BAYER CROPSCIENCE NV

Patent Trials and Appeals Board

Dec 21, 2020

2020002980 (P.T.A.B. Dec. 21, 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.
15/394,485 12/29/2016 Jeroen VAN RIE 039621.00127 4822
4372 7590 12/21/2020
ARENT FOX LLP
1717 K STREET, NW
WASHINGTON, DC 20006-5344
EXAMINER
KOVALENKO, MYKOLA V
ART UNIT PAPER NUMBER
1662
NOTIFICATION DATE DELIVERY MODE
12/21/2020 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):
patentdocket@arentfox.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte JEROEN VAN RIE, FRANK MEULEWAETER,
and GERBEN VAN ELDIK

____________

Appeal 2020-002980
Application 15/394,485
Technology Center 1600
____________

Before JOHN G. NEW, TIMOTHY G. MAJORS, and
DAVID COTTA, Administrative Patent Judges.

MAJORS, Administrative Patent Judge.

DECISION ON APPEAL
Appellant1 submits this appeal2 under 35 U.S.C. § 134(a) involving
claims to a chimeric gene encoding a Cry1C protein having a certain DNA
and amino acid sequence, which claims have been rejected for obviousness
under 35 U.S.C. § 103. We have jurisdiction under 35 U.S.C. § 6.
We REVERSE.

1 “Appellant” refers to “applicant” as defined in 37 C.F.R. § 1.42(a).
Appellant identifies BASF Agricultural Solutions Seed, US LLC, as the real
party-in-interest. Appeal Br. 1. BAYER CROPSCIENCE NV is listed as
applicant on the Bibliographic Data Sheet.
2 Appellant identifies as related our decision in Ex parte Gossele, Appeal
2016-002512 (PTAB Dec. 1, 2017) (hereafter “Gossele”). Appeal Br. 1.
Appeal 2020-002980
Application 15/394,485
2
STATEMENT OF THE CASE
According to the Specification, “[t]he present invention relates to new
gene sequences encoding insecticidal proteins produced by Bacillus
thuringiensis strains,” and to transformed plant cells or plants comprising
such genes. Spec. 1. More specifically, the invention relates to “new
chimeric genes encoding a Cry1C protein,” which the Specification indicates
are useful in protecting plants from insect damage. Id. at 1–2 (indicating the
insect control genes are useful in transgenic vegetables crops in particular,
including cabbage and kale in the genus Brassica). The Specification
explains that, as to the disclosed and claimed DNA sequences encoding the
protein, such sequences display “at most 76.6% sequence identity with the
closest known DNA sequences.” Id.
Claims 1–3, 6–8, 13, 15, 16, 19, 34, and 36 are on appeal. Claim 1 is
illustrative:
1. A chimeric gene comprising the following operably-
linked sequences:
(a) a coding region encoding a Cry1C protein comprising
a DNA sequence with at least 98% sequence identity to the DNA
of any one of SEQ ID Nos. 1, 3, 4 or 6, wherein said Cry1C
protein is a protein comprising the amino acid sequence from the
amino acid at position 29 to the amino acid at position 627 in
SEQ ID No. 2, and
(b) a promoter region capable of directing expression in
plant cells.
Appeal Br. 12. As a further example of the claimed subject matter, claim 13
recites a “transgenic plant or seed, comprising the gene of claim 1 stably
incorporated into its genome,” and claim 19 recites a “method for
controlling insects, comprising: planting or sowing in a field, plants
comprising the chimeric gene of claim 1.” Id. at 13.
Appeal 2020-002980
Application 15/394,485
3
Appellant seeks review of the Examiner’s rejection of:
(a) claims 1–3, 13, 15, 16, and 19 under 35 U.S.C. § 103 as obvious
over Bosch,3 Schünmann,4 Arnaut,5 Aroian,6 Pang,7 and Rose8;
(b) Claims 6–8, 34, and 36 under 35 U.S.C. § 103 as obvious over the
above combination in further view of Van Mellaert9 and Payne.10
Final Act.11 2–17; Ans. 3–25.
ANALYSIS
The Examiner determines that independent claim 1, and several of the
dependent claims, would have been obvious over the combination of Bosch,
Schünmann, Arnaut, Aroian, Pang, and Rose. Final Act. 2–8. According to
the Examiner, Bosch teaches a protein with the same amino acid sequence as
the Cry1C protein of the instant SEQ ID NO: 2 of claim 1. Id. at 3 (citing
Bosch’s SEQ ID NO: 2 and asserting that “[t]he sequence . . . shows a 100%
match to the region between amino acids 29 and 627 of the instant SEQ ID
NO: 2”). The Examiner then reasons that “[d]ue to the properties of the

3 Bosch et al., US 6,204,246 B1, issued Mar. 20, 2001.
4 Petra H. D. Schünmann et al., A suite of novel promoters and terminators
for plant biotechnology, 30 FUNCTIONAL PLANT BIOLOGY 443–452 (2003).
5 Arnaut et al., US 7,169,971 B2, issued Jan. 30, 2007.
6 Aroian et al., US 2010/0024075 A1, published Jan. 28, 2010.
7 Sheng-Zhi Pang et al., An Improved Green Fluorescent Protein Gene as a
Vital Marker in Plants, 112 PLANT PHYSIOL. 893–900 (1996).
8 Alan B. Rose, The effect of intron location on intron-mediated
enhancement of gene expression in Arabidopsis, 40 THE PLANT JOURNAL
744–751 (2004).
9 Van Mellaert et al., US 6,855,873 B1, issued Feb. 15, 2005.
10 Payne, US 5,273,746, issued Dec. 28, 1993.
11 This citation refers to the Examiner’s Final Rejection dated March 21,
2019, and the substance of the rejection of the claims is also repeated in the
Examiner’s Answer on appeal, entered Jan. 13, 2020.
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Application 15/394,485
4
genetic code, the amino acid sequence of Bosch . . . makes obvious the
genus of nucleic acids encoding it.” Id. at 4.
Nevertheless, the Examiner finds that Bosch does not teach “a
chimeric gene comprising the sequence of the instant SEQ ID NO: 1,” the
particular “promoter” sequence recited in certain claims, or transforming
Brassica plants or cells with the chimeric genes to control insects. Id. at 4–
5. The Examiner, therefore, turns to the other references. The Examiner
finds that Schünmann teaches plant expression vectors using a promoter
sequence identical to SEQ ID NO: 19 (i.e., the promoter sequence recited in
claim 2). Id. at 5–7. The Examiner finds that Arnaut teaches transforming
plants with a Cry1B expression construct, that Aroian and Pang teach adding
intron sequences to increase expression in plants, and that Rose teaches
introducing an intron in a coding sequence at a region that is not farther than
1.1 kb from the promoter in order to enhance expression. Id. at 7.
From the above, the Examiner concludes it would have been obvious
to modify the genes of Bosch “using a nucleic acid encoding the instant SEQ
ID NO: 2,” and using the promoter and intron sequences described in the
other cited references to obtain the chimeric gene of claim 1. Id. at 8.
According to the Examiner, the ordinarily skilled person would have been
motivated to combine the teachings “because of the well-known insecticidal
properties of Cry1 proteins, [and] because crops expressing those proteins
are agriculturally desirable.” Id. Further, the Examiner reasons, it was
known that non-translated regions (e.g., the cited introns) could increase
protein expression and, because some of the references are alleged to have
“successfully reduced their inventions to practice,” the person of ordinary
skill would have had a reasonable expectation of success in modifying the
prior art as proposed. Id. at 8–9.
Appeal 2020-002980
Application 15/394,485
5
Appellant raises three primary arguments. First, Appellant argues that
sequences encoding a known protein are not per se obvious, and that the
Examiner’s suggestion to the contrary conflicts with Federal Circuit case
law and decisions of the Board, including the decision in the related Gossele
appeal. Appeal Br. 5–6 (citing cases, and arguing that, like the claims in
Gossele, “the instant claims recite specific nucleic acid sequences” with at
least “98% sequence identity to the DNA of SEQ ID Nos. 1, 3, 4 or 6,” none
of which is “taught or suggested by the references”); Ex parte Gossele,
Appeal 2016-002512 (PTAB Dec. 1, 2017). Further to this point, Appellant
cites the Examiner’s concession that Bosch does not, in fact, teach a gene
with the sequence of SEQ ID NO: 1 as claimed. Id. at 6. Indeed, Appellant
cites evidence showing that, with or without the intron in the coding
sequence, Bosch’s DNA sequence is no better than 67–74% identical to SEQ
ID NO: 1. Id. (citing sequence alignment results at Exhibits A & B to the
Appeal Brief). Appellant contends the Examiner has not shown that the
other references remedy Bosch’s deficiencies and, therefore, “the genus of
nucleic acid sequences encoding SEQ ID NO: 2 [are not obvious], let alone
the claimed DNA sequences.” Id.
Second, Appellant contends that the prior art teaches away from the
claimed synthetic DNA sequences. Id. at 6–7. In particular, Appellant
contends that Strizhov,12 which is alleged to post-date Bosch, describes a
glutamate residue at position 12413 of the Cry1C protein as a “critical error”

12 Strizhov et al., US 6,043,415, issued Mar. 28, 2000. Strizhov teaches,
inter alia, that an alanine residue at position 124 was found to be conserved
in all Cry1C proteins. Strizhov, 10:31–34. And, thus, Strizhov appears to
use synthetic genes that encode alanine, not glutamate, at that position. See
id. at Fig. 2 (noting the amino acid sequence shown as SEQ ID NO: 2).
13 Appellant explains that SEQ ID NO: 2 as claimed has a glutamate (Glu) at
Appeal 2020-002980
Application 15/394,485
6
for protein stability or function that would have discouraged the ordinarily
skilled person from designing a chimeric gene with glutamate at that
position, such as claimed. Id. at 6–9 (citing Strizhov 10:15–22); see also
Strizhov 10:42–46. In further support, Appellant argues the Board
previously found Strizhov was “objective evidence” and a “quintessential
teaching away” that would have discouraged design of a chimeric gene
encoding glutamate at position 124. Appeal Br. 7–9 (emphasis omitted)
(quoting Gossele at 10–11).
Finally, Appellant contends that a skilled artisan following Bosch’s
teachings would not have arrived at the claimed protein because Bosch’s
emphasis is on the use of partial Cry1C protein fragments. Id. at 9–10.
More specifically, Appellant contends that “Bosch’s invention is directed to
the use of a partial Cry1C protein to place domain III of a Cry protein [e.g.,
the amino acid sequence from position 478 to 602 of Cry1C] next to
domains I and II of another Cry protein [e.g., Cry1E].” Id. Hence,
Appellant argues, Bosch’s hybrid proteins are distinct from what is claimed
and modifying Bosch as proposed by the Examiner changes Bosch’s
principle of operation. Id.
The Examiner “bears the initial burden . . . of presenting a prima facie
case of unpatentability.” In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir.
1992). “The Patent Office has the initial duty of supplying the factual basis
for its rejection. It may not . . . resort to speculation, unfounded assumptions
or hindsight reconstruction to supply deficiencies” in the rejection. In re

position 125, and that this position is equivalent to position 124 of the prior
art. Appeal Br. 6–7 (explaining that the difference is due to insertion of an
additional amino acid early in the claimed sequence). The Examiner does
not dispute this point.
Appeal 2020-002980
Application 15/394,485
7
Warner, 379 F.2d 1011, 1017 (CCPA 1967). Upon considering the
argument and evidence of record, we conclude that the preponderance of the
evidence on this record does not support the Examiner’s rejection for
obviousness. We explain below.
The Examiner’s finding that Bosch discloses a protein with the amino
acid sequence (between residues 29–627) that is identical to what is claimed
is undisputed. That, however, does not resolve the issue on appeal.
Claim 1 does not recite merely any DNA sequence capable of
encoding the Cry1C protein with the amino acid sequence of SEQ ID NO: 2.
To the contrary, claim 1 is more limited, and recites a DNA sequence with at
least 98% identity to one of four particular sequences (with the Appellant’s
and Examiner’s emphasis being on SEQ ID NO: 1). And Appellant’s
argument and evidence that the DNA sequence of Bosch encoding those
amino acids is no better than 74% identical to SEQ ID NO: 1 as claimed is
also undisputed. Appeal Br. 6 (Exs. A & B); see also Spec. at 2, 20
(explaining that the claimed sequences differ by at least 23% (about 485
nucleotides) from other sequences known in the art).
To be sure, the skilled person, with knowledge of the relationship
between amino acids and the various codons14 capable of encoding them
could hypothesize and design other DNA sequences from that disclosed in
Bosch. But the number of possible nucleotide sequences encoding a protein

14 As we explained in Gossele, the genetic code is degenerate with several
codons (individual sequences of three nucleotides) specifying the same
amino acid. Gossele at 6 n.13. Because of this degeneracy, and the fact that
most amino acids are encoded by at least two (and sometimes more) distinct
codons, there may be an extraordinarily large number of nucleotide
sequences that may encode a protein—and the potential sequences increase
exponentially as the length of the protein increases. Id.
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Application 15/394,485
8
with over 600 amino acids is potentially vast, and the Examiner has not
made a persuasive showing of how the ordinarily skilled person would have
gone from, for example, Bosch’s sequence with approximately 74% identity
to the claimed sequence identity of 98% or better. Absent a persuasive
evidentiary showing and technical reasoning to explain how that would
predictably occur, the notion that the recited sequence would have been
obvious strikes us as throwing “metaphorical darts at a board”—not a
finding of obviousness predicated on undertaking a “finite number of
identified, predictable solutions.” In re Kubin, 561 F.3d 1351, 1359 (Fed.
Cir. 2009) (citations and internal quotation marks omitted).
In the Answer, the Examiner reiterates that, based on the properties of
the genetic code, “the amino acid sequence of Bosch et al makes obvious the
genus of nucleic acids encoding it.” Ans. 17. The breadth of what the
Examiner means by this assertion is unclear. But, according to the
Examiner, this “statement is consistent with the Federal Circuit’s position in
In re Bell, where the Court stated that ‘the amino acid sequence of a protein
along with knowledge of the genetic code [puts] an inventor in possession of
the genus of nucleic acids capable of encoding the protein.’” Id. (citing In re
Bell, 991 F.2d 781 (Fed. Cir. 1999) (brackets added by the Examiner)).
As an initial matter, the above quoted “statement” is not found in the
Federal Circuit’s decision in In re Bell and, thus, was not made by the court
as the Examiner indicates. See generally Bell. Instead, it appears that the
Examiner quoted a portion of the MPEP related, not to obviousness, but to
the written description requirement under § 112. MPEP § 2163.15

15 In that context, the full sentence reads: “For example, the amino acid
sequence of a protein along with knowledge of the genetic code might put
an inventor in possession of the genus of nucleic acids capable of encoding
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Application 15/394,485
9
That aside, insofar as the Examiner suggests that a particular or
narrow set of DNA sequences would have been obvious once the protein and
its amino acid sequence is known, the court rejected that proposition in Bell.
The claims there recited certain nucleic acid sequences encoding human
insulin-like growth factors I and II (IGF I or IGF II proteins), the amino acid
sequences for which were known in the art. Bell, 991 F.2d at 782; see also
id. n. 3 (representative claim). The court, however, rejected the Patent
Office’s conclusion in that case that a known corresponding link “between a
gene and its encoded protein via the genetic code renders the gene obvious
when the amino acid sequence is known.” Id. at 783–785 (reversing the
Board’s affirmance of the obviousness rejection). As the court explained:
“implicit in that conclusion is the proposition that . . . the established
relationship in the genetic code between a nucleic acid and the protein it
encodes also makes a gene prima facie obvious over its correspondent
protein. We do not accept this proposition.” Id. at 783–84.16 Because that
proposition was rejected in Bell, concerning proteins comprised of about 65–

the protein, but the same information would not place the inventor in
possession of the naturally occurring DNA or mRNA encoding the
protein.” MPEP § 2163 (emphases added). There is quite a difference
between information that “might put” one in possession of the invention and
information that “puts” one in possession of the invention (as suggested by
the brackets inserted by the Examiner). Moreover, as the full sentence
indicates, knowledge of the protein sequence does not necessarily place one
in possession of particular genetic sequences.
16 The court continued, remarking that “[i]t may be true that, knowing the
structure of the protein, one can use the genetic code to hypothesize possible
structures for the corresponding gene and that one thus has the potential for
obtaining that gene. However, because of degeneracy of the genetic code,
there are a vast number of nucleotide sequences that might code for a
specific protein.” Id. at 784; see also id. at n.5 (discussing degeneracy).
Appeal 2020-002980
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10
70 amino acids, which the court noted corresponded to some 1036 different
genetic sequences, we fail to see how it has any application to the
obviousness rejections here for a recited coding sequence with over 600
amino acids—implying a far greater number of potential DNA sequences.
Id. at 784.
The Examiner further responds that, through “codon optimization” of
either a deduced DNA sequence or Bosch’s DNA sequence, one would
arrive at a DNA sequence of claim 1. Ans. 17–18 (asserting that codon
optimization for expression in plants was routine). We agree that codon
optimization was a known technique. But the Examiner still fails to provide
a persuasive showing to explain how and why codon optimization would
have produced a DNA with at least 98% similarity to the sequences claimed
(or anything even approaching that specificity). The Examiner has not
shown, for example, any particular nucleic acid or codon changes that would
have predictably been made to Bosch’s coding sequence to bring that
sequence closer to the recited and claimed identity.
We do not agree, on this record, that Appellant was required to
disprove the Examiner’s vague “codon-optimization” theory or present
evidence of unexpected results to overcome the rejection. Id. at 18
(suggesting Appellant needed to present such evidence).17 Nor has the
Examiner demonstrated sufficiently that the remaining references make up
for Bosch’s deficiencies such that the ordinarily skilled person would have

17 Although based on a different evidentiary record, in a quite similar context
to the arguments and claims here, we noted in Gossele that it could not be
simply assumed that codon optimization would produce the specific DNA
sequences as claimed. Gossele at 7 (noting that, even in prior art sequences
codon optimized for use in plants, the sequences were still significantly
different from the Cry1C DNA sequence there claimed).
Appeal 2020-002980
Application 15/394,485
11
predictably and with a reasonable expectation of success arrived at the
chimeric gene with the specificity recited in claim 1.
For the reasons above, we conclude that the preponderance of the
evidence on this record does not support the Examiner’s conclusion that
claims 1–3, 13, 15, 16, 19 would have been obvious. As the deficiency
discussed above is dispositive, we decline to reach Appellant’s other
arguments (e.g., teaching away). Because the rejection of claims 6–8, 34,
and 36 relies on the alleged obviousness of claim 1, that rejection falls or
similar reasons, and the Examiner has not shown that Van Mellaert or Payne
remedy the issues discussed above. Final Act. 10–14.
CONCLUSION
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1–3, 13, 15,
16, 19
103 Bosch,
Schünmann,
Arnaut, Aroian,
Pang, Rose
1–3, 13,
15, 16, 19
6–8, 34, 36 103 Bosch,
Schünmann,
Arnaut, Aroian,
Pang, Rose, Van
Mellaert, Payne
6–8, 34, 36
Overall
Outcome
1–3, 6–8,
13, 15, 16,
19, 34, 36

REVERSED