Ex Parte Supuran et al

Board of Patent Appeals and Interferences

Apr 28, 2011

11929652 (B.P.A.I. Apr. 28, 2011)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte CLAUDIU SUPURAN, ANDREA SCOZZAFAVA, SILVIA
PASTOREKOVA, and JAROMIR PASTOREK
__________

Appeal 2010-011170
Application 11/929,652
Technology Center 1600
__________

Before TONI R. SCHEINER, ERIC GRIMES, and JEFFREY N.
FREDMAN, Administrative Patent Judges.

Opinion for the Board filed by Administrative Patent Judge GRIMES.
Opinion Dissenting filed by Administrative Patent Judge FREDMAN.
GRIMES, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to methods
of using an antibody that binds activated MN protein. The Examiner has
rejected the claims for lack of adequate written description. We have
jurisdiction under 35 U.S.C. § 6(b). We reverse.
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STATEMENT OF THE CASE
The Specification discloses that “MN protein (renamed to carbonic
anhydrase IX, CA IX) . . . [includes] a catalytically active carbonic
anhydrase [CA] domain” (Spec. 2: 6-9). The Specification discloses that
“hypoxia activates the CA catalytic activity of MN/CA IX” (id. at 9: 18-19).
The Specification discloses that detecting activated MN/CA IX using a
specific inhibitor of activated MN/CA IX is useful in cancer diagnosis and
prognosis (id. at 10: 7-14).
Claims 17 and 33-44 are on appeal. Claim 33 is representative and
reads as follows:
33. A diagnostic/prognostic method for a preneoplastic/neoplastic
disease associated with abnormal MN/CA IX expression, comprising
determining whether MN/CA IX is activated in a vertebrate sample,
comprising:
a) contacting said sample with a specific inhibitor of the activated
form of MN/CA IX's CA domain, wherein said specific inhibitor of the
activated form of MN/CA IX's CA domain is an MN/CA IX-specific
antibody that binds the activated form of MN/CA IX's CA domain and not
the inactive form of MN/CA IX's CA domain, and
b) detecting or detecting and quantifying binding of said specific
inhibitor of the activated form of MN/CA IX's CA domain in said sample;
wherein binding of said inhibitor to MN/CA IX indicates that said
bound MN/CA IX in said sample is activated.
Issue
The Examiner has rejected claims 17 and 33-44 under 35 U.S.C.
§ 112, first paragraph, as lacking adequate written description in the
Specification (Answer 3). The Examiner finds that “the specification
appears to be silent on the structural features of ‘an activated form of
MN/CA IX’s CA domain’ vs. the structural features of an inactive form of
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MN/CA IX CA domain” (id. at 4). The Examiner finds that “the ‘structural
entity’ of activated CA IX appears to be critical. However, while the
specification contemplates the activated form, there is insufficient written
description encompassing a ‘activated form of MN/CA IX’s CA domain’
because the relevant identifying characteristics such as structure or other
physical and/or chemical characteristics are not set forth in the
specification.” (Id.)
Appellants contend that a description of an antigen is adequate to
show possession of an antibody binding that antigen (Appeal Br. 10), and
that the Specification describes an MN/CA IX having an activated CA
domain sufficiently to show possession of that antigen (id. at 11).
The issue presented is: Has the Examiner shown that additional
structural description of an activated form of MN/CA IX’s CA domain
would be required in order for a skilled worker to recognize the
Specification’s description as showing possession of an antibody that binds
specifically to that activated domain?
Findings of Fact
1. The Specification discloses the DNA and amino acid sequences of
the MN/CA IX gene and protein (Spec. 3: 2-5; Figs. 1A-C, 2A-F).
2. The Specification discloses that the “CA domain [aa 135-391; SEQ
ID NO: 5] is spread over 265 aa” (id. at 3: 15, bracketed material in
original).
3. The Specification discloses that “hypoxia activates the CA
catalytic activity of MN/CA IX” (id. at 9: 18-19).
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4. The Specification discloses “MN/CA IX-specific inhibitors which
bind preferentially to the activated form of the CA domain of MN/CA IX,
and not to the inactive form of the CA domain of MN/CA IX. . . . Exemplary
activated MN/CA IX-specific inhibitors include the sulfonamide
Compounds 5, 6, 39 and 92.” (Id. at 9: 24-31.)
5. The Specification provides a working example stating that “in
fluorescence analysis . . . , FITC-labeled Compound 92 was detected only in
hypoxic MDCK-CA IX cells, but was absent from their normoxic
counterparts and from the mock-transfected controls. . . . Lack of the
fluorescence signal in CA IX-negative MDCK cells . . . indicated that only
the hypoxic MDCK-CA IX cells contain the catalytically active CA IX with
the enzyme center accessible to inhibitor.” (Id. at 78: 26-33.)
6. The Specification discloses that “MN/CA IX-specific inhibitors
which are useful according to the methods of the invention may comprise
any molecules that preferentially bind only the activated form of the CA
domain of MN/CA IX, and not the inactive form of the CA domain of
MN/CA IX. Such molecules may be . . . antibodies which selectively bind
the activated form of the CA domain of MN/CA IX.” (Id. at 9: 32 to 10: 4.)
Principles of Law
“[T]he test for sufficiency is whether the disclosure of the application
relied upon reasonably conveys to those skilled in the art that the inventor
had possession of the claimed subject matter as of the filing date.” Ariad
Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en
banc).
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“[T]he written description requirement does not demand either
examples or an actual reduction to practice; a constructive reduction to
practice that in a definite way identifies the claimed invention can satisfy the
written description requirement.” Id. at 1352.
“[A]s long as an applicant has disclosed a ‘fully characterized antigen,’
either by its structure, formula, chemical name, or physical properties, or by
depositing the protein in a public depository, the applicant can then claim an
antibody by its binding affinity to that described antigen.” Noelle v.
Lederman, 355 F.3d 1343, 1349 (Fed. Cir. 2004)
Analysis
We agree with Appellants that the Examiner has not provided an
adequate basis for finding that the Specification provides an inadequate
description of antibodies that bind specifically to the activated CA domain of
MN/CA IX. The Specification discloses the structure (amino acid sequence)
of MN/CA IX and its CA domain. The Specification also discloses that the
CA domain takes on its activated conformation under hypoxic conditions
and that the activated conformation differs from the inactive conformation
because certain sulfonamide compounds bind to it only in its activated
conformation.
Thus, the Specification describes making the activated domain using
hypoxic conditions and identifying it by its specific binding to certain
compounds; the Specification also states that activation makes the catalytic
center accessible to the sulfonamide compounds. In our view, the
Specification’s description would be recognized by those skilled in the art as
showing possession of the activated CA domain based on the description of
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its amino acid sequence and physical properties; specifically, the difference
in its property of binding to certain sulfonamides upon activation. Since the
antigen is adequately described, the description is also adequate to describe
antibodies that bind specifically to the antigen. Noelle, 355 F.3d at 1349.
Conclusion of Law
The Examiner has not shown that additional structural description of
an activated form of MN/CA IX’s CA domain would be required in order for
a skilled worker to recognize the Specification’s description as showing
possession of an antibody that binds specifically to that activated domain.
SUMMARY
We reverse the rejection of claims 17 and 33-44 for lack of adequate
written description.

REVERSED

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DISSENTING OPINION
FREDMAN, Administrative Patent Judge
I respectfully dissent from the Majority’s analysis of the written
description issue. In my opinion, the Examiner’s rejection is consistent with
the reasoning of Centocor Ortho Biotech, Inc. v. Abbott Laboratories, ---
F.3d ----, 2011 WL 635291 (Fed. Cir. 2011).
Additional Findings of Fact
7. The Specification teaches that the “activation of the CA domain
of CA IX could theoretically be detected” (Spec. 40, l. 13; emphasis added).
8. The Examiner finds that “the specification appears to be silent
on antibodies which are specific for the activated form of MN/CA IX’s CA
domain and not the inactive form of MN/CA IX’s CA domain” (Ans. 3-4).
9. The Examiner finds that “one of skill in the art would not
conclude that CA IX in any conformation state was the same structural
entity as activated CA IX, let alone CA IX activated hypoxia” (Ans. 7; see
Applicant’s Amendment 12, filed Apr. 28, 2009).
Additional Principles of Law
“[T]he asserted claims constitute a wish list of properties that a fully-
human, therapeutic TNF- antibody should have: high affinity, neutralizing
activity, and the ability to bind in the same place as the mouse A2 antibody.”
Centocor, 2011 WL 635291 at 7. “The specification at best describes a plan
for making fully-human antibodies and then identifying those that satisfy the
claim limitations. But a ‘mere wish or plan’ for obtaining the claimed
invention is not sufficient.” Id.
While our precedent suggests that written description
for certain antibody claims can be satisfied by disclosing a
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well-characterized antigen, that reasoning applies to
disclosure of newly characterized antigens where creation of
the claimed antibodies is routine. . . . Claiming antibodies
with specific properties . . . can result in a claim that does
not meet written description even if the [target] protein is
disclosed because antibodies with those properties have not
been adequately described.

Id. at 8.
Analysis
In my view, the Majority opinion turns the burden of a written
description rejection on its head. Rather than recognize a burden on
Appellants to provide an actual description in their Specification which
supports the formation of the novel antibody type claimed, the Majority
instead imposes a burden on the Examiner to essentially show that the claim
fails to satisfy the enablement requirement, before a written description
rejection can be written.
I begin by recognizing that Appellants have, in fact, identified a new
feature of the carbonic anhydrase IX enzyme, which is that the enzyme has
two forms. As Appellants explain, “there is a difference between the CA
domain of MN/CA IX, activated under hypoxia, and the catalytically
inactive CA domain of MN/CA IX under normoxia” (Reply Br. 6). I also
acknowledge that Appellants have identified small molecules which exhibit
differential binding to the enzyme in cells only under hypoxia and not under
normoxia (see Reply Br. 6).
The claims, however, are drawn to methods using antibodies which
inhibit and which “bind the activated form of MN/CA IX’s CA domain and
not the inactive form of MN/CA IX’s CA domain” (Claim 17). Thus, the
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written description issue is whether the Specification provides adequate
descriptive support for antibodies which will have the specific properties
required by claim 17.
Analyzing the Specification in light of Centocor, there is no well
characterized antigen since the Specification does not teach how to isolate,
purify, or otherwise prepare the activated form the MN/CA IX enzyme in a
form capable of being used to induce antibodies in an animal or being used
in a display screening method. There is no structural information on how
the “activated” form of the MN/CA IX enzyme differs from the catalytically
inactive form. There is certainly no well characterized antibody since the
Specification does not provide any actual examples of an antibody of the
invention or structural information on such an antibody (FF 8).
When the Majority asserts that there is a working example (see FF 5),
that working example is not an antibody which meets the claim, but rather is
a small molecule which does not fall within the scope of the instant claims.
There are no working examples of antibodies which satisfy the requirements
of the claims.
Appellants’ argument for “routine experimentation” references the
only discussion in the Specification of an antibody specific for an activated
form, omitting the reference (App. Br. 15-16). The Specification teaches
that “monoclonal antibodies have been described which specifically
recognize the epitope of caspases that is characteristic of the activated form
of those proteases [143]” (Spec. 40, ll. 10-12). Reference 143 refers to
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Tanaka1, who teaches that the caspase enzyme in question is subject to
protealytic processing from a “proform” into an “active” form. The
antibody of Tanaka simply recognizes the amino terminus of the cleaved
“active” form (see Tanaka 223, col. 1-2) and cannot otherwise distinguish
between “active” and “inactive” enzyme.
Unlike the situation in Tanaka, Appellants Specification does not
show that MN/CA IX enzyme is cleaved into two forms upon activation, nor
does the Specification show that the enzyme is phosphorylated or otherwise
altered upon activation. Thus, without any teaching of what structural
change, if any, occurs to the MN/CA IX enzyme upon activation, there is
absolutely no support for Appellants’ routine experimentation argument.
This is precisely the sort of situation where Appellants have expressed
a wish. A wish for an antibody with certain functional properties. It is a
fine, useful and desirable wish, but a wish nonetheless. There is no
description of the antigen necessary to obtain this antibody. There is no
description of the antibody itself. There is no description in the
Specification of any method which could be used to obtain this antibody.
The prior art does not teach or suggest methods which would function to
distinguish active and inactive MN/CA IX enzyme. Centocor mandates that
a “‘mere wish or plan’ for obtaining the claimed invention is not sufficient”.
Centocor, 2011 WL 635291 at 7. Here, Appellants Specification lacks even
a plan, retaining only the wish.

1 Tanaka et al., In situ detection of activated caspase-3 in apoptotic
granule neurons in the developing cerebellum in slice cultures and
in vivo, 121 DEVELOPMENTAL BRAIN RESEARCH 223-228 (2000).
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In conclusion, I would affirm the Examiner’s written description
rejection.

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