Ex Parte Marchenko et al

Board of Patent Appeals and Interferences

Sep 1, 2010

11079392 (B.P.A.I. Sep. 1, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte ALEKSEY NIKOLAEVICH MARCHENKO,
SERGEY VLADIMIROVICH BENEVOLENSKY,
ELENA VITALIEVNA KLYACHKO, YURI IVANOVICH KOZLOV,
ELVIRA BORISOVNA VOROSHILOVA, and
MIKHAIL MARKOVICH GUSYATINER
__________

Appeal 2010-008162
Application 11/079,392
Technology Center 1600
__________

Before DONALD E. ADAMS, LORA M. GREEN, and
JEFFREY N. FREDMAN, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL1
This is an appeal under 35 U.S.C. § 134 involving claims to an L-
amino acid producing Escherichia bacterium. The Examiner rejected the

1 The two-month time period for filing an appeal or commencing a
civil action, as recited in 37 C.F.R. § 1.304, or for filing a request
for rehearing, as recited in 37 C.F.R. § 41.52, begins to run from
the “MAIL DATE” (paper delivery mode) or the
“NOTIFICATION DATE” (electronic delivery mode) shown on
the PTOL-90A cover letter attached to this decision.
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Application 11/079,392

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claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We
reverse.
Statement of the Case
The Claims
Claims 1, 6, and 21-25 are on appeal. Claim 1 is
representative of the argued claims. Claim 1 reads as follows:
1. An L-amino acid producing Escherichia
bacterium, comprising enhanced activities of
xylose utilization enzymes, wherein the activities
of the xylose utilization enzymes are enhanced by
increasing the copy number of the Escherichia
xylABFGHR locus or modifying an expression
control sequence so that expression of the
Escherichia xylABFGHR locus is enhanced.

The issues
The Examiner rejected claims 1, 6, 21, 24, and 25 under 35 U.S.C. §
103(a) as obvious over Song2 and Aristidou3 (Ans. 4-8). The Examiner
rejected claims 1, 6, and 21-25 under 35 U.S.C. § 103(a) as obvious over
Song, Aristidou, Blattner,4 and Savrasova5 (Ans. 9-13). Because both
rejections turn on the same question, we consider them together.

2 Sukgil Song and Chankyu Park, Organization and Regulation of
the D-Xylose Operons in Escherichia coli K-12: XylR Acts as a
Transcriptional Activator, 179 J. BACTERIOLOGY 7025-7032
(1997).
3 Aristidou et al., US 7,091,014 B1, issued Aug. 15, 2006.
4 Blattner et al., The Complete Genome Sequence of Escherichia
coli K-12, 277 SCIENCE 1453-1462 (1997).
5 Savrasova et al., US 2004/0229321 A1, published Nov. 18, 2004.
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The Examiner concludes that because Song teaches the “xylose locus
xylABFGHR, xylose transporting genes xylFGH and xylose utilizing genes
xylAB and thus, one of ordinary skill[] in the art would [have] found it
obvious to overexpress the xylose transporting and utilization genes or
whole xylose locus to enhance xylose utilization as a carbon source for
producing biological important substance” (Ans. 6). The Examiner further
concludes that a “skilled artisan would have preferred to use xylose as a
carbon source instead of or in addition to glucose because Savrasova clearly
shows that most strains of E. coli grow in xylose and a skilled artisan was
well aware that xylose is cheaper than glucose and easily available” (id. at
12).
Appellants contend that
Song actually does teach the xylABFGHR operon
from E. coli; however, increasing expression of the operon is
NOT taught or suggested, nor is there any suggestion or
mention of use of this operon to increase production of L-
amino acids in either of the cited references. It is also
acknowledged that Aristidou teaches increased expression of
xylB, which is a gene in the xylABFGHR operon, and the
resulting ethanol (which is not an amino acid, nor related
thereto) production. However, L-amino acid production as a
result of this increased expression is not taught or suggested
by Aristidou. Furthermore, Aristidou do not disclose or
suggest increased expression of the entire xylABFGHR
locus, or the effect of this increased expression on L-amino
acid production.

(App. Br. 7.)
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Appellants also contend that the Marchenko Declaration6 shows that
“increasing expression of just one or two of the genes on the operon leads to
a decrease in growth rate of the bacteria. Therefore, this result actually
teaches away from the claimed invention” (App. Br. 9). Appellants contend
that “[t]herefore, there can be no expectation that the same results achieved
when the entire operon is enhanced can be achieved when only one or two of
the genes on the operon are enhanced” (id.).
Appellants contend that
one would NOT have a motivation or reason to combine the
teachings because, in the prior art, 1) the prior art
microorganism produces ethanol, not an amino acid, 2) the
increase expression shown in the prior art is only of xylB,
not the entire xylose operon, and 3) the submitted
declaratory data shows an actual decrease in L-amino acid
production when increasing expression of only one of the
genes on the operon . . .

(id. at 9-10).
The issue with respect to this rejection is: Does the preponderance of
evidence of record support the Examiner’s conclusion that Song and
Aristidou render obvious an Escherichia bacterium with enhanced activities
of xylose utilization enzymes as required by Claim 1?
Findings of Fact
1. Song teaches the organization of the xyl locus in Figure 1,
reproduced below:

6 Marchenko Declaration, submitted February 8, 2008.
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“FIG. 1. Organization of the xyl locus. The genes xylAB encoding metabolic
enzymes are light gray; the transport components xylFGH are dark gray.
The xylR gene is involved in transcriptional regulation of the xyl genes”
(Song 7027, figure 1 legend).
2. Song teaches that “[p]lasmid pBR322 or pSK274 containing the
xylFGHR genes was transformed into minicell-producing strain CP1023”
(Song 7027, col. 1).
3. Song teaches that “[p]roteins expressed from the xylFGHR
operon were characterized in minicells, derived from CP1023, containing
plasmid pSK274 or pBR322” (Song, 7028, col. 2).
4. Aristidou teaches an “engineered strain of S. cerevisiae carrying
genes for XR and XDH, and xylulokinase (XK) [xylB], is transformed with
a multicopy plasmid carrying the gene GDH2 encoding the NAD-dependent
glutamate dehydrogenase from S. cerevisiae, and a marker gene” (Aristidou,
col. 9, ll. 13-17).
5. Aristidou teaches that “transformants ferment xylose to ethanol
more efficiently than the non-transformed host yeast” (Aristidou, col. 9, ll.
18-20).
6. The Marchenko Declaration provides the following Table,
stating that
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“amplification of xylAB operon led to decreasing the growth rate in a
xylose-containing medium, while [the] growth rate of the xylA-R operon-
amplified strain changed little as compared to the control MG 1655 strain”
(Marchenko Dec. 3 ¶ 8).
Principles of Law
“‘[R]ejections on obviousness grounds cannot be sustained by mere
conclusory statements; instead, there must be some articulated reasoning
with some rational underpinning to support the legal conclusion of
obviousness.”’ KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007).
Analysis
The Examiner finds that “one of ordinary skill[] in the art would
[have] found it obvious to overexpress the xylose transporting and utilization
genes or whole xylose locus to enhance xylose utilization as a carbon source
for producing biological important substance” (Ans. 6).
The Examiner does not rely upon the references to teach the
obviousness of overexpressing the whole xylose locus because neither Song,
Aristidou, Blattner nor Savrasova teach such overexpression. As Appellants
point out “[n]one of the cited references suggest that expression of the entire
xylABFGHR locus could or should be increased for any purpose” (App. Br.
7).
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The Examiner’s reason to overexpress the xylABFGHR locus is that
doing so would enhance xylose utilization. However, this is not like
overexpression of a single nucleic acid to obtain increased amounts of the
resulting protein expression product. The Examiner has not demonstrated
that overexpression of an entire locus will necessarily result in increased
product. That is, due to feedback inhibition (see, e.g., Spec. 16 ¶¶ 0081,
0084) and other forms of regulation, increasing the copy number of the
entire xylABFGHR locus would not necessarily result in increased product.
We therefore agree with Appellants that there is no articulated
reasoning to overexpress the entire xylABFGHR locus by either increasing
the copy number or modifying an expression control sequence as required by
Claim 1.
Conclusion of Law
The evidence of record does not support the Examiner’s conclusion
that Song and Aristidou render obvious an Escherichia bacterium with
enhanced activities of xylose utilization enzymes as required by Claim 1.
SUMMARY
In summary, we reverse the rejection of claims 1, 6, 21, 24, and 25
under 35 U.S.C. § 103(a) as obvious over Song and Aristidou.
We reverse the rejection of claims 1, 6, and 21-25 under 35 U.S.C.
§ 103(a) as obvious over Song, Aristidou, Blattner, and Savrasova.

REVERSED

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