Ex Parte Kai et al

Board of Patent Appeals and Interferences

Jun 28, 2011

10578912 (B.P.A.I. Jun. 28, 2011)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte KEIICHIROU KAI, HITOKI MIYAKE,
and TOSHIHIRO OIKAWA
__________

Appeal 2011-000481
Application 10/578,912
Technology Center 1600
__________

Before TONI R. SCHEINER, ERIC GRIMES, and
MELANIE L. McCOLLUM, Administrative Patent Judges.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a process
for producing a pentose-5-phosphate ester. The Examiner has rejected the
claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm.
STATEMENT OF THE CASE
Claims 1, 4, and 6 are on appeal. The claims have not been argued
separately and therefore stand or fall together. 37 C.F.R. § 41.37(c)(1)(vii).
Claim 1 is representative and reads as follows:
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1. A process for producing a pentose-5-phosphate ester, wherein:
a pentose is reacted with a phosphoric acid donor in the presence of an
acid phosphatase;
the pentose is a pentose in (3S, 4R) or (3R, 4S) and the pentose is
ribose, arabinose or 2-deoxyribose;
the pentose-5-phosphate ester is a pentose-5-phosphate ester in (3S,
4R) or (3R, 4S) and the pentose-5-phosphate ester is a ribose-5-phosphate
ester, an arabinose-5-phosphate ester or a 2-deoxyribose-5-phosphate ester;
the acid phosphatase is an acid phosphatase derived from Shigella
flexneri, and
the pentose is reacted with the phosphoric acid donor at a molar ratio
of not less than 3 fold and not more than 7 fold phosphoric acid donor to
pentose.

Issue
The Examiner has rejected claims 1, 4 and 6 under 35 U.S.C. § 103(a)
as being obvious in view of Tanaka,
1
Asano,
2
and Gross.
3
The Examiner
finds that Tanaka discloses “the phosphorylation of inosine to inosine-5'-
monophosphate by nonspecific acid phosphatases from Shigella flexneri ...
[as well as] the phosphorylation of glucose to glucose-6-phosphate” (Answer
4) but does not teach phosphorylation of a free pentose (id. at 5). The
Examiner finds, however, that it would have been reasonable to expect
Tanaka’s enzyme to phosphorylate the substrates recited in the claims
because Tanaka discloses that “the enzyme is nonspecific” (id. at 6) and “the

1
Tanaka et al., Phosphorylation and dephosphorylation of polyhydroxy
compounds by class A bacterial acid phosphatases, 1 ORG. BIOMOL. CHEM.
2833-2839 (2003).
2
Asano et al., A new enzymatic method of selective phosphorylation of
nucleosides, 6 J. MOL. CATALYSIS B: ENZYMATIC 271-277 (1999).

3
Gross et al., Practical Synthesis of 5-Phospho-D-ribosyl α-1-
Pyrophosphate (PRPP): Enzymatic Routes from Ribose 5-Phosphate or
Ribose, 105 J. AM. CHEM. SOC. 7428-7435 (1983).
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structure of a pentose such as ribose is very similar to the structures of
inosine and glucose with respect to the reaction sites,” providing the
following diagram for illustration:

(Id.).
The Examiner concludes that it would have been obvious to “prepare
a pentose-5-phosphate ester using acid phosphatase from Shigella flexneri in
the presence of pyrophosphate” (id. at 5) because Tanaka supports a
reasonable expectation that the enzyme would act on a pentose substrate and
Gross discloses that “ribose 5-phosphate is an intermediate in the synthesis
of nucleotides, histadine [sic] and tryptophan” (id.), and therefore “such
compounds are useful intermediates” (id. at 6).
Appellants contend that nothing in the cited references guides “one of
ordinary skill in the art towards using the claimed enzyme with the claimed
substrates, as opposed to the countless numbers of other potential candidate
substrates” (Appeal Br. 4). Appellants also contend that one of ordinary
skill in the art would not have had a reasonable basis for expecting that a
Shigella flexneri acid phosphatase would phosphorylate one of the pentose
substrates recited in the claims (id. at 5-6).
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The issue presented is: Does the evidence of record support the
Examiner’s conclusion that one of ordinary skill in the art, based on the cited
references, would have reasonably expected a Shigella flexneri acid
phosphatase to phosphorylate one of the recited pentose substrates?
Findings of Fact
1. Tanaka discloses that “[n]onspecific acid phosphatases (NSAPs)
are bacterial enzymes which are able to catalyse the hydrolysis of phosphate
monoesters” (Tanaka 2833, left col.).
2. Tanaka discloses a study of “the kinetics of the phosphorylation of
glucose and dephosphorylation of glucose-6-phosphate (G6P) catalysed by
the acid phosphatases from Shigella flexneri (PhoN-Sf) and Salmonella
enterica (PhoN-Se)” (id., abstract).
3. Tanaka discloses that the acid phosphatase from Shigella flexneri
(PhoN-Sf) is a nonspecific acid phosphatase (id. at 2833, right col.).
4. Tanaka discloses that “PhoN-Sf is able to phosphorylate glucose
regiospecifically to G6P, glucose-1-phosphate is not formed” (id., abstract).
5. Tanaka discloses that “PhoN-Sf regiospecifically phosphorylates
inosine to inosine-5'-monophosphate” (id.).
6. Tanaka discloses that “[c]onsidering the nature of the substrates
that are phosphorylated it is likely that this class of enzyme is able to
phosphorylate a wide range of hydroxy compounds” (id.).
7. The Examiner finds that Asano discloses the synthesis of inosine
monophosphate with various bacterial and yeast types, using inosine and
tetrasodium pyrophosphate decahydrate in a molar ratio of about 1 to 5
(Answer 5). Appellants do not dispute this finding.
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8. The Examiner finds that Gross discloses that “ribose 5-phosphate
is an intermediate in the synthesis of nucleotides, histadine [sic], and
tryptophan” (Answer 5). Appellants do not dispute this finding.
Principles of Law
“Obviousness does not require absolute predictability of success.…
For obviousness under § 103, all that is required is a reasonable expectation
of success.” In re O’Farrell, 853 F.2d 894, 903-04 (Fed. Cir. 1988).
Analysis
Claim 1 is directed to a process for producing a pentose-5-phosphate
ester by reacting ribose, arabinose or 2-deoxyribose with a phosphoric acid
donor in the presence of an acid phosphatase from Shigella flexneri.
Tanaka discloses that an acid phosphatase from Shigella flexneri
(PhoN-Sf) phosphorylates glucose to G6P and inosine to inosine-5'-
monophosphate. Tanaka also discloses that it is likely that nonspecific acid
phosphatases such as PhoN-Sf are able to phosphorylate a wide range of
hydroxy compounds. We agree with the Examiner that it would have been
obvious to produce ribose-5-phosphate by reacting ribose with a phosphoric
acid donor in the presence of Tanaka’s Shigella flexneri acid phosphatase
because Tanaka discloses that the Shigella flexneri acid phosphatase is likely
to phosphorylate a wide range of hydroxy compounds and Gross discloses
that the resulting product is useful in making nucleotides and amino acids.
Appellants argue that nothing in the cited references guides “one of
ordinary skill in the art towards using the claimed enzyme with the claimed
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substrates, as opposed to the countless numbers of other potential candidate
substrates” (Appeal Br. 4).
This argument is not persuasive. Gross discloses that ribose-5-
phosphate is a useful intermediate and Tanaka discloses an enzymatic
method for the phosphorylation of the ribose component of inosine using a
Shigella flexneri acid phosphatase. Tanaka also discloses that the acid
phosphatase is likely able to phosphorylate a wide range of hydroxyl
substrates. Thus, phosphorylating ribose with the Shigella flexneri acid
phosphatase would have been obvious in view of Tanaka and Gross because
of the structural similarity between free ribose and the ribose component of
inosine.
Appellants argue that one of ordinary skill in the art would not have
reasonably expected that Tanaka’s Shigella flexneri acid phosphatase would
phosphorylate one of the pentose substrates recited in the claims (Appeal Br.
5-6). Appellants argue that the “record is full of evidence that the substrate
specificity of the claimed enzyme cannot be predicted,” even with
compounds that have apparent structural similarity (id. at 4-5).
This argument is not persuasive. Tanaka discloses that its Shigella
flexneri acid phosphatase acts on ribose when it is part of an inosine
molecule, and on free glucose. Tanaka also discloses that its Shigella
flexneri acid phosphatase is a nonspecific acid phosphatase (FF 3) that is
likely to act on “a wide range of hydroxy compounds” (FF 6). These
disclosures support a reasonable expectation that Tanaka’s enzyme would
phosphorylate free ribose, particularly since the phosphorylation of free
glucose shows that the hypoxanthine component of inosine is not required
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for the enzyme to recognize its substrate. Further, in accord with In re
O’Farrell, a conclusion of obviousness does not require an absolute
probability of success, but only requires a reasonable expectation of success,
which is provided by the cited references.
Conclusion of Law
The evidence of record supports the Examiner’s conclusion that one
of ordinary skill in the art, based on the cited references, would have
reasonably expected a Shigella flexneri acid phosphatase to phosphorylate
one of the recited pentose substrates.
SUMMARY
We affirm the rejection of claims 1, 4 and 6 under 35 U.S.C. § 103(a).
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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