Ex Parte Salfeld et al

Patent Trial and Appeal Board

Oct 20, 2017

13965152 (P.T.A.B. Oct. 20, 2017)

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.
13/965,152 08/12/2013 Jochen G. Salfeld 3685.001000E/EKS/KRM 6495
135005 7590 10/20/2017
STERNE, KESSLER, GOLDSTEIN & FOX P.L.L.C.
1100 NEW YORK AVENUE, N.W.
WASHINGTON, DC 20005
EXAMINER
ROMEO, DAVID S
ART UNIT PAPER NUMBER
1647
MAIL DATE DELIVERY MODE
10/20/2017 PAPER
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.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte JOCHEN G. SALFELD, DEBORAH J. ALLEN,
ZEHRA KAYMAKCALAN, BORIS LABKOVSKY,
JOHN A. MANKOVICH, BRIAN T. MCGUINNESS,
ANDREW J. ROBERTS, PAUL SAKORAFAS,
HENDRICUS R.J.M. HOOGENBOOM, DAVID SCHOENHAUT,
TRISTAN J. VAUGHAN, MICHAEL WHITE, and ALISON J. WILTON1
____________

Appeal 2016-000792
Application 13/965,152
Technology Center 1600
____________

Before JEFFREY N. FREDMAN, ULRIKE B. JENKS, and
RYAN H. FLAX, Administrative Patent Judges.

FLAX, Administrative Patent Judge.

DECISION ON APPEAL
This is a decision on appeal under 35 U.S.C. § 134(a) involving
claims directed to a method of treating a human subject having a disease in
which TNFα is detrimental. Claims 6, 8, 21, 22, 27, and 28 are on appeal as
rejected under 35 U.S.C. § 112, first paragraph, as not enabled.2 We have
jurisdiction under 35 U.S.C. § 6(b). We reverse.

1 Appellants identify the Real Party in Interest as “AbbVie Biotechnology
Ltd.” App. Br. 3. Appellants also identify as related U.S. Patent
Application No. 13,738,432 and Appeal No. 2015-004473. Id. at 4.
2 A provisional rejection of claims 6, 8, 21, and 27 for non-statutory double
patenting has been withdrawn. Ans. 6.
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Application 13/965,152

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STATEMENT OF THE CASE
The Specification states:
This invention provides human antibodies, preferably
recombinant human antibodies, that specifically bind to human
TNFα. The antibodies of the invention are characterized by
binding to hTNFα with high affinity and slow dissociation
kinetics and by neutralizing hTNFα activity, including hTNFα-
induced cytotoxicity (in vitro and in vivo) and hTNFα-induced
cellular activation. Antibodies of the invention are further
characterized by binding to hTNFα but not hTNF
(lymphotoxin) and by having the ability to bind to other primate
TNFαs and non-primate TNFαs in addition to human TNFα.
The antibodies of the invention can be full-length (e.g., an
IgG1 or IgG4 antibody) or can comprise only an antigen-binding
portion (e.g., a Fab, F(ab')2 or scFv fragment). The most
preferred recombinant antibody of the invention, termed D2E7,
has a light chain CDR3 domain comprising the amino acid
sequence of SEQ ID NO: 3 and a heavy chain CDR3 domain
comprising the amino acid sequence of SEQ ID NO: 4.
Preferably, the D2E7 antibody has a light chain variable region
(LCVR) comprising the amino acid sequence of SEQ ID NO: 1
and a heavy chain variable region (HCVR) comprising the amino
acid sequence of SEQ ID NO: 2.
Spec. 3:32–4:11.
Claim 6 is representative and is reproduced below:
6. A method of treating a human subject having a disease
in which TNFα is detrimental, comprising administering to the
subject having the disease in which TNFα is detrimental a
therapeutically effective amount of an isolated human antibody
capable of binding human TNFα,
wherein the antibody comprises an IgG1 heavy chain
constant region, a human kappa light chain constant region, a
light chain variable region comprising the amino acid sequence
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Application 13/965,152

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of SEQ ID NO: 3, and a heavy chain variable region comprising
the amino acid sequence of SEQ ID NO: 4,
such that the subject having the disease in which TNFα is
detrimental is treated.
App. Br. 42 (Claims App’x).
The following rejection is on appeal:
Claims 6, 8, 22, 27 and 28 stand rejected under 35 U.S.C. § 112, first
paragraph, as not enabled. Ans. 2.

DISCUSSION
“[A] claim must be read in view of the specification of which it is a
part.” Renishaw PLC v. Marposs Societa' per Azioni, 158 F.3d 1243, 1248
(Fed. Cir. 1998). “The specification acts as a dictionary when it expressly
defines terms used in the claims or when it defines terms by implication.”
Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1582 (Fed. Cir. 1996).
Further, one “does not interpret claim terms in a vacuum, devoid of the
context of the claim as a whole.” Kyocera Wireless Corp. v. Int’l Trade
Com’n, 545 F.3d 1340, 1347 (Fed. Cir. 2003) (citing Hockerson–
Halberstadt, Inc. v. Converse Inc., 183 F.3d 1369, 1374 (Fed.Cir.1999)
(“[p]roper claim construction . . . demands interpretation of the entire claim
in context, not a single element in isolation.”)).
“Section 112 requires that the patent specification enable those skilled
in the art to make and use the full scope of the claimed invention without
undue experimentation. . . . [S]ee also In re Goodman, 11 F.3d 1046, 1050
(Fed. Cir. 1993) (‘[T]he specification must teach those of skill in the art how
to make and how to use the invention as broadly as it is claimed.’).”
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Application 13/965,152

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Invitrogen Corp. v. Clontech Labs. Inc., 429 F.3d 1052, 1070–71 (Fed. Cir.
2005) (internal quotes omitted). Wands factors (predictability, amount of
direction, etc.) are factual inquiries underlying the enablement conclusion.
Enzo Biochem Inc. v. Calgene Inc., 188 F.3d 1362, 1371 (Fed. Cir. 1999)
(referring to In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988)).
The Examiner determined that independent claim 6 was not supported
by an enabling disclosure in the Specification. The Examiner stated:
Although the heavy and light chain CDR3s of D2E7 [having
SEQ ID NO. 3 and 4] may be essential for retaining the binding
characteristics of the antibody in the claimed method, an
antibody portion which consists of less than the antibody
paratope as defined by the three hypervariable regions of an
antibody in the appropriate three dimensional shape would not
be expected to exhibit TNFα binding/neutralization activity. . . .
[And, further,] [o]ther than the presence of SEQ ID NOs: 3 and
4 the scope of the variable chains of the antibody used in the
claimed method [potentially] varies in every imaginable way
from the variable chains of D2E7[, the full-length, preferred
antibody.]
See, e.g., Final Action 10, 13. The Examiner’s contention, here, is that,
while arguably the Specification identifies SEQ ID NOs: 3 and 4 of the
LCVR and HCVR domains, respectively, as important in dictating antibody
biding to TNFα, the Specification does not indicate that these portions of the
antibody, alone, assure such binding and the related therapeutic effect. The
Examiner’s main point in determining that the claims are not enabled is:
An antibody portion which consists of less than the antibody
paratope as defined by the three hypervariable regions of an
antibody in the appropriate three dimensional shape would not
be expected to exhibit TNFα binding/neutralization activity.
Ans. 2; see also id. at 5.
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Application 13/965,152

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Appellants argue that the Examiner’s claim interpretation is not
correct, contending that the Examiner has ignored the claim elements other
than the specifically recited CDR3 hypervariable regions, which overlooks
that the claim recites a complete antibody and not just the amino acid
sequences of SEQ ID NOs: 3 and 4. See, e.g., App. Br. 15. Appellants point
to the definition of the term “antibody” (and “human antibody”) in the
Specification and contend it invokes all the parts thereof, including all CDR
domains. See, e.g., id. at 13–16 (citing Spec. 8:20–32). Appellants argue:
Thus, viewing claim 6 with an appropriate and reasonable
interpretation, the issue for enablement is limited to whether only
routine experimentation would be required to modify regions of
the D2E7 paratope other than CDR3 to find a reasonable number
of antibodies having the required function. As the following
Wands factor analyses will show, the answer to this is
emphatically yes.
Id. at 16.
Appellants argue that, having the preferred D2E7 antibody as a
reference, the skilled artisan could routinely identify where changes, other
than in the CDR3 sequences claimed, could be made, or not. Id. at 18–19.
Appellants argue that Example 1 in the Specification identifies D2E7 and its
binding properties, providing “guideposts” for the skilled artisan to create a
working antibody. Id. at 20. Appellants argue that the SEQ ID NOs: 3 and
4 of the CDR3 domains that are the critical and important portions for
antibody biding activity. See, e.g., id. at 22. Appellants argue that the
Specification identifies, if not directly in relation to the areas of the antibody
outside the recited sequences, various ways to generate, analyze, and screen
an antibody. See, e.g., id. at 23–26. Appellants argue the level of skill in the
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Application 13/965,152

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art is high, i.e., “a Senior Scientist with experience in the design and/or
screening of therapeutic antibodies.” Id. at 26 (this is not disputed).
Appellants submit as evidence the Declaration of Dr. Geoff Davis
(dated Jan. 21, 2015) (“Davis Decl.”). Davis states:
one of ordinary skill in the art would have been able to
produce a human antibody capable of binding human TNFα
having: (1) a full complement of six CDRs, including the recited
light and heavy chain CDR3 amino acid sequences; (2) an IgG1
heavy chain constant region; and (3) a human kappa light chain
constant region as set forth in pending claim 6, predictably and
without undue experimentation based on the knowledge in the
art in 1996 and the teachings of the ’152 application.
Davis Decl. ¶ 13. Davis further states that “the identification of human anti-
human TNFα antibodies having the claimed CDR3 sequences with similar
therapeutic properties as D2E7 would have been trivial based on the
teachings of the ’152 application and the knowledge in the art in 1996.” Id.
¶ 15. Davis states that “techniques such as phage display selection and ‘mix
and match’ methods [and routine screening assays] can be used to select
human heavy and light chains with the same desired binding and
dissociation characteristics as . . . D2E7.” Id. ¶ 16 (citing Spec. 26–27).
Davis identifies “a technique known as chain swapping,” as known in the art
as of February 1996, which can transfer the known binding specificity of a
parent antibody to a derived fully human antibody “with a substantially high
probability of success.” Id. ¶¶ 17–18. Davis also identified a technique
called “chain shuffling,” which can be used with a CDR3-specific library, to
create new antibodies while retaining certain CDR3 sequences, potentially,
to achieve improved affinity for an antigen. Id. ¶ 19–21 (citing, inter alia,
Marks et al., By-Passing Immunization: Building High Affinity Human
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Application 13/965,152

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Antibodies by Chain Shuffling, 10 BIO/TECH. 779–83 (1992)). Davis also
states that “identification of therapeutic antibodies having the CDR3
domains recited in claim 6 would have been achievable in 1996 using
routine assays known in the art . . . particularly neutralization and affinity
assays.” Id. ¶ 24 (citing Spec. 10–11, 41–45, 49).
The above-identified arguments of Appellants represent some, but not
all, of their contentions and evidence, but are sufficient to persuade us that
the Examiner’s rejection should be reversed. The Examiner’s rejection is
premised on an incorrect interpretation of claim 6, which, as argued by
Appellants, sees the claimed method as limited to an antigen binding domain
consisting of only the amino acids of SEQ ID NOs: 3 and 4, while
overlooking that the claimed method comprises a complete antibody, with
all its requisite parts, that binds TNFα. Thus, the claims are directed to
using an antibody having binding domains that necessarily include the
amino acids of SEQ ID NOs. 3 and 4, but also having all the other necessary
parts of an antibody. The evidence submitted by Appellants is persuasive
that the Specification, in view of the knowledge in the art, is enabling of
such a method.

SUMMARY
The rejection under 35 U.S.C. § 112, first paragraph, is reversed.

REVERSED