Ex Parte Rostova et al

Patent Trial and Appeal Board

Dec 21, 2016

13687353 (P.T.A.B. Dec. 21, 2016)

United States Patent and Trademark Office
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
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APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
13/687,353 11/28/2012 Yulia Georgievna Rostova US-430 1766
38108 7590 12/23/2016
CERMAK NAKAJIMA MCGOWAN LLP
127 S. Peyton Street
Suite 210
ALEXANDRIA, VA 22314
EXAMINER
GEBREYESUS, KAGNEW H
ART UNIT PAPER NUMBER
1656
NOTIFICATION DATE DELIVERY MODE
12/23/2016 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte YULIA GEORGIEVNA ROSTOVA,
ELVIRA BORISOVNA VOROSHILOVA, and
MIKHAIL MARKOVICH GUSYATINER1
Appeal 2015-006749
Application 13/687,353
Technology Center 1600
Before DONALD E. ADAMS, RICHARD M. LEBOVITZ, 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 an L-
amino acid-producing bacterium. We have jurisdiction under 35 U.S.C.
§ 6(b).
We affirm.
1 According to Appellants, the real party in interest is Ajinomoto Co., Inc.
(Appeal Br. 3.)
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Application 13/687,353
STATEMENT OF THE CASE
Claims on Appeal
Claims 1, 3—7, and 10 are on appeal.2 (Appendix A, Appeal Br. 12—
13.) Claim 1 is illustrative and reads as follows:
1. An L-amino acid-producing bacterium of the Enterobacteriaceae
family, wherein said bacterium has been modified to attenuate expression of
one or more genes encoding a lysine/arginine/omithine transporter
comprising one or more genes of argT-hisJQMP cluster,
wherein said L-amino acid is selected from the group consisting of L-
lysine, L-arginine, L-omithine, and L-citrulline.
Examiner’s Rejections
1. Claims 1, 3—7, and 10 stand rejected under 35 U.S.C. § 103(a) as
unpatentable over Lu,3 Caldara,4 and Wissenbach.5 (Final Act. 2.)
2 The Examiner states that the claim amendments submitted on Sept. 23,
2014 (after the Final Action dated Feb. 3, 2014), were not entered, as shown
in the Advisory Action dated Oct. 20, 2014. Accordingly, the rejection of
claims 1, 3—7, and 10 was maintained by the Examiner according to the
Final Action. (Ans. 2.) Thus, the rejection as set forth in the Final Action is
the rejection addressed herein, notwithstanding the Examiner’s statement
that, even if the claims as proposed to be amended “were to be admitted,”
the amended claims would remain rejected. (Id.)
3 Chung-Dar Lu, Pathways and regulation of bacterial arginine metabolism
and perspectives for obtaining arginine overproducing strains, 70 Appl.
Microbiol. Biotechnol. 261—72 (2006) (“Lu”).
4 Caldara et al., The arginine regulon of Escherichia coli: whole-system
transcriptome analysis discovers new genes and provides an integrated view
of arginine regulation, 152 Microbiology 3343—54 (2006) (“Caldara”).
5 Wissenbach et al., A third periplasmic transport system for L-arginine in
Escherichia coli: molecular characterization of the artPIQMJ genes,
arginine binding and transport, 17 Molecular Microbiology 675—86 (1995)
(“Wissenbach”).
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Application 13/687,353
2. Claims 1, 3—7, and 10 stand rejected under 35 U.S.C. § 103(a) as
unpatentable over Ueda6 and Caldara. (Id. at 9.)7
FINDINGS OF FACT
We adopt as our own the Examiner’s findings concerning the scope
and content of the prior art. The following findings are included for
emphasis and reference convenience.
FF 1. Lu teaches that “[i]n principle, the yield of L-arginine
production in the industrial scale can be increased by the combination of the
following steps: increased biosynthesis and excretion and decreased
catabolism and uptake.” (Lu 269, left col.)
FF 2. Lu teaches that “[t]o further increase L-arginine production of
[bacterial] strains, it might be helpful to . . . delete argT and artU genes for
arginine uptake.” (Id.)
FF 3. Caldara teaches “ArgR-mediated repression of arginine
biosynthesis and uptake genes.” (Caldara Abstract.)
FF 4. Caldara teaches three arginine uptake systems, including “the
basic amino acid uptake system, designated LAO (lysine, arginine,
ornithine).” (Caldara 3349, left col.)
FF 5. Caldara teaches that the hisJQMP genes of the histidine
transporter are part of the lysine-arginine-omithine (LAO) uptake system
and regulated by arginine. (Caldara Abstract.)
6 Ueda et al., US 8,383,363 Bl, issued Feb. 26, 2013 (“Ueda”).
7 While the Examiner’s statement of rejection includes claim 2, we did not
include cancelled claim 2 in our deliberations. (Final Act. 2 (“Claim 2 has
been cancelled”).)
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FF 6. Caldara teaches “[t]he LAO system consists of the argT-
encoded periplasmic LAO protein which binds lysine, arginine and
ornithine, and membraneous and membrane-associated proteins encoded by
the hisJQMP genes which encode the histidine transporter.” (Caldara 3349,
right col.)
FF 7. Caldara teaches “[t]he present analysis reveals that the
hisJQMP genes are subject to ArgR-mediated repression . . . argT is not
repressed by arginine and [] its transcription remains unchanged in the argR
mutant.” (Caldara 3350, left col.)
FF 8. Caldara teaches that “[t]he histidine transporter appears to be
the only histidine uptake system in E. coli. This could explain its
comparatively weak response to arginine, leaving sufficient residual
expression to ensure the uptake of histidine.” (Id.)
FF 9. Ueda teaches
Methods of modifying uptake or export of L-amino acids in
bacterial cells have been known to improve the L-amino acid-
producing ability of the bacteria. Methods of modifying L-amino
acid uptake include eliminating or decreasing uptake of an L-
amino acid into cells to enhance L-amino acid-producing ability.
Specifically, these methods include a method of deleting the
gluABCD operon, or a part thereof, to eliminate or attenuate
uptake of L-glutamic acid (EP 1038970A).
(Ueda col. 1,11.51-59.)
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ISSUE
Whether a preponderance of evidence of record supports the
Examiner’s conclusion of obviousness under 35 U.S.C. § 103(a).
ANALYSIS
We adopt the Examiner’s findings and agree with the Examiner’s
conclusion that claims 1, 3—7, and 10 would have been obvious to a person
of ordinary skill in the art at the time of the invention. (Ans. 2—24; Adv.
Act. dated Oct. 20, 2014; Final Act. 2—11.) The rejections are affirmed, and
Appellants’ arguments are addressed below. Furthermore, we limit our
consideration to claim 1 because the claims were not separately argued.
Claim 1 requires attenuation of expression of one or more genes of the
argT-hisJQMP cluster. As an initial matter, we note that Appellants
generally argue a lack of motivation by a person of skill in the art, and a lack
of an expectation of success and associated unpredictability. (See Appeal
Br. 5—10; Reply Br. 5.) However, the combinations of Lu and Caldara and
Ueda and Caldara clearly provide the motivation to modify a bacterium by
attenuating expression of one or more genes encoding the LAO transporter
in order to produce L-arginine. (FF 1—9.) The LOA transporter is coded for
by the hisJQMP genes. (FF5.) In particular, Lu and Ueda both teach
deletion or attenuation of genes to decrease amino acid uptake into the cells,
thereby resulting in bacterial production of amino acids (FF 1, 2, and 9), and
Caldara teaches the repression (attenuation) of specific genes associated with
arginine uptake (FF 3—7) that are involved in feedback inhibition of the
arginine biosynthesis pathway. (See Caldera Abstract.) Furthermore, the
reasonable expectation of success requirement does not refer to an
unclaimed result, but rather “refers to the likelihood of success in combining
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references to meet the limitations of the claimed invention.” Intelligent Bio-
Systems, Inc. v. Illumina Cambridge Ltd., 821 F.3d 1359, 1367 (Fed. Cir.
2016). Moreover, “[ojbviousness does not require absolute predictability of
success.”In re O’Farrell, 853 F.2d 894, 903 (Fed. Cir. 1988).
Rejection No 1
Appellants argue that “Lu indicates that deletion of the argT gene is
only one of potentially many possible methods for increasing L-arginine
production. Hence, Lu does not disclose that deletion of argT gene is
effective for improving L-arginine production.” (Appeal Br. 6.) We are not
persuaded. Lu clearly suggests the attenuation of the argT gene to increase
L-arginine production. (FF 2.) Moreover, claim 1 does not recite or require
a particular efficacy of the bacterium or “improving L-arginine production.”
See In re Self, 671 F.2d 1344, 1348 (CCPA 1982) (rejecting arguments “not
based on limitations appearing in the claims”).
Appellants argue that “many arginine uptake systems are known and
their interaction and expression is highly complex.” (Appeal Br. 6.) Thus,
according to Appellants, “it would have been impossible to predict or expect
a specific result from inactivating expression of one or more of the argT-
hisJQMP genes, and clearly a decrease in arginine uptake and a concomitant
improvement in L-arginine production would not have been easily or readily
predicted.” {Id. at 6—'7.) We are not persuaded. Lu expressly suggests
decreasing uptake to increase L-arginine yield. (FF 1.) Absolute
predictability is not required. See O Farrell, 853 F.2d at 903. Moreover,
claim 1 does not recite or require a “specific result” or “improvement in L-
arginine production.” See Intelligent Bio-Systems, 821 F.3d at 1367; Self,
671 F.2d at 1348.
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Appellants argue that a skilled artisan would not have been motivated
to inactivate “any of the genes of the argT-hisJQMP gene cluster, including
the only histidine uptake system, and have an expectation of increasing L-
arginine production,” because a deficiency in the hisJQMP genes would
render a bacterium “completely deficient in the ability to uptake histidine.”
(Appeal Br. 7.) We are not persuaded. Other than a general description of
the histidine uptake system from Caldara, Appellants provide no evidence
concerning the continued ability of the modified bacterium to uptake
histidine or, to the extent histidine uptake is impeded, how that would defeat
the motivation clearly taught by the prior art. See In re Geisler, 116 F.3d
1465, 1470 (Fed. Cir. 1997) (“[Attorney argument [is] not the kind of
factual evidence that is required to rebut a prima facie case of obviousness”).
Moreover, Appellants’ contention appears to be contrary to Caldara’s
statement regarding “sufficient residual expression to ensure the uptake of
histidine” when hisJQMP is repressed. (FF 8.) Furthermore, claim 1 does
not recite or require “increasing” L-arginine production. See Intelligent Bio-
Systems, 821 F.3d at 1367; Self, 671 F.2d at 1348.
Appellants advance several additional arguments regarding the lack of
motivation to attenuate expression of the argT-hisJQMP genes. (Appeal Br.
7—8.) In particular, Appellants argue that under L-arginine-producing
conditions, or fermentation production, where “L-arginine is abundantly
present inside and outside the cells,” expression of the hisJQMP operon will
be repressed and arginine uptake will not occur. {Id. at 8.) In addition,
Appellants argue that
if L-arginine secretion system functions so intensively that the
level of L-arginine inside the cells is not increased, as the Office
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Action states, L-arginine taken from the medium will be
immediately secreted from the cells, and as a result, the uptake
of L-arginine will not affect the levels of L-arginine inside and
outside the cells at all.
(Id.)
We are not persuaded. Lu and Caldara clearly provide the motivation
for the modified bacterium of claim 1. (FF 1—7.) Moreover, Appellants’
arguments about certain conditions or scenarios that are not recited in or
required by claim 1 do not persuasively overcome the clear teachings of the
prior art, including the motivation to modify a bacterium as recited in claim
l.8 See Geisler, 116 F.3d at 1470; Self, 671 F.2d at 1348.
Finally, Appellants argue that “the his.J gene product is not remotely
involved in arginine uptake” and that, therefore, “[t]he skilled artisan would
not have been motivated or had any logical reason to inactivate any of the
genes of the argT-hisJQMP gene cluster, including the his.J gene, with the
expectation of increasing L-arginine production.” (Appeal Br. 8.) We are
not persuaded. Claim 1 merely recites the attenuation of one or more genes
of the argT-hisJQMP cluster, which may or may not include the his.J gene.
(Appeal Br. 12.) Moreover, claim 1 does not recite or require “increasing”
L-arginine production. See Intelligent Bio-Systems, 821 F.3d at 1367; Self,
671 F.2d at 1348.
8 We acknowledge Appellants’ contention that when (or if) the argT gene is
expressed alone, arginine uptake will not occur. (Reply Br. 5.) However,
even if Appellants’ contention is correct, we are not persuaded that “the
Examiner’s logic ... is flawed and unreasonable” (Reply Br. 5), or that
Appellants’ contention establishes a lack of either motivation to combine or
reasonable expectation of success.
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Conclusion of Law
A preponderance of evidence of record supports the Examiner’s
conclusion that claim 1 is obvious under 35 U.S.C. § 103(a) based on Lu,
Caldara, and Wissenbach. Claims 3—7 and 10 were not argued separately
and fall with claim 1.
Rejection No. 2
Appellants note that Ueda is cited for reasons similar to Lu, and
advance some of the same arguments as advanced in connection with
Rejection No. 1 above. (Appeal Br. 9-10.) Accordingly, for the reasons set
forth above, Appellants’ arguments are unpersuasive and Rejection No. 2 is
affirmed.
Conclusion of Law
A preponderance of evidence of record supports the Examiner’s
conclusion that claim 1 is obvious under 35 U.S.C. § 103(a) based on Ueda
and Caldara. Claims 3—7 and 10 were not argued separately and fall with
claim 1.
SUMMARY
We affirm the rejections 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
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