Cigan, Andrew Mark. et al.

Patent Trials and Appeals Board

Jun 26, 2020

2019003067 (P.T.A.B. Jun. 26, 2020)

UNITED STATES PATENT AND TRADEMARK OFFICE
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
14/463,687 08/20/2014 Andrew Mark Cigan BB2284-US-NP 5241
27310 7590 06/26/2020
PIONEER HI-BRED INTERNATIONAL, INC.
7250 NW 62ND AVENUE
PO BOX 552
JOHNSTON, IA 50131-0552
EXAMINER
UYENO, STEPHEN G
ART UNIT PAPER NUMBER
1662
NOTIFICATION DATE DELIVERY MODE
06/26/2020 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
IPsupport@corteva.com
sue.smith@corteva.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte ANDREW MARK CIGAN, SAVERIO CARL FALCO,
HUIRONG GAO, ZHONGSEN LI, ZHAN-BIN LIU, L. ALEKSANDER
LYZNIK, JINRUI SHI, SERGEI SVITASHEV, and JOSHUA K. YOUNG
____________

Appeal 2019-003067
Application 14/463,687
Technology Center 1600
____________

Before ERIC B. GRIMES, TIMOTHY G. MAJORS, and
MICHAEL A. VALEK, Administrative Patent Judges.

VALEK, Administrative Patent Judge.

DECISION ON APPEAL
Appellant1 submits this appeal under 35 U.S.C. § 134(a) involving
claims to a method of modifying a target site in the genome of a plant cell
that have been rejected for anticipation under 35 U.S.C. § 102 and
obviousness under 35 U.S.C. § 103. We have jurisdiction under
35 U.S.C. § 6(b).
We AFFIRM, but designate our affirmance a new ground of rejection
under 37 C.F.R. § 41.50(b).

1 We use the word “Appellant” to refer to “applicant” as defined in
37 C.F.R. § 1.42(a). Appellant identifies Pioneer Hi-Bred International, Inc.
and E.I. DuPont de Nemours & Company as the real parties in interest.
Appeal Br. 3.
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STATEMENT OF THE CASE
“Recombinant DNA technology has made it possible to insert foreign
DNA sequences into the genome of an organism, thus, altering the
organism’s phenotype.” Spec. 1. According to the Specification,
“[a]lthough several approaches have been developed to target a specific site
for modification in the genome of a plant, there still remains a need for more
efficient and effective methods for producing a fertile plant, having an
altered genome comprising specific modifications in a defined region.” Id.
at 2.
Appellant’s Specification describes “compositions and methods for
genome modification of a target sequence in the genome of a plant or plant
cell” that “employ a guide RNA/Cas endonuclease system, wherein the Cas
endonuclease is guided by the guide RNA to recognize and optionally
introduce a double strand break at a specific target site into the genome of a
cell.” Spec. 27. A Cas endonuclease is a protein encoded by a “CRISPER-
associated (Cas)” gene such as Cas9. Id. at 28–29.
Claims 6 and 15–17 are on appeal and can be found in the Claims
Appendix of the Appeal Brief. Claim 6 is illustrative of the claims on
appeal. It reads as follows:
6. A method for modifying a target site in the genome of a
plant cell, the method comprising providing a guide RNA and a
Cas endonuclease to said plant cell, wherein said guide RNA
and Cas endonuclease form a complex that enables the Cas
endonuclease to introduce a double strand break at said target
site.
Appeal Br. 21.
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Appellant filed its Appeal Brief seeking review of Examiner’s
rejection of claims 6 and 15–17 as obvious over Zhang2 and Hein.3 Appeal
Br. 7. In the Answer, Examiner introduced a new ground rejecting claim 6
under 35 U.S.C. § 102 as anticipated by Zhang. Ans. 3. Appellant elected
to maintain the appeal, responding to Examiner’s anticipation rejection in its
Reply Brief. See 37 CFR § 41.39(b)(2). Both rejections are before us now.4
I. ZHANG’S DISCLOSURE
Before we address Appellant’s arguments concerning the anticipation
and obviousness rejections, we must first clarify the scope of the disclosure
in Zhang that qualifies as prior art to Appellant’s application. Both of
Examiner’s rejections are based on Zhang, an issued U.S. patent, which
claims priority to a series of four provisional applications. Examiner,
however, does not articulate support for the rejections by citing to the
disclosure in Zhang. Instead, Examiner cites only to the disclosure in one of
Zhang’s provisional applications, i.e., no. 61/736,527 (the “’527
Provisional”). See Final Act. 2–4; Ans. 3–4, 6–7. Appellant likewise does
not address the disclosure in Zhang and responds only to Examiner’s
findings premised on the disclosure in the ’527 Provisional. See Appeal Br.
7 (noting that “[c]onsistent with the Examiner’s citations in the Final Office
Action . . . all citations of Zhang by Appellants are to the specification of

2 US 8,697,359 B1, issued Apr. 15, 2014 (“Zhang”).
3 US 5,959,177, issued Sept. 28, 1997 (“Hein").
4 Examiner’s Answer additionally refers to certain non-statutory double
patenting rejections. See Ans. 9–13. Appellant explains that it filed terminal
disclaimers to overcome those rejections (Reply Br. 13) and Examiner’s
Advisory Action mailed August 2, 2018 indicates those rejections were
previously overcome. Thus, those rejections are not before us now.
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61/736,527”).
But according to statute, it is the issued patent, not the provisional
application, that is considered prior art. See 35 U.S.C. § 102(a)(2) (“A
person shall be entitled to a patent unless . . . the claimed invention was
described in a patent issued under section 151 . . in which the patent . . .
names another inventor and was effectively filed before the effective filing
date of the claimed invention.”). In this case, the distinction between the
patent and the provisional application is significant because the disclosure in
Zhang is materially broader than that in just the ’527 Provisional. Of
particular relevance to Appellant’s claims and arguments on appeal, Zhang
provides additional disclosure regarding the use of CRISPR-Cas systems to
edit the genome of plant cells (see, e.g., Zhang 26:55–27:31) as well as an
example describing methods for “[u]sing Cas9 to Target and Manipulate
Plant Genes” (id. at 54:27–67:56 (Ex. 7)). These disclosures are not part of
the ’527 Provisional.
Instead, the additional plant-related disclosures and example noted
above seem to originate in Zhang provisional application no. 61/835,931
(the “’931 Provisional”). Compare Zhang 26:55–27:31; 54:27–67:56 with
’931 Provisional ¶¶ 148–150; 475–491 (Ex. 15). The ’931 Provisional has a
filing date of June 17, 2013, and is the last-filed of Zhang’s four provisional
applications. However, like all of Zhang’s provisional applications, the
filing date of the ’931 Provisional antedates the earliest possible effective
filing date of Appellant’s present application.5

5 Indeed, Zhang’s non-provisional filing date (i.e., October 15, 2013)
antedates all but two of the five provisional applications to which
Appellant’s present application claims priority. We do not analyze whether
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The Federal Circuit has explained the conditions under which an
issued patent is entitled to the filing date of a provisional application for
prior art purposes, stating
that for a non-provisional application to claim priority to a
provisional application for prior art purposes, ‘the specification
of the provisional [application] must contain a written
description of the invention . . . in such full, clear, concise, and
exact terms, to enable an ordinarily skilled artisan to practice
the invention claimed in the non-provisional application.’
Further, we have previously stated that ‘for the non-provisional
utility application to be afforded the priority date of the
provisional application . . . the written description of the
provisional must adequately support the claims of the non-
provisional application.
Amgen Inc. v. Sanofi, 872 F.3d 1367, 1380 (Fed. Cir. 2017) (quoting
Dynamic Drinkware, LLC v. National Graphics, Inc., 800 F.3d 1375, 1378
(Fed. Cir. 2015) and New Railhead Mfg., LLC v. Vermeer Mfg. Co., 298
F.3d 1290, 1294 (Fed. Cir. 2002)) (alterations in original). Thus, if the

Appellant’s claims are entitled to the benefit of its two earliest-filed
provisional applications (i.e., Appl. No. 61/868,706 filed August 22, 2013
and Appl. No. 61/882,532 filed September 25, 2013) because we determine
that Zhang is prior art at least as of the filing date of the ’931 Provisional
and therefore necessarily antedates the present application. We leave it to
Examiner to consider whether Appellant’s claims are indeed entitled to the
benefit of its earliest-filed provisional applications should the issue arise
upon continued prosecution. See MPEP 211.05(A) (“If the filing date of the
earlier provisional application is necessary, for example, in the case of an
interference or to overcome a reference, care must be taken to ensure that the
disclosure filed as the provisional application adequately provides (1) a
written description of the subject matter of the claim(s) at issue in the later
filed nonprovisional application, and (2) an enabling disclosure to permit
one of ordinary skill in the art to make and use the claimed invention in the
later filed nonprovisional application without undue experimentation.”)
(emphasis added).
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above requirements are satisfied for Zhang’s provisional applications, Zhang
is prior art at least as of the filing date of the last-filed provisional, i.e., the
’931 Provisional.
On the present record, we determine that Zhang meets the above
requirements. Zhang claim 1 recites a method of using a CRISPR-Cas9
system to alter expression of a gene product in a eukaryotic cell. Zhang,
139:1–22. Appellant does not dispute that the ’527 Provisional provides
sufficient support for this method in animal cells. See Appeal Br. 11 (“[The
’527 Provisional] contemplated non-plant vectors, organisms, transfected
cell lines, and host cells (mentioned in Paragraphs [0049], [0078], [00054-
0055], [0061], and [0052) along with contemplated genomic targets in over
one hundred pages (e.g., Table A and Pages 143–260).”). Indeed, in
addition to extensive disclosure regarding CRISPR-Cas systems, Zhang’s
provisional applications provide a number of detailed examples
demonstrating the use of CRISPR-Cas systems to edit target sites within the
genome of eukaryotic cells and thereby alter the expression of a gene
product. See, e.g., ’527 Provisional ¶¶ 150–203; Provisional Appl. No.
61/748,427 ¶¶ 155–235; Provisional Appl. No. 61/791,409 ¶¶ 175–255; ’931
Provisional ¶¶ 185–491.
Regarding plant cells specifically, the ’931 Provisional explains that
the same CRISPR-Cas9 systems it demonstrates for use in animal cells can
also be used to edit eukaryotic cells in plants. ’931 Provisional ¶ 148
(stating that “reference herein to animal cells may also apply, mutatis
mutandis, to plant cells unless otherwise apparent”). In addition, the ’931
Provisional incorporates by reference techniques for plant transformation
from other references (see id. ¶ 148) and provides an example describing
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methods of using a CRISPR-Cas9 system to alter the expression of a gene
product in micro-algae, i.e., plant cells (id. ¶¶ 475–491). All of these
disclosures, which are incorporated into Zhang from its provisional
applications, “are presumptively enabling.” See In re Antor Media Corp.,
689 F.3d 1282, 1287 (Fed. Cir. 2012). As explained below, Appellant has
not provided persuasive argument nor evidence to overcome that
presumption.
For these reasons, we determine that Zhang’s provisional applications
provide adequate description for and are sufficient to enable Zhang claim 1.
Therefore, Zhang is prior art to the present application. See Amgen, 872
F.3d at 1380. This means that it is Zhang, the issued patent and not just the
disclosure in the ’529 Provisional, which should be evaluated in considering
whether Zhang anticipates or renders obvious Appellant’s claims. We do so
below.
II. ANTICIPATION REJECTION
Issue
The issue for this rejection is whether a preponderance of the evidence
supports Examiner’s conclusion that Zhang anticipates the method of using a
guide RNA and a Cas endonuclease to modify a target site in the genome of
a plant cell as recited in claim 6.
Findings of Fact
FF1. Zhang discloses “systems, methods and compositions for altering
expression of target gene sequences and related gene products” including
“methods of directing CRISPR complex formation in eukaryotic cells and
methods for utilizing the CRISPR-Cas system.” Zhang, Abstr. Zhang
explains that
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[t]he CRISPR/Cas or the CRISPR-Cas system (both terms are
used interchangeably throughout this application) does not
require the generation of customized proteins to target specific
sequences but rather a single Cas enzyme can be programmed
by a short RNA molecule to recognize a specific DNA target, in
other words the Cas enzyme can be recruited to a specific DNA
target using said short RNA molecule.
Id. at 2:13–20.
FF2. Zhang discloses methods for “altering or modifying expression of one
or more gene products” comprising
introducing into a eukaryotic cell containing and expressing
DNA molecules encoding the one or more gene products an
engineered, non-naturally occurring vector system comprising
one or more vectors comprising: a) a first regulatory element
operably linked to one or more Clustered Regularly Interspaced
Short Palindromic Repeats (CRISPR)--CRISPR associated
(Cas) system guide RNAs that hybridize with target sequences
in genomic loci of the DNA molecules encoding the one or
more gene products, b) a second regulatory element operably
linked to a Type-II Cas9 protein, wherein components ( a) and
(b) are located on same or different vectors of the system,
whereby the guide RNAs target the genomic loci of the DNA
molecules encoding the one or more gene products and the
Cas9 protein cleaves the genomic loci of the DNA molecules
encoding the one or more gene products, whereby expression of
the one or more gene products is altered; and, wherein the Cas9
protein and the guide RNAs do not naturally occur together.
The invention comprehends the expression of two or more gene
products being altered and the vectors of the system further
comprising one or more nuclear localization signal(s)
(NLS(s)). The invention comprehends the guide RNAs
comprising a guide sequence fused to a tracr sequence. The
invention further comprehends the Cas9 protein being codon
optimized for expression in the eukaryotic cell.
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Zhang, 2:30–56. Zhang further explains that the Cas enzyme and guide
RNA form a “complex” that is directed by the guide RNA to a target
sequence in the genome of the eukaryotic cell being edited. See, e.g., Zhang,
3:44–67; 6:47–59.
FF3. Zhang discloses that in a CRISPR-Cas system, the Cas protein
“directs cleavage of one or two strands at the location of the target sequence”
of the guide RNA. Zhang, 4:27–29, 6:26–28; see also id. at 18:32–47
(teaching that Cas9 can be modified “from a nuclease that cleaves both
strands to a nickase (cleaves a single strand)”).
FF4. Zhang discloses that the organism whose genome is modified using
the methods it describes “may be a plant.” Zhang, 6:45; see also id. at 26:3–
8 (explaining that “one or more vectors described herein are used to produce
a . . . transgenic plant.”).
FF5. Zhang discloses that “[w]ith recent advances in crop genomics, the
ability to use CRISPIR-Cas systems to perform efficient and cost effective
gene editing and manipulation will allow the rapid selection and comparison
of single and multiplexed genetic manipulations to transform such genomes
for improved production and enhanced traits.” Id. at 26:55–60. Zhang
explains that the “present invention” provides “plant breeders . . . with a new
tool to induce mutations.” Id. at 27:25–26. “Accordingly, one skilled in the
art can analyze the genome of sources of resistance genes, with more
precision than previous mutagenic agents and hence accelerate and improve
plant breeding programs.” Id. at 27:26–32.
FF6. Zhang further teaches that methods for producing transgenic plants
are known in the art (Zhang, 26:9–10) and incorporates by reference the
disclosures in “U.S. Pat. No. 6,603,061––Agrobacterium-Mediated Plant
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Transformation Method; U.S. Pat. No. 7,868,149––Plant Genome Sequences
and Uses Thereof and US 2009/0100536––Transgenic Plants with Enhanced
Agronomic Traits” and “Morrell et al ‘Crop genomics: advances and
applications’ Nat Rev Genet. 2011 Dec. 29; 13(2):85-96.” Id. at 26:60–27:3.
FF7. Zhang discloses Example 7, which is titled “Engineering of Plants
(Micro-Algae) Using Cas9 to Target and Manipulate Plant Genes.” Zhang,
54:29–31. In Example 7, Zhang discloses three methods for delivering Cas9
and a guide RNA into plant cells. See id. at 54:33–47. Zhang further
provides the nucleotide sequences for cassettes that include the Cas9
endonuclease as well as the sequence for a guide RNA that may be used in
these methods. Id. at 54:48–62:11.
FF8. Zhang Example 7 also discloses a method for producing “a line of
Chlamydomonas reinhardtii,” i.e., algae, “that expresses Cas9
constitutively.” See Zhang, 62:12–67:56. Zhang discloses that “[t]his can be
done by using pChlamy1 (linearized using PvuI) and selecting for
hygromycin resistant colonies” and provides the nucleotide sequence for
“pChalmyl1 containing Cas9.” Id. According to Zhang, “to achieve gene
knockout” in such Cas9-expressing algae “one simply needs to deliver RNA
for the guide RNA” and “for homologous recombination” one “deliver[s]
guideRNA as well as a linearized homologous recombination template.” Id.
at 62:17–20.
Analysis
We agree with Examiner that claim 6 is anticipated by Zhang. In
particular, Example 7 of Zhang discloses methods for modifying a target cite
in the genome of a plant cells comprising the delivery of a guide RNA and
Cas endonuclease to a plant cell. FF7–FF8. In addition, Zhang teaches that
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the guide RNA and Cas endonuclease form a complex that enables to the
Cas endonuclease to introduce a double strand break at the site targeted by
the guide RNA. FF2–FF3.
We are not persuaded by Appellant’s argument that Examiner’s
anticipation rejection is premised on “mere speculation.” See Reply Br. 5–6.
Zhang specifically describes methods for modifying a target site in the
genome of a plant cell comprising the step of providing a guide RNA and
Cas9 endonuclease to such cells. FF4–FF8. Moreover, with respect to the
“wherein” clause of claim 6, Zhang explains that in the CRISPR-Cas
systems it describes the guide RNA and Cas9 endonuclease form a complex
that enables Cas9 to introduce a double strand break in the DNA at a target
cite in the genome. FF2–FF3. Thus, Zhang, in fact, discloses all of the
elements of claim 6 “arranged or combined in the same way as in the claim.”
In re Gleave, 560 F.3d 1331, 1334 (Fed. Cir. 2009) (quotations omitted).
Appellant’s argument that Zhang does not provide an enabling
disclosure for plant cells is also unpersuasive. See Reply Br. 6–8. First,
Zhang describes the use of CRISPR-Cas systems to introduce double strand
breaks as specific sites within the genome of eukaryotic cells. FF1–FF3.
Second, Zhang teaches that these techniques can be used in plant cells and
incorporates additional disclosure from a number of references relating to
the generation of transgenic plants. FF4–FF6. Third, Zhang discloses an
example specifically directed to the application of a CRISPR-Cas system
and other techniques to produce modified plant cells. FF7–FF8. These
disclosures are presumed to be enabled and sufficient to establish a prima
facie case of anticipation. See Antor, 689 F.3d at 1289. “[T]he burden
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[then] shifts to the applicant to submit rebuttal evidence of nonenablement.”
Id.
Appellant has failed to persuasively explain, much less provide
evidence, showing that Zhang’s disclosures are not enabled for plant cells.
Appellant asserts that Zhang “did not provide adequate instruction for how
an RNA-guided Cas endonuclease complex could be provided or used in
plant cells without undue experimentation” and that “[t]he step in Claim 6 of
‘providing a guide RNA and a Cas endonuclease to said plant cell’ was not
taught by Zhang’s mentioning of a generic method of introducing DNA into
a cell.” Reply Br. 8. Those arguments, however, ignore the methods taught
in Zhang Example 7. FF7–FF8. Nor does Appellant address the other plant-
related disclosure (see FF4–FF6) that Zhang provides and incorporates by
reference. In a single sentence in its Reply Brief, and without further
explanation, Appellant asserts that “a prophetic description for unicellular
microalgae . . . do[es] not satisfy the enabling requirement.”6 Reply Br. 7.
However, even assuming Zhang Example 7 is a prophetic example, as
opposed to a working one, that example and the other plant-related
disclosures in Zhang are still presumptively enabled. See Antor, 689 F.3d at
1289–90 (“[T]he mere use of forward-looking language (such as terms like
‘should’) does not show one way or another whether a person of ordinary
skill in the art would have to engage in undue experimentation” because “the
invention in a prior art publication need not have actually been made or

6 We note that this is the only time in its briefing Appellant appears to
acknowledge Zhang’s broader disclosure regarding the use of CRISPR-Cas
systems in plant cells, beyond that which Examiner cited to in the ’529
Provisional.
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performed to satisfy enablement.”). Appellant has not shown that undue
experimentation would be required to follow those teachings.
Instead, Appellant contrasts what it characterizes as “vague references
scattered across Zhang” with the present Specification that, according to
Appellant, “provides forty examples of specific compositions and detailed
methods for creating modifications in a plant cell using an RNA-guided Cas
endonuclease.” Reply Br. 7. That comparison, however, is unpersuasive.
First, Appellant’s comparison does not distinguish claim 6 because claim 6
is not limited to any particular method for using a RNA-guided Cas
endonuclease to modify the genome of a plant cell and therefore directly
reads on the methods disclosed in Zhang Example 7. Second, Appellant has
not identified any particular disclosure that it contends is: (1) necessary to
enable Zhang’s teachings regarding the use of CRISPR-Cas systems in plant
cells; and (2) not expressly disclosed, nor incorporated by reference, in
Zhang. It may be that Appellant’s Specification provides additional
disclosure pertinent to the use of an RNA-guided Cas endonuclease that
Zhang lacks, but claim 6 does not recite such. Moreover, Appellant has not
provided sufficient argument and evidence to overcome the presumption that
Zhang’s teachings, including the particular methods taught in Zhang
Example 7, are enabled.
For these reasons, we determine that the preponderance of the
evidence supports a determination that claim 6 is anticipated by Zhang and
therefore affirm the rejection. Because our rationale for affirming the
rejection is substantially based on disclosure in Zhang that was not
previously cited by Examiner, we designate this affirmance a new ground of
rejection.
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III. OBVIOUSNESS REJECTION
Issue
Appellant does not argue Examiner’s rejection of claims 15–17
separately from claim 6. Thus, claims 15–17 stand or fall with claim 6. See
37 C.F.R. § 41.37(c)(1)(iv).
Accordingly, the issue before us is whether a preponderance of the
evidence supports Examiner’s conclusion that Zhang in combination with
Hein renders the method in claim 6 obvious.
Additional Findings of Fact
FF9. Hein “relates to expression and assembly of foreign multimeric
proteins––e.g., antibodies––in plants, as well as to transgenic plants that
express such proteins.” Hein, Abstr. Hein teaches various methods for
producing transgenic plants containing a multimeric protein by introducing
DNA to transform the genome of a plant cell. See id. at 10:28–15:57.
FF10. Hein teaches that the methods it describes for producing transgenic
plants can be used in dicots, including tobacco, tomato, legumes, and alfalfa;
monocots, including grasses, corn, oats, wheat, and barley; as well as “lower
plants” such as algae. Hein, 19:20–29.
Analysis
Examiner finds
Zhang teaches a method providing a vector system comprising
one or more vectors, wherein the vector system comprises (a) a
regulatory element operably linked to a guide [RNA] sequence,
that when expressed, directs sequence-specific binding of a
CRISPR complex to a target sequence in a eukaryotic cell,
wherein the CRISPR complex comprises a [Cas] enzyme
complexed with the guide sequence . . . .
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Ans. 7 (citing ’527 Provisional ¶ 4). Examiner further determines that
Zhang “contemplates applying their method in transgenic plants,” but “does
not expressly teach transformed monocots such as maize or transformed
dicots such as soybean.” Id. at 7 (citing ’527 Provisional ¶ 79). Examiner
concludes that it would have been obvious for a skilled artisan to combine
Zhang’s “method of introducing double strand breaks into the genome of
eukaryotic cells” using a CRISPR-Cas system “with the teachings of Hein to
modify the genome of other plants that are routinely transformed,” including
both monocots and dicots as recited in Appellant’s dependent claims. Id.
We agree with Examiner’s findings (see FF1–FF10) and conclusion of
obvious. In addition to the teachings Examiner cites from ’527 Provisional,
we note that Zhang expressly teaches that its methods for using CRISPR-Cas
systems to induce double stand breaks at target locations in genome provide
a new tool for plant breeders to produce transgenic crops with improved
traits and incorporates by reference various disclosures relating to techniques
for producing transgenic plants. FF5–FF6. As such, Zhang provides an
express motivation to combine its teachings with those in Hein. In addition,
Zhang provides specific methods for delivering a Cas9 endonuclease and
guide RNA into plant cells (FF7–FF8) and teaches that in such systems the
Cas9 complex introduces a double strand break at the location targeted by
the guide RNA (FF2–FF3).
We are not persuaded by Appellant’s arguments that “[t]he sole
appearance of the word ‘plant’ in the ‘527 [Provisional] is in Paragraph
[0079]” and “Zhang does not provide any method for testing of CRISPR-Cas
compositions in plants, or for modification of a plant cell genome with a Cas
endonuclease and guide RNA complex.” See Appeal Br. 10–14. While
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Appellant’s characterization of the ’527 Provisional is correct, Appellant’s
arguments ignore the disclosure in Zhang regarding the use of CRISPR-Cas
systems in plant cells. See FF4–FF8.
Appellant’s argument that a skilled artisan would not have a
reasonable expectation of success “because of plant cell/animal cell
differences” is likewise unpersuasive. See Appeal Br. 14–15. As explained
above, Zhang teaches that CRISPR-Cas systems can be used in both animal
and plant cells and provides specific methods and vectors for doing so. See
FF1–FF8. Zhang’s teachings are sufficient to support a prima facie case of
obviousness for claim 6, particularly given that “[t]he reasonable expectation
of success requirement for obviousness does not necessitate an absolute
certainty for success.” Par Pharm., Inc. v. TWI Pharms., Inc., 773 F.3d
1186, 1198 (Fed. Cir. 2014). Thus, while it is no doubt true that “plant cells
are different from animal cells” (Appeal Br. 14), Appellant has not provided
sufficient, evidence–backed argument to demonstrate that any of those
differences would have resulted in one of ordinary skill in the art to lacking
a reasonable expectation that Zhang’s CRISPR-Cas systems could be
successfully used in plants.
Appellant’s reliance on the Appellees’ arguments to the Federal
Circuit in Appeal No. 2017-1907 (“CAFC Brief”) does not demonstrate
otherwise. See Appeal Br. 14. The arguments Appellant cites in the CAFC
Brief relate to differences between prokaryotic and eukaryotic cells and
whether one of skill in the art would have had a reasonable expectation of
successfully engineering a CRISPR-Cas system for eukaryotes. Id.
Appellant asserts that the “difference in cell type” between plant and animal
cells is “analogous to the challenges alleged by [Appellees] when comparing
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Cas endonuclease mediated genome editing of eukaryotic cells versus
prokaryotic cells.” Id. That assertion, however, is merely attorney
argument. See In re De Blauwe, 736 F.2d 699, 705 (Fed. Cir. 1984)
(explaining that arguments and conclusions unsupported by factual evidence
carry no evidentiary weight). Appellant has not provided evidence
demonstrating how, if at all, the arguments regarding prokaryotic and
eukaryotic cells in the CAFC Brief are relevant to whether a skilled artisan
would reasonably expected that Zhang’s teachings could be successfully
applied in plants.
Appellant’s reliance on Shukla7 and the Zhang Article8 (see Appeal
Br. 15–17) is similarly unpersuasive because Appellant has not persuasively
shown that the subject matter of these articles relates to whether one of
ordinary skill in the art would have had a reasonable expectation that
Zhang’s teachings regarding CRISPR-Cas systems could be successfully
applied to plants. Shukla describes the use of a different technology, i.e.,
Zinc-Finger Nucleases (“ZFNs”) to edit the genome of a species of maize.
See Shukla, 437. According to Appellant, ZFNs “had previously been
described as a gene editing tool in mammalian (human) cells,” but Shukla
evidences that “additional ZFN method development was necessary for use
in plant cells.” Appeal Br. 16. The Zhang Article describes experiments
with another technology, Transcription Activator-Like Effector Nucleases
(“TALENs”). Zhang Article, 20. Similar to its argument concerning

7 Shukla et al., Precise Genome Modification in the Crop Species Zea Mays
Using Zinc-Finger Nucleases, 459 Nature 437–41 (2009) (“Shukla”).
8 Zhang et al., Transcription Activator-Like Effector Nucleases Enable
Efficient Plant Genome Engineering, 161 Plant Physiology 20–27 (2013)
(“Zhang Article”).
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Shukla, Appellant urges that the Zhang Article shows additional
development was necessary before TALENs could be successfully used in
plants. See Appeal Br. 16–17. The problem with both arguments is that
even if we assume the premise is correct, i.e., some amount of additional
work was required to adapt ZFNs and TALENs before those technologies
could be successfully used in plants, Appellant has not persuasively
demonstrated how the any of the difficulties allegedly encountered with
adapting ZFNs and TALENs to work in plants relates to Zhang’s teachings
regarding the use of CRISPR-Cas systems. Again, these are different
technologies and Appellant offers nothing other than attorney argument in
its attempt to relate them to the teachings in Zhang.9
Moreover, even if Appellant had provided evidence to connect the
arguments between the different types of cells in the CAFC Brief and the
different technologies in Shukla and the Zhang Article to facts of the
rejections here, Appellant still has not addressed how any of this overcomes
Zhang’s express teaching that its CRISPR-Cas systems can be used to edit
the genome of crops and other plants (FF4–FF7) and particular methods for
doing so described in Example 7 (FF7–FF8). It may be, as Appellant urges,
that the examples in the “instant application [demonstrates successful
genome editing of a plant cell with a Cas endonuclease and guide RNA . . .
with specific compositions and methods,” but the present claims are not
limited to any specific composition or method in those examples. See

9 We further note Zhang’s teaching that unlike other gene editing
technologies CRISPR-Cas systems do not require the creation of customized
proteins to target specific sequences, but rather are targeted by changing the
guide RNA. FF1.
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Appeal Br. 11. Thus, Appellant’s arguments do not distinguish the present
claims over the asserted combination of Zhang and Hein.
For these reasons, we determine that the preponderance of the
evidence supports Examiner’s conclusion that claims 6 and 15–17 are
obvious over Zhang and Hein. However, as before, we recognize that much
of the disclosure in Zhang supporting our affirmance was not previously
cited by Examiner. Accordingly, in order to provide Appellant an
opportunity to fully respond, we designate our affirmance a new ground of
rejection.
DECISION SUMMARY
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed New
Ground
6 102 Zhang 6 6
6, 15–17 103 Zhang, Hein 6, 15–17 6, 15–17
Overall
Outcome
6, 15–17 6, 15–17
FINALITY AND RESPONSE
This decision contains a new ground of rejection pursuant to
37 C.F.R. § 41.50(b). 37 C.F.R. § 41.50(b) provides “[a] new ground of
rejection pursuant to this paragraph shall not be considered final for judicial
review.”
37 C.F.R. § 41.50(b) also provides that the Appellant, WITHIN TWO
MONTHS FROM THE DATE OF THE DECISION, must exercise one of
the following two options with respect to the new ground of rejection to
avoid termination of the appeal as to the rejected claims:
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(1) Reopen prosecution. Submit an appropriate
amendment of the claims so rejected or new evidence relating
to the claims so rejected, or both, and have the matter
reconsidered by the examiner, in which event the prosecution
will be remanded to the examiner. . . .
(2) Request rehearing. Request that the proceeding be
reheard under § 41.52 by the Board upon the same record. . . .

AFFIRMED; 37 C.F.R. § 41.50(b)