Mikhail Kharisovich. Ziyatdinov et al.

Patent Trials and Appeals Board

Oct 10, 2019

13432519 - (D) (P.T.A.B. Oct. 10, 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.
13/432,519 03/28/2012 Mikhail Kharisovich Ziyatdinov US-413 1432
38108 7590 10/10/2019
CERMAK NAKAJIMA MCGOWAN LLP
127 S. PEYTON STREET
SUITE 210
ALEXANDRIA, VA 22314
EXAMINER
LEE, JAE W
ART UNIT PAPER NUMBER
1656
NOTIFICATION DATE DELIVERY MODE
10/10/2019 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):
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PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte MIKHAIL KHARISOVICH ZIYATDINOV,
VIKTOR VASILIEVICH SAMSONOV, and
MIKHAIL MARKOVICH GUSYATINER
____________

Appeal 2018-004761
Application 13/432,519
Technology Center 1600
____________

Before DEMETRA J. MILLS, RICHARD M. LEBOVITZ, and
RICHARD J. SMITH, Administrative Patent Judges.

SMITH, Administrative Patent Judge.

DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the
Examiner’s decision to reject claims 12–14 and 18–24. 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 Ajinomoto
Co., Inc. Appeal Br. 3.

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STATEMENT OF THE CASE
Background
“The present invention relates to the microbiological industry, and
specifically to a method for producing an L-cysteine, L-cystine, a derivative
or precursor thereof or a mixture thereof using a bacterium of
Enterobacteriaceae family which has been modified to have enhanced
expression of the genes involved in the process of sulphur assimilation.”
Spec. ¶ 2.
Claims on Appeal
Claims 12–14 and 18–24 are on appeal. Appeal Br. 13–14 (Appendix
A). Claim 12, the only independent claim on appeal, is illustrative and reads
as follows:
12. A method for producing a compound selected from the
group consisting of L-cysteine, L-cystine, derivatives thereof,
and precursors thereof, which comprises cultivating an L-
cysteine-producing bacterium of Enterobacteriaceae family in a
culture medium containing sulphate, and collecting the
compound from the culture medium,
wherein the bacterium has been modified to have
enhanced expression of the cysDNC genes.
Id. at 13.
Dependent claim 18 reads as follows:
18. The method according to claim 12, wherein the bacterium
has additionally been modified to have enhanced expression of
cysQ gene.
Id.
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Examiner’s Rejection
Claims 12–14 and 18–24 stand finally rejected under 35 U.S.C.
§ 103(a) as unpatentable over Siebelt,2 Sheremet’eva,3 Neuwald,4 and
Sekowska.5 Final Act. 2;6 Ans. 3.
FINDINGS OF FACT
The following findings are included for emphasis and reference
purposes.
FF 1. Siebelt teaches a method for producing L-amino acids comprising
cultivating a bacterium of the Enterobacteriaceae family in a culture
medium containing sulfate, which produces the desired amino acid, and in
which the bacterium has been modified so that the cysDNC genes are
enhanced (over-expressed), the method further including collection of the
desired L-amino acid. Siebelt 44, ll. 1–19 (claim 1); 6, ll. 15–22; 18, ll. 23–
34; 31, l. 11–34, l. 2 (Example 5); Ans. 4.
FF 2. The term L-amino acids, as used in Siebelt, includes L-cysteine. Id. at
3, ll. 14–18.
FF 3. Siebelt teaches that “microorganisms of the Enterobacteriaceae family
produce L-amino acids . . . in an improved manner after enhancement, in

2 Siebelt et al., WO 03/006666 A2, published Jan. 23, 2003 (“Siebelt”).
3 Sheremet’eva et al., US 2006/0286643 A1, published Dec. 21, 2006
(“Sheremet’eva”).
4 A.F. Neuwald et al., cysQ, a Gene Needed for Cysteine Synthesis in
Escherichia coli K-12 Only during Aerobic Growth, JOURNAL OF
BACTERIOLOGY 174(2), 415–25 (1992) (“Neuwald”).
5 A. Sekowska et al., Sulfur Metabolism in Escherichia coli and Related
Bacteria: Facts and Fiction, J. MOL. MICROBIOL. BIOTECHNOL. 2(2), 145–77
(2000) (“Sekowska”).
6 Office Action dated May 30, 2017.
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particular over-expression, of at least one or more of the genes of the
cysteine biosynthesis pathway chosen from the group consisting of . . . cysD,
cysN, cysC.” Id. at 6, ll. 15–21; claim 1.
FF 4. Neuwald teaches that the cysQ gene is needed for cysteine synthesis,
and that because “[p]revious work had suggested that 3'-phosphoadenoside
5'-phosphosulfate is toxic if allowed to accumulate, [] we propose that CysQ
helps control the pool of 3'-phosphoadenoside 5'-phosphosulfate, or its use
in sulfite synthesis.” Neuwald 415 (Abstract).
ISSUE
Whether a preponderance of the evidence of record supports the
Examiner’s conclusion of obviousness under 35 U.S.C. § 103(a).
ANALYSIS
Appellant argues claims 12–14 and 19–24 as a group, and separately
argues claim 18. We select claim 12 as representative of the group, and
separately address claim 12 and claim 18.
We agree with the Examiner’s conclusion that claims 12 and 18
would have been obvious to a person of ordinary skill in the art at the time
of the invention based on the cited prior art. Ans. 3–5; FF 1–4. We address
Appellant’s arguments below.
As an initial matter, we find that claim 12 would have been obvious in
view of Siebelt alone for the reasons set forth in the Answer. Ans. 4, 6–8;
FF 1–3. Moreover, we do not find that Sheremet’eva, Neuwald, or
Sekowska are necessary to support the obviousness rejection of claim 12.
See In re Bush, 296 F.2d 491, 496 (CCPA 1961) (holding that the Board
may rely on fewer references than relied upon by the Examiner without
designating it as a new ground of rejection).
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Claim 12
Appellant argues that although “Siebelt discloses methods of
overexpressing one or two of the genes of the cysDNC cluster for producing
various L-amino acids, and provide[s] one example of overexpressing all
three specifically to produce L-threonine, it fails to disclose or suggest the
claimed method of producing cysteine or its derivatives.” Appeal Br. 6; see
also Reply Br. 4–5.
We are not persuaded by this argument. Siebelt “‘must be considered
not only for what it expressly teaches, but also for what it fairly suggests.’”
In re Baird, 16 F.3d 380, 383 (Fed. Cir. 1994) (quoting In re Burckel, 592
F.2d 1175, 1179 (CCPA 1979)). Here, Siebelt clearly teaches and suggests
all of the limitations of claim 12, specifically disclosing a “bacterium” which
“has been modified to have enhanced expression of the cysDNC genes.” FF
1–3. Moreover, the fact that Example 5 of Siebelt is directed to producing
L-threonine by enhancing the cysDNC genes does not diminish Siebelt’s
teachings and suggestions as a whole regarding the production of L-amino
acids generally, including the production of the claimed L-cysteine (FF 2).
See In re Mills, 470 F.2d 649, 651 (CCPA 1972) (“a reference is not limited
to the disclosure of specific working examples”); see also In re Applied
Materials, 692 F.3d 1289, 1298 (Fed. Cir. 2012) (“A reference must be
considered for everything that it teaches, not simply the described invention
or a preferred embodiment.”).
In response to the Examiner’s statement that Sekowska teaches that
“reactions performed by cysDN and cysC consume ATP and are clearly rate-
limiting,” thus providing a motivation to overexpress those genes (Non-Final
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Act 5),7 Appellant argues that Sekowska indicates that, “the CysDN reaction
can be rate-limiting. However, Sekowska does not disclose or suggest that a
phosphosulfate, or PAPS,[8] is not sufficiently produced due to insufficient
CysDN activity.” Appeal Br. 7. Appellant thus argues that, “the rate-
limiting effect is not due to the conversion speed but to the equilibrium
constant, and hence, the person of ordinary skill in the art would not have
expected that L-cysteine production can be improved by enhancing the
expression of cysDNC gene(s).” Id.
The Examiner disagrees with Appellant’s analysis of Sekowska, but
also states that the methods taught by Siebelt alone are sufficient to establish
obviousness, including a reason to practice Siebelt’s methods and a
reasonable expectation of success in practicing those methods to meet the
limitations of claim 12, even without the teachings of Sekowska. Ans. 5–8.
The Examiner specifically states that Siebelt’s teaching “of overexpressing
cysDNC genes of the cysteine biosynthesis pathway which in turn []
improves the production of L-amino acids . . . provides strong motivation for
one of skill in the art to practice such methods.” Id. at 8. We further note
that claim 12 does not recite or require improved production of L-cysteine,
L-cystine, derivatives thereof, or precursors thereof. Appeal Br. 13.
Appellant argues that the claimed method includes several steps,
including the step of collecting L-cysteine, and that “[c]learly, none of the
cited references disclose or suggest this step, which represents a distinct

7 Office Action dated Nov. 22, 2016.
8 Sekowska uses the acronym PAPS for 3' phosphoadenosine
phosphosulfate. See Sekowska 146, right col.
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difference between the claimed method and the method of Siebelt, which is a
method for producing L-threonine.” Appeal Br. 8.
We are not persuaded by this argument. As the Examiner explains,
Siebelt teaches that the desired L-amino acid can be isolated or collected.
Ans. 8–9 (quoting claim 1 of Siebelt); FF 1. The Examiner further states
that given Siebelt’s teaching that the “bacterium of Enterobacteriaceae
family is modified to have enhanced expression of all three cysDNC genes
in the cysteine biosynthesis pathway for increased production [of a desired
L-amino acid including L-cysteine],” one of ordinary skill in the art would
have been “motivated to collect any or all L-cysteine overproduced by said
modified bacterium.” Id. at 9.
Claim 18
The rejection of claim 18 relies on the combined teachings of Siebelt
and Neuwald. See Ans. 4; FF 1–4; see Bush, 296 F.2d at 496.
Appellant argues that “[t]he cysQ gene is not disclosed or suggested in
S[ie]belt.”9 Appeal Br. 9, 11. Appellant further argues that “Neuwald
actually discloses that CysQ is necessary for L-cysteine synthesis, not
production so that the amino acid can be collected from the culture
medium.” Appeal Br. 9. Appellant argues further that, “the actual function
of CysQ is not identified or disclosed.” Id. Thus, according to Appellant,
“the person of ordinary skill in the art would not have expected that L-

9 Our decision does not rely on whether Siebelt teaches enhanced expression
of the cysQ gene (e.g., by referring to cysH and/or cysI), but Siebelt does
teach enhanced expression of genes of the cysteine biosynthesis pathway.
See FF 1, 4.

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cysteine production can be improved by enhancing the expression of cysQ
gene based only on the knowledge that CysQ may be involved in one step
among many sequential and complicated steps in L-cysteine biosynthesis.”
Id. at 9–10.
We are not persuaded by these arguments. Appellant’s argument
regarding Neuwald’s disclosure of “L-cysteine synthesis, not production,” is
based on the contention that Neuwald does not teach “production so that the
amino acid can be collected from the culture medium.” Id. at 9. That is,
according to Appellant, Neuwald teaches how L-cysteine is made, but not its
production and subsequent collection. Id.
Even if we viewed Neuwald’s teachings as so limited, it would not
change our decision because, as discussed above, Siebelt teaches production
and isolation (collection) of the desired amino acid from the culture medium.
Siebelt 44, ll. 1–19; FF 1. As the Examiner explains, Neuwald teaches that
cysQ is required for cysteine biosynthesis, and therefore “one would have
been motivated to enhance expression of cysQ in addition to cysDNC
because the cell culture medium taught by Siebelt [] is enriched with sulfate
and also because cysQ plays a crucial role in sulfate assimilation during
cysteine biosynthesis by controlling the pool of 3'-phosphoadensoside 5'-
phosphosulfate.” Ans. 9–10 (citing Neuwald 415, Abstract, left col.); see
also FF 4. Neuwald thus provides a reason to enhance expression of the
cysQ gene, which need not be for the same reason that Appellant enhances
expression of the cysQ gene. See KSR Int’l Co. v. Teleflex Inc., 550 U.S.
398, 419 (2007) (“[i]n determining whether the subject matter of a patent
claim is obvious, neither the particular motivation nor the avowed purpose
of the patentee controls”).
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Appellant argues that Neuwald teaches away from the present
invention and, accordingly, “there would not have been any motivation to
enhance the expression of the cysQ gene with any reasonable expectation of
success.” Appeal Br. 10. This argument is premised on the contentions that
(1) “the person of ordinary skill in the art would have likely concluded from
[Neuwald] that if excess PAPS[10] is wasted when L-cysteine is
overproduced, L-cysteine production would decrease,” and (2) “[t]hat is, the
person of ordinary skill in the art would [not] have expected that L-cysteine
production is improved by enhancing the expression of cysQ gene.” Id.
We are not persuaded by these arguments. Appellant’s arguments fail
to show how Neuwald criticizes, discredits, or otherwise discourages one of
ordinary skill in the art from the subject matter of the claimed invention. See
In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004).
Appellant’s first premise is a single sentence (without citation) that
does not provide adequate factual basis, evidence, or explanation for the
contention that “if excess PAPS is wasted when L-cysteine is overproduced,
L-cysteine production would decrease.” Appeal Br. 10 (emphasis added).
That sentence does not persuasively explain how overproduction of L-
cysteine causes L-cysteine production to decrease, based on the teachings of
Neuwald. An argument made by counsel in a brief does not substitute for
evidence lacking in the record. Estee Lauder, Inc. v. L’Oréal, S.A., 129 F.3d
588, 595 (Fed. Cir. 1997).

10 Neuwald refers to 3'-phosphoadenosine 5'-phosphosulfate as “PAPS.”
Neuwald 415, right col.
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Appellant’s second premise incorrectly assumes that the reason for
enhancing expression of the cysQ gene must be to improve L-cysteine
production. But, as the Examiner explains, a motivation (based on
Neuwald) is to control the pool of 3'-phosphoadensoside 5'-phosphosulfate
(which may be toxic if allowed to accumulate) in the sulfate enriched culture
medium of Siebelt. Ans. 9–10; FF 4; see also KSR, 550 U.S. at 419.
Appellant fails to specifically address the Examiner’s indicated motivation
with factual evidence.
Prior Decision
Appellant refers to a previous decision in this application dated
September 23, 2016.11 Appeal Br. 11. According to Appellant, “the only
reason [in the Prior Decision] for upholding the rejection of claim 12” was
that prior claim 12 did not require enhanced expression of “the combination
of all three genes of cysDNC.” Id. (citing Prior Decision 5). Thus,
according to Appellant, “prima facie obviousness has been clearly rebutted.”
Id.
Claim 12 in the Prior Decision was different in several ways from
current claim 12. Compare Prior Decision 2 with Appeal Br. 13. In
response to Appellant’s argument in the Prior Decision that “Siebelt ‘does
not disclose or suggest increased expression of the combination of all the
three genes of cysDNC cluster,’” we found that “claim 12 does not require
enhanced expression of ‘the combination of all the three genes of cysDNC’
as Appellants contend.” Prior Decision 5. That finding was not a statement

11 Ex parte Ziyatdinov, Appeal No. 2014-003823 (PTAB Sept. 23, 2016)
(“Prior Decision”).
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that a claim reciting the combination of all three genes of cysDNC would be
patentable over Siebelt. Moreover, Finding of Fact 1 in the Prior Decision
expressly states that Siebelt taught enhanced expression of “one or more”
genes, including cysD, cysN, and cysC. Id. at 3 (FF 1). Siebelt thus
expressly teaches “the combination of all the three genes of cysDNC.” See
FF 1, supra.
CONCLUSION
A preponderance of evidence of record supports the Examiner’s
conclusion that claims 12 and 18 would have been obvious under 35 U.S.C.
§ 103(a). Claims 13, 14, and 19–24 were not argued separately and fall
with claim 12.
SUMMARY
Claims
Rejected
35 U.S.C. § Basis Affirmed Reversed
12–14, 18–
24
§ 103(a) Siebelt,
Sheremet’eva,
Neuwald,
Sekowska
12–14, 18–
24

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).

AFFIRMED