Ex Parte Kim et al

Patent Trial and Appeal Board

Oct 26, 2018

13327624 (P.T.A.B. Oct. 26, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/327,624 12/15/2011
826 7590 10/30/2018
ALSTON & BIRD LLP
BANK OF AMERICA PLAZA
101 SOUTH TRYON STREET, SUITE 4000
CHARLOTTE, NC 28280-4000
FIRST NAMED INVENTOR
Kyung Jin Kim
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
057763-413409 2461
EXAMINER
SAOUD, CHRISTINE J
ART UNIT PAPER NUMBER
1647
NOTIFICATION DATE DELIVERY MODE
10/30/2018 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):
usptomail@alston.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte KYUNG JIN KIM, LIHONG WANG, HANGIL PARK, and
MAXIMILANO VASQUEZ
Appeal2017-006385
Application 13/327,624 1
Technology Center 1600
Before JEFFREY N. FREDMAN, RICHARD J. SMITH, and
DAVID COTTA, Administrative Patent Judges.
COTT A, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
of treating cancer in a patient. The Examiner rejected the claims on appeal
under 35 U.S.C. § l 12(a) for failure to comply with the written description
requirement.
We affirm.
STATEMENT OF THE CASE
The Specification discloses that "[h]uman FGF2 [fibroblast growth
factor 2] is an 18 kDa non-glycosylated polypeptide consisting of 146 amino
1 According to Appellants, the real party in interest is Galaxy Biotech, LLC.
App. Br. 2.
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Application 13/327,624
acids in the mature form derived from a 155 [amino acid] precursor." Spec.
,r 6. "FGF2 and other FGFs are believed to play a role in cancer, both by
stimulating angiogenesis and tumor cells directly." Id. ,r 9. According to the
Specification, "[p ]olyclonal antibodies ( antiserum) to FGF2 have been
reported to inhibit tumor growth of a transplantable chondrosarcoma in
mice, neutralize various activities of FGF2 in vitro, and to inhibit growth of
U87 glioma cell intracranial xenografts when applied locally." Id. ,r 10
(internal citations omitted). While certain anti-FGF2 monoclonal antibodies
("mAb") have been shown "not to block tumor angiogenesis in vivo," other
monoclonal antibodies have been taught to inhibit growth and/or
proliferation of gliomas, colon tumor xenografts, non-small cell lung cancer
cell lines, U87MG glioma, T98G glioma, and HeLa cell xenografts. Id.
The Specification discloses that "the invention provides a neutralizing
mAb to human basic fibroblast growth factor (FGF2)." Id. ,r 12. According
to the Specification, the mAb of the invention "inhibits at least one, and
preferably several or all biological activities of FGF2, including binding to
one or more of the four FGF receptors FGFRl-4; inducing proliferation of
fibroblasts, endothelial cells, Mv 1 Lu mink lung epithelial cells, and/or
various human tumor cells; and inducing angiogenesis." Id. "Exemplary
antibodies are GAL-F2 and its chimeric and humanized forms, and mAbs
which have the same epitope or compete for binding with GAL-F2." Id.
GALF2 is the monoclonal antibody produced by hybridoma PT A-8864. Id.
,r 74.
2
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Application 13/327,624
Claims 2, 3, 8, 15, and 16 are on appeal. 2 Claim 15, the only
independent claim on appeal, is illustrative and reads as follows:
15. A method of treating cancer in a patient comprising
administering to the patient a pharmaceutical composition
comprising a mAb that competes for binding to FGF2 with an
antibody produced by hybridoma PTA-8864, wherein the mAb
neutralizes FGF2 and the cancer is a type of cancer that
responds to FGF2.
App. Br. 7 (Claim App.).
The Examiner rejected claims 2, 3, 8, 15, and 16 under 35 U.S.C.
§ 112 for failure to comply with the written description requirement.
ANALYSIS
A description adequate to satisfy 35 U.S.C. § 112, first paragraph,
must "'clearly allow persons of ordinary skill in the art to recognize that
[the inventor] invented what is claimed.'" Ariad Pharms., Inc. v. Eli Lilly &
Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en bane) (citation omitted,
alteration in original). "[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." Id.
Claim 15 requires a "mAb that competes for binding to FGF2 with an
antibody produced by hybridoma PTA-8864." The Examiner found that
while the amino acid sequence of FGF2 was known, immunizing an animal
with FGF2 will generate antibodies "directed to a number of different
epitopes and not necessarily to the same epitope which is bound by the
2 In a February 22, 2016 Advisory Action, the Examiner entered an
amendment cancelling claims 1, 4--7, 9-14 and 21. These claims are thus
not part of this appeal.
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Application 13/327,624
antibody produced by hybridoma PTA-8864." Ans. 8. The Examiner thus
found that knowledge of the amino acid sequence of FGF2, by itself, did not
put Appellants in possession of monoclonal antibodies that compete for
binding with FGF2 with an antibody produced by hybridoma PTA-8864. Id.
In determining that the Specification did not support the claimed
monoclonal antibody, the Examiner considered whether the Specification
disclosed: a "complete or partial structure, physical and/or chemical
properties, functional characteristics, structure/function correlation, methods
of making the claimed product, or any combination thereof." Final Act. 4.
The Examiner found that the only one of these factors described in the
Specification was "a functional recitation of competing for binding." Id.
The Examiner also found that there was "no structure recited which would
provide for such a function ( e.g. recitation of epitope )" and thus the skilled
artisan could not "envision the detailed chemical structure of the
encompassed genus of antibodies ... until reduction to practice has
occurred, regardless of the complexity or simplicity of the method of
isolation." Id. Absent a recitation of "distinguishing identifying
characteristics," the Examiner concluded that "the [S]pecification does not
provide adequate written description support of the claimed genus." Id. at
3--4.
We agree with the Examiner that the Specification does not support
the claimed genus of monoclonal antibodies. We address Appellants
arguments below.
Appellants argue that antibodies can be described by reference to the
epitope to which they bind without a structural description of representative
antibodies of the claimed genus. Reply Br. 2; App. Br. 4 ( citing Noelle v.
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Lederman, 355 F.3d 1343 (Fed. Cir. 2004). Appellants then argue that an
epitope can be defined not only by the sequence of amino acids forming the
epitope, but also by "a competition assay in which the genus of antibodies
compete with an archetypal antibody for binding to a well-defined antigen."
Reply Br. 2. More specifically, Appellants argue that the requirement that
the claimed monoclonal antibody competes for binding to FGF2 with an
antibody produced by hybridoma PTA-8864 "serves to physically define a
locus within FGF2 to which a claimed genus of antibodies binds and
distinguish the claimed antibody from prior antibodies binding elsewhere on
FGF2 (see Example 4)." Id. We are not persuaded
While the Federal Circuit has recognized that "the written description
requirement can in some cases be satisfied by functional description," it has
made clear that "such functional description can be sufficient only if there is
also a structure-function relationship known to those of ordinary skill in the
art." In re Wallach, 378 F.3d 1330, 1335 (Fed. Cir. 2004); see also, Enzo
Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 964 (Fed. Cir. 2002)
(holding that the written description requirement would be satisfied "if the
functional characteristic of preferential binding ... were coupled with a
disclosed correlation between that function and a structure that is sufficiently
known or disclosed"); Amgen Inc. v. Sanofi, 782 F.3d 1367, 1378 (Fed. Cir.
2017) (holding that an "adequate written description must contain enough
information about the actual makeup of the claimed products"). 3 Here,
Appellants provide a functional description of the claimed antibody- i.e.,
3 Amgen also states that "the 'newly characterized antigen' test" relied upon
by Appellants "flouts basic legal principles of the written description
requirement." 782 F.3d at 1378.
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Application 13/327,624
that it competes for binding to FGF2 with antibodies produced by hybridoma
PTA-8864- but Appellants do not identify, and we do not find, any
disclosure of a correlation between the claimed function and the structure of
the antibodies that perform that function.
This case is thus similar to Centocor Ortho Biotech, Inc. v. Abbott
Laboratories, 636 F.3d 1341 (Fed. Cir. 2011). In Centocor, patentee
claimed an antibody or antibody fragment that competitively inhibits binding
of A2 (a mouse antibody) and that binds an epitope of TNF-a with a
specified affinity. 4 636 F.3d at 1346. Both TNF-a protein and antibodies to
that protein were known in the literature. Id. at 1352. Patentee argued that
the patent at issue satisfied the written description for the claimed antibodies
because it "not only describes the antibodies by their binding affinity for
TNF-a, but further describes the antibodies by specifying that they
competitively inhibit binding of the A2 mouse antibody to TNF-a." Id. at
1349. The Federal Circuit rejected this argument, finding that "[a]t bottom,
the asserted claims constitute a wish list of properties that a fully-human,
therapeutic TNF-a antibody should have: high affinity, neutralizing activity,
4 The claim at issue in Centocor reads:
An isolated recombinant anti-TNF-a anti-body or antigen-
binding fragment thereof, said antibody or antigen-binding
fragment comprising a human constant region, wherein said
antibody or antigen binding fragment (i) competitively inhibits
binding of A2 (ATCC Accession No. PTA-7045) to human
TNF-a, and (ii) binds to a neutralizing epitope of human TNF-a
in vivo with an affinity of at least lxl08 liter/mole, measured as
an association constant (Ka), as determined by Scatchard
analysis.
636 F.3d at 1346.
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and the ability to bind in the same place as the mouse A2 antibody." Id. at
1351. The court explained that "[t]he specification at best describes a plan
for making fully-human antibodies and then identifying those that satisfy the
claim limitations." Id.
In finding that the specification at issue did not provide written
description support for the claimed antibodies, the Centocor court
recognized that the written description does not require examples or an
actual reduction to practice, but clarified that "it does demand ... that one of
skill in the art can 'visualize or recognize' the claimed antibodies based on
the specification's disclosure." Id. at 1353. "In other words the
specification must demonstrate constructive possession." Id; see also,
AbbVie Deutschland GmbH & Co., KG., v. Janssen Biotech, Inc., 759 F.3d
1285, 1301 (Fed. Cir. 2014) (reiterating requirement for structure-function
correlation in functionally defined claims and finding that the patents at
issue do not meet the written description requirement because they "do not
describe any common structural features of the claimed antibodies.").
Here, as in Centocor, Appellant seeks to ground written description
support for a claimed antibody in its competitive inhibition of another
antibody (here, the "monoclonal antibody produced by hybridoma
PTA-8864," in Centocor, mouse A2 antibody) and in the description of a
known antigen (here FGF2, in Centocor, TNF-a). While we recognize that
the state of the art has progressed since the Federal Circuit's decision in
Centocor, the basic problem remains that the description at issue must allow
one of skill in the art to "visualize or recognize" the claimed antibodies.
Here, the evidence of record does not support that the skilled artisan would
have visualized or recognized the claimed antibodies based on the
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description provided. As in Centocor, the Specification provides only a plan
for identifying the claimed antibodies.
Appellants argue that their disclosure of GAL-F2 - the monoclonal
antibody produced by hybridoma PTA-8864 - is representative of the
claimed genus, and thus satisfies the written description requirement,
because it "can be used to identify other antibodies falling within the genus."
App. Br. 3. As support, Appellants rely on paragraph 38 of the
Specification, which states:
Once a single, archetypal anti-human-FGF2 mAb, for example
GAL-F2, has been isolated that has the desired properties
described herein of neutralizing FGF2, it is straightforward to
generate other mAbs with similar properties, by using art-
known methods. For example, mice may be immunized with
FGF2 as described above, hybridomas produced, and the
resulting mAbs screened for the ability to compete with the
archetypal mAb for binding to FGF2. Mice can also be
immunized with a smaller fragment of FGF2 containing the
epitope to which GAL-F2 binds. The epitope can be localized
by, e.g., screening for binding to a series of overlapping
peptides spanning FGF2.
Spec. ,r 38. We are not persuaded.
We acknowledge that the Specification describes methods that can be
used to screen for mAb's that compete with GAL-F2. However, this is not
sufficient to show that the inventors were in possession of the genus of
antibodies that compete with GAL-F2. University of Rochester v. G.D.
Searle & Co., Inc., 358 F.3d 916, 927 (Fed. Cir. 2004) (finding that the
disclosure of "assays for screening compounds, including peptides,
polynucleotides, and small organic molecules to identify those that inhibit
the expression or activity of the PGHS-2 gene product," did not satisfy the
written description requirement for claims requiring administration of a
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Application 13/327,624
"compound that selectively inhibits PGHS-2"); see also, Ariad
Pharmaceuticals, Inc., v. Eli Lilly and Company, 598 F.3d 1336, 1344
(Fed. Cir. 2010) (recognizing distinction between requirements for written
description and enablement); Centrocor, 636 F.3d 1350 ("The fact that a
fully-human antibody could be made does not suffice to show that the
inventors ... possessed such an antibody.").
Appellants argue that written description support for the genus of
antibodies that compete with GAL-F2 is provided by the description in the
Specification of GAL-F2 because "the GAL-F2 antibody competes with
itself for binding to FGF2." App. Br. 3. We are not persuaded that the
description of a single antibody- GAL-F2 -is representative of the claimed
genus. In particular, we agree with the examiner that "disclosure of this
antibody does not provide an adequate written description of what structures
are necessary to generate an antibody that would compete with ... GAL-F2"
and that an antibody that competes for binding to FGF2 with GAL-F2
"could have any structure as long as it binds to the same epitope ( or similar
epitope ). " Ans. 6.
We recognize that the specification also describes humanized and
chimeric forms of GAL-F2 antibody which would compete with GAL-F2 for
binding to GFG2. However, we agree with the Examiner that these
antibodies are not representative of the claimed genus because "they contain
the same CDRs [complementarity determining regions] as the GAL-F2
antibody." Id. at 7.
Accordingly, we affirm the Examiner's rejection of claim 15.
Because they were not argued separately, claims 2, 3, 8, and 16 fall with
claim 15.
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SUMMARY
For the reasons discussed above, and those set forth in the Examiner's
Answer and Final Office Action, we affirm the Examiner's rejection of
claims 2, 3, 8, 15, and 16 under 35 U.S.C. § 112 for failure to comply with
the written description requirement.
AFFIRMED
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