Armand Bensussan et al.

Patent Trials and Appeals Board

Oct 29, 2020

2020001893 (P.T.A.B. Oct. 29, 2020)

UNITED STATES PATENT AND TRADEMARK OFFICE
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.
13/996,097 06/20/2013 Armand Bensussan INNAT.025NP 2522
20995 7590 10/29/2020
KNOBBE MARTENS OLSON & BEAR LLP
2040 MAIN STREET
FOURTEENTH FLOOR
IRVINE, CA 92614
EXAMINER
MOSELEY II, NELSON B
ART UNIT PAPER NUMBER
1642
NOTIFICATION DATE DELIVERY MODE
10/29/2020 ELECTRONIC
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.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
efiling@knobbe.com
jayna.cartee@knobbe.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ARMAND BENSUSSAN, NATHALIE BONNEFOY-BERARD,
JEAN-FRANCOIS ELIAOU, GILLES ALBERICI, and JEREMY BASTID1
Appeal 2020-001893
Application 13/996,097
Technology Center 1600
Before ERIC B. GRIMES, JEFFREY N. FREDMAN, and RACHEL H.
TOWNSEND, Administrative Patent Judges.
GRIMES, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to
methods of treatment and diagnosis using anti-CD39 antibodies, which have
been rejected for lack of adequate written descriptive support. We have
jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.

1 Appellant identifies the real parties in interest as Institut National de la
Sante et de la Recherche Medicale, Orega Biotech, and Innate Pharma SAS.
Appeal Br. 3. We use the word “Appellant” to refer to “applicant” as defined
in 37 C.F.R. § 1.42.
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STATEMENT OF THE CASE
“CD39 is an integral membrane protein . . . with nucleoside
triphosphate diphosphohydrolase activity.” Spec. 1:8–10. “In humans, CD39
is mainly expressed by regulatory T cells (Treg).” Id. at 1:10–11. “In cancers
infiltrated with CD39 positive Tregs, CD39 plays a key role because it
increases tumor angiogenesis and suppress[es] the immune antitumor
response by initiating the generation of adenosine.” Id. at 1:11–14.
“The present invention relates to a CD39 antibody for inhibiting the
immunosuppressive effects of a CD39-expressing cancerous cell.” Id. at
1:26–27.
Claims 1, 9, and 13 are on appeal. Claim 1, reproduced below, is
illustrative (emphasis added to disputed limitation):
1. A method for inhibiting the immunosuppressive
effects of CD39-expressing haematological cancerous cells,
comprising:
identifying a haematological cancer as comprising CD39-
expressing haematological cancerous cells; and
contacting said CD39-expressing haematological
cancerous cell with an anti-CD39 antibody in an amount
effective to block or decrease CD39-expressing haematological
cancerous cell-mediated inhibition or suppression of the
immune response, wherein said anti-CD39 antibody is selected
from the group consisting of:
a) the monoclonal antibody BY40 produced by the
hybridoma cell line deposited with the CNCM under the
accession number CNCM I-3889,
b) the monoclonal antibody BA54g produced by the
hybridoma cell line deposited with the CNCM under the
accession number CNCM I-4171,
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c) the monoclonal antibody BY12 produced by the
hybridoma cell line deposited with the CNCM under the
accession number CNCM I-5319; and
d) a monoclonal antibody that is a function-conservative
variant of the monoclonal antibody of (a), (b) or (c).
OPINION
Claims 1, 9, and 13 stand rejected under 35 U.S.C. § 112, first
paragraph, for failing to comply with the written description requirement.
Ans. 3. The Examiner finds that
parts a) - c) of the claims satisfy the written description
requirement of 35 U.S.C. 112, first paragraph. However the
claims fail to satisfy the written description requirement of 35
U.S.C. 112, first paragraph, due to the recitation of a “function-
conservative variant” of the BY40, BA54g, and BY12
antibodies, which is recited in part d) of the claims.
Ans. 10.
The Examiner points to the Specification’s definition of “function-
conservative variant” and concludes that the claims encompass “a broad
genus of antibodies, specifically amino acid variants of BY40, BA54g,
and/or BY12 that share between 70% and 99% homology with BY40,
BA54g, and/or BY12 and possess the same functional characteristics of
BY40, BA54g, and/or BY12.” Id. at 6.
The Examiner finds that the Specification “does not appear to . . .
disclose[] any function-conservative variants of BY40, BA54g, and/or
BY12. Therefore the specification does not provide adequate written
description for the entire claimed genus by disclosing a representative
number of species.” Id. at 7. The Examiner also finds that the Specification
does not “disclose[] relevant, identifying characteristics of antigen-binding
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domain amino acid sequences that confer the functional characteristics of
BY40, BA54g, and/or BY12, because the instant specification does not
provide structural antibody features that correlate with said functional
characteristics.” Id.
The Examiner cites McCarthy2 and Lin3 as evidence that “even a
single amino acid substitution within the CDR [complementarity
determining region] of an antibody antigen-binding domain may alter the
function of an antibody.” Id. at 8. Thus, the Examiner concludes that “given
the unpredictability associated with antibody CDR region changes on
antibody function and given the lack of particularity with which the claimed
antibodies are described . . . the specification would not reasonably convey
to the skilled artisan that Applicant had possession of the claimed
invention.” Id.
We agree with the Examiner that the Specification does not provide
an adequate written description of the claimed genus of “function-
conservative variant[s]” of the specific antibodies recited in the claims. “The
essence of the written description requirement is that a patent applicant, as
part of the bargain with the public, must describe his or her invention so that
the public will know what it is and that he or she has truly made the claimed

2 McCarthy et al., “Altering the fine specificity of an anti-Legionella single
chain antibody by a single amino acid insertion,” J. Immunol. Methods
251:137–149 (2001).
3 Lin et al., “Improved affinity of a chicken single-chain antibody to avian
infectious bronchitis virus by site-directed mutagenesis of complementarity-
determining region H3,” African J. Biotechnol. 10(79):18294–18302 (2011).
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invention.” AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc., 759
F.3d 1285, 1298 (Fed. Cir. 2014).
[A] sufficient description of a genus . . . requires the disclosure
of either a representative number of species falling within the
scope of the genus or structural features common to the
members of the genus so that one of skill in the art can
“visualize or recognize” the members of the genus.
Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1350 (Fed. Cir. 2010).
“[F]unctional claim language can meet the written description requirement
when the art has established a correlation between structure and function.”
Id. “But merely drawing a fence around the outer limits of a purported genus
is not an adequate substitute for describing a variety of materials constituting
the genus and showing that one has invented a genus and not just a species.”
Id.
As the Examiner found, Appellant’s Specification describes the three
specific monoclonal antibodies (mAbs) recited in parts a) through c) of the
claims, including the amino acid sequences of the light chain and heavy
chain variable regions of each antibody. See Tables 1 and 3 (as amended
June 8, 2018). The Examiner’s rejection, however, is based on the “function-
conservative variant[s]” of these mAbs that are recited in part d) of the
claims. See Ans. 10.
The Specification defines “function-conservative variants” as follows:
“Function-conservative variants” are those in which a given
amino acid residue in a protein or enzyme has been changed
without altering the overall conformation and function of the
polypeptide, including, but not limited to, replacement of an
amino acid with one having similar properties (such as, for
example, polarity, hydrogen bonding potential, acidic, basic,
hydrophobic, aromatic, and the like). Amino acids other than
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those indicated as conserved may differ in a protein so that the
percent protein or amino acid sequence similarity between any
two proteins of similar function may vary and may be, for
example, from 70% to 99% as determined according to an
alignment scheme such as by the Cluster Method, wherein
similarity is based on the MEGALIGN algorithm. A “function-
conservative variant” also includes a polypeptide which has at
least 60% amino acid identity as determined by BLAST or
FASTA algorithms, preferably at least 75%, more preferably at
least 85%, still preferably at least 90%, and even more
preferably at least 95%, and which has the same or substantially
similar properties or functions as the native or parent protein to
which it is compared.
Spec. 21:5–18. Thus, the Specification defines a “function-conservative
variant” as an antibody having as little as 60% amino acid identity (as
determined by BLAST or FASTA algorithms) to one of the recited mAbs,
and having “the same or substantially similar properties or functions.”
The Specification does not expressly define what “properties or
functions [of] the native or parent protein” (Spec. 21:17–18) are relevant to
determining whether another antibody is a function-conservative variant of
one of the recited mAbs. In the context of the claimed methods, we interpret
a “function-conservative variant” to be an antibody that binds to and inhibits
CD39 enzymatic activity. See Spec. 34:11–19: “[T]he three antibodies
BA54g, BY12 and BY40 inhibited CD39 activity in a dose dependant [sic]
manner. . . . CD39 mAbs BA54g, BY12 and BY40 are able to decrease
CD39 enzymatic activity and are thus promising tools to block tumor-CD39
mediated immunosuppression.”
The Specification does not describe any variants of BA54g, BY12, or
BY40 that retain the activity of binding to CD39 and inhibiting its enzymatic
activity. The Specification does not, in fact, describe any variants of BA54g,
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BY12, or BY40 whatsoever. Therefore, the Specification does not describe
“a representative number of species falling within the scope of the genus.”
Ariad, 598 F.3d at 1350.
As noted above, the Specification describes the amino acid sequence
of the heavy and light chain variable regions, including the complementarity
determining regions (CDRs), of each of BA54g, BY12, and BY40. Spec.,
Tables 1 and 3. Those sequences, however, vary substantially. For example,
the VH CDR1 domain of BY40 is eight amino acids long (Table 1), but it is
twenty-one amino acids long in BA54g (Table 3), and five amino acids long
in BY12 (Table 3). The Specification provides no description of the
structural features (i.e., amino acids) of the variable regions of BA54g,
BY12, and BY40 that are important to their function of binding to and
inhibiting the enzymatic activity of CD39. See Spec. 8–13. Therefore, the
Specification fails to describe the claimed genus by describing structural
features that correlate with the recited function.
In summary, the Specification fails to describe the claimed genus of
“function-conservative variant[s]” of BA54g, BY12, and BY40 by
describing a representative number of species or a correlation between
structure and function. See Ariad, 598 F.3d at 1350. The claimed “function-
conservative variant[s]” are therefore not supported by a written description
sufficient to satisfy 35 U.S.C. § 112, first paragraph.
Appellant argues that “the application amply demonstrates possession
of the recited antibodies through teaching of representative species and their
corresponding amino acid structure.” Appeal Br. 5. Appellant points to the
Specification’s “Examples 1–7 (pages 30–34) and Figures 1, 3, 4 and 7 . . . ,
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which demonstrate the blocking and down-regulation effects that are
induced by the CD39 antibodies BY40, BY12 and BA54g.” Id. Appellant
argues that “[t]hus, the specification discloses at least three representative
antibodies and their functions. In addition, the amino acid sequences of the
CDRs for each of the antibodies BY40, BA54g and BY12 are disclosed in
the application.” Id.
This argument is unpersuasive. The Examiner has found that the
specific mAbs recited in the claims—BY40, BY12, and BA54g—are
supported by an adequate written description. The rejection is based on the
lack of an adequate description of the claimed function-conservative
variants, which by definition (Spec. 21:5–9) differ structurally from the three
recited mAbs. Therefore, BY40, BY12, and BA54g are not species within
the genus of function-conservative variants of those mAbs, and the
structures of BY40, BY12, and BA54g are not representative of the claimed
genus.
Appellant also argues that “the ‘function-conservative variants’ of
these antibodies were also further described in the specification at pages
21:3–22:11.” Appeal Br. 5–6.
This argument is also unpersuasive. The cited passage in the
Specification defines the terms “function-conservative variants” and
“substantially homologous” or “substantially similar” amino acid sequences,
and provides general guidance on types of amino acid substitutions that
might be made “in a protein structure without appreciable loss of activity.”
Spec. 21:27–28. However, it does not describe any specific variant of BY40,
BY12, or BA54g in which “a given amino acid residue in a protein or
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enzyme has been changed without altering the overall conformation and
function of the polypeptide” (Spec. 21:5–7); i.e., a “function-conservative
variant.” Nor does the general description that Appellant points to describe a
correlation between the structure of BY40, BY12, and BA54g and the
function of binding to and inhibiting the enzymatic activity of CD39. The
discussion that Appellant relies on therefore does not provide a description
of the claimed function-conservative variants that satisfies the requirements
of 35 U.S.C. § 112, first paragraph.
DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1, 9, 13 112, first
paragraph
Written Description 1, 9, 13

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). See 37 C.F.R.
§ 1.136(a)(1)(iv).
AFFIRMED