Ex Parte Iwatani et al

Patent Trial and Appeal Board

Dec 23, 2016

12055438 (P.T.A.B. Dec. 23, 2016)

United States Patent and Trademark Office
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
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Alexandria, Virginia 22313-1450
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APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
12/055,438 03/26/2008 Shintaro Iwatani US-254 7791
38108 7590 12/28/2016
CERMAK NAKAJIMA MCGOWAN LLP
127 S. Peyton Street
Suite 210
ALEXANDRIA, VA 22314
EXAMINER
HUTSON, RICHARD G
ART UNIT PAPER NUMBER
1652
NOTIFICATION DATE DELIVERY MODE
12/28/2016 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
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte SHINTARO IWATANI, AKIRA IMAIZUMI,
YOSHIHIRO USUDA, and KAZUHIKO MATSUI
Appeal 2015-006812
Application 12/055,438
Technology Center 1600
Before RICHARD M. LEBOVITZ, JEFFREY N. FREDMAN and
JOHN E. SCHNEIDER, Administrative Patent Judges.
LEBOVITZ, Administrative Patent Judge.
DECISION ON APPEAL
This appeal involves claims directed to a method for producing an L-
amino acid comprising culturing a bacterium of the family
Enterobacteriaceae. The Examiner rejected the claims as obvious under 35
U.S.C. § 103(a). We have jurisdiction under 35 U.S.C. § 134. The
obviousness rejection is reversed.
STATEMENT OF CASE
Appellants appeal from the final rejection by the Examiner of claims 1
and 4—13.
Appeal 2015-006812
Application 12/055,438
Claims 1 and 4—13 stand rejected by the Examiner under 35 U.S.C. §
103(a) (pre-AIA) as obvious in view of Ma et al.1 and Nishino et al.2
Claim 1, the only independent claim on appeal, reads as follows
1. A method for producing an E-amino acid comprising:
A) culturing in a medium a bacterium of the family
Enterobacteriaceae which has an ability to produce an L-amino
acid and which has been modified to increase the expression of
a gene selected from the group consisting of evgA, gadE, ydeO,
and combinations thereof,
B) producing and accumulating the L-amino acid in the
medium, and
C) collecting the L-amino acid from the medium,
wherein expression of said gene(s) is/are increased by a
method selected from the group consisting of:
a) increasing the copy number of said gene(s),
b) modifying an expression regulatory sequence of said
gene(s),
c) modifying the bacterium so that the expression of an
evgS gene that encodes a sensor kinase is increased by a method
selected from the group consisting of:
i) increasing the copy number of the evgS gene,
ii) modifying the expression regulatory sequence
of the evgS gene, and
iii) combinations thereof; and
d) combinations thereof, and
wherein said L-amino acid is selected from the group
consisting of a basic amino acid, a hydroxymonoamino-
carboxylic acid, and an aromatic amino acid,
1 Characterization of EvyAS-YdeO-GadE Branched Regulatory Circuit
Governing Glutamate-Dependent Acid Resistance in Escherichia coli, J. of
Bacteriology, 186(21) 7378-7389, Nov. 2004) (“Ma”).
2 Global Analysis of Genes Regulated by EvgA of the Two-Component
Regulatory System in Escherichia coli, J. of Bacteriology, 185(8) 2667—
2672, April 2003 (“Nishino”).
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Appeal 2015-006812
Application 12/055,438
wherein the basic amino acid is selected from the group
consisting of L-lysine, L-omithine, L-arginine, L-histidine, and
L-citralline;
wherein the hydroxymonoaminocarboxylic acid is
selected from the group consisting of L-threonine and L-serine;
and
wherein the aromatic amino acid is selected from the
group consisting of L-tryptophan, L-phenylalanine, and L-
tyrosine.
ISSUE
Claim 1 is directed to a method of producing an L-amino acid
comprising three steps. The first step A) involves culturing a bacteria of the
family Enterobacteriaceae in a medium, where the bacteria has increased
expression of the evgA gene. The Specification teaches that E. coli is a
member of the Enterobacteriaceae. Spec. 6. EvgA is a gene which codes
for a response regulator transcription factor known to regulate the
transcription of many genes. Id. The second step B) of the claimed method
is of “producing and accumulating the L-amino acid in the medium.” The
third step C) is of “collecting the L-amino acid from the medium. The claim
recites that increased expression of the gene is achieved by one of four ways,
including “a) increasing the copy number” of evgA.
The Examiner found that Ma describes culturing E. coli bacteria in a
medium in which the evgA gene is over expressed from the pQEevgA
plasmid. Ans. 2. The Examiner found that extracts of protein are collected.
The Examiner found that although Ma did not perform its method with the
intent to produce an L-amino acid, E. coli has an inherent ability to produce
L-amino acids and the steps carried out by Ma would result in the production
of L-amino acid. Id., 3. The Examiner further found that Nishino provides
the reason to assay and measure L-amino acid in the medium. Id., 6.
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Appeal 2015-006812
Application 12/055,438
Appellants contend that Ma does not disclose steps B) and C). Appeal
Br. 7-8.
DISCUSSION
The Examiner’s finding that E. coli, having increased expression of
evgA as described in Ma, would secrete L-amino acid into the medium is
supported by a preponderance of the evidence. The Examiner cited evidence
in the Specification that many microorganisms produce L-amino acids,
including E. coli. Ans. 4; Final Rej. 4, 7. Appellants did not challenged the
Examiner’s finding or provide evidence to the contrary. Appellants appear
to concede that Ma’s E. coli produces L-amino acid: “Essentially, in the
presently claimed subject matter, the L-amino acids are present in the
medium, and not in the cells as in Ma.” Appeal Br. 8. However, Appellants
have not provided evidence or a scientific basis for the statement that the L-
amino acids are inside the cell, rather than being secreted into the medium.
An argument made by counsel in a brief does not substitute for evidence
lacking in the record. Estee Lauder Inc. v. L ’Oreal, S.A., 129 F.3d 588, 595
(Fed. Cir. 1997). Thus, while it is true that Ma does not disclose that L-
amino acid is secreted into the culture medium (Appeal Br. 6—7),
Appellants’ did not demonstrate error in the Examiner’s finding that the E.
coli in Ma would inherently meet step B) of “producing and accumulating
the L-amino acid in the medium.”
After the L-amino acids are B) “produced] and accumulated] ... in
the medium,” step C) of claim 1 requires “collecting the L-amino acid from
the medium” in which the bacteria was cultured. The term “collect” means
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Appeal 2015-006812
Application 12/055,438
to “bring together” or “to gather or exact” from sources.3 The Specification
teaches that “L-amino acids can be collected from the fermentation broth
using a combination of a conventional ion-exchange resin method,
precipitation method, and other known methods.” Spec. 1123. We
therefore interpret “collecting the L-amino acid from the medium” to mean
that the L-amino acid is gathered, such as purifying it or separating it from
the medium, in which it accumulated in during step B).
To meet this collecting step, the Examiner cited Fig. 1 of Ma in which
Western blots of “extracts” were analyzed for expression of proteins. The
extracts were prepared from cells, not the medium. In the Material and
Methods section of Ma, Ma states that “cells were collected by
centrifugation” of the culture media, suspended in detergent, and then
samples “were prepared and subjected to Western blot analysis.” Ma 7379.
The extracts are therefore of cells. The Examiner did not identify disclosure
in Ma where the medium in which the cells were grown was subjected to
further processing or extraction.4 Rather, the disclosure in Ma identified by
the Examiner to meet step C) of the claim involves separating and collecting
cells from the medium; however, merely obtaining the culture medium free
of cells is not “C) collecting the L-amino acid from the medium” because it
3 https://www.merriam-webster.com/dictionary/collect (accessed Dec. 10,
2016).
4 We note that the Examiner had originally relied upon this teaching in Ma
when the claims included “collecting the L-amino acid from . . . the
bacterium” and the rejection was anticipation under 35 U.S.C. § 102.
Claims (Mar. 26, 2008); Office Action 5 (Dec. 28, 2010). The “collecting
from bacterium” language was subsequently canceled from the claims.
Claims accompanying Applicant Remarks (Mar. 28, 2011).
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Appeal 2015-006812
Application 12/055,438
does not gather the L-amino acid from the medium, but merely isolated the
medium without further extracting the amino acid from it.
The Examiner cited Nishino for providing a reason to “measure the
level of various components of the culture medium,” including D-sugars and
L-amino acids. Ans. 4. The Examiner stated that the “reason one of skill in
the art would focus on those components of the cell and medium for which
transporters are know[n] is the known association of the evgA protein with
various transporters, specifically amino acid transporters as taught by both
Ma et al. and Nishino et al.” Id. The Examiner stated that the reason the
skilled worker would “assay and measure” L-amino acid in the medium is
based on the teaching in Nishino that overexpression of evgA results in the
increased expression of the gadC amino acid transporter. Id., 6.
Nishino teaches that gadC expression is increased by evgA, but lists it
as a “Predicted amino acid transporter.” Nishino 2668 (Table 2). The
Examiner did not establish that gadC is associated with increased secretion
of L-amino acid into the medium. Thus, we agree with Appellants that the
Examiner did not establish a nexus because neither Ma nor Nishino
discusses or suggests amino acid transport or production in relation to the
evgA gene. Appeal Br. 7.
Furthermore, even were there reason to measure L-amino acids in the
medium, the Examiner did not provide sufficient evidence that one of
ordinary skill in the art would have had reason to gather or separate the L-
amino acid from the medium of Ma as required by claim 1. The Examiner
refers to “the motivation to assay and measure the various levels of cellular
metabolites in the cell medium as a result of evgA over expression would
inherently involve the collecting of the L-amino acids from the medium.”
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Application 12/055,438
Ans. 6. However, the Examiner did not explain how assaying L-amino acid
in the medium is inherently “collecting” the amino acid as required by claim
1. Assaying itself requires no collection, only detection.
The Examiner has the burden to establish a case of prima facie
obviousness considering the factors set out by the Supreme Court in Graham
v. John Deere, 383 U.S. 1 (1966). In re Bell, 991 F.2d 781, 783 (Fed. Cir.
1993); In re Rijckaert, 9 F.3d 1531, 1532 (Fed. Cir. 1993); In re
Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992). In this case, the Examiner
did not establish a reason to collect F-amino acid from the medium of Ma in
which E. coli overexpressing the evgA gene were culture. Consequently, we
are compelled to reverse the obviousness rejection of claim 1 and claims 4—
13 which depend from it.
REVERSED
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