Ex Parte Srivastava et al

Patent Trial and Appeal Board

Dec 21, 2018

14287599 (P.T.A.B. Dec. 21, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
14/287,599 05/27/2014
158352 7590 12/26/2018
MH2 Technology Law Group, LLP (with HJF)
Timothy B. Donaldson
1951 KIDWELL DRIVE
SUITE 310
TYSONS CORNER, VA 22182
FIRST NAMED INVENTOR
Shiv Srivastava
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.
HMJ-109-US-Ol 6606
EXAMINER
NATARAJAN, MEERA
ART UNIT PAPER NUMBER
1643
NOTIFICATION DATE DELIVERY MODE
12/26/2018 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):
docketing@mh2law.com
swilliams@mh2law.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte SHIV SRIVASTAVA, SHYH-HAN TAN, and ALBERT DOBI 1
Appeal2017-010877
Application 14/287 ,599
Technology Center 1600
Before ERIC B. GRIMES, JOHN E. SCHNEIDER, and
RACHEL H. TOWNSEND, Administrative Patent Judges.
SCHNEIDER, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal2 under 35 U.S.C. § 134 of the Examiner's rejection
of claims to a monoclonal antibody that have been rejected for failure to
comply with the written description requirement and as obvious. We have
jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
1 Appellants identify the Real Party in Interest as The Henry M. Jackson
Foundation For The Advancement Of Military Medicine, Inc. Br. 3.
2 We have considered and herein refer to the Specification of May 27, 2014
("Spec."); Final Office Action of June 2, 2016 ("Final Act."); Appeal Brief
of Jan. 27, 2017 ("Br."); and Examiner's Answer of May 26, 2017 ("Ans.").
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Application 14/287 ,599
STATEMENT OF THE CASE
"The ETS-related gene (ERG) proto-oncogene is overexpressed in 60-
70% of prostate tumors as a result of recurring gene fusions involving
TMPRSS2 and the ETS family of genes." Spec. ,r 3. "Although, the ERG
proto-oncogene was initially characterized more than twenty years ago ...
currently there is no available antibody for detecting ERG in clinical
specimens." Spec. ,r 7. The Specification discloses "antibodies that bind to
human ERG and can be used, for example, in methods of detecting and
treating cancers associated with ERG fusion events and/or ERG
overexpression, such as prostate cancer." Spec. ,r 9.
Claims 1, 4 and 18-20 are on appeal. 3 Claim 1 is illustrative and
reads as follows:
1. A monoclonal antibody that binds a
conformational epitope formed by amino acids 42-
66 of SEQ ID NO: 1.
The claims stand rejected as follows:
Claims 1, 4 and 18-20 have been rejected under 35 U.S.C. § 112, first
paragraph for failure to comply with the written description requirement.
Claims 1, 4 and 18-20 have been rejected under 35 U.S.C. § I03(a) as
unpatentable over Tomlins. 4
3 Claims 6-17 are pending in the application but have been withdrawn from
consideration. Final Act. 1. Claim 5 was canceled in Supplemental
Amendment filed Jan. 27, 2017.
4 Tomlins et al., US 2007/0212702 Al, published Sept. 13, 2007
( "T omlins ").
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Application 14/287 ,599
THE WRITTEN DESCRIPTION REJECTION
Issue
The issue with respect to this rejection is whether the subject matter of
the claims is described in the Specification in such a way as to reasonably
convey to one skilled in the art that the inventors had possession of the
invention at the time the application was filed.
The Examiner finds that the claims are broadly drawn to any antibody
which binds to a conformational epitope formed by amino acids 42---66 of
SEQ ID NO: 1 and any competing antibodies which bind to SEQ ID NO: 1.
Final Act. 3. The Examiner finds that the Specification only describes one
anti-ERG antibody which binds to an epitope within amino acids 42-66 of
SEQ ID NO: 1. Id. The Examiner finds that the Specification does not
provide adequate written description of a sufficient representative number of
antibodies falling within the scope of the genus and has not described the
antibody structural features common or shared among the antibodies having
the claimed binding function sufficient to describe the entire genus of
antibodies meeting the claims. Final Act. 3--4. Regarding the lack of
structure/function description, the Examiner further finds that "the CDR
sequences of one antibody do not predict the CDR sequence/structure of any
and all other anti-ERG antibodies and competing antibodies yet to be
discovered that function as claimed." Final Act. 5.
Appellants contend that the genus of antibodies can be adequately
described by functional characteristics of preferential binding where there is
disclosed or known correlations between structure and function. Br. 11.
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Application 14/287 ,599
Appellants argue that where, as in the present case, the antigen is fully
characterized, the written description requirement is met. Br 12-18.
Discussion
In support of their position, Appellants rely on the Federal Circuit's
decisions in Enzo Biochem v. Gen-Probe, Inc., 323 F.3d 956, 964 (Fed. Cir.
2002) and Noelle v. Lederman, 355 F. 3d 1341 (Fed. Cir. 2004) which
purportedly set forth what has been called the "newly characterized antigen"
test. Br. 11. Appellants also rely the PTO's Written Description Training
Materials Revision 1 dated March 25, 2008, which provide an example
(Example 13) embodying the test set forth in Enzo and Noelle. Br. 12.
Appellants' reliance on Enzo and Noelle is misplaced. While the
court in Noelle did discuss what is referred to as the "newly characterized
antigen" test, the Federal Circuit has recently rejected such a test. Amgen
Inc. v. Sanofi, 872 F.3d 1367, 1378-79 (Fed. Cir. 2017). At issue in Amgen
was the district court's jury instruction which read
In the case of a claim to antibodies, the correlation
between structure and function may also be satisfied by the
disclosure of a newly characterized antigen by its structure,
formula, chemical name, or physical properties if you find that
the level of skill and knowledge in the art of antibodies at the
time of filing was such that the production of antibodies against
such an antigen was conventional and routine.
Id. at 1376. The Federal Circuit concluded that the instruction was "not
legally sound and [was] not based on any binding precedent." Id.
In reaching its conclusion the Federal Circuit reviewed the cases
which purported to set forth the newly characterized antigen test including
Noelle. Id. at 1376-77. The court concluded that in each of the prior cases
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the reference to the newly characterized antigen test was dicta and not
binding precedent. Id.
The Federal Circuit went on to find that the newly characterized
antigen test ran afoul of the Federal Circuit's precedent inAriad Pharm.,
Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en bane). Id.
at 1378. The court noted that the focus of the inquiry is whether the written
description contains enough information about the claimed products. Id.
The court held that describing the antigens, which was not the claimed
invention, did not satisfy the written description requirement when
Id.
it has been, at the least, hotly disputed that knowledge of the
chemical structure of an antigen gives the required kind of
structure-identifying information about the corresponding
antibodies. See, e.g., J.A. 1241 (549:5-16) (Appellants' expert
Dr. Eck testifying that knowing "that an antibody binds to a
particular amino acid on PCSK9 ... does not tell you anything at
all about the structure of the antibody"); J.A. 1314 (836:9-11)
(Appellees' expert Dr. Petsko being informed of Dr. Eck's
testimony and responding that "[m]y opinion is that [he's]
right"); Centocor, 636 F.3d at 1352 (analogizing the antibody-
antigen relationship as searching for a key "on a ring with a
million keys on it") (internal citations and quotation marks
omitted).
The claims currently on appeal present the same deficiency as the
claims in Amgen and where there is no evidence that knowledge of the
chemical structure of an antigen gives the required kind of structure-
identifying information about the corresponding antibodies Appellants
attempt to describe the invention by describing something that is not the
invention: viz., the antigens to which the antibodies may bind. Appellants
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have not pointed to anything else in the disclosure that describes the
antibodies as required by the test set forth in Ariad.
Appellants' reliance on the PTO' s training materials is also misplaced.
In a memo 5 issued in February of this year, the PTO issued a clarification
regarding the law of written description as it applies to antibodies stating:
In view of the Amgen decision, adequate written description of
a newly characterized antigen alone should not be considered
adequate written description of a claimed antibody to that
newly characterized antigen, even when preparation of such an
antibody is routine and conventional.
The Memo goes on to state that "Examples in the 2008 Written Description
Training Materials Are Outdated." and should NOT be relied upon as
reflecting the current state of the law. Id. at 2. The Memo explains that
Id.
USPTO personnel should continue to follow the guidance in the
MPEP regarding written description (see, e.g., MPEP 2161.01
and 2163 ), except insofar as MPEP 2163 indicates that
disclosure of a fully characterized antigen may provide written
descriptive support of an antibody to that antigen.
Conclusion of Law
We conclude that the Examiner properly found that the claims do not
comply with the written description requirement.
5 USPTO, Clarification of Written Description Guidance For Claims Drawn
to Antibodies and Status of 2008 Training Materials, Feb. 22, 2018
(available at
httQs://www.usnto.gov/sites/defauH/files/documents/amgen 22feb2018.Qd!)
("memo").
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THE OBVIOUSNESS REJECTION
Issue
The issue with respect to this rejection is whether a preponderance of
the evidence supports the Examiner's conclusion that the subject matter of
the claims would have been obvious over Tomlins.
The Examiner finds that Tomlins teaches prostate cancer related
markers including ERG. Non-Final Act. 6 7. The Examiner finds that
Tomlins teaches using the disclosed proteins, including fragments,
derivatives and analogs as immunogens to create antibodies which can be
used in diagnostic, research and therapeutic methods. Id. The Examiner
finds that Tomlins teaches a fragment of ERG2 having the sequence
VPQQDWLSQP, which is a sequence within amino acids 42---66 of SEQ ID
NO: 1. Id. The Examiner finds that "an antibody directed to the
"VPQQDWLSQP" peptide fragment would inherently compete for binding
with a polypeptide consisting of amino acids 42---66 for binding to a
polypeptide having instant SEQ ID NO: 1." Id.
The Examiner concludes
it would have been prima facie obvious to make
monoclonal antibodies to the prior art peptide
(VPQQDWLSQP) and it is clear given the identity of the
instantly claimed SEQ ID NO: 1 and the peptide of Tomlins et
al. (VPQQDWLSQP) that a subset of the antibodies produced
would be expected to bind to the claimed sequence shown in
SEQ ID NO: 1. One would have been motivated to produce
monoclonal antibodies to the amino acid sequence of
"VPQQDWLSQP" given the cited reference specifically
suggests making the antibodies for purposes of diagnostic,
6 Non-Final Office Action of Feb 4, 2016 ("Non-Final Act.").
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research, and therapeutic methods (see paragraph [0103] of
Tomlins et al).
Final Act. 9-10.
Appellants contend that one skilled in the art would not have been
motivated to produce an antibody against native ERG that selectively binds
to VPQQDWLSQP or to generate antibodies using that peptide. Br. 20.
Appellant argues that the disclosure of the peptide sequence is part of a
discussion of trypsin derived peptides and nothing in Tomlins suggest use of
these peptides to produce antibodies. Br. 21.
Appellants contend that, at the time the invention was made, one
skilled in the art would not have had a reasonable expectation that use of the
short peptide disclosed in Tomlins would produce an antibody that would
bind to a conformational epitope formed by amino acids 4266 of SEQ ID
NO: 1. Br. 22-23. In support of this contention, Appellants rely on Tanaka7
which purports to teach that peptides with fewer than 9 amino acids fail to
induce an effective antibody response. Id.
Principles of Law
[T]he examiner bears the initial burden, on review of the
prior art or on any other ground, of presenting a prim a f acie
case ofunpatentability. If that burden is met, the burden of
coming forward with evidence or argument shifts to the
applicant.
After evidence or argument is submitted by the applicant
in response, patentability is determined on the totality of the
7 T. Tanaka et al., Efficient generation of antibodies to oncoproteins by using
synthetic peptide antigens, 82 Proc. Natl. Acad. Sci. USA 3400 (1985)
("Tanaka")
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record, by a preponderance of evidence with due consideration
to persuasiveness of argument.
In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992).
"The consistent criterion for determination of obviousness is whether
the prior art would have suggested to one of ordinary skill in the art that this
process should be carried out and would have a reasonable likelihood of
success, viewed in the light of the prior art. Both the suggestion and the
expectation of success must be founded in the prior art, not in the applicant's
disclosure." In re Dow Chemical Co., 837 F.2d 469,473 (Fed. Cir. 1988)
( citations omitted).
"[T]he question is whether there is something in the prior art as a
whole to suggest the desirability, and thus the obviousness, of making the
combination, not whether there is something in the prior art as a whole to
suggest that the combination is the most desirable combination available."
In re Fulton, 391 F.3d 1195, 1200 (Fed. Cir. 2004) (citation omitted).
Analysis
We adopt the Examiner's findings of fact, reasoning on scope and
content of the prior art, and conclusions set out in the Final Action and
Answer regarding this rejection. We find the Examiner has established that
the subject matter of the claims would have been obvious to one of ordinary
skill in the art at the time the invention was made over Tomlins. Appellants
have not produced evidence showing, or persuasively argued, that the
Examiner's determinations on obviousness are incorrect. Only those
arguments made by Appellants in the Brief have been considered in this
Decision. Arguments not presented in the Brief are waived. See 3 7 C.F .R.
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§ 4I.37(c)(l)(iv) (2015). We have identified claim 1 as representative;
therefore, all claims fall with claim 1. We address Appellants' arguments
below.
Appellants contend that there is no suggestion in Tomlins to produce
an antibody against native ERG that binds to VPQQDWLSQP. Br. 20.
Appellants argue that the peptide is merely one that was produced in
conjunction with mapping the ERG2 protein and nothing in Tomlins
suggests using the peptide to produce an antibody. Br. 21. Appellants point
out that when Tomlins intends to use a peptide to produce an antibody,
Tomlins specifically identifies the peptide as such. Id. citing Tomlins Figs.
22-25 and Example 13.
We have considered Appellants argument and are not persuaded.
Claim 1 is directed to an antibody that binds to a conformational epitope
formed by amino acids 42---66 of SEQ ID NO: 1. Nothing in claim 1 refers to
an antibody against native ERG. Thus Appellants are arguing a limitation
not found in the claims. Furthermore, Tomlins also teaches the fragment
VPQQDWLSQP. (Table 14 and Example 17.)
In addition, T omlins teaches
The gene fusion proteins of the present invention,
including fragments, derivatives and analogs thereof, may be
used as immunogens to produce antibodies having use in the
diagnostic, research, and therapeutic methods described below.
The antibodies may be polyclonal or monoclonal, chimeric,
humanized, single chain or Fab fragments.
Tomlins ,r 103. Clearly Tomlins teaches that a fragment, such as the peptide
VPQQDWLSQP, produced by digesting ERG2, can be used to produce
antibodies.
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Appellants contention that Tomlins does not specifically teach using
the fragment to produce antibodies whereas Tomlins specifically teaches
using other fragments to produce antibodies is also unpersuasive. Given the
general teaching of Tomlins cited above, the fact that Tomlins does not
specifically exemplify using VPQQDWLSQP to produce antibodies does
not teach away from using the peptide to produce antibodies. In a section
103 inquiry, 'the fact that a specific [embodiment] is taught to be preferred
is not controlling, since all disclosures of the prior art, including unpreferred
embodiments, must be considered.'" Merck & Co. Inc. v. Biocraft Labs.,
Inc., 874 F.2d 804, 807 (Fed. Cir. 1989) (quoting In re Lamberti, 545 F.2d
747, 750, 192 USPQ 278,280 (CCPA 1976).)_(holding that the prior art's
disclosure of a multitude of combinations failed to render any particular
formulation less obvious).
Appellants also argue that one skilled in the art would not have e
reasonable expectation of success in using the VPQQDWLSQP peptide
disclosed in Tomlins to produce an antibody that would bind to the epitope
recited in claim 1. Br. 22-23. In support of this contention, Appellants cite
to Tanaka which teaches that short peptides do not produce antibodies
capable of binding to their native oncoproteins. Br. 22.
Again, we find Appellants' argument unpersuasive. Tanaka teaches
that "fewer than 10 amino acid residues failed to induce effective antibody
responses." Tanaka, 3403. Thus, one skilled in the art would read the term
smaller peptide to mean one comprising 9 amino acids or less. The peptide
at issue contains 10 amino acids. In addition, Tanaka tested antibodies
against a relatively few number of oncogenes which did not include the
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oncogene relating to ERG. Tanaka, Table 1. We do not agree with
Appellants that one skilled in the art reading Tanaka would not have had a
reasonable expectation of success in producing an antibody which binds to
the recited region.
Conclusion of Law
We conclude that a preponderance of the evidence supports the
Examiner's conclusion that the subject matter of claims 1 would have been
obvious over Tomlins.
Claims 4 and 18-20 have not been argued separately and therefore fall
with claim 1. 37 C.F.R. § 4I.37(c)(l)(iv).
SUMMARY
We affirm the rejection under 35 U.S.C. § 112, first paragraph.
We affirm the rejection under 35 U.S.C. § 103(a).
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).
AFFIRMED
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