Ex Parte Lode et al

Board of Patent Appeals and Interferences

Mar 31, 2006

09502732 (B.P.A.I. Mar. 31, 2006)

The opinion in support of the decision being entered today was not written
for publication and is not binding precedent of the Board.

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte HOLGER N. LODE, RALPH A. REISFELD,
DAVID A. CHERESH and STEPHEN D. GILLIES
__________

Appeal No. 2006-0273
Application No. 09/502,732
__________

HEARD: March 23, 2006
__________

Before SCHEINER, MILLS, and GRIMES, Administrative Patent Judges.

MILLS, Administrative Patent Judge.

DECISION ON APPEAL
This is a decision on appeal under 35 U.S.C. §134 from the examiner's final
rejection of claims 22, 23, 25, 31, 33, 36, 38, 44, and 46-51, which are all of the claims
pending in this application. Claim 22 is representative and reads as follows:
22. A therapeutic composition comprising at least one angiogenesis inhibiting
agent, which is an αvβ3 antagonist, and at least one anti-tumor immunotherapeutic
agent, which is a fusion protein comprising cytokine IL-2 and an Ig heavy chain that
immunoreacts with a tumor associated antigen target.

Appeal No. 2006-0273
Application No. 09/502,732

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The references cited by the examiner are:

Brooks et al. (Brooks) 5,753,230 May 19, 1998
(filed Mar. 18, 1994)

Zasloff et al (Zasloff) 6,147,060 Nov. 14, 2000
(filed Apr. 25, 1997)

Xiang et al. (Xiang), “Elimination of Established Murine Colon Carcinoma Metastases by
Antibody-Interleukin 2 Fusion Protein Therapy,” Cancer Research, Vol. 57, No. 21, pp.
4948-4955 (1997)

Folkman et al. (Folkman), “Angiogenesis in cancer, vascular, rheumatoid and other
disease,” Nature Medicine, Vol. 1, No. 1, pp. 27-31 (1995)

Grounds of Rejection
Claims 22, 23, 25, 31, 33, 36, 38, 44, and 46-51 stand rejected under 35 U.S.C.
§103(a) as obvious over Brooks and Xiang in view of Folkman and Zasloff.
We reverse this rejection.

DISCUSSION
Procedural History
We previously remanded this application to the examiner on November 21, 2003
(Appeal No. 2003-1039) to revisit evidence of synergism submitted by appellants, and
to review the relevance of the disclosures of the Folkman publication and Zasloff patent
to the then pending claims. At the time of the remand, the claims were directed to a
therapeutic composition comprising at least one angiogenesis inhibiting agent; and at
least one anti-tumor immunotherapeutic agent, said anti-tumor immunotherapeutic
agent comprising a cell-effector component joined to a tumor associated antigen
Appeal No. 2006-0273
Application No. 09/502,732

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targeting component. Following the remand, the examiner reopened prosecution and
the appellants amended the application claims to recite a specific angiogenesis inhibitor
and immunotherapeutic agent. The amended claims are now before us on appeal.
The examiner rejects the claims for obviousness over Brooks and Xiang in view of
Folkman and Zasloff.

Obviousness
Claims 22, 23, 25, 31, 33, 36, 38, 44, and 46-51 stand rejected under 35 U.S.C.
§103(a) as obvious over Brooks and Xiang in view of Folkman and Zasloff.
In rejecting claims under 35 U.S.C. § 103, the examiner bears the initial burden
of presenting a prima facie case of obviousness. See In re Rijckaert, 9 F.3d 1531,
1532, 28 USPQ2d 1955, 1956 (Fed. Cir. 1993). A prima facie case of obviousness is
established when the teachings from the prior art itself would appear to have suggested
the claimed subject matter to a person of ordinary skill in the art. In re Bell, 991 F.2d
781, 783, 26 USPQ2d 1529, 1531 (Fed. Cir. 1993). An obviousness analysis requires
that the prior art both suggest the claimed subject matter and reveal a reasonable
expectation of success to one reasonably skilled in the art. In re Vaeck, 947 F.2d 488,
493, 20 USPQ2d 1438, 1442 (Fed. Cir. 1991). With this as background, we analyze
the prior art applied by the examiner in the rejection of the claims on appeal.

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Application No. 09/502,732

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The examiner argues that the two primary references, Brooks and Xiang,
anticipate each therapeutic agent. The examiner acknowledges that neither Brooks or
Xiang teaches the combination of both an angiogenesis inhibiting agent and an anti-
tumor immunotherapeutic agent, but cites In re Kerkhoven1 in support of the rejection
stating that it is “prima facie obvious to combine two compositions each of which is
taught in the prior art to be useful for the same purpose, in order to form a third
composition that is to be used for the very same purpose” since “the idea of combining
them flows logically from their having been individually taught in the prior art.” Answer,
page 4.
In addition, the examiner argues that Folkman suggests a greater additive
advantage in combining antiangiogenic agents with cytotoxic agents and that Zasloff
“successfully demonstrate[d] synergistic effects with a known anti-angiogenic agent in
combination with cytotoxic therapy.” Answer, page 6. We further note that the
examiner admits that the data in the specification evidence a synergistic result for the
claimed composition (Answer, page 5), but submits that such a synergistic result would
have been expected in view of the teachings of Folkman and Zasloff.
Assuming, arguendo, that the examiner has established a prima facie case of
obviousness, we turn to appellants’ argument and evidence of unexpected synergistic
effects for the claimed combination of therapeutic agents.

1 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
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Application No. 09/502,732

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Appellants argue that Folkman does not teach or suggest the specific
combination now claimed and that Folkman does not teach or suggest that any specific
combination of therapeutic agents will provide synergistic results. Brief, page 5.
Appellants further argue that (Brief, pages 5-6)
The Folkman article, ... cites a single article by Teicher et al. Int. J.
Cancer, 1994,57(6):920-925 (of record), [which] ... discusses a number
of combinations of antitumor drugs with anti-angiogenic agents. Some
combinations, such as TNP-470 and minocycline (both anti-angiogenic) in
combination with cyclophosphoramide (a cytotoxic agent) led to
significantly reduced numbers and size of metastases (See Tables II, IV
and IV) compared to treatment with the agents by themselves. Other
combinations, however, such as TNP-470 and/or minocycline in
combination with CDDP, melphalan, or BCMU did not provide any
significant improvement in number or size of metastases (see Table II,
and IV) compared to treatment with the agents by themselves. Thus, even
in the Teicher et al. study, the effectiveness of a given combination of
antiangiogenic agent and cytotoxic agent was shown to be unpredictable.
...
Accordingly, one of ordinary skill in the art would not have had a
reasonable expectation of success in combining the agents of Brooks et
al, and Xiang et al. to afford the presently claimed invention...

In our view, the examiner has not adequately addressed appellants’ evidence
that synergy would have been unexpected. We conclude that appellants’ evidence
reasonably establishes that the therapeutic synergistic results obtained from the
combination of an αvβ3 antagonist and a fusion protein comprising cytokine IL-2 and an
Ig heavy chain would have been unexpected to one of ordinary skill in the art at the time
of filing of the present application, and thus overcomes the rejection under 35 U.S.C. §
103.
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Application No. 09/502,732

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In view of the above, the rejection of the claims under 35 U.S.C. § 103 is
reversed.
CONCLUSION
We therefore reverse the rejection of the claims for obviousness over Brooks and
Xiang in view of Folkman and Zasloff.

REVERSED

)
TONI R. SCHEINER )
Administrative Patent Judge )
)
)
) BOARD OF PATENT
DEMETRA J. MILLS )
Administrative Patent Judge ) APPEALS AND
)
) INTERFERENCES
)
ERIC GRIMES )
Administrative Patent Judge )

Appeal No. 2006-0273
Application No. 09/502,732

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