNA are covalently linked to one
       another with intervening nucleotides,
       wherein the single molecule DNA-
       targeting RNA forms a complex with the
       Cas9 protein,
       whereby the single molecule DNA-
       targeting RNA targets the target se-
       quence, and the Cas9 protein cleaves the
       target DNA molecule.
J.A. 9665. The claims in Broad’s patents and application
are limited to use in eukaryotic cells. Claim 1 of U.S.
Patent No. 8,697,359 is representative:
    1. A method of altering expression of at least one
    gene product comprising introducing into a eu-
    karyotic cell containing and expressing a DNA
    molecule having a target sequence and encoding
    the gene product an engineered, non-naturally oc-
    curring Clustered Regularly Interspaced Short
    Palindromic Repeats (CRISPR)—CRISPR associ-
    ated (Cas) (CRISPR-Cas) system comprising one
    or more vectors comprising:
       a) a first regulatory element operable in a
       eukaryotic cell operably linked to at least
       one nucleotide sequence encoding a
       CRISPR-Cas system guide RNA that hy-
       bridizes with the target sequence, and
UNIVERSITY OF CALIFORNIA   v. BROAD INSTITUTE, INC.       5

       b) a second regulatory element operable in
       a eukaryotic cell operably linked to a nu-
       cleotide sequence encoding a Type-II Cas9
       protein,
   wherein components (a) and (b) are located on
   same or different vectors of the system, whereby
   the guide RNA targets the target sequence and
   the Cas9 protein cleaves the DNA molecule,
   whereby expression of the at least one gene prod-
   uct is altered; and, wherein the Cas9 protein and
   the guide RNA do not naturally occur together.
J.A. 1831.
    The Board instituted an interference, and Broad
moved to terminate the interference, arguing its claims
are patentably distinct from UC’s claims because a person
of ordinary skill in the art would not have had a reasona-
ble expectation that the CRISPR-Cas9 system would work
successfully in a eukaryotic cell. J.A. 7, 13. The Board
determined there was no interference-in-fact because,
given the differences between eukaryotic and prokaryotic
systems, a person of ordinary skill in the art would not
have had a reasonable expectation of success in applying
the CRISPR-Cas9 system in eukaryotes. J.A. 48–49. It
determined, therefore, that UC’s claims to the use of
CRISPR-Cas9 did not render obvious Broad’s claims to its
use in eukaryotes. J.A. 49.
    UC timely appeals. We have jurisdiction over appeals
of interferences under 28 U.S.C. § 1295(a)(4)(A) as it
existed prior to changes made by the America Invents Act
(“AIA”). See Technical Corrections—Leahy–Smith Ameri-
ca Invents Act, Pub. L. No. 112-274, 126 Stat. 2456, 2458
(2013).
                       DISCUSSION
     If two parties claim patentably indistinct subject mat-
ter, under pre-AIA 35 U.S.C. § 102(g), a patent may only
6         UNIVERSITY OF CALIFORNIA   v. BROAD INSTITUTE, INC.

be awarded to the first inventor. 2 Whether an interfer-
ence occurs is determined by comparing the involved
claims. Noelle v. Lederman, 355 F.3d 1343, 1352 (Fed.
Cir. 2004). The Board applies a two-way test to deter-
mine whether the claims are patentably distinct, asking
whether “the subject matter of a claim of one party would,
if prior art, have anticipated or rendered obvious the
subject matter of a claim of the opposing party and vice
versa.” 37 C.F.R. § 41.203(a). If the two-way test is not
met, no interference-in-fact exists.
     When an interference-in-fact turns on whether one set
of claims renders obvious the subject matter of another
set of claims, the standard of review mirrors that in an
obviousness review. Medichem, S.A. v. Rolabo, S.L., 353
F.3d 928, 932 (Fed. Cir. 2003). Obviousness is a question
of law based on underlying facts. WBIP, LLC v. Kohler
Co., 829 F.3d 1317, 1326 (Fed. Cir. 2016). In Graham v.
John Deere Co., 383 U.S. 1, 17–18 (1966), the Supreme
Court set forth factors for assessing obviousness. The
Graham factors—(1) the scope and content of the prior
art; (2) the differences between the claims and the prior
art; (3) the level of ordinary skill in the art; and
(4) objective considerations of nonobviousness—are ques-
tions of fact reviewed for substantial evidence. Arctic Cat
Inc. v. Bombardier Recreational Prods. Inc., 876 F.3d
1350, 1358 (Fed. Cir. 2017).
    An obviousness determination requires finding that a
person of ordinary skill in the art would have been moti-
vated to combine or modify the teachings in the prior art

    2    The AIA replaced the first-to-invent rule with a
first-inventor-to-file rule, but the prior rule continues to
apply in this interference. See Leahy-Smith America
Invents Act, Pub. L. No. 112-29, sec. 3(n)(2), 125 Stat.
284, 293 (2011); Storer v. Clark, 860 F.3d 1340, 1342 (Fed.
Cir. 2017).
UNIVERSITY OF CALIFORNIA   v. BROAD INSTITUTE, INC.      7

and would have had a reasonable expectation of success in
doing so. In re Stepan Co., 868 F.3d 1342, 1345–46 (Fed.
Cir. 2017). “Whether a person of ordinary skill in the art
would have been motivated to modify or combine teach-
ings in the prior art, and whether he would have had a
reasonable expectation of success, are questions of fact.”
Id. at 1346. We review the Board’s ultimate conclusion of
obviousness de novo, and the underlying factual findings
for substantial evidence. In re Mouttet, 686 F.3d 1322,
1330–31 (Fed. Cir. 2012).
    This case turns in its entirety on the substantial evi-
dence standard. The Board found a person of ordinary
skill in the art would not have had a reasonable expecta-
tion of success in applying the CRISPR-Cas9 system in
eukaryotic cells. J.A. 48–49. Given the mixture of evi-
dence in the record, we hold that substantial evidence
supports the Board’s finding that there was not a reason-
able expectation of success, and we affirm. UC argues
that the Board: (1) improperly adopted a rigid test for
obviousness that required the prior art contain specific
instructions, and (2) erred in dismissing evidence of
simultaneous invention as irrelevant. For the reasons set
forth below, we hold the Board did not err in its analysis.
           Reasonable Expectation of Success
     The Board found that a person of ordinary skill in the
art would not have had a reasonable expectation of suc-
cess in applying the CRISPR-Cas9 system in a eukaryotic
cell. J.A. 48–49. It concluded, therefore, that if UC’s
claims were prior art, they would not have rendered
Broad’s claims obvious, so there was no interference-in-
fact. J.A. 49. Substantial evidence supports the Board’s
finding that there would not have been a reasonable
expectation of success.
    Broad’s expert Dr. Paul Simons testified as to the dif-
ferences between prokaryotic systems and eukaryotic
systems that rendered the application of the CRISPR-
8         UNIVERSITY OF CALIFORNIA   v. BROAD INSTITUTE, INC.

Cas9 system in eukaryotic cells unpredictable. He ex-
plained that the function of the CRISPR-Cas9 system is
dependent on the proper folding of the Cas9 protein.
J.A. 5526 at ¶ 6.9. He explained that folding is particu-
larly important for the CRISPR-Cas9 system because of
the conformational changes the Cas9 protein undergoes in
performing its function. Id. He further explained that
differences in cellular conditions can cause differences in
protein folding, id., and elaborated on some of the differ-
ences between prokaryotic and eukaryotic cellular condi-
tions that would make the functionality of CRISPR-Cas9
in eukaryotes unpredictable, J.A. 5527 at ¶ 6.13. These
included: intracellular temperature, the concentration of
various ions, pH, and the presence of other molecules that
may be present in one type of cell, but not the other. Id.
    Dr. Simons identified additional concerns involving
the CRISPR-Cas9 system which he testified would have
caused a skilled artisan not to have a reasonable expecta-
tion that it would work in eukaryotic cells. The CRISPR-
Cas9 system relies on two RNA components, crRNA and
tracrRNA. J.A. 5528 at ¶ 6.15. Eukaryotic cells contain a
number of molecules, known as ribonucleases, which are
not present in prokaryotic cells, that cut up RNA mole-
cules. J.A. 5528–29 at ¶¶ 6.15–6.16. Eukaryotic cells also
contain systems that degrade double-stranded RNA. The
CRISPR-Cas9 system contains a section of double-
stranded RNA where the crRNA binds with the tracrRNA,
adding additional uncertainty. J.A. 5529–30 at ¶¶ 6.17–
6.20. Dr. Simons suggested a person of ordinary skill in
the art would have been concerned that the CRISPR-Cas9
system could result in an excessive number of double-
stranded DNA breaks given factors such as the greater
size of the human genome compared to typical bacterial
genome and the frequency with which similar DNA se-
quences appear in the human genome. J.A. 5530–32 at
¶¶ 6.22–6.27. He testified that these differences made it
such that a skilled artisan would not have had a reasona-
UNIVERSITY OF CALIFORNIA   v. BROAD INSTITUTE, INC.       9

ble expectation of success in applying CRISPR-Cas9 in
eukaryotic cells. J.A. 5532 at ¶ 6.27.
    In a September 2012 article, UC’s expert witness Dr.
Dana Carroll recognized many of the same issues that
could arise in attempting to apply the CRISPR-Cas9
system in eukaryotic cells. These included the possibility
that CRISPR-Cas9 might be degraded by nucleases in
eukaryotic cells and that toxicity could result from its use
in eukaryotic cells. J.A. 4797. He also noted potential
problems arising from the fact that, unlike prokaryotic
DNA, eukaryotic DNA exists in a chromatin complex, in
which the DNA is wrapped around protein structures.
J.A. 4797. He stated that “[t]here is no guarantee that
Cas9 will work effectively on a chromatin target or that
the required DNA-RNA hybrid can be stabilized in that
context.” J.A. 4797; accord J.A. 9111. He further noted
that the efficacy of prior systems relying on gene editing
through base pairing “remains discouragingly low in most
cases.” J.A. 4797. Ultimately, Dr. Carroll concluded that
whether the CRISPR-Cas9 system will work in eukary-
otes “remains to be seen” and “[o]nly attempts to apply
the system in eukaryotes will address these concerns.”
J.A. 4797. This is substantial evidence that skilled arti-
sans believed many problems could arise in implementing
the CRISPR-Cas9 system in eukaryotes, which the Board
viewed as indicating that an ordinarily skilled artisan
would have lacked a reasonable expectation of success.
    The Board was also presented evidence of statements
by the UC inventors acknowledging doubts and frustra-
tions about engineering CRISPR-Cas9 systems to function
in eukaryotic cells and noting the significance of Broad’s
success. One of the named inventors, Dr. Jennifer Doud-
na, acknowledged the “huge bottleneck” in making genetic
modifications in animals and humans, J.A. 5911, and
after the publication of the initial UC research, she stated
“[o]ur 2012 paper was a big success, but there was a
problem. We weren’t sure if CRISPR/Cas9 would work in
10        UNIVERSITY OF CALIFORNIA   v. BROAD INSTITUTE, INC.

eukaryotes,” J.A. 5880. She also explained that she had
“many frustrations” in getting CRISPR-Cas9 to work in
human cells, and that she thought success in doing so
would be “a profound discovery.” J.A. 5908. Evidence in
the record also suggested her colleagues recognized
Broad’s development was significant. When a colleague
contacted Dr. Doudna to inform her of Broad’s success he
stated “I hope you’re sitting down,” “CRISPR is turning
out to be absolutely spectacular in [Broad researcher]
George Church’s hands.” J.A. 5908. The Board viewed
this evidence as indicating that an ordinarily skilled
artisan would have lacked a reasonable expectation of
success. 3
    The Board also considered evidence regarding the de-
velopment of other gene editing systems. It found several
of these were not particularly informative in assessing the
reasonable expectation of success of CRISPR-Cas9.
Specifically, it found that the prior art TALEN and zinc
finger nuclease (“ZFN”) systems were not analogous to
CRISPR-Cas9 because they have their origins in eukary-
otic domains and that the adaptability of small prokaryot-
ic protein systems like Cre would not have informed the
expectation of success for the larger CRISPR-Cas9 com-
plex. J.A. 17 (citing J.A. 4797), 41, 43. Broad presented

     3  UC also argues the Board erred in giving “near-
dispositive weight” to statements by Dr. Doudna and Dr.
Carroll, which it claims were misinterpreted by the
Board. The Board considered a variety of statements
made by both Dr. Doudna and Dr. Carroll. In doing so, it
afforded the statements weight depending on the contexts
in which they were made and their relevance to its analy-
sis. See J.A. 14–23. To the extent UC argues the Board
erred in its reading of these statements in the contexts in
which they arose, we conclude substantial evidence sup-
ports the Board’s interpretation.
UNIVERSITY OF CALIFORNIA   v. BROAD INSTITUTE, INC.       11

evidence regarding three other systems derived from
prokaryotes that had been adapted for use in eukaryotes:
riboswitches, ribozyme systems, and group II introns.
The Board found that in each instance there was either
limited efficacy or the technology required a specific
strategy to adapt it for use in eukaryotic cells. J.A. 36–38.
Broad presented expert testimony that only a few ri-
boswitches had been successfully adapted to work in
eukaryotes, and a prior art article explained that differ-
ences in RNA folding in vivo versus in a cellular environ-
ment may prevent the riboswitches from working. J.A. 36
(citing J.A. 5537–38 at ¶ 6.47; J.A 5893). Based on expert
testimony and an earlier publication, the Board found
that although some success was achieved using ribozyme
systems, “that success required a specific strategy devel-
oped particularly for ribozymes.”            J.A. 38 (citing
J.A. 5889–90). As to group II introns, there was evidence
before the Board that despite 16 years of experimental
efforts and the development of a specific strategy to
increase the likelihood of success for that system, their
use in eukaryotes remained limited. J.A. 5535–36 at
¶¶ 6.37–39; J.A. 8653–56 at ¶¶ 1.45–53. This substantial
evidence supports the Board’s finding that the success in
applying similar prokaryotic systems in eukaryotes was
unpredictable and had relied on tailoring particular
conditions to the technology. J.A. 37–39. The Board also
found that “one skilled in the art would have expected
that the CRISPR-Cas9 system would have also required
its own set of unique conditions.” J.A. 39. We conclude
the record evidence is sufficient to support that finding.
    In light of the record evidence, which includes expert
testimony, contemporaneous statements made by skilled
artisans, statements by the UC inventors themselves, and
prior art failures, we conclude that the Board’s fact-
finding as to a lack of reasonable expectation of success is
supported by substantial evidence.
12        UNIVERSITY OF CALIFORNIA   v. BROAD INSTITUTE, INC.

    UC expended substantial time and effort to convince
this court that substantial evidence supports the view it
would like us to adopt, namely, that a person of ordinary
skill would have had a reasonable expectation of success
in implementing the CRISPR-Cas9 system in eukaryotes.
There is certainly evidence in the record that could sup-
port this position. The prior art contained a number of
techniques that had been used for adapting prokaryotic
systems for use in eukaryotic cells, obstacles adopting
other prokaryotic systems had been overcome, and Dr.
Carroll suggested using those techniques to implement
CRISPR-Cas9 in eukaryotes. We are, however, an appel-
late body. We do not reweigh the evidence. It is not our
role to ask whether substantial evidence supports fact-
findings not made by the Board, but instead whether such
evidence supports the findings that were in fact made.
Here, we conclude that it does.
                   Specific Instructions
     UC argues the Board erred in adopting a test requir-
ing that there be specific instructions in the prior art to
establish a reasonable likelihood of success. Appellants’
Opening Br. 19 (“its requirement that the art contain
‘specific instructions’”), 21 (“expressly refused to find
obviousness because the prior art lacked ‘specific instruc-
tions’”), 31 (“requiring that the prior art contain ‘specific
instructions’”; “insisted that the prior art must contain
‘instructions that are specifically relevant’”; “fell short
because it did not provide specific instructions”). It ar-
gues that instead of asking whether the claimed invention
is “the product not of innovation but of ordinary skill and
common sense,” the Board adopted a rigid test for obvi-
ousness that formalistically looked for specific instruc-
tions in the prior art while ignoring “the inferences and
creative steps that a person of ordinary skill in the art
would employ” without the need for specific guidance.
Appellants’ Opening Br. 27 (quoting KSR Int’l Co. v.
Teleflex Inc., 550 U.S. 398, 418, 420 (2007)). The Board
UNIVERSITY OF CALIFORNIA   v. BROAD INSTITUTE, INC.      13

did not adopt a test requiring there be specific instruc-
tions in the art in order to make a finding of a reasonable
expectation of success, and we see no error in its analysis.
     The Board acknowledged that certainty in the art is
not required, J.A. 12, and performed a factual analysis
based on the correct legal standard. In considering
whether there was a reasonable expectation of success, it
stated that it “look[ed] to whether or not there were
instructions in the prior art that would be specifically
relevant to CRISPR-Cas9,” as well as “whether there are
examples in the prior art of the success or failure of
similar systems.” J.A. 28–29. The Board noted that
“[s]pecific instructions that are relevant to the claimed
subject matter or success in similar methods or products
have directed findings of a reasonable expectation of
success.” J.A. 28. It further noted that in other cases the
combination of only generalized instructions and evidence
of failures with similar subject matter indicated there was
not a reasonable likelihood of success. J.A. 28. It made
clear that the determination “depends on the specific
nature of what was known from the prior art about closely
related subject matter.” J.A. 28. We see no error in these
statements of law—the Board did not hold specific in-
structions were needed.
    In this case, the Board found there would not have
been specific instructions in the art as to CRISPR-Cas9
that would have given one of ordinary skill in the art a
reasonable expectation of success, and it was “persuaded
that the failure demonstrated with other systems would
have indicated the lack of a reasonable expectation of
success.” J.A. 45–46. At no point did the Board suggest it
found there would not have been a reasonable expectation
of success solely because there were not specific instruc-
tions in the art describing how to apply CRISPR-Cas9 in
eukaryotes. We see no error in the Board’s consideration
of the lack of specific instructions in conjunction with
14        UNIVERSITY OF CALIFORNIA   v. BROAD INSTITUTE, INC.

prior failures at adapting prokaryotic systems to eukary-
otic cells based on general instructions.
     Treatment of Simultaneous Invention Evidence
     UC argues the Board erred in dismissing evidence of
simultaneous invention as irrelevant. It argues simulta-
neous invention can be compelling evidence of obvious-
ness, because it shows the claimed invention “was the
product only of ordinary mechanical skill or engineering
skill,” rather than genuine invention. Appellants’ Open-
ing Br. 37 (quoting Geo. M. Martin Co. v. All Mech. Sys.
Int’l, 618 F.3d 1294, 1305–06 (Fed. Cir. 2010)). It argues
simultaneous invention is strong objective evidence of
what constituted the level of ordinary skill in the art and
is relevant as a secondary consideration under the fourth
Graham factor. It argues six research groups inde-
pendently applied CRISPR-Cas9 in eukaryotic cells
within months of its disclosures, a secondary considera-
tion which the Board failed to address. The Board, how-
ever, did not treat this evidence as irrelevant. Instead,
the Board expressly recognized the relevance of simulta-
neous invention to the question of obviousness. J.A. 23.
    Simultaneous invention may serve as evidence of ob-
viousness when considered in light of all of the circum-
stances. Lindemann Maschinenfabrik GMBH v. Am.
Hoist & Derrick Co., 730 F.2d 1452, 1460 (Fed. Cir. 1984).
We have recognized that simultaneous invention may
bear upon the obviousness analysis in two ways. Mon-
arch Knitting Mach. Corp. v. Sulzer Morat GmbH, 139
F.3d 877, 883 (Fed. Cir. 1998). First, it is evidence of the
level of skill in the art. Id. Second, it constitutes objec-
tive evidence that persons of ordinary skill in the art
understood the problem and a solution to that problem.
Id. Inherent in the existence of interference practice is
the principle that evidence of simultaneous invention
cannot alone show obviousness, otherwise any claims
involved in an interference would be unpatentable for
UNIVERSITY OF CALIFORNIA   v. BROAD INSTITUTE, INC.      15

obviousness. Lindemann, 730 F.2d at 1460. The weight
of evidence of simultaneous invention must, therefore, be
carefully considered in light of all the circumstances. See
Monarch Knitting, 139 F.3d at 883.
    In August 2012, the Jinek 2012 paper was published
explaining the CRISPR-Cas9 system and its use in vitro
using isolated components. There is no dispute that this
represented a breakthrough in the art. The fact that six
research groups succeeded in applying this technology in
eukaryotic cells within a short period of time after this is
certainly strong evidence that there was a motivation to
combine the prior art in this manner. The Board express-
ly recognized UC’s evidence of simultaneous invention in
this context, and it concluded the evidence of simultane-
ous invention was evidence of the motivation to combine
the prior art references but did not “necessarily” indicate
an expectation of success prior to the completion of the
experiments. J.A. 23.
    UC would have the Board read more into this evi-
dence and infer that because several research teams
pursued a particular approach, and that approach was
ultimately successful, they must have expected that
approach to work. It argued to the Board that absent an
expectation of success, multiple groups “would not have
undertaken the use of UC’s Type-II CRISPR-Cas system
in eukaryotic cells.” J.A. 245. The Board rejected this
bright-line rule and instead determined in this instance
the evidence of simultaneous invention did not establish a
reasonable expectation of success given the “specific
context of the art at the time.” See J.A. 23–25. The Board
explained that “[e]ach case must be decided in its particu-
lar context, including the characteristics of the science or
technology, its state of advance, the nature of the known
choices, the specificity or generality of the prior art, and
the predictability of results in the area of interest.”
J.A. 25 (quoting Abbott Labs. v. Sandoz, Inc., 544 F.3d
1341, 1352 (Fed. Cir. 2008)). We do not see any error in
16        UNIVERSITY OF CALIFORNIA   v. BROAD INSTITUTE, INC.

this analysis. Contrary to UC’s claims, the Board recog-
nized that UC’s evidence of simultaneous invention is
relevant to the obviousness determination. We consider
Broad’s evidence of simultaneous invention, along with
evidence regarding the state of the art, the statements of
the inventors, failures involving similar technologies, and
the remainder of the record evidence, and conclude the
Board’s finding is supported by substantial evidence.
                       CONCLUSION
    For the foregoing reasons, we affirm the Board’s
judgment of no interference-in-fact. The Board performed
a thorough analysis of the factual evidence and considered
a variety of statements by experts for both parties and the
inventors, past failures and successes in the field, evi-
dence of simultaneous invention, and the extent to which
the art provided instructions for applying the CRISPR-
Cas9 technology in a new environment. In light of this
exhaustive analysis and on this record, we conclude that
substantial evidence supports the Board’s finding that
there was not a reasonable expectation of success, and the
Board did not err in its determination that there is no
interference-in-fact.
    We have considered UC’s remaining arguments and
find them unpersuasive. We note that this case is about
the scope of two sets of applied-for claims, and whether
those claims are patentably distinct. It is not a ruling on
the validity of either set of claims.
                      AFFIRMED