Schopke, Christian et al.

Patent Trials and Appeals Board

Oct 29, 2019

12245610 - (D) (P.T.A.B. Oct. 29, 2019)

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.
12/245,610 10/03/2008 Christian Schopke CIBUS-004-UT 4395
35938 7590 10/29/2019
Acuity Law Group, P.C.
12707 High Bluff Drive
Suite 200
San Diego, CA 92130-2037
EXAMINER
KRUSE, DAVID H
ART UNIT PAPER NUMBER
1663
NOTIFICATION DATE DELIVERY MODE
10/29/2019 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):
docketing@acuitylg.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte CHRISTIAN SCHOPKE, GREG F. W. GOCAL,
KEITH WALKER, and PETER R. BEETHAM
Appeal 2018-000616
Application 12/245,610
Technology Center 1600
Before JEFFREY N. FREDMAN, TAWEN CHANG, and
DAVID COTTA, Administrative Patent Judges.

CHANG, Administrative Patent Judge.
DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the
Examiner’s decision to reject claims.2 We have jurisdiction under
35 U.S.C. § 6(b).
We AFFIRM.

1 We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42. Appellant identifies the real party in interest as Cibus US
LLC. Appeal Br. 4.
2 An oral hearing was held on Oct. 7, 2019.
Appeal 2018-000616
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BACKGROUND
The nuclear-encoded chloroplast enzyme acetohydroxyacid
synthase or acetolactate synthase (AHAS or ALS . . .) catalyses
the first common step in the biosynthesis of the branched-chain
amino acids leucine, isoleucine and valine. This enzyme . . . is
the site of action for several distinct classes of herbicides,
including the sulfonylureas, imidazolinones and
triazolopyrimidines. Resistance to a sulfonylurea,
chlorsulfuron, has been shown . . . to result from single amino
acid substitutions within the AHAS enzyme.
Rutledge 31 (citations omitted).3 The invention relates to “the field of
herbicide resistant plants and seeds and more specifically to mutations in the
acetohydroxyacid synthase (AHAS) gene and protein.” Spec. ¶ 2.

CLAIMED SUBJECT MATTER
The claims are directed to a method for targeted alternation of a
Brassica napus plant cell. Claim 152 is illustrative:
152. A method for targeted alteration of a Brassica napus plant
cell, comprising:

introducing into the plant cell gene repair oligonucleobase
comprising at least one mismatch with respect to an
acetohydroxyacid synthase (AHAS) I gene naturally present in
the plant cell genome, the mismatch selected to introduce a
tryptophan to leucine mutation in the AHAS I gene at a position
corresponding to residue W574 of SEQ ID NO: 1;

identifying a plant cell having substantially normal growth and
AHAS catalytic activity in the presence of an AHAS-inhibiting

3 Robert G. Rutledge, Molecular Characterization and Genetic Origin of
Brassica Napus Acetohydroxyacid Synthase Multigene Family, 229
MOLECULAR AND GENERAL GENETICS 31 (1991) (“Rutledge”).

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herbicide as compared to a corresponding plant cell retaining
the tryptophan at the position corresponding to residue W574 of
SEQ ID NO: 1; and

regenerating from the identified plant cell a non-transgenic
herbicide-resistant Brassica napus plant having the tryptophan
to leucine mutation at the position corresponding to residue
W574 of SEQ ID NO: 1.

Appeal Br. 12 (Claims App.).

REJECTION
Claims 152 and 1544 are rejected under pre-AIA 35 U.S.C. § 103(a)
as being unpatentable over Hawkes,5 Arntzen,6 Rutledge, Beetham,7 and
Kochevenko.8 Ans. 2.

DISCUSSION
The Examiner has rejected claims 152 and 154 as obvious over
Hawkes, Arntzen, Rutledge, Beetham, and Kochevenko. The Examiner
finds that Hawkes teaches “introducing a donor mutagenic nucleobase

4 Both the Examiner and Appellant state that it is claim 157, in addition to
claim 152, that is rejected an under appeal. Ans. 2; Appeal Br. 5. However,
claim 157 has been cancelled, and claims 152 and 154 are the only claims
that have not been cancelled or withdrawn. Appeal Br. 12 (Claims App.).
5 Hawkes et al., GB 2 326 163 A, published Dec. 16, 1998 (“Hawkes”).
6 Arntzen et al., US 7,094,606 B2, issued Aug. 22, 2006 (“Arntzen”).
7 Beetham et al., US 6,870,075 B1, issued Mar. 22, 2005 (“Beetham”).
8 Andrej Kochevenko et al, Chimeric RNA/DNA Oligonucleotide-Based
Site-Specific Modification of the Tobacco Acetolacetate Syntase Gene, 132
PLANT PHYSIOLOGY 174 (2003) (“Kochevenko”).

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wherein the duplex acceptor DNA sequence is an AHAS gene.” Ans. 2.
The Examiner finds that Arntzen teaches
a method for producing an herbicide-resistant plant comprising
introducing into a plant cell a recombinagenic oligonucleobase
that targets an ALS (syn. AHAS) gene, selecting a plant cell
having substantially normal growth and catalytic activity as
compared to a corresponding wild-type plant cell in the
presence of an AHAS-inhibiting herbicide and regenerating a
non-transgenic herbicide resistant plant having a mutated
AHAS gene from said plant cell at claim 4; wherein the plant
cell is a canola (Brassica napus) at claim 7. Arntzen . . .
teach[es] that an alanine205-to-aspartic acid, a tryptophan591-to-
leucine, a tryptophan591-to-serine and a serine660-to-asparagin
mutation can be introduced into an ALS gene to confer
sulfonylurea and imidazolinone herbicide resistance.
Tryptophan591 of Arntzen corresponds to tryptophan574 of the
instant claims. Arntzen . . . teach[es] that it is understood that
in most plants the gene encoding ALS has been duplicated and
that a mutation can be introduced into any allele of either ALS
gene.
Id. at 3 (citation omitted). The Examiner finds that Rutledge teaches that
“the coding sequence of the Brassica napus AHAS1, AHAS2, and AHAS3
genes were known in the art at the time of . . . Arntzen” and that Beetham
teaches introducing a recombinagenic oligonuclobase into a plant cell. Id.
Finally, the Examiner finds that Kochevenko teaches (1) “introducing a
mixed [RNA] into a tobacco plant protoplast to modify an AHAS gene;” (2)
substituting, in an AHAS gene, a leucine for a tryptophan corresponding to
W574 in the SEQ ID NO: 1 of claim 152; and (3) “introducing into a plant
cell a gene repair oligonucleobase, identifying a plant cell[,] and
regenerating a non-transgenic herbicide-resistant plant having the tryptophan
to leucine mutation.” Id. at 3–4 (citation omitted).
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Appellant contends that, based on the cited references, a skilled
artisan would not have had “a reasonable expectation of success in
producing a W574L mutation in B. napus AHAS I.” Appeal Br. 10.

A. Issue
Whether, based on the cited combination of prior art, a skilled artisan
would have had reason to introduce a tryptophan to leucine mutation in the
AHAS I gene of a Brassica napus plant cell, at a position corresponding to
residue W574 of SEQ ID NO: 1, with a reasonable expectation of success.

B. Findings of Fact
1. Hawkes teaches
[a] method of producing plants which exhibit an agronomically
desirable trait comprises mutating or otherwise modifying in
situ in a plant cell at least one gene and regenerating from a cell
exhibiting the said trait fertile morphologically normal whole
plants, and is characterised in that a polynucleotide is
introduced into the plant cell, the said polynucleotide
comprising at least one region which is substantially
complementary to the gene, which gene when mutated or
otherwise modified provides for the agronomically desirable
trait the region in the said polynucleotide containing at least one
base mismatch in comparison with the like region in the said
gene, so that the region in the said gene is altered by the DNA
repair/replication system of the cell to include the said
mismatch.
Hawke Abstract.
2. Hawkes teaches that “[t]he agronomically desirable trait may be
herbicide resistance.” Id.; see also id. at 1:24–25.
3. Hawkes teaches that “[t]he protein encoding region of the gene
may encode an enzyme selected from a group consisting of EPSPS, GOX,
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PAT, HPPD, ACC, ALS, BNX and protox and known mutated or variant
forms thereof.” Id. at 2:24–26. The Examiner finds, and Appellant does not
dispute, that ALS is synonymous with AHAS. Ans. 3.
4. Hawkes teaches that the method of its invention may be applied
to a cell of oilseed rape, which Appellant acknowledges to be Brassica
napus. Hawkes 3:13-18; Appeal Br. 4.
5. Hawkes teaches using a mixed ribo-deoxyribonucleic acid to
introduce a mutation into the target gene, wherein the mixed ribo-
deoxyribonucleic acid has two regions homologous with the sequence of the
target site, flanking an interposed heterologous region. Hawkes 5:20–28.
6. Hawkes teaches that “[t]he change to be introduced into the
target gene is encoded by the heterologous region” and that “[t]he change to
be introduced may be a change in one or more bases of the target gene
sequence or the addition of one or more bases.” Id. at 6:8–10.
7. Arntzen teaches “use of duplex oligonucleotides about 25 to 30
base pairs to introduce site specific genetic alterations in plant cells,”
wherein “plants having the genetic alteration can be generated from the
altered cells” thereafter. Arntzen Abstract.
8. Arntzen teaches that its invention “allows the skilled
practitioner to make a specific alteration of a specific pre-existing gene of a
plant.” Id. at 1:20–22.
9. In particular, Arntzen teaches using mixed duplex
oligonucleotides (MDON) to effect genetic changes, wherein the MDON
comprises sequences that are homologous to a first and second fragment of
the target gene as well as a “region of difference, termed the ‘heterologous
region,’” which “can effect an insertion or deletion, or can contain one or
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more bases that are mismatched with the sequence of target gene so as to
effect a substitution,” such that “the target gene becomes homologous with
the sequence of the MDON.” Id. at 1:31–58.
10. Arntzen teaches that the genetic changes effected by its
invention can be used to introduce a selectable trait and that “[t]he selectable
trait can . . . be . . . herbicide resistance.” Id. at 7:49–50, 8:7–9.
11. Arntzen teaches that “[i]n one embodiment of the invention a
MDON is used to introduce a mutation into an Acetolactate synthase (ALS)
gene, which is also termed the aceto-hydroxy amino acid synthase (AHAS)
gene.” Id. at 8:31–34.
12. Arntzen teaches that “[s]ulfonylurea herbicides and imidazoline
herbicides are inhibitors of the wild type ALS enzymes” but that prior art
teaches “several mutations (hereinafter, a “Bedbrook Mutation”) that were
found to render yeast ALS enzymes resistant to sulfonylurea herbicides” and
that are stated to “make[] a plant resistant to sulfonylurea and imidazoline
herbicides when introduced into a plant ALS gene.” Id. at 8:34–36, 40–46.
13. Arntzen teaches that
[t]hree of the Bedbrook mutations were, in fact, shown to
confer herbicide resistance in a plant, namely the substitutions
Pro→Ala197 Ala→Asp205 and Trp→Leu591. Rajasekaran reports
that mutations Trp→Ser591 caused resistance to sulfonylurea
and imidazoline and that Ser→Asn660 caused resistance to
imidazoline herbicides. . . . According to the invention any
substitution for the naturally occurring amino and [sic] at
position 660 or one of the positions listed in Table 2 of
Bedbrook, which is hereby incorporated by reference, can be
used to make a selectable mutation in the ALS gene of a plant.
Id. at 8:49–54, 8:66–9:3.
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14. The Examiner finds, and Appellant does not dispute that
“Tryptophan591 of Arntzen corresponds to tryptophan574 of the instant
claims.” Ans. 3.
15. Arntzen teaches that “[i]t is understood that in most plants the
gene encoding ALS has been duplicated” and that “[a] mutation can be
introduced into any allele of either ALS gene.” Arntzen 8:46–48.
16. The Examiner finds, and Appellant does not dispute, that
Rutledge teaches the coding sequence of the AHAS1, AHAS2, and AHAS3
genes for Brassica napus. Ans. 3; Rutledge Fig. 2. The AHAS1 and
AHAS3 genes of B. napus “share extensive homology.” Rutledge Abstract,
Fig. 2; see also Ouellet 321 (Teaching that “AHAS1 and AHAS3, which are
located in the C and A genomes, respectively, are highly conserved with
respect to each other in nucleotide sequences.”) (citing Rutledge).9
17. Beetham teaches production of a non-transgenic plant resistant
to a particular type of herbicide by using a “recombinagenic oligonucleobase
to make a desired mutation in the chromosomeal or episomal sequences of a
plant in the gene encoding” a specific enzyme (EPSPS). Beetham Abstract.
18. Beetham teaches methods of introducing recombinagenic
oligonucleobase into a plant cell. Id. at 4:22–24.
19. Beetham teaches that the recombinagenic oligonucleobase may
be a single stranded oligodeoxynucleotide mutational vector (SSOMV). Id.
at 10:1–4 (claim 3).

9 Therese Ouellet et al., Members of the Acetohydroxyacid Synthase
Multigene Family of Brassica napus Have Divergent Patterns of Expression,
2 THE PLANT J. 321 (1992) (“Ouellet”).
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20. Kochevenko teaches that “[s]ingle amino acid substitutions at
either of two crucial positions in acetolactate synthase (ALS) result in a
chlorsulfuron-insensitive form of this enzyme and, as a consequence, a
herbicide-resistant phenotype.” (Kochevenko Abstract.) In particular,
Kochevenko teaches that “[l]ines with proline-196-alanine, threonine,
glutamine, or serine substitutions or with tryptophan-573-leucine
substitutions were highly resistant at both cellular and whole plant levels.”
Id.
21. Kochevenko teaches that
[t]he allotetraploid species tobacco has two genetically unlinked
loci, SuRA and SuRB, for ALS. Mutations in either SuRA (Pro-
196-Glu and Pro-196-Thr) or SuRB (Pro-196-Ser) locus result
in single amino acid replacements at position 196 and a
herbicide-resistant phenotype. It was also shown that the S4-
Hra mutant of tobacco bearing two linked mutations within
locus SuRB had amino acid substitutions at positions 196 (Pro-
196-Ala) and 573 (Trp-573-Leu), and it was more resistant
to chlorsulfuron. . . . Interestingly, the same type of amino
acid change (Trp to Leu) in the conserved region near the C
terminus of ALS (as a result of 1-bp substitution, G to T)
resulted in sulfonylurea resistance in a Xanthium sp. and
Brassica napus. Moreover, in cocklebur (Xanthium), all
possible mutations affecting the Trp at this position were
investigated using site-directed mutagenesis, and only Trp-Leu
substitutions yielded an active, herbicide-insensitive form of
ALS.
Id. at 175 (citations omitted).
22. Kochevenko teaches a strategy of gene alteration using
chimeric RNA/DNA oligonucleotides (i.e., chimeras), wherein the chimera
is identical to a targeted gene except for a single nucleotide, which
“produces a mismatched base that is presumably recognized by endogenous
repair machinery.” Id. at 174.
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23. Kochevenko teaches using “olionucleotide-mediated strategy to
create single point mutations at different positions with ALS genomic
sequences of tobacco,” that “[s]equence analysis confirmed that application
of oligonucleotides with various targeting sequences resulted in the
production of predicted alterations, and that “assay of ALS activity in the
leaves of resistant lines in the presence of chlorsulfuron demonstrated the
appearance of an herbicide-insensitive form of the enzyme.” Id. at 175.
24. In particular, Kochevendo designed two chimeric RNA/DNA
oligonucleotides “to obtain separate targeted single-nucleotide conversion at
two different positions within either [SuRA or SuRB],” wherein ChALS-588
and ChALS-1719 are respectively designed to lead to “amino acid changes
Pro-Gln at position 196 and Trp-Leu at 573, respectively” and to an
herbicide-insensitive form of ALS. Id.
25. Kochevenko teaches that its experiments “clearly demonstrated
that single amino acid substitution Trp-573-Leu alone can provide a
chlorsulfuron-resistant phenotype.” Id. at 179.
26. Kochevenko teaches that “[c]hlorsulfuron-resistant plants were
regenerated from calli after mesophyll protoplast electroporation or leaf
tissue particle bombardment with these specifically constructed chimeras.”
Id. at Abstract.

C. Analysis
Unless otherwise noted, we adopt the Examiner’s findings of fact and
reasoning regarding the scope and content of the prior art (April 27, 2016
Office Act. 3–6; Ans. 2–10; FF1–26) and agree with the Examiner that
claims 152 and 154 would have been obvious over the combination of
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Hawkes, Arntzen, Rutledge, Beetham, and Kochevenko. Only those
arguments timely made by Appellant in the briefs have been considered;
arguments not so presented in the briefs are waived. See 37 C.F.R. §
41.37(c)(1)(iv) (2015); see also Ex parte Borden, 93 USPQ2d 1473, 1474
(BPAI 2010) (informative) (“Any bases for asserting error, whether factual
or legal, that are not raised in the principal brief are waived.”). We address
Appellant’s arguments below.
Appellant concedes that the prior art discloses the W574L mutation in
the B. napus AHAS III gene. Appeal Br. 6–7. However, Appellant
contends that a skilled artisan would not have had “a reasonable expectation
of success in producing a W574L mutation in B. napus AHAS I,” because
“[t]he literature indicates that the AHAS . . . genes . . . are not simply
equivalent to one another such that a mutation in one is applicable to the
other.” Appeal Br. 6, 10; see also Reply Br. 4–5.
Appellant first argues that, while a W574L mutation of the B. napus
AHAS III gene has long been known in the prior art, as evidenced by Tan10
and Hattori,11 such a mutation has never been described in the AHAS I gene
recited in the claims. Appeal Br. 6–7; see also Reply Br. 4. Appellant
argues that, while Hawkes mentions that ALS (i.e., AHAS) is a gene that
may be targeted for mutation, it makes no specific reference to “any
particular mutations within any AHAS gene,” “AHAS in the context of B.

10 Siyuan Tan et al., Imidazolinone-Tolerant Crops: History, Current Status
and Future, 61 PEST MGMT. SCI. 246 (2005).
11 Jiro Hattori et al., An Acetohydroxy Acid Synthase Mutant Reveals a
Single Site Involved in Multiple Herbicide Resistance, 246 MOLECULAR &
GENERAL GENETICS 419 (1995).
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napus,” or “AHAS I in B. napus,” much less any reference to “introducing a
W574L mutation into B. napus AHAS I.” Appeal Br. 8; see also Reply Br.
3. Appellant similarly argues that, while Arntzen teaches “general methods
for introducing mutations into cells” and teaches that transgenic plants
containing certain mutated yeast AHAS genes are herbicide resistant, “the
present claims do not relate to transgenic plants, but rather to mutations in
the endogenous B. napus genomic copy of AHAS I.” Appeal Br. 8–9; see
also Reply Br. 3. Finally, Appellant argues that Rutledge and Beetham also
do not “make any reference to introducing a W574L mutation into B. napus
AHAS I.” Appeal Br. 9.
We are not persuaded. “Non-obviousness cannot be established by
attacking references individually where the rejection is based upon the
teachings of a combination of references. . . . [The reference] must be read,
not in isolation, but for what it fairly teaches in combination with the prior
art as a whole.” In re Merck & Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986).
In this case, Appellant concedes that a W574L mutation in the B.
napus AHAS III gene is known, Appeal Br. 6–7, and the prior art taken
together teaches that this and corresponding Trp→Leu mutations in other
plant AHAS genes confer herbicide resistance, FF12–14, FF20, FF21, FF24,
and FF25, and also teaches that AHAS I and AHAS III genes are highly
conserved in B. napus, FF16. The prior art further teaches a method of
“mak[ing] a specific alteration of a specific pre-existing gene of a plant”
such as the AHAS gene of B. napus in order to confer, e.g., herbicide
resistance. See FF1–14, FF17–19, FF22, FF24, and FF25. Finally, the prior
art teaches that “[i]t is understood that in most plants the gene encoding ALS
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has been duplicated” and that “[a] mutation can be introduced into any allele
of either ALS gene.”12 FF15.
Given all of the above, including particularly the highly conserved
nature of the two AHAS genes and the teaching in Arntzen that a mutation
can be introduced into any allele of the various AHAS genes, we agree with
the Examiner that a skilled artisan would have had reason to introduce
mutation corresponding to W574L in the AHAS I gene of B. napus, in order
to confer herbicide resistance, with a reasonable expectation of success in
doing so.
With respect to Appellant’s contention that a mutation has never been
described in the B. napus AHAS I gene despite the fact that the W574L
mutation in the AHAS III gene has long been known in the prior art, see,
e.g., Appeal Br. 6–7, we note that Appellant has submitted no evidence that
there has been a long-felt need to achieve the W574L mutation in the AHAS
I gene in particular, given that W574L mutation in the AHAS III gene is
known and provides the same benefit of herbicide resistance. Texas
Instruments Inc. v. U.S. Int’l Trade Comm’n, 988 F.2d 1165, 1178
(explaining that “long-felt need is analyzed as of the date of an articulated
identified problem and evidence of efforts to solve that problem”).

12 During oral argument, Appellant argued that the AHAS I and AHAS III
genes in B. napus are not duplications. Tr. 10:12–11:2. In particular,
Rutledge teaches that “B. napus is an allotetraploid believed to originate
from an interspecific cross between B. campestris, the A genome donor and
B. oleracea, the C genome donor.” Rutledge 31. Rutledge further teaches
that AHAS III originates from the A genome, while AHAS I originates from
the C genome. Id. at Abstract. We are not persuaded, because, regardless of
the origins of AHAS I and AHAS III genes, their nucleotide sequences are
highly conserved as compared to each other. FF16.
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Appellant argues that Kochevenko, together with van der Vyver13 and
Lee,14 supports the argument that a skilled artisan would not have had a
reasonable expectation of success in arriving at a W574L mutation in the B.
napus AHAS I gene. Appeal Br. 9; see also Reply Br. 3, 4. In particular,
Appellant notes that Kochevenko teaches mutations in an allotetraploid
tobacco genome that contain two highly conserved AHAS genes, SuRA and
SuRB. Appeal Br. 9. Appellant further notes that, “despite designing
RNA/DNA oligonucleotides to achieve mutations in ‘either of these genes,’
[a Trp-Leu] mutation was obtained only in the SuRB gene; the equivalent
mutation was not observed in the other ‘highly conserved’ SuRA gene.”
Appeal Br. 9; see also Reply Br. 3, 4. Appellant thus contends that
Kochevenko, like Tan, demonstrates that simply because a particular
mutation (W574L) was possible in one allopolyploid gene (tobacco SuRB,
B. napus AHAS III), the same mutation may not be available in a different
but highly conserved gene (tobacco SuRA, B. napus AHAS I). Appeal Br.
10; see also Reply Br. 4.
While we acknowledge Appellant’s argument, we are not persuaded.
As an initial matter, it is not clear that Kochevenko teaches that the
Trp→Leu mutation occurred only in the SuRB gene. Appellant points to the
portion in Kochevenko that teaches that, when chimeric oligonucleotide
ChALS-1719, designed to alter the codon for Trp-573, was introduced into

13 Christell van der Vyver, In vitro Selection of Transgenic Sugarcane
Callus Utilizing a Plant Gene Encoding a Mutant Form of Acetolactate
Synthase, 49 IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY—PLANT 198
(2013) (“van der Vyver”).
14 Kathleen Y. Lee et al., The Molecular Basis of Sulfonylurea Herbicide
Resistance in Tobacco, 7 THE EMBO J. 1241 (1988) (“Lee”).
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tobacco cells, “the observed change was limited to a single nucleotide
substitution (G to T) at position 1,719.” Appeal Br. 9. This statement,
however, should be read in the context of the next sentence, i.e., that “the
codon for Pro-196 was unchanged.” See Kochevenko 177. Thus, this
appears to be a statement that only the expected G to T substitution at
position 1,719 was observed, and no substitution occurred at position 588,
when ChALS-1719 was introduced into tobacco cells. It is not clear that the
substitution only occurred in one of the AHAS genes but not the other.
Appellant argue, however, that Lee and van der Vyver make clear that
the Trp-573 mutation occurred only in the SuRB gene. Tr. 13:14–23. While
Lee teaches that “two separate substitutions, one at Pro-196 and a second at
Trp-573 in the SuRB locus . . . result in an herbicide resistance phenotype,”
Lee was published before Kochevenko and does not address the results
obtained by Kochevenko. Similarly, while van der Vyver cites to
Kochevenko in stating that “[t]he mutant ALS SurB isoform (alsb) was
isolated from tobacco cDNA” and the existence of the Trp-573-Leu amino
acid substitution confirmed, van der Vyver does not teach that Kochevenko
did not achieve a corresponding mutation in the SuRA gene. van der Vyver
201.
More importantly, assuming for argument’s sake that the Trp→Leu
mutation occurred only in the SuRB and not the SuRA gene in Kochevenko,
Appellant has not provided any persuasive evidence, only attorney
arguments, that a skilled artisan would not have reasonably expected to be
able to achieve the corresponding mutation in either the SuRA gene in
tobacco or the AHAS I gene in B. napus with routine experimentation.
Attorney arguments cannot substitute for evidence. In re Geisler, 116 F.3d
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1465, 1470 (Fed. Cir. 1997). Neither has Appellant pointed to any step in
the claimed method that distinguishes the claimed method from the method
taught in the prior art.
In this regard, we also note that Arntzen teaches that its method for
introducing mutations “allows the skilled practitioner to make a specific
alteration of a specific pre-existing gene of a plant.” FF8. Likewise,
Kochevenko teaches that its ChALS-1719 is designed to obtain a single-
nucleotide conversion at position 1719 (leading to amino acid change Trp-
Leu at 573) within either SuRA or SuRB gene. “[A] prior art printed
publication cited by an examiner is presumptively enabling barring any
showing to the contrary by a patent applicant,” In re Antor Media Corp., 689
F.3d 1282, 1288 (Fed. Cir. 2012), and Appellant has not provided persuasive
evidence, only attorney argument, that prior art references such as Arntzen
would not have allowed a skilled artisan to introduce a specific alteration
(i.e., the nucleotide mutation(s) that would result in the Trp-573-Leu
substitution) of a specific pre-existing gene of a plant (i.e., the AHAS I gene
of B. napus).
Finally, Appellant contends in the Reply Brief that “achieving the
W574L mutation in AHAS I is an unexpected result, based on literature.”
Reply Br. 5. We are not persuaded for the same reasons discussed above,
namely that Appellant has only provided attorney argument, and not
persuasive evidence, that achieving a W574L mutation in AHAS I is an
unexpected result.
Accordingly, we affirm the Examiner’s rejection of claims 152 over
the combination of Hawkes, Arntzen, Rutledge, Beetham, and Kochevenko.
Claim 154, which was not separately argued, falls with claim 152.
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CONCLUSION
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
152, 154 103(a) Hawkes, Arntzen,
Rutledge, Beetham,
Kochevenko
152, 154
Overall
Outcome

152, 154

TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a). See 37 C.F.R.
§ 1.136(a)(1)(iv).

AFFIRMED