Ex Parte Ziyatdinov et al

Patent Trial and Appeal Board

Sep 21, 2016

13432519 (P.T.A.B. Sep. 21, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/432,519 03/28/2012
38108 7590 09/23/2016
CERMAK NAKAJIMA MCGOWAN LLP
127 S. Peyton Street
Suite 210
ALEXANDRIA, VA 22314
FIRST NAMED INVENTOR
Mikhail Kharisovich Ziyatdinov
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
US-413 1432
EXAMINER
LEE,JAEW
ART UNIT PAPER NUMBER
1656
NOTIFICATION DATE DELIVERY MODE
09/23/2016 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):
cgoode@cnmiplaw.com
ip@cnmiplaw.com
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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, VIKTOR V ASILIEVICH, and
MIKHAIL MARKOVICH1
Appeal2014-003823
Application 13/432,519
Technology Center 1600
Before DEMETRA J. MILLS, LORA M. GREEN, and
RICHARD J. SMITH, Administrative Patent Judges.
SMITH, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
for producing a compound that have been rejected as obvious. We have
jurisdiction under 35 U.S.C. § 6(b).
We affirm.
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
1 According to Appellants, the real party in interest is Ajinomoto Co., Inc.
(Appeal Br. 3.)
Appeal2014-003823
Application 13/432,519
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. ii 2.)
Claims on Appeal
Claims 12-15 and 18-24 are on appeal. (Appendix A, Appeal Br. 12-
13.) Independent claim 12 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 one or more genes involved in the process of sulphur assimilation, and
wherein said one or more genes involved in the process of sulphur
assimilation comprise the cysQ gene or the cysDNC genes.
Examiner's Rejection
Claims 12-15 and 18-24 stand rejected under 35 U.S.C. § 103(a) as
unpatentable over Siebelt,2 Neuwald,3 and Sheremet'eva.4 (Ans. 2.)
Claims 13-15 and 19-24 were not argued separately, and therefore, as
to those claims, we limit our discussion to claim 12, the only independent
claim.
2 Siebelt et al., WO 03/006666 A2, published Jan. 23, 2003 ("Siebelt").
3 Neuwald et al., cysQ, a Gene Needed for Cysteine Synthesis in Escherichia
coli K-12 Only during Aerobic Growth, 174 JOURNAL OF BACTERIOLOGY 2,
415-25 (1992) ("Neuwald").
4 Sheremet'eva et al., US 2006/0286643 Al, published Dec. 21, 2006
("Sheremet' eva").
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Application 13/432,519
FINDINGS OF FACT
We adopt as our own the Examiner's findings and analysis concerning
the scope and content of the prior art. The following findings are included
for emphasis and reference convenience.
FF 1. Siebelt teaches a method for the preparation of L-amino acids
comprising fermentation of microorganisms of the Enterobacteriaceae
family which produce the desired amino acid, and in which at least one or
more of the genes of the cysteine biosynthesis pathway, including cysD,
cysN, cysC, and cysH, are enhanced (over-expressed), the method further
including isolation of the desired L-amino acid. (Siebelt 44, 11. 1-19 (claim
1 ).)
FF 2. The term L-amino acids, as used in Siebelt, includes L-cysteine. (Id.
3' 11. 14--18.)
FF 3. Siebelt teaches that "microorganisms of the Enterobacteriaceae family
produce L-amino acids ... in an improved manner after enhancement, in
particular over-expression, of at least one or more of ... cysD, cysN, cysC
... [and] cysH." (Id. 6, 11. 15-22.)
FF 4. The Specification states that "[t]here are many genes involved in the
process of sulphur assimilation including the genes involved in sulphate
activation (cysD, cysN, cysC) and adenosine 3'-phosphate 5'-
phosphosulphate (PAPS) degradation ( cysQ)." (Spec. i-f 5.)
FF 5. The Examiner finds that "[a]lthough Siebelt [] do[ es] not mention that
cysD, CysN or CysC genes are involved in the process of sulphur
assimilation, i.e., sulphate activation, it is an inherent property of cysD, cysN
or cysC genes to be involved in such process." (Ans. 3; see FF 4.)
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Application 13/432,519
FF 6. The Examiner finds that the art is inconsistent in the nomenclature of
the genes involved in the cysteine biosynthesis pathway, and provides the
following Table for clarification:
l .................................................. J .. §!~-~_g_[L .............................. .L~~-~~Y§J.Q ............................... ~P.P.~~J.§:~J~~§. ....................... J
! A gene encoding i CysH I CysH CysQ I
! Phosphoadenosine i (see p. 10., IL 23· I (see p. 415, 2nc col.) {see p. 2, paragrapr1 I
! phosphosu!fate i 35) I 0005) I
i .. !:~~!:!!:'.~§.~§.JP.:~P..§.L ...... L. .................................................... L .......................................................................................................... !
! Additional i C:,.tsl/CysQ is a I CysQ controls the I
! d!sclosure i NADPH sulfite I levels of CysH I
! ! reductase I (PAPS) I
i i {see p. 10., IL 13· I (see p ·416, ·1st wt, I
! i 22) I 1st ara ra h} I
(Ans. 5.)
FF 7. Siebelt teaches that cysH (i.e. Appellants' cysQ) is a gene of the
cysteine biosynthesis pathway. (Siebelt 10, 1. 23-35; FF 6.)
FF 8. Neuwald teaches that the cysQ gene is needed for cysteine synthesis
and that CysQ helps control the pool of PAPS, or its use in sulfite synthesis.
(N euwald 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
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. 2-5; FF 1-8.) We
address Appellants' arguments below.
As an initial matter, we find that claims 12 and 18 are obvious in view
of Siebelt for the reasons set forth in the Answer. (FF 1-7.) Moreover, we
do not find that N euwald (or Sheremet' eva) are necessary to support the
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Appeal2014-003823
Application 13/432,519
obviousness rejection of claims 12 and 18. See Jn re Bush, 296 F.2d 491,
496 ( CCP A 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).
Claim 12
Siebelt
Appellants argue that Siebelt "does not disclose or suggest increased
expression of the combination of all the three genes of cysDNC cluster or the
cysQ gene in a method for producing L-cysteine." (Appeal Br. 6, 8.)
We are not persuaded by Appellants' arguments. Claim 12 recites
"one or more genes" which comprise "the cysQ gene or the cysDNC genes."
(Appeal Br. 12.) Thus, claim 12 does not require enhanced expression of
"the combination of all the three genes of cysDNC' as Appellants contend.
(Ans. 7.) Consistent with the doctrine of claim differentiation, this
construction is further borne out by claim 18, which is indirectly dependent
on claim 12 and recites "one or more genes of the cysDNC cluster." (Id.)
Claim 18 would be incongruent if claim 12 was limited to the combination
of all three cysDNC genes.
Although claim 12 does not require increased expression of the cysQ
gene, provided one or more genes of cysDNC are expressed, Siebelt also
discloses increased expression of the cysQ gene in its process for the
preparation of L-amino acids. As the Examiner explains, Siebelt teaches
that "over-expression of one or more genes of the cysteine biosynthesis
pathway including cysH (Appellants' cysQ) ... improve[s] the production of
L-amino acids." (Ans. 10; see also FF 3, 6, and 7.) Siebelt also makes clear
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Appeal2014-003823
Application 13/432,519
that its reference to L-amino acids, and specifically improved production
thereof, includes L-cysteine. (FF 2.)
Motivation to Enhance Expression
Appellants make several arguments, generally based on Neuwald and
the L-cysteine biosynthesis pathway, 5 for example, that a person of ordinary
skill in the art would not have been motivated to increase expression of the
cysQ gene or the cysDNC genes. (Appeal Br. 8-9.)
In particular, as to the increased expression of the cysQ gene,
Appellants argue that
(Id.)
L-cysteine is synthesized via a series of sequential steps using a
plurality of enzymes, and hence, the necessary steps for
improving L-cysteine production will differ depending on a
variety of factors, such as, for example, which step is the rate-
limiting step. Therefore, the disclosure in Neuwald that CysQ is
beneficial for L-cysteine synthesis does not necessarily mean,
nor would this fact suggest to the skilled art worker, that L-
cysteine production can be improved by enhancing the
expression of cysQ gene. . . . N euv,rald refers to the possibility
that CysQ is involved in sulfite generation or that CysQ
sequesters or consumes excess PAPS or the like . . . the person
or ordinary skill in the art could not have expected that L-
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.
Appellants make a similar argument regarding the increased
expression of the cysDNC genes; namely, that
5 Figure 1 ofNeuwald illustrates the pathway of cysteine biosynthesis.
(Neuwald 416, FIG. 1.)
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Appeal2014-003823
Application 13/432,519
(Id.)
the person of ordinary skill in the art would not have been
motivated to choose to increase the expression of the CysDNC
genes for the purpose of increasing production of L-cysteine.
This is because the rate-limiting feature is simply due to the fact
that the equilibrium of the CysDN reaction is strongly guided in
the reverse direction, that is, towards ATP synthesis. Therefore,
the rate-limiting aspect is not caused by insufficient amounts of
CysDN, and so even by increasing CysDN, the equilibrium of
the reaction will not be shifted in the forward direction, that is,
towards APS generation.
Appellants also point to Sekowska6 to argue that "the rate-limiting
effect [of the CysDN reaction] is not due to the conversion speed but to the
equilibrium constant" and, therefore, "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)." (Appeal Br. 9-10, citing
Sekowska 146, par. bridging left and right cols.)
We are unpersuaded by Appellants' arguments. We note that Siebelt
teaches and suggests improved production of L-amino acids, including L-
cysteine, by increased expression of the cysH (i.e. cysQ) and cysDNC genes.
(FF 2, 3.) That teaching alone suggests the subject matter of claim 12.
Moreover, Appellants cannot establish nonobviousness by arguing Neuwald
separately from Siebelt. See In re Merck & Co., Inc., 800 F .2d 1091, 1097
(Fed. Cir. 1986) (citing In re Keller, 642 F.2d 413, 425 (CCPA 1981))
(nonobviousness cannot be established by attacking references individually
where the Examiner bases the rejection on a combination of references). In
6 Sekowska et al., Sulfur Metabolism in Escherichia coli and Related
Bacteria: Facts and Fiction, J. MOL. MICROBIOL. BIOTECHNOL 2(2), 145-77
(2000) ("Sekowska").
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Application 13/432,519
addition, we are unpersuaded by Appellants' arguments regarding Neuwald
and the pathway for L-cysteine synthesis for the reasons set forth in the
Examiner's Answer. (Ans. 6-10.)
Teaching Away
Appellants argue that Neuwald teaches away from the present
invention based on its reference to the possibility "that CysQ is involved in
sulfite generation or that CysQ sequesters or consumes excess PAPS or the
like." (Appeal Br. 9, citing Neuwald 423-24; see also Reply Br. 4.) In
particular, Appellants argue that a person of ordinary skill in the art would
therefore not have been motivated to enhance expression of the cysQ gene
because they "would have likely concluded from [Neuwald] that if excess
PAPS is wasted when L-cysteine is overproduced, L-cysteine production
would decrease." (Appeal Br. 9.)
We are not persuaded. Siebelt discloses the subject matter of the
claimed invention. Appellants have failed to show how the combination of
Siebelt and 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). Moreover, Appellants'
teaching away argument is contradicted by the express teaching of Siebelt
that production of L-amino acids, including L-cysteine, is improved by
enhancement (over-expression) of cysH ( cysQ). (FF 3.) Furthermore, claim
12 does not require enhanced expression of the cysQ gene. (Appeal Br. 12.)
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Appeal2014-003823
Application 13/432,519
Claim 18
Claim 18 recites "[t]he method according to claim 15,7 wherein the
bacterium has been modified to have enhanced expression of cysQ gene and
one or more genes of cysDNC cluster." (Appeal Br. 12.) Appellants argue
that "claim 18 limits the claims to a combined use of the cysQ gene and the
cysDNC gene(s)," and that the Examiner has failed to explain how the prior
art discloses this combination. (Id. 10.) We are not persuaded. Claim 18
clearly recites the combination of the cysQ gene and "one or more" of the
genes of the cysDNC cluster. Moreover, given that cysH corresponds to
Appellants' cysQ (Ans. 10, FF 6), and Siebelt teaches the combination of
cysH with cysD, cysN, and cysC (FF 3), claim 18 would have been obvious
to a person of ordinary skill based on the disclosure of Siebelt.
CONCLUSION
A preponderance of evidence of record supports the Examiner's
conclusion that claims 12 and 18 are obvious under 35 U.S.C. § 103(a).
Claims 13-15 and 19-24 were not argued separately and fall with
claim 12.
SUMMARY
We affirm the rejection of all claims on appeal.
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
7 Claim 15 depends on claim 12. (Appeal Br. 12.)
9