Xencor, Inc.

Patent Trials and Appeals Board

Apr 1, 2020

14216705 - (D) (P.T.A.B. Apr. 1, 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.
14/216,705 03/17/2014 GREGORY MOORE 067461-5167-US01 3723
67374 7590 04/01/2020
MORGAN, LEWIS & BOCKIUS LLP (SP)
ONE MARKET, SPEAR STREET TOWER, SUITE 2800
SAN FRANCISCO, CA 94105
EXAMINER
AEDER, SEAN E
ART UNIT PAPER NUMBER
1642
NOTIFICATION DATE DELIVERY MODE
04/01/2020 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):
DONALD.MIXON@MORGANLEWIS.COM
SFIPDOCKETING@MORGANLEWIS.COM
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte GREGORY MOORE, MATTHEW BERNETT,
RUMANA RASHID, and JOHN R. DESJARLAIS

Appeal 2019-002635
Application 14/216,705
Technology Center 1600
Before FRANCISCO C. PRATS, TAWEN CHANG, and DAVID COTTA,
Administrative Patent Judges.
CHANG, Administrative Patent Judge.
DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the
Examiner’s decision to reject claims 58, 76–79, and 81–98. We have
jurisdiction under 35 U.S.C. § 6(b).
We REVERSE.

1 We use the word “Appellant” to refer to “applicant” as defined in
37 C.F.R. § 1.42. Appellant identifies the real party in interest as Xencor,
Incorporated. Appeal Br. 4.
Appeal 2019-002635
Application 14/216,705

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BACKGROUND
The Specification states that one method of enhancing clinical
efficacy of antibodies is to engineer bispecifics, i.e., “single immunoglobulin
molecule[s] [that] co-engage[] two different antigens.” Spec. ¶ 2.
The Specification teaches that “bispecifics generated from antibody
fragments suffer biophysical and pharmacokinetic hurdles” because
“antibody fragments typically lack the constant region of the antibody with
its associated functional properties, including larger size, high stability, and
binding to various Fc receptors and ligands that maintain a long half-life in
serum . . . or serve as binding sites for purification.” The Specification
further teaches that “a drawback of [bispecifics] built with full length
antibody -like formats is that they engage co-target antigens multivalently in
the absence of the primary target antigen, leading to nonspecific activation
and potentially toxicity.” Spec. ¶¶ 3, 6.
According to the Specification, “[t]he present invention solves this
problem by introducing a novel set of bispecific formats that enable the
multivalent co-engagement of distinct target antigens.” Spec. ¶ 6. For
example, the Specification teaches that a “heterodimeric scaffold that finds
particular use in the present invention” is one in which “one heavy chain of
the antibody contains [a] single chain Fv (“scFv” . . . ) and the other heavy
chain is a ‘regular’ FAb format, comprising a variable heavy chain and a
light chain.” Spec. ¶ 99. The Specification teaches that “[t]his structure is
sometimes referred to . . . as ‘triple F’ format (scFv-FAb-Fc) or the ‘bottle-
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opener’ format.”2 Id. The “triple F”/“bottle-opener” format is depicted in
Figure 1B, which is reproduced below:

Figure 1B “depicts the ‘triple F’ format (sometimes also referred to as the
‘bottle-opener’ configuration).” Id. ¶ 21.
Further according to the Specification, the present invention “provides
novel heterodimerization variants that allow for better formation and
purification of heterodimeric proteins, including antibodies.” Spec. ¶ 6.

CLAIMED SUBJECT MATTER
The claims are directed to a heterodimeric protein, nucleic acids
encoding portions thereof, and methods of making such proteins. Claim 81
is illustrative:
81. A composition comprising a heterodimeric antibody
comprising:
a) a first monomer comprising:
i) a first variant Fc domain; and
ii) an [sic] single chain variable fragment (scFv),
wherein said scFv region comprises a first variable heavy chain,
a variable light chain and a scFv linker, wherein said scFv

2 We understand Fv to refer to the antibody “variable” region, Spec. ¶ 2,
FAb to refer to the “antigen binding” fragment, and Fc to refer to the
“fragment crystallizable” region.
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linker covalently attaches said first variable heavy chain and
said variable light chain;
b) a second monomer comprising a VH-CH1-hinge-CH2-
CH3 monomer, wherein VH is a second variable heavy chain
and CH2-CH3 is a second variant Fe domain; and
c) a light chain,
wherein said first variant Fc domain and second variant
Fc domain comprise a S364K/E357Q : L368D/K370S amino
acid substitution set, wherein numbering is according to the EU
index as in Kabat.
Appeal Br. Claims App. A.

REJECTION(S)
A. Claims 58, 76–79, and 81–98 are rejected on the ground of
obviousness-type nonstatutory double patenting as being unpatentable
over claims 59–61,3 74, 77, 79, and 82–87 of copending Application
No. 14/952,786, now claims 1–11 of U.S. Patent No. 10,526,417 B2.
Ans. 3.
B. Claims 58, 76–79, and 81–98 are provisionally rejected on the ground
of obviousness-type nonstatutory double patenting as being
unpatentable over claims 22, 83, 84, 86, 87, 89–91, 96, 97, and 99–
103 of copending Application No. 14/155,334. Ans. 5.

OPINION
A. Issue
The Examiner has rejected the claims on appeal on the ground of
obviousness-type nonstatutory double patenting over claims 59–61, 74, 77,

3 Claim 60 of the ’786 application was cancelled. See June 26, 2019
Amendment and Response to Office Action 2 (Listing of Claims).
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79, and 82–87 of the ’786 application (now claims 1–11 of the ’417 patent),
and, provisionally, on the ground of obviousness-type nonstatutory double
patenting over claims 22, 83, 84, 86, 87, 89–91, 96, 97, and 99–103 of the
’334 application. The same issues are dispositive to both rejections; we
therefore discuss them together.
1. Basis for the rejections
The Examiner finds that the claims on appeal are directed to
heterodimeric antibodies with a “bottle opener”/“triple F” structure
comprising specific mutations in the Fc region. Ans. 3.
The Examiner finds that the claims of the ’417 patent and ’334
application are also directed to heterodimeric antibodies with a “bottle
opener”/“triple F” structure. Ans. 3, 5. The Examiner finds that, while
“[c]laims of the [’417 patent and ’334 application] do not recite particular
mutations in the Fc region recited by the instant claims . . . , the
specification[s] of the [’417 patent and ’334 application] disclose[] . . .
heterodimeric antibodies of the [’417 patent and the ’334 application that]
include . . . the Fc mutations recited by the instant claims.” Id. at 3–4, 5.
The Examiner concludes that, “[e]ven though the instant claims recite
specificities not explicitly recited by the claims of the [’417 patent and ’334
application] (such as a S364K/E357Q : L368D/K370S amino acid
substitution set), species of the instant claims encompassed by the claims of
the [’417 patent and ’334 application] are disclosed as claimed embodiments
in the specification of the [’417 patent and ’334 application],” and,
accordingly, “the instant claims are not patentably distinct from the claims
of the [’417 patent and ’334 application].” Id. at 4, 6.
2. Appellant’s contentions
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Appellant contends that “whether the alleged claims of a reference
patent ‘encompass’ the present claims is not the standard for determining
obviousness-type double patenting” and that the Examiner impermissibly
relied on the disclosures of the ’417 patent and ’334 application as prior art.
Appeal Br. 28–29, 45.
The issue with respect to these rejections is whether the Examiner’s
reliance on the disclosures of the ’417 patent and/or ’334 application in
making the rejections is a permissible use of the disclosures to learn the
meaning of terms and interpret the coverage of the reference claims or an
impermissible use of the disclosures as prior art.
B. Analysis
The predecessor of our reviewing court has explained that, in
considering whether a claim in an application is unpatentable on the basis of
obviousness-type double patenting, “the [reference] patent disclosure may
not be used as prior art.” In re Vogel, 422 F.2d 438, 441 (CCPA 1970). The
Court further explained that
[t]his does not mean that the disclosure may not be used at all.
. . . [I]n certain instances it may be used as a dictionary to learn
the meaning of terms in a claim. It may also be used as
required to answer the . . . question [of whether any claim in the
application defines merely an obvious variation of the invention
disclosed and claimed in the patent.] The disclosure . . . sets
forth at least one tangible embodiment within the claim, and it
is less difficult and more meaningful to judge whether that
thing has been modified in an obvious manner. It must be
noted that this use of the disclosure is not in contravention of
the cases forbidding its use as prior art, nor is it applying the
patent as a reference under 35 U.S.C. § 103, since only the
disclosure of the invention claimed in the patent may be
examined.
Id. at 441–442.
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In this case, the claims on appeal all require a heterodimeric
protein/antibody or heterodimeric Fc domain comprising, respectively, a
first and second Fc domain or a first and second Fc monomer, wherein the
Fc domains or monomers comprise specific amino acid substitutions.
Appeal Br. Claims App. A.
The Examiner has not pointed to any claim of the ’417 patent or the
’334 application that comprise the recited amino acid substitutions in the Fc
domains, but relies instead on the specifications of the reference applications
to suggest these missing elements.
As discussed in greater detail below in the context of each cited
reference application and patent, we find that each of the rejections
improperly relies on the specification of the reference patent or
application as prior art in concluding that the claims on appeal are an
obvious variant of the reference claims,4 rather than merely using the
reference specifications to construe the reference claims and determine their
coverage. Accordingly, we agree with Appellant that the Examiner has not
adequately explained how the claims on appeal define an obvious variant of
the cited claims of the ’417 patent and the ’334 application.
1. The ’417 patent
The claims of the ’417 patent are directed to a heterodimeric anti-CD3
and anti-CD38 antibody comprising: (1) a first monomer comprising (a) a
first Fc domain covalently attached via its N-terminus and a domain linker to
(b) an anti-CD3 scFv comprising an scFv variable light domain, linker, and

4 The Examiner has not suggested that the cited reference applications and
patents otherwise qualify as prior art.
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variable heavy domain and comprising recited amino acid sequences; (2) a
second monomer comprising (a) a heavy chain comprising a CD38-binding
variable domain comprising recited amino acid sequences and (b) a constant
domain comprising a second Fc domain; and (3) a light chain comprising (a)
a CD38-binding variable domain comprising recited amino acid sequences
and (b) a constant domain.5 ’417 patent, claim 1; see also Appeal Br. 55
(Claims App. B).
The Examiner does not explain, except by relying on the ’417 patent
specification, why an antibody comprising Fc domains comprising specific
amino acid substitutions is not patentably distinct from an antibody
comprising generic Fc domains. In particular, the Examiner asserts that,
although the reference claims “do not recite particular mutations in the Fc
region recited by the instant claims,” the specification of the reference
application (now patent) “discloses . . . mutations recited by the instant
claims.” Ans. 3–4. The Examiner asserts, therefore, that “as defined by the
specification of the reference application [(now patent)], claims of the
reference application directed to heterodimeric[]antibodies comprising an Fc
region include ‘bottle opener’/‘triple F’ structure heterodimeric antibodies
with the Fc mutations recited by the instant claims.” Id. at 4. Citing In re

5 Claims 1–4 of the ’417 patent are directed to the antibody; claim 5 is
directed to a nucleic acid composition encoding the antibody; claim 6 is
directed to a related expression vector composition; claims 7 and 8 are
directed to host cells comprising the nucleic acid and the expression vector
compositions; claims 9 and 10 are directed to methods of making the
antibody; and claim 11 is directed to method of treating cancer by
administering the antibody. ’417 patent, claims 1–11; see also Appeal Br.
55–58 (Claims App. B).
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Basell Poliolefine Italia S.P.A., 547 F.3d 1371 (Fed. Cir. 2008), the
Examiner asserts that the rejection’s reliance on the specification of the ’417
patent is proper because the specification “may be used to learn the meaning
of terms and interpreting the coverage of a claim.” Id. (internal quotation
marks omitted).
We are not persuaded. We do not read Basell Poliolefine as
suggesting that a claim to a species is not patentably distinct from a
reference claim to a genus simply because the reference specification
discloses the species. Rather, the Basell Poliolefine court found that the
claims on appeal and reference claims all, in essence, “consist of various
permutations of polymerization of olefins with various numbers of carbon
atoms using catalysts of titanium halides and aluminum alkyls,” even if
“some expressions are generic to others.” Basell Poliofine, 547 F.3d at
1378. Indeed, the court acknowledged that “a generic expression does not
render obvious all of the species that it encompasses,” but emphasized that
the claims at issue in Basell Poliofine “are both generic and specific to each
other in interchangeable ways, involving the same groups of species.” Id.
In contrast, the claims on appeal here recite at most a species (an antibody
comprising Fc domains comprising specific amino acid substitutions) within
the broad genus recited in the reference claims (an antibody comprising Fc
domains).
Finally, we acknowledge that the Basell Poliofine court cites to the
fact that the reference patent specification refers to specific olefins, as an
indication that “those olefins were intended to fall within the meaning of the
[reference] claims” and as support for the conclusion that the claims on
appeal are invalid for obviousness-type double patenting. Basell Poliofine,
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547 F.3d at 1378. We note, however, that ethylene, propylene, butane, etc.
were known in the art, whereas in this case the Examiner has provided no
evidence that a skilled artisan would have had knowledge of the amino acid
substitutions recited in the claims on appeal, absent the disclosure in the
reference specification. On the record before us, therefore, the Examiner’s
reliance on the disclosure in the reference specification to render the claims
on appeal obvious is an impermissible use of the reference specification as
prior art, rather than a permissible use of the specification as an aid to
interpret the coverage of the reference claim.

2. The ’334 Application
The claims of the ’334 application are directed to a heterodimeric
antibody comprising (1) a first heavy chain comprising (a) a Fc domain and
(b) a scFv region that binds CD3 comprising a charged linker and variable
heavy and light chains comprising certain recited sequences; (2) a second
heavy chain having a recited structure; and (3) a light chain. Appeal Br. 50,
62 (Claims App. D). Claims 90, 91, 96, 97, and 101–103 further recite that
the first and second Fc domains of the antibody are variant Fc domains,
including as compared to a parent Fc polypeptide such as a human IgG1,
IgG2, and IgG4 Fc polypeptide. Id. at 63–64. However, none of the claims
recites the specific amino acid substitutions recited in the claims on appeal.
The Examiner does not explain, except by relying on the ’334
application specification, why an antibody comprising Fc domains
comprising specific amino acid substitutions is not patentably distinct from
an antibody comprising generic Fc domains, including generic variant Fc
domains. In particular, the Examiner asserts that, although the reference
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claims “do not recite particular mutations in the Fc region recited by the
instant claims,” “the specification of the reference application discloses . . .
mutations recited by the instant claims.” Ans. 5. The Examiner asserts,
therefore, that “as defined by the specification of the reference application,
claims of the reference application directed to ‘bottle opener’/’triple F’
structure heterodimeric[]antibodies comprising an Fc region include
heterodimeric[]antibodies with the Fc mutations recited by the instant
claims.” Id. at 5–6. Citing Basell Poliolefine, the Examiner asserts that the
rejection’s reliance on the specification of the ’334 application is proper
because the specification “may be used to learn the meaning of terms and
interpreting the coverage of a claim.” Id. at 6 (internal quotation marks
omitted).
For the same reasons discussed above with respect to the double
patenting rejection over claims of the ’417 patent, we find that the
Examiner’s reliance on the disclosures in the ’334 application to be an
impermissible use of the reference disclosures as prior art, rather than a
permissible use of the disclosures as an aid to interpret the coverage of the
reference claim.

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CONCLUSION
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
58, 76–79,
81–98
Obviousness-type
Double Patenting:
’417 patent
58, 76–
79, 81–98
58, 76–79,
81–98
Obviousness-type
Double Patenting:
’334 application
58, 76–
79, 81–98
Overall
Outcome
58, 76–
79, 81–98

REVERSED