Ex Parte Rieping et al

Patent Trial and Appeal Board

Jun 11, 2013

10114043 (P.T.A.B. Jun. 11, 2013)

UNITED STATES PATENT AND TRADEMARK OFFICE
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BEFORE THE PATENT TRIAL AND APPEAL BOARD
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Ex parte MECHTHILD RIEPING and THOMAS HERMANN
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Appeal 2011-007939
Application 10/114,043
Technology Center 1600
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Before TONI R. SCHEINER, LORA M. GREEN, and
ANNETTE R. REIMERS, Administrative Patent Judges.

GREEN, Administrative Patent Judge.

DECISION ON APPEAL
This is a decision on appeal1 under 35 U.S.C. § 134 from the
Examiner’s rejection of claims 77, 79-82, 85-87, and 90-99. We have
jurisdiction under 35 U.S.C. § 6(b).
We affirm.

1 The Real Party in Interest is Evonik Degussa GMBH (App. Br. 2).
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STATEMENT OF THE CASE
Claim 77 is representative of the claims on appeal, and reads as
follows:
77. A process for the production of an L-amino acid, comprising:
(a) culturing an enterobacterium of the genus Escherichia in a medium
for a time and under conditions suitable for producing the L-amino acid,
wherein the enterobacterium is modified in a manner to inactivate the dgsA
gene wherein said inactivated dgsA gene encodes a non-functional dgsA
peptide, and wherein the enterobaterium produces the L-amino acid prior to
modification, and wherein the production of the L-amino acid during
culturing is improved in the modified enterobacterium compared to the
enterobacterium prior to modification,
(b) enriching the L-amino acid in the medium; and
(c) recovering or isolating the L-amino acid from said medium,
wherein the dgsA gene of the modified Escherichia has been inactivated by
one or more methods of mutagenesis selected from the group consisting of
deletion of all or part of the dgsA gene, insertional mutagenesis due to
homologous recombination in the dgsA gene and transition or transversion
mutagenesis with incorporation of a non-sense mutation in the dgsA gene,
wherein the dgsA gene comprises a polynucleotide which encodes the
polypeptide of SEQIDNO:2.

The following grounds of rejection are before us for review:
I. Claims 77, 79-82, 85-87, 90, 91, 94, and 95 stand rejected under 35
U.S.C. § 103(a) as being rendered obvious by the combination of
Pompejus,2 Tanaka,3 Lee,4 Kikuchi,5 and Slocum6 (Ans. 4).

2 Pompejus et al., US 6,884,614 B1, Apr. 26, 2005.
3 Yuya Tanaka et al., Negative regulation of the pts operon by MIc:
mechanism underlying glucose induction in Escherichia coli, 4 GENES TO
CELLS, 391-399 (1999).
4 Sung-Jae Lee et al., Signal transduction between a membrane-bound
transporter, PtsG, and a soluble transcription factor, MIc, of Escherichia
coli, 19(20) EMBO J., 5353-5361 (2000).
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II. Claims 92, 93, and 96-99 stand rejected under 35 U.S.C. § 103(a)
as being rendered obvious by the combination of Pompejus,
Tanaka, Lee, Kikuchi, and Slocum, as further combined with
Shimizu7 (Ans. 8).

ISSUE
Does the preponderance of evidence of record support the Examiner’s
conclusion that the combination of Pompejus, Tanaka, Lee, Kikuchi, and
Slocum renders the method of producing an L-amino acid of claim 77
obvious?

FINDINGS OF FACT
FF1. The Specification teaches that the invention “is based on the discovery
[that] microorganisms of the family Enterobacteriaceae which naturally
produce L-amino acids do so more effectively under conditions in which the
nucleotide sequence coding for the dgsA gene is attenuated” (Spec. 2).
FF2. DgsA is the same gene as mlc (Ans. 4).
FF3. We adopt the Examiner’s findings and conclusions as to the
obviousness rejections (see Ans. 4-9).

5 Kikuchi et al., US 5,932,453, Aug. 3, 1999.
6 Mary K. Slocum et al., Genetics of Methyl-Accepting Chemotaxis Proteins
in Escherichia coli: Null Phenotypes of the tar and tap Genes, 163 (2) J. OF
BACTERIOLOGY, 586-594 (1985).
7 Shimizu et al., US 5,445,948, Aug. 29, 1995.
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FF4. Plumbridge,8 relied upon by Appellants, teaches that Mlc represses
several genes implicated in the uptake of glucose, such as ptsG (Plumbridge,
Abstract).
FF5. Plumbridge teaches further that “[a]ll Mlc repressed genes are also
controlled by cAMP/CAP” (id.).
FF6. Nam,9 relied upon by Appellants, teaches that glucose induction of
several genes in E. Coli is mediated by the global repressor, Mlc (Nam,
Abstract).
FF7. Nam teaches that PTS (phosphoenolpyruvate:sugar
phosphotransferase system) proteins are involved in glucose transport (id. at
491, paragraph bridging cols. 1 and 2).
FF8. Figure 6 of Nam shows the negative feedback loop, showing how Mlc
represses the expression of PTS proteins (id. at 496).

ANALYSIS
Appellants argue that one would not have inactivated the dgsA gene
as it is a global regulator of various genes, such as pts (App. Br. 7 (citing
Lee, Shin, and Plumbridge)). Appellants argue further that Plumbridge
teaches that different families of proteins also act as repressors of pts genes,
and also teaches that all genes that are repressed by mlc are also controlled

8 Jacqueline Plumbridge, Regulation of PTS Gene Expression by the
Homologous Transcriptional Regulators, MIc and NagC, in Escherichia
coli, HORIZON SCIENTIFIC PRESS, 371-380 (2001).
9 Nam et al., The Escherichia coli glucose transporter enzyme IICBGlc
recruits the global repressor MLC, 20 THE EMBO JOURNAL 491-498
(2001).
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by cAMP/CAP (App. Br. 7). Thus, Appellants assert, the ordinary artisan
“could not have reasonably predicted that inactivating the mlc (dgsA) gene
would have resulted in the increased production of L-amino acids” (id.).
Appellants argue that while the combination suggested by the
Examiner may have been obvious to try, because of the complexities of
biological systems, “it would not have been reasonable to know what would
result, let alone an increased production in amino acids from the bacteria”
(App. Br. 9). Appellants cite Nam for its teaching that bacteria will sense
and adapt to changes in their environment (id. (citing Nam, p. 491)).
Appellants also cite Nam for its teaching that the five operons identified as
members of the Mlc regulon have cAMP-CRP binding sites, as well as an
MLC binding site, and thus are under dual regulation (App. Br. 9 (citing
Nam, p. 492)). Thus, Appellants argue,
those skilled in the art had to expect a deficiency in robustness
of the production strain by switching off the mlc gene which, in
turn, would affect the course of fermentation and the changing
environment conditions in a negative manner. Therefore, that
the inventors discovered something different could not have
been reasonably predicted. See Rieping Declaration.

(App. Br. 9-10.)
As noted by the Examiner, at the time of invention, mlc was known to
negatively regulate “‘genes implicated in sugar utilization systems, notably
the phosphotranferase systems (PTS) genes’” (Ans. 9 (Quoting Lee,
Abstract)). Thus, we agree with the Examiner that as Pompejus teaches
modifying PTS proteins to release the proteins from negative regulation to
allow for increased production of fine chemicals, such as L-amino acids
(Pompejus, col. 3, ll. 2-8; Ans. 6), it would have been obvious to the
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ordinary artisan to inactivate the mlc gene, which was known to negatively
regulate expression of PTS, to achieve the same result.
Appellants’ reliance on Plumbridge and Nam does not convince us
otherwise. Again, as noted above, Pompejus teaches modifying PTS
proteins to release the proteins from negative regulation to allow for
increased production of fine chemicals, such as L-amino acids, and mlc is a
known negative regulator of PTS proteins. Moreover, while Appellants
point out Plumbridge teaches that the genes that are repressed by mlc are
also repressed by cAMP/CAP, Appellants do not explain why the ordinary
artisan would expect that additional regulation would prevent the
inactivation of the Mlc gene to have any effect on increased production of
fine chemicals, such as L-amino acids. It appears Appellants are only using
that teaching of Plumbridge, along with Nam, to demonstrate the complexity
of biological systems.
We thus agree with the Examiner that the ordinary artisan would have
had a reasonable expectation of success that inactivating the Mlc gene would
have a positive effect on glucose metabolism, allowing for increased
production of fine chemicals, such as L-amino acids, as taught by Pompejus.
In re O’Farrell, 853 F.2d 894, 903 (Fed. Cir. 1988) (noting that all that is
required is a reasonable expectation of success, not absolute predictability of
success). We note further that while claim 77 requires improved production
of the desired amino acid, it does not specify what level of improvement is
required. Thus, claim 77 encompasses any level of improvement over the
unmodified enterobacterium.
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As to the Declaration of the inventor, Mechthild Rieping, it essentially
reiterates the arguments made above as to Nam (see Rieping Declaration,
¶¶ 8-11). Those arguments are not found to be convincing for the reasons
set forth above.
We thus, affirm the rejection as to claim 77. As Appellants do not
argue claims 79, 80, 82, 85-87, 90, 91, 94, and 95 separately, those claims
fall with claim 77. 37 C.F.R. § 41.37(c)(1)(vii).
As to the addition of Shimuzu in Rejection II, Appellants do not argue
the rejection separately (App. Br. 7). We thus, affirm that rejection for the
reasons set forth above.
Appellants argue that claims 81, 98, and 99 are separately patentable,
as the claims specify that L-threonine is the L-amino acid (App. Br. 10). As
Appellants provide no argument or evidence as to why L-threonine is
separately patentable, we affirm the rejections as to claims 81, 98, and 99 as
well. See 37 C.F.R. § 41.67(vii) (“A statement which merely points out
what a claim recites will not be considered an argument for separate
patentability of the claim.”) Moreover, we note that the Rieping Declaration
specifically states that “once it is shown that the cell is capable of producing
increased amounts of a single amino acid (threonine) as was done in the
examples of the application, one could reasonably expect and, in fact test
without any considerable difficulty, what other amino acids are similarly
increased” (Rieping Declaration, ¶ 4). Thus, the Declaration supports that
the production of one amino acid over another is not patentably distinct.

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SUMMARY
The rejections on appeal are affirmed.

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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