Ex Parte Kakehi et al

Board of Patent Appeals and Interferences

Mar 24, 2009

10798339 (B.P.A.I. Mar. 24, 2009)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte MASAHIRO KAKEHI, YOSHIHIRO USUDA,
YUKIKO TABIRA, and SHINICHI SUGIMOTO
__________

Appeal 2008-56971
Application 10/798,339
Technology Center 1600
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Decided:2 March 24, 2009
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Before DEMETRA J. MILLS, LORA M. GREEN, and
FRANCISCO C. PRATS, Administrative Patent Judges.

MILLS, Administrative Patent Judge.

DECISION ON APPEAL

1 Heard March 19, 2009.
2 The two-month time period for filing an appeal or commencing a civil
action, as recited in 37 C.F.R. § 1.304, begins to run from the decided date
shown on this page of the decision. The time period does not run from the
Mail Date (paper delivery) or Notification Date (electronic delivery).

Appeal 2008-1365
Application 10/143,156

STATEMENT OF CASE
This is an appeal under 35 U.S.C. § 134. The Examiner has rejected
the claims for obviousness. We have jurisdiction under 35 U.S.C. § 6(b).
The following claim is representative.
9. A method for producing nucleoside 5'-phosphate ester, comprising the
steps of culturing a bacterium belonging to Escherichia coli having an
ability to produce nucleoside 5'-phosphate ester, in which expression of
ushA gene and aphA gene is decreased as compared to a wild type strain by
mutating or disrupting the ushA gene and the aphA gene, in a medium to
produce and accumulate nucleoside 5'-phosphate ester in a medium, and
collecting the nucleoside 5'-phosphate ester from the medium, wherein the
nucleoside 5'- phosphate ester is selected from the group consisting of
inosine 5'-phosphate ester and guanosine 5'-phosphate ester, and wherein the
5'-nucleotidase activity in the periplasm is substantially eliminated.

Cited References
Matsui et al. EP 1 004 663 A1 May 31, 2000

Thaller et al., Identification of the gene (aphA) encoding the class B acid
phosphatase/phosphotransferase of Escherichia coli MG1655 and
characterization of its product, 146 FEMS MICROBIOLOGY LETTERS 191-198
(1997).

A. Cowman and I.R. Beacham, Molecular cloning of the gene (ush) from
Escherichia coli specifying periplasmic UDP-sugar hydrolase (5’-
nucleotidase), 12 GENE 281-286 (1980).

Grounds of Rejection
1. Claims 9, 13, and 14 are rejected under 35 U.S.C. § 103(a) as being
unpatentable over Thaller et al. alone or in view of Cowman et al.
2. Claims 9 and 11-14 are rejected under 35 U.S.C. § 103(a) as being
unpatentable over Thaller et al. alone or in view of Cowman et al. and
further in view of Matsui et al.
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Appeal 2008-5697
Application 10/798,339

ISSUE
The Examiner concludes that:
It would have been obvious to one of ordinary skill in the
art at the time the invention was made to produce E. coli
mutants having non-functional, for example, disrupted ushA
gene and aphA gene. The motivation to produce such mutants
is provided by Thaller et al. who teach 5'-nucleotide
dephosphorylating activity of ushA gene and aphA gene.
Mutants with disrupted ushA gene and aphA gene would have a
higher yield of 5'-nucleotides.

(Ans. 4.)

Appellants contend that there is no teaching in Thaller or Cowman
that “decreasing expression of the gene would lead to enhanced production
of nucleoside 5'-phosphate esters.” (App. Br. 3.) Appellants further argue
that neither Thaller nor Cowman, either alone or in combination, “suggest
that decreasing expression of ushA gene and aphA gene or disrupting those
genes would substantially eliminate the 5'-nucleotidase activity in the
periplasm, as claimed.” (Id. at 4.)
The issue is: Does the combination of Thaller with Cowman disclose
or suggest a method that results in a decrease in ushA gene and aphA gene as
compared to a wild type and wherein the 5'-nucleotidase activity in the
periplasm is substantially eliminated?

FINDINGS OF FACT
1. Claims 9, 13, and 14 are rejected under 35 U.S.C. §103(a) as being
unpatentable over Thaller alone or in view of Cowman. (Ans. 3.)

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Appeal 2008-5697
Application 10/798,339
2. Thaller teaches “the sequence of the aphA gene (page 193, Figure 1).”
(Ans. 3.)
3. Thaller “further characterize 5'- nucleotidase activity of the E. coli AphA
enzyme (page 195, Table 1).” Id.
4. Thaller teaches that “another 5'-nucleotidase in E. coli is UshA (page
197, 2nd column, last paragraph). They suggest producing strains carrying
aphA mutations (page 198).” Id.
5. Cowman “teach[es] the ushA gene from E. coli encoding a 5'-
nucleotidase.” Id.
6. The Examiner concludes that
It would have been obvious to one of ordinary skill in the
art at the time the invention was made to produce E. coli
mutants having non-functional, for example, disrupted ushA
gene and aphA gene. The motivation to produce such mutants
is provided by Thaller et al. who teach 5'-nucleotide
dephosphorylating activity of ushA gene and aphA gene.
Mutants with disrupted ushA gene and aphA gene would have a
higher yield of 5'-nucleotides.

Id. at 4.
7. The Examiner concludes that “[o]ne of ordinary skill in the art at the
time the invention was made would have a reasonable expectation of success
because the structures of both ushA gene and aphA gene were known at the
time the invention was made and methods for disrupting known genes were
widely used.” Id.
8. Claims 9 and 11-14 are rejected under 35 U.S.C. 103(a) as being
unpatentable over Thaller et al. alone or in view of Cowman et al. and
further in view of Matsui et al. Id.
9. Matsui teaches

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Appeal 2008-5697
Application 10/798,339
[A] method for producing purine nucleosides such as inosine
and guanosine which are important as intermediate compounds
for synthesis of 5'-inosinic acid and 5'- guanylic acid (page 2,
[001], lines 5-7). They teach a microorganism which acquired
the purine nucleoside-producing ability because of an increase
of an activity of an enzyme involved in the purine nucleoside
biosynthesis due to its gene overexpression (page 2, [0007]).

(Ans. 4.)

10. Matsui teaches “that enzyme can be PRPP amidotransferase that is
desensitized (page 2, [0008]).” Id.
11. Matsui teaches “the mutation Lys326Glu in PRPP amidotransferase
gene (purF) resulting in desensitizing the feedback inhibition (page 6,
[0055]; page 10, [0076])) and E. coli comprising said mutant PRPP
amidotransferase (page 11).” Id. at 4-5.
12. Matsui “further teach[es] that in order to efficiently utilize the purF
gene, it can be used with other genes involved in the IMP biosynthesis such
as IMP dehydrogenase gene (guaB) and GMP synthetase gene (guaA) (page
7, [0064]).” Id. at 5.
13. The Examiner concludes that
It would have been obvious to one of ordinary skill in the
art at the time the invention was made to produce E. coli
mutants having non-functional, for example, disrupted ushA
gene and aphA gene thus preventing the decomposition of
inosine 5'- phosphate ester and guanosine 5'-phosphate ester
and additional genes such as purF, guaA and guaB that increase
their production.
Id.

14. The Examiner concludes that “[t]he motivation to produce such mutants
is provided by Thaller et al. who teach 5'-nucleotide dephosphorylating

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Appeal 2008-5697
Application 10/798,339
activity of ushA gene and aphA gene and Matsui et al. who teach the role of
purF, guaA and guaB in the nucleotide biosynthesis.” (Ans. 5.)
15. The Examiner concludes that “[o]ne of ordinary skill in the art at the
time the invention was made would have a reasonable expectation of success
because the structures of all involved genes were known at the time the
invention was made and methods for mutation of known genes were widely
used.” Id.

PRINCIPLES OF LAW
“In rejecting claims under 35 U.S.C. § 103, the examiner bears the
initial burden of presenting a prima facie case of obviousness.” In re
Rijckaert, 9 F.3d 1531, 1532 (Fed. Cir. 1993) (citations omitted). Only if
that burden is met, does the burden of coming forward with evidence or
argument shift to the applicant. In order to determine whether a prima facie
case of obviousness has been established, we considered the factors set forth
in Graham v. John Deere Co., 383 U.S. 1, 17 (1996); (1) the scope and
content of the prior art; (2) the differences between the prior art and the
claims at issue; (3) the level of ordinary skill in the relevant art; and (4)
objective evidence of nonobviousness, if present.

ANALYSIS
Appellants contend that there is no teaching in Thaller that
“decreasing expression of the gene would lead to enhanced production of
nucleoside 5’-phosphate esters.” (App. Br. 3.) Appellants further argue
there is no teaching in Cowman that “decreasing expression of the gene
would lead to enhanced production of nucleoside 5’phosphate esters.” Id.
Appellants further argue that neither Thaller nor Cowman “suggest

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Appeal 2008-5697
Application 10/798,339
disrupting expression of the ushA and aphA genes, respectively, to [sic] for
the purpose of preparing nucleoside 5'-phosphate esters.” Id. Appellants
argue that the cited references fail to suggest that decreasing expression of
the ushA and aphA genes by mutating or disrupting those genes alone would
substantially eliminate the 5'-nucleotidase activity in the periplasm, as
claimed. (Reply Br. 1.)
The Examiner responds, arguing that
[I]t would have been reasonable to expect that the
elimination of enzymes (aphA and ushA) that decompose the
product (nucleoside 5'-phosphate ester)… would be beneficial
for the production of the product . . . . No unexpected results
have been shown or argued by Appellant.

(Ans. 6.)

We find the Appellants have the better argument. The Examiner may
be correct that the genes in the cited references encode enzymes that degrade
nucleoside 5'-phosphate ester. However, we do not find that the Examiner
has provided adequate evidence that one of ordinary skill in the art was
provided a sufficient suggestion from Thaller, Cowman, and/or Matsui that a
decrease in production of the ushA and aphA genes would substantially
eliminate the 5'-nucleotidase activity in the periplasm, as claimed.
We therefore do not agree with the Examiner that the cited references
suggest the claimed fermentation method of producing a nucleoside 5'-
phosphate ester in which expression of the ushA and aphA gene is
decreased. We do not find that Matsui overcomes the deficiencies of the
combination of Thaller and Cowman. The appealed obviousness rejections
are therefore reversed.

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Appeal 2008-5697
Application 10/798,339
REVERSED

cdc

OBLON, SPIVAK, MCCLELLAND MAIER & NEUSTADT, P.C.
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ALEXANDRIA VA 22314

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