Kymab Limited

Patent Trials and Appeals Board

Jul 20, 2021

2021000865 (P.T.A.B. Jul. 20, 2021)

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.
15/661,658 07/27/2017 Jamie Campbell 718420: SA9-610USCON3 3819
17387 7590 07/20/2021
Lathrop GPM LLP | Sanofi-Aventis
28 State Street
Boston, MA 02109
EXAMINER
GAMBEL, PHILLIP
ART UNIT PAPER NUMBER
1644
NOTIFICATION DATE DELIVERY MODE
07/20/2021 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):
bostonpatent@lathropgage.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
________________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
________________

Ex parte JAMIE CAMPBELL, STEVE HOLMES,
IAN KIRBY, and MIHA KOSMAC1
________________

Appeal 2021-000865
Application 15/661,658
Technology Center 1600
________________

Before JOHN G. NEW, RYAN H. FLAX, and
DAVID COTTA, Administrative Patent Judges.

NEW, Administrative Patent Judge.

DECISION ON APPEAL

1 We use the term “Appellant” to refer to the “applicant” as defined in
37 C.F.R. § 1.142. Appellant identifies Kymab Limited as the real party-
in-interest. App. Br. 3. Oral argument was heard on June 1, 2021, and a
transcript of the hearing (“Trans.”) is part of the record.
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SUMMARY
Appellant files this appeal under 35 U.S.C. § 134(a) from the
Examiner’s Final Rejection of claims 54, 55, 58, 60–75, 78–81, 83, 84, 86–
104, 107–110, 112, and 113 as unpatentable under 35 U.S.C. § 112, first
paragraph, as failing to comply with the written description requirement.
We have jurisdiction under 35 U.S.C. § 6(b).
We REVERSE.

NATURE OF THE CLAIMED INVENTION
Appellant’s claimed invention is directed to anti-human OX40L
antibodies, new medical uses and methods. Spec. Abstr.

REPRESENTATIVE CLAIM
Independent claims 54 and 86 are representative of the claims on
appeal. Claim 54 recites:
54. A method of treating an autoimmune disease or condition,
a systemic inflammatory disease or condition, or
transplant rejection in a human subject, comprising
administering to the subject an anti-OX40L antibody or
antibody fragment that specifically binds to an hOX40L
epitope and comprises a heavy chain and a light chain
wherein:

a. the heavy chain comprises:

i. a VH region having at least 90%
identity to the amino acid sequence of
SEQ ID NO: 34; and

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ii. a heavy chain constant region having
the amino acid sequence of SEQID
NO: 128; and

b. the light chain comprises:

i. a VL region having at least 90%
identity to the amino acid sequence of
SEQ ID NO: 48; and

ii. a light chain constant region;

wherein the anti-OX40L antibody or antibody fragment is
administered intravenously or subcutaneously to said
subject in an amount effective to decrease secretion of IL-
2.

App. Br. 18. Claim 86 recites:

86. A method of treating an autoimmune disease or condition,
a systemic inflammatory disease or condition, or
transplant rejection in a human subject, comprising
administering to the subject an anti-OX40L antibody or
antibody fragment that specifically binds to an hOX40L
epitope and comprises a heavy chain and a light chain and
wherein:

a. the heavy chain comprises a VH region
having at least 95% identity to the amino acid
sequence of SEQ ID NO: 34; and

b. the light chain comprises a VL region having
at least 95% identity to the amino acid sequence of
SEQ ID NO: 48;

wherein the anti-OX40L antibody or antibody fragment is
administered intravenously or subcutaneously to said
subject in an amount effective to decrease secretion of IL-
2.
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Id. at 23.

ISSUE AND ANALYSIS
We decline to agree with and adopt the Examiner’s findings,
reasoning, and conclusion that the claims lack the requisite written
descriptive support in Appellant’s Specification. We address below the
arguments raised by Appellant.

Issue 1: Claims 54, 55, 58, 60–75, 78–81, 83, and 84
Appellant argues that the Examiner erred in finding that Appellant’s
Specification failed to satisfy the written description requirement by “not
defining a heavy/light chains [sic] or six (6) [complementarity-determining
regions] (“CDRs”).” App. Br. 9.

Analysis
The Examiner finds that the claims are drawn to antagonistic anti-
OX40L antibodies. Non-Final Act. 6 (entered December 1, 2017).2 The
Examiner finds that, given the well-known high level of polymorphism of
immunoglobulins/antibodies, a person of ordinary skill in the art would not
have understood that Appellant was in possession of the vast repertoire of
antibodies and the unlimited number of antibodies encompassed by the
claimed invention. Id. Specifically, the Examiner find that a skilled artisan

2 In the Final Office Action of January 21, 2020, the Examiner incorporates
by reference the findings and conclusions of the cited Non–Final Action.
See Final Act. 3 (“The rejections of record can be found in the previous
Office Action, mailed 07/26/2019” (this rejection, in turn, refers back to
the Non-Final Action cited in the text supra)). For this reason, we rely
herein upon the original findings of the Non-Final Action.
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would have understood that Appellant was not in possession of the structural
attributes of a representative number of species possessed by the members of
the genus of antagonistic anti-OX40L antibodies and antigen-binding
fragments broadly encompassed by the claimed invention. Id. The
Examiner finds that a person of ordinary skill in the art would have
understood that Appellant’s Specification fails to disclose a representative
number of species to describe the claimed genus. Id.
The Examiner notes that it is well established in the art that the
formation of an intact antigen-binding site generally requires the association
of the complete heavy and light chain variable regions of a given antibody,
each of which consists of three CDRs that provide the majority of the
contact residues for the binding of the antibody to its target epitope. Non-
Final Act. 6. The Examiner finds that the amino acid sequences
and conformations of each of the heavy and light chain CDRs are critical in
maintaining the antigen binding specificity and affinity characteristic of the
parent immunoglobulin. Id. The Examiner finds that all of the heavy and
light chain CDRs should be in their proper order and in the context of
framework sequences that maintain their required conformation so as to
provide a binding molecule having antigen-binding function. Id. The
Examiner also finds that proper association of heavy and light chain
variable regions is required in order to form functional antigen binding sites.
Id.
Furthermore, the Examiner finds, even minor changes in the amino
acid sequences of the heavy and light variable regions, particularly in the
CDRs, may dramatically affect antigen-binding function. Non-Final Act. 7
(citing S. Rudikoff et al., Single Amino Acid Substitution Altering Antigen-
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Binding Specificity, 79 PROC. NAT’L ACAD. SCI. USA 1979–83 (1982)
(“Rudikoff”)). The Examiner finds that Rudikoff teaches that the alteration
of a single amino acid in the CDR of a phosphocholine-binding myeloma
protein results in the loss of antigen-binding function. Id.
In further support of this finding, the Examiner also points to the
similar teachings of PM Colman et al., Effects of Amino Acid Sequence
Changes on Antibody-Antigen Interactions, 145(1) RES. IMMUNOL. 33–36
(1994) (“Colman”) on the effects of amino acid sequence changes on
antibody-antigen interactions, and PH Kussie et al., A Single Engineered
Amino Acid Substitution Changes Antibody Fine Specificity, 152 J.
IMMUNOL. 146–52 (1994) (“Kussie”) (teaching that the substitution of a
single amino acid can totally ablate antigen binding).
The Examiner next points to C. Chen et al., Enhancement and
Destruction of Antibody Function by Somatic Mutation: Unequal
Occurrence is Controlled by V Gene Combinatorial Associations, 14(12)
EMBO J., 14: 2784–94 (1995) (“Chen”). The Examiner finds that Chen
teaches that the substitution of a single amino acid can totally ablate antigen
and that the same substitution in closely related antibodies can have opposite
effects binding. The Examiner finds that Chen teaches, by way of
example, that the effects of identical substitutions in related antibodies DI6
and TI5 increased antigen binding in one antibody while ablating it in the
other. Id.
The Examiner therefore finds that, with respect to the diverse
specificities encompassed by the claimed invention, a skilled artisan would
have known that a single amino acid substitution in a common allele ablates
binding of an antibody and that there can be a dissociation of
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immunoreactivity from other biological activities when constructing
analogs. Non-Final Act. 7.
The Examiner finds that Appellant relies upon screening approaches
to evaluate and identify antibodies having the relevant sequence/residue
structures that contribute to, or affect various variables associated with
antibody specificity to various antigen/epitope specificities. Non-Final Act.
7. This includes, the Examiner finds, various levels of sequence identity and
modifications such as substitutions/mutations with various biological
activities including decreasing or inhibiting binding of OX40F to OX40, and
biological activity such as IF-2/IF-13 secretion to treat subject having
a disease/disorder, including the elected species GVHD. Id. (citing
generally Spec.).
However, the Examiner finds that Appellant’s Specification does not
provide sufficient description of the structure, epitope characterization,
specificity and pharmacological properties of the large family of
antibodies recited in the claimed methods. Non-Final Act. 7. The Examiner
finds that the Specification does not provide a sufficient description showing
possession of the necessary functional characteristics coupled with a known
or disclosed correlation between function and structure sufficient to show
the applicant was in possession of the genus of antagonistic anti-OX40L
antibodies, broadly encompassed by the claimed invention. Id. at 8.
The Examiner further finds that the claims do not define the relevant
identifying structural characteristics, namely the relevant amino acid
sequences of the claimed antagonistic anti-OX40L antibodies/variants
that would identify the claimed antibodies/variants encompassing the
various modifications as well as defining a heavy/light chains or six CDRs
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encompassed by the claimed antibody specificity and functional attributes.
Non-Final Act. 8.
Furthermore, the Examiner finds, the Appellant’s Specification does
not provide a sufficient description showing of possession of the necessary
functional characteristics coupled with a known or disclosed
correlation between function and structure. Non-Final Act. 8. Nor,
Examiner finds, does it demonstrate possession by a combination of such
identifying characteristics, sufficient to show the applicant was in possession
of the genus of anti-OX40L antibodies and variants thereof encompassing
various structures, specificities and functions, broadly encompassed by
the claimed invention. Id.
The Examiner concludes that Appellant was not in possession of the
claimed genus of “specificities” and “variants thereof” in the absence of
providing sufficient structural characteristics of the genus of such
“specificities and variants thereof” coupled with a known or disclosed
correlation between function and structure in the claims. The Examiner
further concludes that Appellant’s Specification fails to provide a disclosure
of which amino acids are required for the claimed antagonistic anti-OX40L
antibodies that retain the appropriate structural and functional attributes
claimed. Id. at 8–9.
Appellant argues that the claims provide sufficient structure-
identifying information to demonstrate possession of the claimed anti-
OX40L antibodies. App. Br. 9. Specifically, argues Appellant, independent
claim 54 defines the heavy and light chains of the anti-OX40L antibody or
antibody fragment of the invention. Id. Appellant points out that claim 54
recites a heavy chain comprising a VH region having at least 90% identity to
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the amino acid sequence of SEQ ID NO: 34 and a heavy chain constant
region having the amino acid sequence of SEQ ID NO: 128, as well as a
light chain comprising a VL region having at least 90% identity to the amino
acid sequence of SEQ ID NO: 48 and a light chain constant region. Id.
Therefore, Appellant asserts, the “heavy/light chains or six (6) CDRs” are
defined in the claims by the recited VH and VL regions, which have 90%
identity to SEQ ID NO: 34 and SEQ ID NO: 48, respectively. Id. (citing
Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 964 (Fed. Cir. 2002)).
Appellant contends that the Specification correlates the claimed
structure to the required claimed function of an antibody or antibody
fragment that specifically binds to an hOX4L epitope. App. Br. 10. By way
of example, Appellant points to representative antibody, 2D10, an anti-
OX40L antibody, as shown by Figure 1 of the Specification, which
demonstrates the anti-OX40L activity of 2D10 in an HTRF Ligand/Receptor
Neutralization assay. Id. Appellant argues that the Specification also
provides a detailed description of how to test the claimed antibodies,
including representative antibody 2D10, on recombinant OX40L-induced
IL-2 release from primary isolated T cells. Id. (citing Spec. ¶¶ 628– 0632,
Example 3). According to Appellant, a person of ordinary skill in the art
would have recognized that the correlation between hOX4L binding and
decreased secretion of IL-2 by administering the claimed antibodies. Id.
Appellant argues further that the representative species of anti-OX40L
antibody disclosed in the Specification (i.e., 2D10) satisfies the claim
limitations of an antibody or fragment thereof comprising a VH region
having at least 90% identity to the amino acid sequence of SEQ
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ID NO: 34 and a VL region having at least 90% identity to the amino acid
sequence of SEQ ID NO: 48. App. Br. 10–11. By way of example,
Appellant again points to representative antibody 2D10, which comprises a
VH region identical to SEQ ID NO: 34 and a VL region identical to SEQ ID
NO: 48, thereby supporting claims 54, 55, 58, 60–75, 78–81, 83, and 84. Id.
at 11.
Appellant argues that, taking together the variable domain sequences
and anti-OX40L activity of the representative antibody, 2D10, the
Specification supports claims reciting an anti-OX40L antibody comprising a
VH region having at least 90% identity to the amino acid sequence of SEQ
ID NO: 34 and a VL region having at least 90% identity to the amino acid
sequence of SEQ ID NO: 48. App. Br. 11. Appellant contends that a person
of ordinary skill in the art would have been able to visualize or recognize the
identity of the members of this genus, based on the distinguishing structural
characteristics recited in the claims, coupled with the structure-function
relationships disclosed in the Specification. Id.
Appellant points to our reviewing court’s decision in AbbVie
Deutschland GmbH & Co v. Janssen Biotech, Inc. as explaining that if:
[T]he genus is not large or, even if it is, the specification
discloses species representing the genus throughout its scope, the
requirement may be met. On the other hand, analogizing the
genus to a plot of land, if the disclosed species only abide in a
corner of the genus, one has not described the genus sufficiently
to show that the inventor invented, or had possession of, the
genus.

App. Br. 11 (quoting 759 F.3d 1285, 1299–1300 (Fed. Cir. 2014)).
Appellant contends that the claimed genus requires 90% sequence identity
with defined heavy and light chains of the anti-OX40L antibodies and the
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Specification discloses species representing the genus. Id. at 11–12.
Therefore, argues Appellant, the genus is described sufficiently to show that
Applicant had possession of the claimed anti-OX40L antibodies. Id. at 12.
Appellant argues that the Examiner’s reliance upon Amgen Inc. v.
Sanofi, 872 F.3d 1367 (2017) (Fed. Cir. 2017) and the USPTO’s Memo on
the Clarification of Written Description Guidance for Claims Drawn to
Antibodies and Status of 2008 Training Materials (February 22, 2018) (the
“USPTO Memo”) is misplaced. App. Br. 12 (see Final Act. 4). According
to Appellant, both Amgen and the USPTO Memo reject the “newly
characterized antigen” test and find that such a disclosure, by itself, does not
constitute adequate written description. Id. However, argues Appellant, the
claims on appeal do not rely solely upon the ability of the anti-OX40L
antibody or antibody of the invention to specifically bind to an hOX40L
epitope. Id. Rather, Appellant contends, the claims provide structure-
identifying information including the structure of at least the heavy and light
chain variable regions of the anti-OX40L antibody or antibody fragment of
the invention, in addition to reciting a specific binding activity. Id.
Therefore, and contrary to the Examiner’s reasoning, Appellant
argues, neither Amgen nor the USPTO memo require the claims to recite a
specific amino acid sequence for the entire heavy and light chains of the
anti-OX40L antibody or antibody fragment to establish adequate written
description and possession of the genus. App. Br. 12. Appellant asserts that
the structural features recited in claim 54 adequately describe and
demonstrate possession of the antibody genus of the invention. Id.
Appellant takes issue with the Examiner’s finding that “even minor
changes in the amino acid sequence of the heavy and light variable regions,
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particularly in the CDRs, may dramatically affect antigen-binding function,”
as taught by Rudikoff and the other cited references. App. Br. 12 (quoting
Final Act. 10). However, argues Appellant, there is no requirement that the
claims recite the specific amino acid sequence of the heavy and light chains
or six CDR sequences to satisfy the written description requirement. Id. at
12–13. Rather, Appellant contends, the:
[W]ritten description requirement can be met by “show[ing] that
an invention is complete by disclosure of sufficiently detailed,
relevant identifying characteristics … i.e., complete or partial
structure, other physical and/or chemical properties, functional
characteristics when coupled with a known or disclosed
correlation between function and structure, or some combination
of such characteristics.”

Id. at 13 (quoting Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 964
(Fed. Cir. 2002) (quoting USPTO, Guidelines for Examination of Patent
Applications Under the 35 U.S.C. 112, ¶ 1 “Written Description”
Requirement, 66 Fed. Reg. 1099 (Jan. 5, 2001))). Appellant contends that
the claims on appeal provide structure-identifying information, including
90% sequence identity to at least the heavy and light chain variable regions
of the recited antibodies or antibody fragments, in addition to reciting a
specific binding activity. Id.
Appellant contends, therefore, that a skilled artisan would have
recognized that some modifications, such as conservative modifications,
could have been made to the claimed VH and VL regions, while still allowing
for antibody binding and decreased secretion of IL-2. App. Br. 13 (citing
Spec. ¶¶ 551, 552). Appellant asserts that a skilled artisan could have used
routine techniques, such as immunoassays or BIAcoreTM, to predict antibody
binding to the hOX40L antigen and thus design antibodies falling within the
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scope of the claims. Id. (citing Spec. ¶ 333). Appellant therefore contends,
based on the Specification’s disclosures and the knowledge within the art, a
skilled artisan would conclude that Appellant was in possession of the
claimed anti-OX40L antibodies at the time of filing. Id.
The Examiner responds that independent claim 54 and its dependent
claims, are functional claims, which require the function of binding to a
hOX40L epitope, and treating a disease or condition (i.e., GVHD). Ans. 8.
The Examiner finds that Appellant has not disclosed a correlation between
the function recited in the claims and corresponding structures that provide
these functions, nor has Appellant disclosed a representative number of
species. Id. The Examiner notes that a single species is not representative
of a genus, particularly when there is substantial variation within the genus,
and where one must describe a sufficient variety of species to reflect the
variation within the genus. Id. (citing, e.g. MPEP 2163 II(A)(3)(a))(ii)).
The Examiner concludes that Appellant has not met the requirements of
written description as set forth in the MPEP and held in Court decisions. Id.
By way of example, Appellant points to the breadth of the instant
claims. Ans. 8. The Examiner finds that claim 54 allows for up to 10%
variation within each of SEQ ID NOS. 34 and 48, and points out that these
sequences are 127 and 107 amino acids long, respectively. Id. The
Examiner reasons that that means that up to 12 amino acids can be
substituted within SEQ ID NO: 34, and up to 10 amino acids can be
substituted within SEQ ID NO: 48. Id. at 8–9. The Examiner finds that the
claims encompass antibodies where at least one complete CDR is substituted
from each of the VH and the VL. Id. at 9. The Examiner therefore finds that,
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given that at each residue any one of 19 other amino acids could appear,
claim 54 encompasses a very broad genus. Id.
The Examiner further finds that this means that for SEQ ID NO: 34,
over two (2) quadrillion possible amino acid sequences (i.e., 19 to the 12th
power) are within the scope of the claim, and for SEQ ID NO: 48, this is
over six (6) trillion sequences (19 to the 10th power). Ans. 9.
The Examiner notes that, to show invention, a patentee must convey
in its disclosure that is had possession of the claimed subject matter as of the
filing date. Ans. 9. The Examiner further notes that demonstrating
possession requires a precise definition of the invention. Id. (citing Amgen,
872 F.3d at 1358). To provide this precise definition for a claim to a genus,
an applicant must disclose “a representative number of species within the
scope of the genus of structural features common to the members of the
genus so that one of skill in the art can visualize or recognize the member of
the genus.” Id. (quoting Amgen, 872 F.3d at 1358). The Examiner
concludes that Appellant has not met this requirement. Id.
The Examiner concludes that, given the claimed broad class of
antibodies, and in the absence of sufficient disclosure of relevant identifying
characteristics for the broadly claimed class of anti-OX40L antibodies
comprising 90–95% sequence identity to certain SEQ ID NOS. of variable
regions recited in the claims, Appellant must establish a reasonable
structure-function correlation either within the specification or by reference
to the knowledge of one skilled in the art with functional claims. Id. (citing,
generally, Abbvie). The Examiner finds that Appellant’s Specification the
describes, at most, a schema for making “anti-OX40L antibodies”
comprising 90–95% sequence identity to certain SEQ ID NOS. of variable
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regions and then identifying those that satisfy claim limitations. Id. But, the
Examiner concludes, a “wish or plan” for obtaining claimed invention is
insufficient. Id. (quoting Centocor Ortho Biotech Inc. v. Abbott Labs., 636
F.3d 1341, 1348 (Fed. Cir. 2011)).
We find that Appellant has the better position. The Examiner’s
findings to the contrary notwithstanding, the claimed antibodies are not
exclusively claimed functionally, but are also claimed structurally, i.e., by
requiring that the light and heavy chains have a structure corresponding to
90–95% of the recited SEQ ID NOS. Furthermore, the number of possible
substitutions is relatively small: the variable regions of the antibodies
comprise approximately 100 amino acid sequences, and so the total number
of potential substitutions is no more than 10–12. See Trans. 4–5.
Additionally, the Specification provides at least two embodiments
antibodies: 2D10 and 10A07, that are fully functional in their antigen-
binding capabilities.3 See Spec. Ex. 3. We find that a comparison of the
SEQ ID NOs of the 2D10 and 10A07 antibody CDRs provides guidance to a
person of ordinary skill in the art as to where in the amino acid sequence
changes could be made without significantly impairing antigen-binding
functionality.
Furthermore, Appellant’s Specification provides additional guidance
for a person of ordinary skill to understand the amino acid loci that can be

3 The 10A07 antibody disclosed in the Specification actually falls outside the
scope of the claims. The 2D10 antibody has 100% homology to the recited
SEQ ID Nos 34 and 48. The 10A07 antibody has approximately 87%
homology, and thus falls outside of the scope of the claims but still retains
full antigen-binding functionality. See Spec. Ex. 3, and compare SEQ ID
NOs 1–32 (10A07) and 33–64 (2D10) pp. 138–143.
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substituted without impairing functionality. Specifically, paragraph [0398]
of the Specification discloses:
In a specific embodiment, the present invention provides for
antibodies that specifically bind to a hOX40L antigen, said
antibodies comprising the amino acid sequence of one or more
of the CDRs in the sequence listing (i.e. Seq ID No:4, Seq ID
No: 10, Seq ID No:36, Seq ID No:42, Seq ID No:68, Seq ID
No:74, Seq ID No:96 or Seq ID No: 102, in particular, Seq ID
No:36 or Seq ID No:42 for HCDRl; Seq ID No:6, Seq ID No:
12, Seq ID No:38, Seq ID No:44, Seq ID No:70, Seq ID No:76,
Seq ID No:98 or Seq ID No:104, in particular Seq ID No:38 or
Seq ID No:44 for HCDR2; Seq ID No:8, Seq ID No: 14, Seq ID
No:40, Seq ID No:46, Seq ID No:72, Seq ID No:78, Seq ID No:
100 or Seq ID No: 106, in particular Seq ID No:40 or Seq ID
No:46 for HCDR3; Seq ID No: 18, Seq ID No:24, Seq ID No:50,
Seq ID No:56, Seq ID No:82, Seq ID No:88, Seq ID No:110 or
Seq ID No:116, in particular Seq ID No:50 or Seq ID No:56 for
LCDRl; Seq ID No:20, Seq ID No:26, Seq ID No:52, Seq ID
No:58, Seq ID No:84, Seq ID No:90, Seq ID No: 112 or Seq ID
No: 118, in particular Seq ID No:52 or Seq ID No:58 for LCDR2;
and Seq ID No:22, Seq ID No:28, Seq ID No:54, Seq ID No:60,
Seq ID No:86, Seq ID No:92, Seq ID No: 114 or Seq ID No: 120,
in particular Seq ID No:54 or Seq ID No:60 for LCDR3) and
human framework regions with one or more amino acid
substitutions at one, two, three or more of the following residues:
(a) rare framework residues that differ between the murine
antibody framework (i.e., donor antibody framework) and the
human antibody framework (i.e., acceptor antibody framework);
(b) Vernier zone residues when differing between donor antibody
framework and acceptor antibody framework; (c) interchain
packing residues at the VH/VL interface that differ between the
donor antibody framework and the acceptor antibody
framework; (d) canonical residues which differ between the
donor antibody framework and the acceptor antibody framework
sequences, particularly the framework regions crucial for the
definition of the canonical class of the murine antibody CDR
loops; (e) residues that are adjacent to a CDR; (g) residues
capable of interacting with the antigen; (h) residues capable of
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interacting with the CDR; and (i) contact residues between the
VH domain and the VL domain. In certain embodiments,
antibodies that specifically bind to a hOX40L antigen
comprising the human framework regions with one or more
amino acid substitutions at one, two, three or more of the above-
identified residues are antagonistic hOX40L antibodies.

Furthermore, paragraph [0399] of the Specification discloses:

The present invention encompasses antibodies that specifically
bind to a hOX40L antigen, said antibodies comprising the amino
acid sequence of the VH domain and/or VL domain in the
sequence listing (i.e. Seq ID No:2, Seq ID No:34, Seq ID No:66
or Seq ID No:94, in particular Seq ID No:34 for VH domains;
Seq ID No:16, Seq ID No:48, Seq ID No:80, or Seq ID No:108,
in particular Seq ID No:48 for VL domains) but having mutations
(e.g., one or more amino acid substitutions) in the framework
regions. In certain embodiments, antibodies that specifically bind
to a hOX40L antigen comprise the amino acid sequence of the
VH domain and/or VL domain or an antigen-binding fragment
thereof of an antibody disclosed in the Examples with one or
more amino acid residue substitutions in the framework regions
of the VH and/or VL domains.

We conclude that, given these disclosures of Appellant’s
Specification, Appellant has sufficiently described the structural properties
of the claimed antibodies such that a person of ordinary skill in the art would
understand that Appellant was in possession of the invention at the time of
filing, and we reverse the Examiner’s rejection of claims 54, 55, 58, 60–75,
78–81, 83, and 84.

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Issue 2: claims 86–104, 107–110, 112, and 113
Appellant argues that the Examiner erred in finding that Appellant
failed to satisfy the written description requirement by “not defining a
heavy/light chains or six (6) CDRs.” App. Br. 14 (quoting Final Act. 9)

Analysis
Appellant repeats the arguments with respect to claims 54, 55, 58, 60–
75, 78–81, 83, and 84, as identified above. Specifically, Appellant argues
that the Specification correlates the claimed structure to the required claimed
function of an antibody or antibody fragment that specifically binds to an
hOX4L epitope, and further discloses multiple representative anti-OX40L
antibodies comprising a VH region having at least 95% identity to the amino
acid sequence of SEQ ID NO: 34 and a VL region having at least 95%
identity to the amino acid sequence of SEQ ID NO: 48. App. Br. 15.
Appellant further points to Ex parte Bandman, No. 2004-2319
(B.P.A.I. 2005), where the Board reversed the examiner’s rejection of claims
under the written description requirement, finding that the genus of
polynucleotide sequences having at least 95% sequence identity to a
particular SEQ ID NO were sufficiently described. App. Br. 15. In
Bandman, the Board compared the circumstances of the case with those
addressed by the Federal Circuit in Enzo Biochem, in which the Federal
Circuit determined that an “[a]dequate written description may be present
for a genus of nucleic acids based on their hybridization properties, ‘if they
hybridize under highly stringent conditions to known sequences because
such conditions dictate that all species within the genus will be structurally
Appeal 2021-000865
Application 15/661,658

19
similar.” Bandman, No. 2004-2319 at 6 (quoting Enzo Biochem, 323 F.3d at
1327).
For the reasons in our analysis of Issue 1 above, we agree with
Appellant that the disclosures of the Specification provide written
descriptive support of the claimed antibodies sufficient to inform a person of
ordinary skill in the art that Appellant was in possession of the claimed
invention at the time of filing. We consequently reverse the Examiner’s
rejection of claims 86–104, 107–110, 112, and 113.

CONCLUSION
The rejection of claims 54, 55, 58, 60–75, 78–81, 83, 84, 86–104,
107–110 and 112, 113 as unpatentable under 35 U.S.C. § 112, first
paragraph, is reversed.

REVERSED

Claim(s)
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
54, 55, 58, 60–
75, 78–81, 83,
84, 86–104,
107–110, 112,
113
112 Written description 54, 55, 58,
60–75,
78–81, 83,
84, 86–
104, 107–
110, 112,
113