Ex Parte Conti et al

Patent Trial and Appeal Board

Mar 26, 2013

11836033 (P.T.A.B. Mar. 26, 2013)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte PETER S. CONTI,
MIAN M. ALAUDDIN, and JOHN D. FISSEKIS,
__________

Appeal 2011-010982
Application 11/836,033
Technology Center 1600
__________

Before DONALD E. ADAMS, LORA M. GREEN, and
FRANCISCO C. PRATS, Administrative Patent Judges.

PRATS, Administrative Patent Judge.

DECISION ON APPEAL
This appeal under 35 U.S.C. § 134 involves claims to in vivo imaging
compositions, and processes of using them. The Examiner entered
rejections for obviousness.
We have jurisdiction under 35 U.S.C. § 6(b). We reverse.
STATEMENT OF THE CASE
Claims 1-16, 22, and 23 stand rejected and appealed (App. Br. 2).
Claims 1, 5, and 22, the independent claims, illustrate the appealed subject
matter and read as follows:
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1. A composition for in vivo imaging of a biological
material, comprising:
an imaging agent in dosage unit form, wherein the unit dose of
the imaging agent comprises a sufficient amount for in vivo diagnostic
imaging of a 2'-deoxy-2'-[
18
F]-labeled or a 3'-deoxy-3'-[
18
F]-labeled
purine nucleoside analog for being detected in vivo; and
a physiologically acceptable carrier or adjuvant.

5. An in vivo method for imaging a biological material in a
subject, comprising:
administering to said subject a sufficient amount of a
composition comprising a 2'-deoxy-2'-[
18
F]-labeled or a 3'-deoxy-3'-
[
18
F]-labeled purine nucleoside analog to provide an imageable
concentration of said analog in said biological material; and
detecting emissions from said radioactive fluorine of said
analog, thereby forming an image of said biological material.

22. A method for imaging a tumor in a patient, the method
comprising:
administering to a patient an composition comprising [
18
F]-
FAA in an amount sufficient to provide an imageable concentration of
said [
18
F]-FAA; and
detecting emissions from said radioactive fluorine of said [
18
F]-
FAA, thereby forming an image of said tumor.

The following rejections are before us for review:
(1) Claims 1, 2, 4-6, and 8-16, under 35 U.S.C. § 103(a) as obvious
over Wright
1
and Klecker
2
(Ans. 4-6); and
(2) Claims 1-3, 5-7, 9-16, 22, and 23, under 35 U.S.C. § 103(a) as
obvious over Watanabe,
3
Klecker, Pankiewicz,
4
and DeGrado
5
(Ans. 6-9).

1
J.A. Wright and N.F. Taylor, Fluorocarbohydrates Part XVIII. 9-(3-
deoxy-3-fluoro-β-D-xylofuranosyl)adenine and 9-(3-deoxy-3-fluoro-α-D-
arabinofuranosyl)adenine, 6 CARBOHYD. RES. 347-354 (1968).
2
U.S. Patent No. 6,753,309 B2 (filed Apr. 16, 2002).
3
U.S. Patent No. 4,751,221 (issued Jun. 14, 1988).
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OBVIOUSNESS – WRIGHT AND KLECKER
The Examiner cited Wright as evidence that a fluorinated purine
analogue encompassed by the rejected claims was known in the art, but
conceded that Wright did not describe an
18
F-labeled version of that
compound, “or the [claimed] method of in vivo imaging a biological
material” (Ans. 5). To address that deficiency, the Examiner cited Klecker
as disclosing the use of
18
F-labeled nucleoside analogues for in vivo PET
imaging methods (see id.).
Based on the references‟ teachings, the Examiner concluded that an
ordinary artisan would have considered it obvious to “use an
18
F radiolabel
as taught by Klecker et al. for the 9-(3-deoxy-3-fluoro-β-D-xylofuranosyl)
adenine nucleoside of Wright et al. to provide a nucleoside that can be
examined for it‟s [sic] ability as a PET agent” (id. at 6).
As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992):
[T]he examiner bears the initial burden . . . of presenting a
prima facie case of unpatentability. . . .
After evidence or argument is submitted by the applicant
in response, patentability is determined on the totality of the
record, by a preponderance of evidence with due consideration
to persuasiveness of argument.

In KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 415 (2007), while the
Supreme Court emphasized “an expansive and flexible approach” to the
obviousness question, it also reaffirmed the importance of determining

4
Krzysztof W. Pankiewicz et al., A Synthesis of 9-(2-Deoxy-2-fluoro-β-D-
arabinofuranosyl)adenine and Hypoxanthine. An Effect of C3'-Endo to C2'-
Endo Conformational Shift on the Reaction Course of 2'-Hydroxyl Group
with DAST, 57 J. ORG. CHEM. 553-559 (1992).
5
U.S. Patent App. Pub. No. 2002/0061279 A1 (filed Apr. 30, 2001).
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“whether there was an apparent reason to combine the known elements in
the fashion claimed by the patent at issue.” Id. at 418.
Ultimately, therefore, “[i]n determining whether obviousness is
established by combining the teachings of the prior art, the test is what the
combined teachings of the references would have suggested to those of
ordinary skill in the art.” In re GPAC Inc., 57 F.3d 1573, 1581 (Fed. Cir.
1995) (internal quotations omitted).
We agree with Appellants that a preponderance of the evidence does
not support the Examiner‟s finding that the cited references would have
prompted an ordinary artisan to label Wright‟s nucleoside analogue with
18
F,
nor are we persuaded that the Examiner has adequately explained why the
cited references would have suggested using that labeled analogue in the
imaging processes described in Klecker.
We note that Klecker discloses using
18
F-labeled nucleoside analogues
in its imaging processes (see, e.g. Klecker, col. 4, ll. 59-64 (“It is an object
of the present invention to provide compounds and methods useful for
external imaging applications. In preferred embodiments, the invention
includes the selection, preparation, and uses of nucleosides labeled with
fluorine-18 (
18
F), a positron emitter.”)).
As Appellants point out, however, Klecker focuses almost exclusively
on thymidine and/or uridine analogues in its methods, rather than the purine
analogues described in Wright and recited in Appellants‟ claims:
Thymidine is a particularly useful probe for monitoring
growth/DNA synthesis, because it is the only nucleoside for
which direct incorporation of exogenously applied nucleoside
into DNA is common by “salvage” pathways. There is no
dependence upon the ribonucleotide pathways for the
incorporation of thymidine. Thymidine itself is unsuitable as a
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probe in these imaging technologies, since the molecule is
rapidly degraded in the body. Analogues of thymidine such as
FMAU and FIAU are excellent imaging probes, because they:
1) completely follow thymidine pathways for incorporation into
DNA; 2) are not degraded by catabolic enzymes; and 3) can be
labeled with
18
F, the most desirable atom for positron imaging.

(Id. at col. 3, ll. 44-57; see also id., generally.)
As Appellants also point out, Wright provides essentially no
information as to the utility of its adenine analogues, nor does Wright say
anything about the biochemical or catabolic properties of its compounds (see
Wright generally).
Given Klecker‟s almost singular focus on using thymidine/uridine
analogues in its methods, we are not persuaded that Klecker would have
prompted an ordinary artisan to label Wright‟s purine analogue with
18
F, or
to use the resulting labeled compound in Klecker‟s in vivo imaging methods.
The Examiner argues that while Klecker exemplifies the use of
pyrimidines, uridine in particular, the claimed “purine moiety and
pyrimidine moiety are structu[r]ally related” (Ans. 10). Moreover, the
Examiner argues, Klecker teaches that cell proliferation requires DNA
synthesis, and that “administration of nucleosides which have been
radiolabeled with a positron emitter provides the ability to externally
monitor event[s] occur[r]ing within the body by use of PET” (id.). The
Examiner urges, therefore, that “it would have been obvious to one
ordinarily skilled in the art to substitute one nucleoside analogue for an
analogous nucleodoside [sic] analogue for the uptake into the tumor cells to
shut down the cell cycle” (id.).
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We are not persuaded. Again, given Klecker‟s nearly exclusive focus
on thymidine/uridine (i.e. pyrimidine) analogues, we are not persuaded that
an ordinary artisan would have considered Wright‟s purine nucleoside
analogues to be useful as substantial equivalents in Klecker‟s processes, as
the Examiner suggests.
Moreover, while the Examiner also suggests that an ordinary artisan
would have expected Wright‟s compounds, when labeled, to be incorporated
into tumor cell DNA so as to enable imaging or cell cycle arrest, the
Examiner points to no clear or specific evidence supporting that suggestion.
Rather, as noted above, and as Appellants point out, Wright says essentially
nothing about the utility and biochemical properties of its compounds.
We note Klecker‟s statement that, in certain embodiments, “the
analogues may be used for imaging applications even though not
incorporated into DNA” (Klecker, col. 4, ll. 40-41). We are not persuaded,
however, that this statement is sufficient to suggest that any labeled
nucleoside analogue would be useful in Klecker‟s processes, particularly
given Klecker‟s strong emphasis on using thymidine/uridine analogues.
As the Federal Circuit has explained, even post-KSR, “patents are not
barred just because it was obvious „to explore a new technology or general
approach that seemed to be a promising field of experimentation, where the
prior art gave only general guidance as to the particular form of the claimed
invention or how to achieve it.‟” Procter & Gamble Co. v. Teva
Pharmaceuticals USA, Inc., 566 F.3d 989, 997 (Fed. Cir. 2009) (quoting In
re O’Farrell, 853 F.2d 894, 903 (Fed. Cir. 1988)).
In sum, as we are not persuaded that a preponderance of the evidence
supports the Examiner‟s finding that Wright and Klecker would have
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prompted an ordinary artisan to prepare an
18
F-labeled version of Wright‟s
compounds, or to have used those compounds in Klecker‟s imaging
methods, we reverse the Examiner‟s obviousness rejection of claims 1, 2, 4-
6, and 8-16 over those references.
OBVIOUSNESS –
WATANABE, KLECKER, PANKIEWICZ, AND DEGRADO
The Examiner applied a similar rationale to that discussed above in
rejecting claims 1-3, 5-7, 9-16, 22, and 23 over Watanabe, Klecker,
Pankiewicz, and DeGrado.
Specifically, the Examiner cited Watanabe as describing
pharmaceutically active fluorinated arabinofuranosyl adenine analogues
encompassed by the rejected claims, but conceded that Watanabe did not
describe
18
F-labeled versions of those compounds, nor did Watanabe
describe “the method of in vivo imaging a biological material or the method
of synthesizing” the claimed compounds (Ans. 6-7).
To address those deficiencies, the Examiner again cited Klecker for its
disclosure of using
18
F-labeled nucleoside analogues for in vivo PET
imaging methods (see id. at 7). The Examiner also noted that Klecker, as
well as Pankiewicz and DeGrado, suggested that Appellants‟ methods for
preparing the claimed compounds would have been considered obvious by
an ordinary artisan (id. at 9).
Based on the references‟ teachings, the Examiner concluded that an
ordinary artisan would have considered it obvious to “substitute an
18
F
radiolabel as taught by Klecker et al. for fluorine in the 2'-deoxy-2'-fluoro-β-
D-arabinofuranosyl nucleoside of Watanabe et al. to predictably generate an
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18
F radiolabeled nucleoside that can be examined for it‟s [sic] ability as a
PET agent” (id. at 9)
The Examiner reasoned:
Klecker et al. teaches that the
18
F-nucleosides are selected for
their effectiveness against tumors in humans and their
incorporation into DNA (column 3, lines 6-13; column 4, lines
59+). Thus, it would be predictable that an
18
F-labeled 2'-
deoxy-2'-fluoro-β-D-arabinofuranosyl nucleoside of Watanabe
et al. would be a suitable agent for PET imaging as it is an
antitumor agent and is incorporated into DNA.

(Id.; see also id. at 14 (“[T]he nucleosides of Watanabe are taught to be
taken up by tumors and have inhibitory activity.”).)
We are not persuaded that a preponderance of the evidence supports
the Examiner‟s conclusion of obviousness.
We note that Watanabe discloses fluorinated arabinofuranosyl purine
nucleoside analogues which are described as being “potentially” useful as
antiparasitic agents (Watanabe, col. 1, ll. 13-16). We also note Watanabe‟s
statement that “[t]he free nucleosides (Formula I) and their acid addition
salts are useful therapeutic agents exhibiting anti-parasitic and/or anticancer
activity” (id. at col. 5, ll. 28-30), as well as the disclosure that certain of
Watanabe‟s purine analogues have in vitro activity against certain human
tumor cell lines (id. at col. 8, l. 65, through col. 9, l. 30).
We acknowledge these teachings of therapeutic activity. The
Examiner does not, however, direct us to, nor do we see, any clear or
specific teachings in Watanabe to support the Examiner‟s assertion that the
purine analogues are incorporated into DNA and/or are taken up by tumors.
Indeed, as Appellants point out, beyond therapeutic activity, the
Examiner points us to no discussion in Watanabe regarding the properties of
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its compounds such that an ordinary artisan would reasonably have been
able to predict they would be useful in Klecker‟s imaging processes. While
we note the synthesis schemes in Pankiewicz and DeGrado, the Examiner
again does not point us to any teaching in either of those references
suggesting that Watanabe‟s purine analogues, if labeled, would be useful in
Klecker‟s PET imaging methods.
Accordingly, we again agree with Appellants that the preponderance
of the evidence does not support the Examiner‟s prima facie case of
obviousness. As noted above, given Klecker‟s almost exclusive focus on its
thymidine/uridine analogues, and the rationale behind their suitability as
PET imaging agents, we are not persuaded that Klecker would have
prompted an ordinary artisan to label Watanabe‟s purine compounds in order
to use them in Klecker‟s imaging methods, as the Examiner posits.
Moreover, particularly given Klecker‟s strong emphasis on using
thymidine/uridine analogues, we are not persuaded that therapeutic activity,
in and of itself, would have led an ordinary artisan to reason that Watanabe‟s
purine analogues would be useful in Klecker‟s processes.
Therefore, as we are not persuaded that a preponderance of the
evidence supports the Examiner‟s finding that Watanabe, Klecker,
Pankiewicz, and DeGrado would have prompted an ordinary artisan to
prepare an
18
F-labeled version of Watanabe‟s compounds, or to have used
those compounds in Klecker‟s imaging methods, we reverse the Examiner‟s
obviousness rejection of claims 1-3, 5-7, 9-16, 22, and 23 over those
references.
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SUMMARY
We reverse the Examiner‟s obviousness rejection of claims 1, 2, 4-6,
and 8-16 over Wright and Klecker.
We also reverse the Examiner‟s obviousness rejection of claims 1-3,
5-7, 9-16, 22, and 23 over Watanabe, Klecker, Pankiewicz, and DeGrado.

REVERSED

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