Ex Parte Abraham

Board of Patent Appeals and Interferences

Dec 21, 2011

10995061 (B.P.A.I. Dec. 21, 2011)

UNITED STATES PATENT AND TRADEMARKOFFICE
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
10/995,061 11/22/2004 Edward H. Abraham 3418.1000-004 2589
21005 7590 12/21/2011
HAMILTON, BROOK, SMITH & REYNOLDS, P.C.
530 VIRGINIA ROAD
P.O. BOX 9133
CONCORD, MA 01742-9133
EXAMINER
PERREIRA, MELISSA JEAN
ART UNIT PAPER NUMBER
1618
MAIL DATE DELIVERY MODE
12/21/2011 PAPER
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.
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte EDWARD H. ABRAHAM
__________

Appeal 2011-008030
Application 10/995,061
Technology Center 1600
__________

Before ERIC GRIMES, JEFFREY N. FREDMAN, and ERICA A.
FRANKLIN, Administrative Patent Judges.

FRANKLIN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to
compounds comprising a 11C-labeled adenosine group. The Patent
Examiner rejected the claims as obvious. We have jurisdiction under
35 U.S.C. § 6(b). We affirm.

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STATEMENT OF THE CASE
Claims 16-20 are on appeal. Claim 16 is representative and reads as
follows:
16. A compound comprising a 2-11C -labeled adenosine group wherein the
compound is selected from the group consisting of 2-11C -adenosine, 2-11C -
AMP, 2-11C -ADP, and 2-11C -ATP.

The Examiner rejected claims 16-20 under 35 U.S.C. § 103(a) as
unpatentable over Meyer1 and Kassis.2
Claims 17-20 have not been argued separately and therefore stand or
fall with claim 16. 37 C.F.R. § 41.37(c)(1)(vii).

OBVIOUSNESS
The Issue
The Examiner’s position is that Meyer disclosed adenosine-2-13C 5´-
phosphate, wherein the 2-position of the adenosine is labeled with 13C.
(Ans. 4.) The Examiner found that Meyer taught that synthesis of this
compound involved using 13C labeled formaldehyde. (Id.) Additionally, the
Examiner found that Meyer taught that its “synthetic scheme”
advantageously introduced a radioactive carbon label in the last step, which
allowed for the preparation of radioactive carbon labeled adenine
nucleotides. (Id.) However, the Examiner found that Meyer did not disclose
a 11C-label at the 2-position of adenine. (Id.)

1 Rich B. Meyer et al., A Convenient Synthesis of Carbon Labelled Adenine
Nucleotides: Adenosine-2-13C 5’-Phosphate, 18 J. LABELLED COMPOUNDS
AND RADIOPHARMACEUTICALS, 1119-1122 (1980).
2 US Patent No. 5,811,073 issued to Amin I. Kassis et al., Sep. 22, 1998.
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The Examiner found that Kassis disclosed 11C-labeled adenine useful
for Positron Emission Tomography (PET). (Id.) The Examiner also found
that Kassis disclosed that the 11C-label may be in one or more sites of the
deoxynucleosides or deoxynucleotides, such as adenine. (Id.)
According to the Examiner, it would have been obvious to a person of
ordinary skill in the art at the time the invention was made to label Meyer’s
compound at the 2-position with the 11C radioisotope of Kassis because
Meyer suggested the inclusion of a radioactive carbon atom at the 2-position
of its compound and there are only a finite number of radioactive carbon
atoms to label at the 2-position. (Id.) Further, the Examiner found that an
artisan would have been motivated to use of radioactive isotope 11C because
it allows for the advantage of PET imaging, unlike 13C. (Id.) According to
the Examiner, a skilled artisan would have had a reasonable expectation of
success in substituting the 13C of Meyer for the 11C of Kassis by modifying
the synthetic scheme of Meyer to include using a 11C formaldehyde instead
of a 13C formaldehyde. (Id.) The Examiner further found that Mathews,3 a
reference submitted by Appellant, used 11C formaldehyde in a reaction
scheme to prepare 11C[AMP] in 34 minutes without degradation. (Id. at 4-
5.)
Appellant contends that the Examiner’s cited references did not teach
or suggest the claimed invention or provide a reasonable expectation of
successfully achieving the claimed invention. (App. Br. 5.) In particular,
Appellant asserts that “an appropriate synthesis route for 11C adenine or 11C

3 William B. Mathews et al., Synthesis and Biodistribution of
[11C]Adenosine 5'-Monophosphate ([11C]AMP), 7 MOL. IMAGING BIOL. 203-
208 (2005).
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adenosine compounds was not identified in the references cited or known to
one of ordinary skill in the art at the time of Appellant’s invention.” (Id.)
According to Appellant, Meyer “is specific to 13C incorporation into a
compound” and did not teach or suggest “mak[ing] the molecular
modification generally to other isotopes or specifically to radioactive 11C.”
(Id. at 7.) Additionally, Appellant asserts that a skilled artisan would not
have made modification to Meyer’s compound because “isotopes of carbon
11C and 13C are markedly different.” (Id.) Further, Appellant asserts that
Meyer’s method of labeling “utilize[d] a synthesis route that present[ed]
technological difficulties when applied to an isotope with a short life, such
as carbon 11.” (Id. at 9.)
Appellant also asserts that Kassis did not disclose techniques for
labeling adenine or adenosine with carbon 11. (Id.) Further, Appellant
asserts that Kassis described only radiolabeled deoxyribonucleotides and
deoxyribonucleosides, and that a skilled artisan “would not equate
oxygenated adenosine with deoxygenated adenosine.” (Id. at 8.) As
“[e]vidence of the non-equivalence,” Appellant submits Moyer’s4 disclosure
that “[t]he specificity of deoxyadenosine 5- triphosphate was not equivalent
to the oxygenated form, ATP in the luciferase reaction.” (Id. at 9.) Further,
Appellant asserts that the Examiner relied on Mathews, which post dates the
claimed invention and “merely recites the state of the art after Appellant’s
disclosure.” (Id.)

4 James D. Moyer et al., Nucleoside Triphosphate Specificity of Firefly
Luciferase, 131 ANALYTICAL BIOCHEM., 187-189 (1983).

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The issue is whether the record supports the Examiner’s conclusion
that the combined teachings of Meyer and Kassis, along with the ordinary
skill in the art at the time of the invention, would have made the claimed
compounds obvious.
Findings of Fact
1. We agree with the Examiner’s explicit findings regarding the scope
and content of the prior art references. (See Ans. 4-5.)
2. Meyer stated that “[a]nother attractive aspect of this synthetic scheme
is that the carbon label is introduced at the last step of the sequence, making
it particularly useful for the preparation of radioactive carbon labeled
adenine nucleotides.” (Meyer 1120.)
3. Kassis stated that “[t]echniques for labeling with non-halogen
radioisotopes (such as C11) are … well-known….” (Kassis col. 4, ll. 58-60.)
4. The Specification states, “[m]ethods for radiolabeling adenine
nucleotides with labels such as 13C have been described by Meyer ….
Methods have also been described for synthesis of 15NH2- adenosine. Such
methods can be routinely adapted by those of skill in the art to produce
radiolabeled adenosine or an adenosine containing molecule with a
radiolabel such as 11C, 18F or 13NH2 for use in PET.” (Spec. 6, ll. 9-
14)(emphasis added).
5. Moyer stated that “[a]ll 12 nucleoside triphosphates examined as
substrates of firefly luciferase produced light significantly greater than
background and in proportion to concentration.” (Moyer 188.)
6. Moyer stated that “[t]he deoxyribonucleotides were less active than
the corresponding ribonucleotides.” (Id.)
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7. Moyer stated that “ATP was greater than 50-fold more active than
dATP, which was the second most effective substrate.” (Id.)
8. We find that Moyer provided evidence that while the specificity of
firefly luciferase is not equivalent for ATP and dATP, both nucleoside
triphosphates were effective substrates of firefly luciferase. (FF-5, 6, 7.)
Principles of Law
The question of obviousness is resolved on the basis of underlying
factual determinations including (1) the scope and content of the prior art,
(2) any differences between the claimed subject matter and the prior art, (3)
the level of skill in the art, and (4) where in evidence, so-called secondary
considerations. Graham v. John Deere Co., 383 U.S. 1, 17-18 (1966).
“If a person of ordinary skill can implement a predictable variation, §
103 likely bars its patentability.” KSR Int’l Co. v. Teleflex Inc., 550 U.S.
398, 417 (2007).
Analysis
After considering all the evidence and arguments, we conclude that
the record supports a conclusion of prima facie obviousness. We are not
persuaded of nonobviousness by Appellant’s assertions that: (i) Meyer “is
specific to 13C incorporation into a compound” and did not teach or suggest
“mak[ing] the molecular modification generally to other isotopes or
specifically to radioactive 11C” (App. Br. 7); (ii) a skilled artisan would not
have made modification to Meyer’s compound because “isotopes of carbon
11C and 13C are markedly different” (id.); (iii) Meyer’s method of labeling
“utilize[d] a synthesis route that present[ed] technological difficulties when
applied to an isotope with a short life, such as carbon 11” (id. at 9); and (iv)
“an appropriate synthesis route for 11C adenine or 11C adenosine compounds
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was not identified in the references cited or known to one of ordinary skill in
the art at the time of Appellant’s invention” (id. at 5).
Appellant asserts that a Graham analysis reveals that none of the
references teach or suggest the claimed invention (App. Br. 5). However,
Appellant has not properly considered “the scope and content of the prior
art.” See Graham, 383 U.S. at 17-18. In particular, Appellant has not
acknowledged Meyer’s teaching that its synthesis scheme is “particularly
useful for the preparation of radioactive carbon labeled adenine nucleotides”
by introducing the carbon label at the last step of the sequence. (FF-2; Ans.
4.) We agree with the Examiner (Ans. 5) that Meyer’s teaching would have
suggested to a skilled artisan at the time of the invention that Meyer’s
method could be used with a radioactive carbon label, such as 11C, to prepare
a radioactive carbon labeled adenine nucleotide.
Further, Appellant has not properly considered “the level of ordinary
skill in the art.” See Graham, 383 U.S. at 17-18. According to Appellant,
“an appropriate synthesis route for 11C adenine or 11C adenosine compounds
was not … known to one of ordinary skill in the art at the time of
Appellant’s invention.” (App. Br. 5.)
We are not persuaded by this argument as it contradicts disclosures in
Kassis and Appellant’s Specification regarding the skill in the art at the time
of the invention. Kassis disclosed that “[t]echniques for labeling with non-
halogen radioisotopes (such as C11) are … well known and include the
technique referred to in Kubota.” (FF-3.) This disclosure is not diminished
by Appellant’s assertion that Kubota only referred to synthesizing a carbon
11-methyl methionine (App. Br. 10) as Kassis only referenced Kubota as an
example of such known carbon labeling techniques. Moreover, Appellant’s
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Specification states that “[m]ethods for radiolabeling adenine nucleotides
with labels such as 13C have been described by Meyer” and further states
that “[s]uch methods can be routinely adapted by those of skill in the art to
produce radiolabeled adenosine or an adenosine containing molecule with a
radiolabel such as 11C… for use in PET.” (FF-4.) Therefore, in view of the
combined prior art and the skill in the art, as described by Kassis and
Appellant’s Specification, we conclude that the Examiner’s proposed
modification of Meyer merely involved a predictable variation which could
have been implemented by a person of ordinary skill in the art. See KSR
Int’l Co., 550 U.S. at 417.
Appellant also asserts that the “rejection also fails to provide evidence
supporting the equivalency of the compounds of Kassis and Appellant’s
claimed compounds.” (App. Br. 8.) According to Appellant, the “claimed
compounds are structurally different than Kassis’ deoxygenated nucleosides
and nucleotides” and a skilled artisan “would not equate oxygenated
adenosine with deoxygenated adenosine.” (Id.) Appellant asserts that
“[a]bsent some structure-activity data indicating deoxyadenosine and
oxyadenosine equivalency for the compounds being claimed, it is improper
to assume that deoxygenation would result in a comparably effective PET
agent for tumor imaging and adenylate metabolism.” (Id.) Further,
Appellant asserts that Moyer provided “[e]vidence of the non-equivalence”
by demonstrating that “[t]he specificity of deoxyadenosine 5- triphosphate
was not equivalent to the oxygenated form, ATP in the luciferase reaction.”
(Id. at 9.)
We remain unpersuaded of nonobviousness by this argument. The
Examiner did not “assume that deoxygenation would result in a comparably
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effective PET agent for tumor imaging and adenylate metabolism” (id.) as
oxygenated adenosine. Nor is such comparative effectiveness required for
the Examiner’s rejection, as this is not a limitation recited in the claims.
Rather, the Examiner relied on Kassis as teaching that 11C was a known PET
tracer at the time of the invention and that a 11C-labeled adenine was useful
for PET. (Ans. 4, 10.) Appellant has not supported the contention that a
skilled artisan would not have considered a compound comprising a 11C-
labeled oxygenated adenosine group useful in PET with factual evidence.
Instead, Appellant submitted evidence demonstrating that “[t]he specificity
of deoxyadenosine 5- triphosphate was not equivalent to the oxygenated
form, ATP in a luciferase reaction.” (App. Br. 9, citing Moyer.) However,
Moyer also provided evidence that both the oxygenated and deoxygenated
nucleoside triphosphates were “effective substrate[s]” of firefly luciferase.
(See FF-5, 6, 7, 8.) Thus, Appellant has not established that Kassis would
not have suggested to a skilled artisan at the time of the invention that a 11C-
labeled adenine, whether deoxygenated or oxygenated, would have been
useful for PET.
Further, while we agree that Mathews post dates the Appellant’s
claimed invention and “recites the state of the art after Appellant’s
disclosure” (see App. Br. 9) the Examiner did not rely on Mathews to reject
the claims. Rather, the Examiner rejected the claims over Meyer and Kassis.
In particular, the Examiner found that when modifying Meyer to produce a
11C- labeled adenine nucleotide, a skilled artisan would have had a
reasonable expectation of doing so by using a 11C formaldehyde in place of
the 13C formaldehyde used by Meyer to produce a 13C-labeled adenine
nucleotide. (Ans. 4.) The Examiner referred to Mathews as evidence
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submitted by Appellant and found that its disclosure indeed used 11C
formaldehyde in its preparation of 11C[AMP]. (Id. at 4-5.)
Accordingly, we affirm the Examiner’s obviousness rejection.

CONCLUSION OF LAW
The record supports the Examiner’s conclusion that the combined
teachings of Meyer and Kassis, along with the ordinary skill in the art at the
time of the invention, would have made the claimed compounds obvious.

SUMMARY
We affirm the rejection of claims 16-20 under 35 U.S.C. § 103(a) as
unpatentable over Meyer and Kassis.

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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