Elanco Tiergesundheit AG

Patent Trials and Appeals Board

Mar 10, 2020

15685257 - (D) (P.T.A.B. Mar. 10, 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.
15/685,257 08/24/2017 Sarah Rue X20568A 1980
159715 7590 03/10/2020
Elanco US Inc.
Patent Division
2500 Innovation Way
Greenfield, IN 46140
EXAMINER
SKELDING, ZACHARY S
ART UNIT PAPER NUMBER
1644
NOTIFICATION DATE DELIVERY MODE
03/10/2020 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):
patents@elanco.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte SARAH RUE, BRENDAN ECKELMAN,
QUINN L. DEVERAUX, and MARC NASOFF

Appeal 2019-005727
Application 15/685,257
Technology Center 1600
Before RICHARD M. LEBOVITZ, FRANCISCO C. PRATS, and
JAMIE T. WISZ, Administrative Patent Judges.

WISZ, Administrative Patent Judge.

DECISION ON APPEAL

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Application 15/685,257

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STATEMENT OF THE CASE
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the
Examiner’s decision to reject claims 21–23. We have jurisdiction under
35 U.S.C. § 6(b).
We AFFIRM.
CLAIMED SUBJECT MATTER
The Specification describes reagents and methods for preventing
and/or treating canine disease conditions (e.g., lymphoma) and states that
“epitopes of canine-CD20 have been identified that may be targeted to
deplete canine blood and/or tissues of B cell lymphoma cells.” Spec. 1. The
Specification further states that “[i]mmunogens have been identified, as
described herein, that may be used to induce and/or enhance an immune
response (e.g., the production of antibodies) suitable for use in preventing
and/or treating these diseases.” Id. Claim 21 is illustrative of the claimed
subject matter and is reproduced below:
21. An isolated monoclonal antibody comprising at least one set
of variable region amino acid sequences selected from the
group consisting of:
a light chain variable region (LC-V) comprising the
sequence of
DIVMTQAAPSVPVTPGESVSISCRSX1KX2LLHRX3X4N
TYLYWFLQRPGQSPQLLIYRMSNLASGVPDRFSGSGS
GTAFTLRISRVEAEDVGVYYCMQHLEFPFTFGGGTKL
EIK (SEQ ID NO.:17) and a heavy chain variable region
(HC-V) comprising the sequence of
EVQLQQSGPELVKPGASVKISCKASGYTFTDYYNINW

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 Elanco
Tiergesundheit AG. Appeal Br. 2.
Appeal 2019-005727
Application 15/685,257

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VKQSHGKSLEWIGDINPNNGDTSYNQKFKGKAPL
TVDKSSSTAYMEVRSLTSEDSAVYFCARGGVLRYPY
YYVMDYWGQGTSVTVSS (SEQ ID NO.: 11);
where X1 is any amino acid other than asparagine (N) when
X2 is serine (S) or threonine (T);
where X2 is any amino acid other than S or T when X1 is N;
where X3 is an amino acid selected from the group
consisting of alanine (A), glutamic acid (E), phenylalanine
(F), histidine (H), isoleucine (I), lysine (K), leucine (L),
proline (P), glutamine (Q), arginine (R), threonine (T),
valine (V) and tyrosine (Y), when X4 is glycine (G); and
where X4 is an amino acid selected from the group
consisting of A, E, F, H, I, K, L, P, Q, R, V, Y, and
tryptophan (W), when X3 is N;
an LC-V comprising the sequence of
DIVMTQAAPSVPVTPGESVSISCRSX1KX2LLHRX3X4N
TYLYWFLQRPGQSPQLLIYRMSNLASGVPDRFSGSGS
GTAFTLRISRVEAEDVGVYYCMQHLEFPFTFGGGTKL
EIK (SEQ ID N0.:17) and a HC-V comprising the sequence
of
EVQLQQSGPELVKPGASVKISCKASGYTFTDYYMNW
VKQSHGKSLEWIGDINPNX3X4DTSYNQKFKGKAPL
TVDKSSSTAYMEVRSLTSEDSAVYFCARGGVLRYPY
YYVMDYWGQGTSVTVSS (SEQ ID NO.: 18),
where X1 is any amino acid other than N when X2 is S or T;
where X2 is any amino acid other than S or T when X1 is N;
where X3 is an amino acid selected from the group
consisting of A, E, F, H, I, K, L, P, Q, R, T, V and Y, when
X4 is G; and
where X4 is an amino acid selected from the group
consisting of A, E, F, H, I, K, L, P, Q, R, V, Y, and W, when
X3 is N;
an LC-V comprising the sequence of
DIVMTQAAPSVPVTPGESVSISCRSNKSLLHRNGNTYL
YWFLQRPGQSPQLLIYRMSNLASGVPDRFSGSGSGTA
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FTLRISRVEAEDVGVYYCMQH LEFPFTFGGGTKLEIK
(SEQ ID NO.: 9) and a HC-V comprising the sequence of
EVQLQQSGPELVKPGASVKISCKASGYTFTDYYMNW
VKQSHGKSLE WIGDINPNX3X4DTSYNQKFKGKAPL
TVDKSSSTAYMEVRSLTSEDSAVYFCARGGVLRYPY
YYVMDYWGQGTSVTVSS (SEQ ID NO.: 18);
where X3 is an amino acid selected from the group
consisting of A, E, F, H, I, K, L, P, Q, R, T, V and Y, when
X4 is G; and
where X4 is an amino acid selected from the group
consisting of A, E, F, H, I, K, L, P, Q, R, V, Y, and W, when
X3 is N; and,
an LC-V comprising the sequence of
DIVMTQSQKFMSRSVGDRVSVTCKASQNVGPNVA
WYQQRPGQSPKPLIYSASYRYSGVPDRFTGSGSGTDF
TLTISNVQSEDLAEYFCQQYNNYP YTFGGGTKLEIK
(SEQ ID NO.: 13) and a HC-V comprising the sequence of
EVQLQQSGAELVRPGASVKLSCTASGFNIKDDYNIHW
VKQRPEQGLEWIGWIX5X6EX3X4HTKY
ASKFQGKATITADTSSNTA YLQLSSLTSEDTA
VYYCTSLRHYYGSSYVSPHYYWGQGTTLTVSS (SEQ
ID NO.: 19); where X3 is an amino acid selected from the
group consisting of A, E, F, H, I, K, L, P, Q, R, T, V and Y,
when X4 is G;
where X4 is an amino acid selected from the group
consisting of A, E, F, H, I, K, L, P, Q, R, V, Y, and W, when
X3 is N;
where X5 is any amino acid other than aspartic acid (D); and
where X6 is any amino acid other than P; and
wherein the antibody binds canine CD20 with an affinity
(Kd) of at least 20 nM.
Claims App.
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REJECTIONS
The Examiner rejected claims 21–23 under 35 U.S.C. § 112, first
paragraph, as failing to comply with the written description requirement.
ISSUES AND ANALYSIS
To satisfy the written description requirement under 35 U.S.C. § 112,
first paragraph, the specification must “reasonably convey[] to those skilled
in the art that the inventor had possession” of the claimed invention as of the
filing date. Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351
(Fed. Cir. 2010) (en banc). The written description requirement for a
claimed 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.” Id. at 1350.
A “representative number of species” means that the species which
are adequately described are representative of the entire genus. MPEP
§ 2163. Thus, when there is substantial variation within the genus, one must
describe a sufficient variety of species to reflect the variation within the
genus. Id. (citing AbbVie Deutschland GmbH & Co., KG v. Janssen
Biotech, Inc., 759 F.3d 1285, 1300 (Fed. Cir. 2014) (Claims directed to a
functionally defined genus of antibodies were not supported by a disclosure
that “only describe[d] one type of structurally similar antibodies” that “are
not representative of the full variety or scope of the genus.”)).
The Examiner finds that claims 21–23 “are drawn to a genus of
mutant forms of the anti-C20 1G1 and 1G10 antibodies wherein certain
residues in the CDR1 of the light chain (X1, X2, X3, and X4) and/or the
CDR2 of the heavy chain (X3, X4, X5, and X6) of these antibodies can be
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nearly any residue insofar as the mutated 1G1 or 1G10 antibody binds
canine CD20 with an affinity (Kd) of at least 20 nM.” Ans. 5. The
Examiner further finds that
the genus of potential antibodies encompassed in the claim
breadth is enormous involving many millions of potential
members and yet the instant specification does not disclose
what antibody structure of these many millions of potential
variants is critical to the ability of the variant to bind canine
CD20 with a Kd of at least 20 nM.
Final Act. 3.
According to the Examiner, the Specification describes the cloning of
the 1G1, 1G10, and 1E4 antibodies, as well as variants of the 1E4 antibody.
Ans. 5. However, these 1E4 variants are not claimed; rather, mutant, amino-
acid substituted forms of 1G10 and 1G1 antibodies are claimed. Id. at 8.
The Examiner finds that the 1G1, 1G10, and 1E4 antibodies have “notably
different CDRs and framework regions and thus appear to be derived from
different germline variable domain sequences.” Id. at 5.
The Examiner also finds that
showing that one particular antibody - 1E4 - tolerates four
particular amino acid changes when such changes are present in
four 1E4 variants each having a single change - N33K, G34K,
G34Q or G34A - does not inform the skilled artisan as to the
tolerance/intolerance of the 1E4 antibody or structurally distinct
antibody like 1G10 to changes in other CDR residues or to
changes in multiple CDR residues.
Id. at 4.
The Examiner also finds that the Specification “does not disclose, and
the skilled artisan cannot predict, which particular combinations of X1, X2,
X3, X4, X5 and X6 light and heavy chain amino acids contained within the
claimed genus of 1G1 and 1G10 mutants are sufficient to support binding to
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canine CD20 with a Kd of at least 20 nM.” Ans. 15. In fact, the Examiner
finds that the Specification “does not reduce to practice any antibodies
having any combinations of variant amino acids that bind canine CD20 with
an affinity of (Kd) at least 20 nM.” Id. at 12–13.
The Examiner concludes that, given:
(i) the notably different CDR and framework sequences of
the 1E4, 1G1 and 1G10 antibodies,
(ii) the unpredictability in the art associated with making
mutations to multiple residues within a given CDR, and
(iii) the lack of any actual reduction to practice of mutant
antibodies having an affinity (Kd) of at least 20 nM
encompassed in the breadth of the instant claims,
the skilled artisan would not recognize possession of the claimed
genus of antibodies from the teachings of the instant
specification.
Ans. 11.
Appellant argues that the Specification contains adequate written
description for the variable regions and each of the point mutations claimed.
Appeal Br. 10.2 Specifically, Appellant argues that the Specification
adequately discloses “certain residues which can be substituted with certain
other amino acids without the loss of antibody function.” Id. at 11.
Appellant also cites to Ex parte Grosmaire, Appeal No. 2017-006468
(PTAB Oct. 10, 2018) as evidence of the Board finding that the written
description requirement is satisfied even when antibodies are claimed only
by their six CDR sequences. Id.

2 The Appeal Brief does not include page numbers so we have included our
own page numbers, starting on the first page as page 1, and numbering the
remaining pages consecutively.
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Appellant further asserts that claim 21 “contains extensive peptide
sequence information, over 96% of which is fixed” and “[t]he variability in
the remainder of the sequences is distinctly described.” Id. at 12–13.
Therefore, according to Appellant, “[t]hese sequences are sufficient to
satisfy any structural requirement and to provide context for the functional
element of the claim” such that a “person of skill in the art would understand
the subject matter being claimed and the scope of the claims.” Id. at 13.
Appellant also contends that the Specification identifies the region of
canine CD20 bound by three antibodies in Figure 2A and the method of
determining the structure of an antibody bound to human CD20 is known as
shown in Du.3 Id. at 12. Therefore, according to Appellant, a person of skill
in the art could determine the three-dimensional structure of cell surface
expressed canine CD20 and the particular residues of the 1E4, 1G10, and
1G1 antibodies that form the canine CD20-binding paratope without undue
experimentation. Id.
The Examiner responds that, although the Specification discloses
certain regions of CD20 that are bound by the 1E4, 1G10 and 1G1
antibodies, “this assay only shows that certain amino acid residues of canine
CD20 are required for binding of these antibodies” and “does not
demonstrate that these are all or the only residues bound by the 1E4, 1G10
and 1G1 antibodies, and the skilled artisan cannot know from the teachings
of the instant specification which, if any, additional residues of canine CD20
are bound by the disclosed antibodies.” Final Act. 5.

3 Du et al., Structural Basis for Recognition of CD20 by Therapeutic
Antibody Rituximab, J. Biol. Chem., 15073–15080 (2007) (“Du”).
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The Examiner also finds that “[t]here is no apparent structural
relationship between the antibody of the instant claims and the rituximab
antibody of [Du]” and that the claimed antibodies bind canine CD20 while
rituximab binds human CD20. Ans. 17. Furthermore, the Examiner
contends, the 1E4, 1G10 and 1G1 antibodies do not tolerate the substitution
of human CD20 sequences into their canine epitope as shown in Figures
2A–B. Id. Therefore, according to the Examiner, “[t]he skilled artisan
cannot just apply the crystallization methods of [Du] to the crystallization of
the 1G10 and 1G1 antibodies bound to canine CD20 in the absence of undue
experimentation” because “these are unrelated antibodies binding
structurally distinct antigens.” Id.
We find that the Examiner’s position is supported by a preponderance
of the evidence. The Specification does not disclose 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, 598 F.3d at
1350. As found by the Examiner, the Specification does not disclose any
members of the claimed genus because it does not disclose any 1G10 or 1G1
antibodies having any combination of variant amino acids that bind canine
CD20 with an affinity of (Kd) at least 20 nM.
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)
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(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”). Here,
Appellant provides a functional description of the claimed antibody — i.e.,
that it binds canine CD20 with an affinity (Kd) of at least 20 nM — but we
do not find sufficient disclosure of a correlation between the claimed
function and the structure of the antibodies that perform that function.
Appellant asserts that claim 21 “contains extensive peptide sequence
information, over 96% of which is fixed” and “[t]he variability in the
remainder of the sequences is distinctly described.” Appeal Br. 12–13.
However, we agree with the Examiner that the Specification’s disclosure of
a few 1E4 antibody mutants, each with only a single mutation, is not
sufficient to demonstrate possession of the claimed genus of structurally
dissimilar 1G1 and 1G10 antibody mutants, with multiple mutations, that
bind canine CD20 with an affinity (Kd) of at least 20 nM. We, therefore,
agree with the Examiner that the Specification does not disclose, and the
skilled artisan cannot predict based on the disclosure in the Specification,
which particular combinations of X1 to X6 light and heavy chain amino acids
are sufficient to support the claimed binding to canine CD20.
Appellant’s citation to Ex parte Grosmaire is inapposite because, in
that case, the claims recited the CDR sequences, without any mutations, and
the Specification described the CDR sequences that had to be present in
order to meet the claimed binding limitation. Grosmaire at *5. In contrast,
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the current claims include multiple potential amino acid substitutions in the
light and heavy chain CDRs, and, as discussed above, the Specification does
not include any examples of mutations within the 1G1 and 1G10 antibodies
that result in antibodies that can bind to canine CD20 with an affinity (Kd) of
at least 20 nM.
Appellant also argues that, even if the claimed mutations resulted in
decreased affinity of antibody 1G10 by almost 100-fold, “those variants
would still have an affinity greater than 20 nM and thus the variants would
meet the functional limitation of the claim.” However, Appellant has not
provided any basis for this statement and, “[a]ttorneys’ argument is no
substitute for evidence.” Johnston v. IVAC Corp., 885 F.2d 1574, 1581 (Fed.
Cir. 1989).
We are also not persuaded by Appellant’s argument that the
Specification identifies the region of canine CD20 bound by three antibodies
and the method of determining the structure of an antibody bound to human
CD20 is known, so a person of skill in the art could generate epitope binding
data for the claimed antibodies without undue experimentation. Appeal Br.
12. We agree with the Examiner that the Specification only shows that
certain amino acid residues of canine CD20 are required for binding these
unsubstituted antibodies but does not disclose which particular CDR
residues of the 1G10 and 1G1 antibodies form the canine CD20-binding
paratope. Furthermore, we also agree that information regarding rituximab’s
binding to human CD20 as disclosed in Du is not sufficient to provide one of
ordinary skill in the art with an understanding of how mutants of different
antibodies (1G10 and 1G1) might bind to a different antigen (canine CD20).
Also, the fact that it might be obvious to determine which, if any, species of
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antibody encompassed by the genus of claim 21 meets the claimed binding
limitation does not demonstrate that Appellant possessed those antibodies.
See Ariad, 598 F.3d at 1352 (“[A] description that merely renders the
invention obvious does not satisfy the requirement.”).
For the reasons described herein and those already of record, we
sustain the Examiner’s rejection of independent claim 21 under 35 U.S.C.
§ 112 as lacking sufficient written description. Claims 22–23 are not argued
separately, and, therefore, fall with claim 21. See 37 C.F.R.
§ 41.37(c)(1)(iv).
CONCLUSION
For the reasons described herein and those already of record, we
affirm the Examiner’s rejection of claims 21–23.
DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
21–23 112, first
paragraph
Written
Description
21–23

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