Ex Parte Talor

Patent Trial and Appeal Board

Oct 11, 2017

11625202 (P.T.A.B. Oct. 11, 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.
CS-l 10/CONT 8037
EXAMINER
DIBRINO, MARIANNE
ART UNIT PAPER NUMBER
1644
MAIL DATE DELIVERY MODE
11/625,202 01/19/2007
7590
Roger C. Hahn
HAHN & VOIGHT PLLC
Suite 620
1012 14th Street, NW
Washington, DC 20005
Eyal I. Talor
10/11/2017 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 EYAL I. TALOR1
Appeal 2016-005456
Application 11/625,202
Technology Center 1600
Before TIMOTHY G. MAJORS, RACHEL H. TOWNSEND, and
DEVON ZASTROW NEWMAN, Administrative Patent Judges.
MAJORS, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
conjugated peptide, which have been rejected as nonenabled. We have
jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
STATEMENT OF THE CASE
Appellant’s “invention relates to a conjugated peptide for conferring
protection against autoimmune diseases, such as, for example, myocarditis
1 Appellant identifies the Real Party in Interest as Cel-Sci Corporation.
(App. Br. 3.)
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Application 11/625,202
and autoimmune thyroid disease, allergic diseases, asthma, host-versus graft
and graft-versus-host disease.” (Spec. 1.)
Claims 1, 4—7, 9, 15, and 16 are on appeal. Claims 1 and 9 are
illustrative and reproduced below:
1. A conjugated peptide of the formula (I)
Pi-X-P3 (I)
or the reverso form of the formula (II)
P3-X-Pi (II)
where Pi is an antigenic peptide selected from the group
consisting of SEQ ID NO:l, SEQ ID NO:4, SEQ ID NO:5, SEQ
ID NO:6, SEQ ID NO:7, SEQ ID NO: 8, SEQ ID NO:9, and SEQ
ID NO: 10;
P3 is a peptide having a sequence corresponding to the
sequence of a peptide P2 after modification thereof; wherein the
peptide P2 comprises the amino acid sequence including residues
135 to 149 of the P2 domain of the human HLA Class II molecule
and wherein the peptide P3 [sic] comprises the sequence of P2
modified by substitution or deletion of at least one of residues
139 to 143 or by insertion of an amino acid at any one of
positions 139 to 143, and,
x is a direct bond or a divalent linking group.
9. A pharmacological composition comprising a conjugated
peptide as set forth in claim 1 and a pharmaceutically effective
carrier.
(App. Br. 13—14 (Claims App.)).
Appellant previously elected claims of Group I (drawn to a conjugated
peptide comprising an antigenic peptide), and the Appellant elected the
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species SEQ ID NO: 1 (My-1) for Pi, SEQ ID NO:2 for P3, and a divalent
linking group for “x.” (See Apr. 14, 2008 Resp. to Restriction Req. 2.)
The claims stand rejected under 35 U.S.C. § 112, first paragraph (pre-
AIA), for failing to comply with the enablement requirement.
DISCUSSION
The issue with respect to this rejection is: has the Examiner
established by a preponderance of the evidence that the Specification does
not enable the claimed invention?
When rejecting a claim under the enablement requirement
of section 112, the PTO bears an initial burden of setting forth a
reasonable explanation as to why it believes that the scope of
protection provided by that claim is not adequately enabled by
the description of the invention provided in the specification of
the application. ... If the PTO meets this burden, the burden
then shifts to the applicant to provide suitable proofs indicating
that the specification is indeed enabling.
In re Wright, 999 F.2d 1557, 1561—62 (Fed. Cir. 1993). “[T]o be enabling,
the specification of a patent must teach those skilled in the art how to make
and use the full scope of the claimed invention without ‘undue
experimentation.’” Id. at 1561 (citation omitted).
Factors to be considered in determining whether a disclosure
would require undue experimentation ... include (1) the quantity
of experimentation necessary, (2) the amount of direction or
guidance presented, (3) the presence or absence of working
examples, (4) the nature of the invention, (5) the state of the prior
art, (6) the relative skill of those in the art, (7) the predictability
or unpredictability of the art, and (8) the breadth of the claims.
In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988).
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Appellant does not argue the claims separately. We select claims 1
and 9 (reproduced above) as representative of the claims on appeal. 37
C.F.R. §41.37(c)(l)(iv).
The Examiner rejected claims 1 and 9, finding that the Specification
does not adequately enable the ordinarily skilled person to use the invention.
The Examiner finds:
The specification does not disclose how to use the instant
invention, a conjugated peptide of the formula claimed in claim
1, wherein Pi is an antigenic peptide SEQ ID NO: 1 (the My-1
peptide also recited in dependent claims 4 and 5) and P3 is
NGQEEXAGVVSTGLI (peptide G from the P2 domain of HLA
class II, amino acid residues 135—149) wherein the sequence is
modified by substitution, deletion or insertion at position 140
(base claim 1).
(Final Act. 2.)2 The Examiner finds “[t]he specification has not enabled the
breadth of the claimed invention because the claims encompass a peptide
that may bind to a T cell accessory molecule and may be immunostimulating
or may induce an aberrant immune response.” {Id. at 2.) According to the
Examiner, however, “the disclosed use of the claimed conjugated peptide
and composition thereof is to interact with the TCR while preventing the
modified TCBL portion from attaching to the TCBL receptor on the T cell,
i.e., in this instance CD4 in the case of the class II HLA peptide.” {Id. at 2—3
(emphasis added).) In other words, the disclosed use of the conjugated
peptides and compositions containing the same is “to shift the response from
2 The residue “X” in the amino acid sequence (135—149) of peptide G
represents a site of deletion or site for the insertion of one or more amino
acids. {See, e.g., Spec. 9:11—21 (“Xaa is a direct bond or one or more amino
acids replacing Lys”).)
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T cell activation to inhibition/suppression in an antigen specific manner.”
{Id. at 3 (citing Spec. 3:2—25).) Moreover, the Examiner finds, “[t]he state
of the art is such that it is unpredictable in the absence of appropriate
evidence whether the claimed composition can be used, including in a
pharmacological composition,” as recited in claim 9. {Id. at 3.)
The Examiner finds the claims are broad and the art is unpredictable,
particularly as to whether modified constructs would activate versus inhibit
an immune response. {Id. at 3 4.) In support, the Examiner finds the claims
encompass “deletion of the ‘K’ [lysine] at position 140 in SEQ ID NO: 2 or
insertion of one or more amino acid residues at position 140, or at any of the
other recited positions in addition.” {Id. at 3.) According to the Examiner,
there are literally millions of potential sequence modifications encompassed
by the claims.3 (Ans. 7.)
The Examiner points to several publications as further illustrating
unpredictability in the art. The Examiner finds that Zimmerman4 and Goel5
teach that G peptide-antigenic peptide conjugates (unmodified) are immune-
stimulating, but induce different immune responses — predominantly Thl-
type response for Zimmerman and Th2-type response in Goel. (Final Act.
3 {See Ans. 7 (“The instant claims encompass a peptide conjugate
comprising a P3 peptide that is modified [by] at least one of residues 139—
143 .... This is up to 205 x 2 permutations or 6,400,000 . . . .”).)
4 Zimmerman et al., WO 99/16710 Al, published Apr. 8, 1999.
5 N. Goel et al., A L.E.A.P.S.™ heteroconjugate vaccine containing a Tcell
epitope from HSV-1 glycoprotein D elicits Thl responses and protection, 21
Vaccine 4410-20 (2003).
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3^4; see also Ans. 8.) The Examiner finds that, although Konig6 teaches
that modification of residues between positions 137 and 142 provided
“decreased interaction with human CD4 in some instances,” Konig modified
the MHC class II beta chain of mice, not the human MHC class II beta 2
domain as recited in the claims. (Ans. 6.) The Examiner also cites
Cammarota,7 which compared binding of various residues from human
MHC II beta chains to CD4. (Ans. 6—7.) The Examiner finds Cammarota
teaches that peptides with residues 138—158 bind about a third as well as
peptides with residues 134—148, and that Cammarota concludes residues at
the N-terminus are directly involved in peptide binding to CD4. {Id. at 7.)8
As the Examiner explains, the first four amino acid residues (i.e., 134 to
137) at the N-terminus of the 134—148 peptide “are not the residues that are
altered in the instant claims.” (Id.) After considering the references, the
Examiner finds, “it is unpredictable that the P3 peptide portion of the
claimed peptide conjugate and pharmaceutical composition thereof, can
reduce or eliminate binding of said conjugate to CD4.” {Id. at 8.)
The Examiner finds the Specification lacks sufficient guidance and
includes no examples showing that the claimed peptide constructs provide
the disclosed use. (Final Act. 3—4.) The Examiner finds the Specification
6 R. Konig et al., MHC class II interaction with CD4 mediated by a region
analogous to the MHC class I binding site for CD8, 356 Nature 796—98
(1992).
7 G. Cammarota et al., Identification of a CD4 binding site on the [$2 domain
ofHLA-DR molecules, 356 Nature 799—801 (1992).
8 {See Cammarota 801 (“The fact that peptide 138—152 is considerably less
potent than peptide 134—148 in binding CD4 argues for direct involvement
of the residues on the N-terminus of the 134—148 peptide in binding
CD4.”).)
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describes some constructs (e.g., single amino acid deletions and substitutions
for peptide G at residues 138—141), but that these constructs are disclosed in
“a prophetic manner” only. (Id.) According to the Examiner, “[t]he
specification does not provide working examples of these or any other
peptides, nor does it provide working examples that show that they do not
bind to the same T cell accessory molecule as the unmodified peptide or
inhibit activation of said T cells.” (Id.)
The Examiner finds “[tjhere is no evidence of record either in the
specification or in Applicant’s prior submitted evidentiary references to
address what mutations are sufficient to abrogate binding to CD4
sufficiently to produce the disclosed function and pharmacological effect.”
(Id. at 5.) Without sufficient evidence, the Examiner finds undue
experimentation would be required to use the invention for its disclosed
purpose — inhibition/suppression of the immune response in an antigen
specific manner. (Id. at 4—5; see also Ans. 3—5 and 8.) So, the Examiner
concludes, the claims are nonenabled. (Final Act. 2—5; Ans. 2—8.)
Unless otherwise stated, we agree with and adopt the Examiner’s
findings, explanation, and conclusion that claims 1 and 9 fail to satisfy the
enablement requirement.
Below we address the Appellant’s arguments.
As an initial matter, we note that Appellant does not persuasively
challenge the Examiner’s findings that the pending claims are broad and in
an unpredictable art. To the contrary, Appellant admits this is an
“unpredictable field” and an “unpredictable art.” (App. Br. 11—12.) Nor
does the Appellant challenge the Examiner’s finding that there are no
working examples in the Specification. Indeed, Appellant fails to identify
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any working example or data in the Specification to show suppression of an
immune response by any modified peptide construct encompassed by the
claims. Appellant nonetheless argues the claims are enabled for reasons
discussed below.
Appellant argues claim 1 is directed to a conjugated peptide, and “wot
a particular method or use of T cell activation, inhibition/suppression, or
stimulation.” (App. Br. 5—6.) Appellant cites the MPEP, which in pertinent
part recites: “[W]hen a compound or composition claim is not limited by a
recited use, any enabled use that would reasonably correlate with the entire
scope of the claim is sufficient to preclude a rejection for nonenablement
based on how to use.” (See MPEP § 2164.01(c); see also App. Br. 6.)9
Appellant then cites various disclosures in the Specification for the
proposition that an ordinarily skilled person “would have understood how to
make the peptides recited in the claims.” (Id. at 7—8.)
Appellant’s argument is unpersuasive. The issue is not whether a
skilled artisan could make the peptide conjugates. We agree the
Specification provides a sufficient disclosure of how this could be done, and
9 Appellant further cites to authority for the propositions that: (i) presence of
an inoperative embodiment does not necessarily render a claim nonenabled,
and; (ii) that complete data showing safety and effectiveness of the invention
is not necessary and better left to regulators like the FDA. (App. Br. 7
(citing Atlas Powder Co. v. E.I. du Pont de Nemours & Co, 750 F.2d 1569,
1577 (Fed. Cir. 1984) and Scott v. Finney, 34 F.3d 1058, 1063 (Fed. Cir.
1994) for propositions (i) and (ii) respectively.) We observe that Scott
related to a priority contest in an interference and what the junior party was
required to show to establish actual reduction to practice; the case did not
relate specifically to a rejection for enablement under § 112, first paragraph.
Scott, 34 F.3d 1061-63.
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we do not understand the Examiner to assert otherwise. (Ans. 3.) The issue
is whether the ordinarily skilled person could use the claimed peptide
conjugates for the apparent purpose disclosed in the Specification —
inhibition or suppression of a T-cell response in an antigen specific manner
to confer protection against autoimmune diseases — without undue
experimentation. (See, e.g., Spec. 3:16—25, 7:5—13, 8:8—15.) Appellant does
not identify any other use of the claimed conjugates, but instead “confirm(s)
the disclosed use.” (Ans. 5.) Also, as the Examiner points out, the
Specification does not disclose any diagnostic use for the conjugated
peptides (Final Act. 4; Ans. 8), and Appellant does not argue to the contrary.
Appellant has not identified any disclosed use, apart from the one cited by
the Examiner, that “reasonably correlate [s] with the entire scope of the
claim.” (See MPEP § 2164.01(c).) But the issue remains whether that
disclosed use is enabled.
Regarding the enablement of an invention’s use, the Federal Circuit’s
decision in Rasmusson is instructive. Rasmusson v. SmithKline Beecham
Corp., 413 F.3d 1318, 1322—23 (Fed. Cir. 2005.) As the court explained:
[Tjhis court has stated that an applicant’s failure to disclose how
to use an invention may support a rejection under either section
112, paragraph 1 for lack of enablement, or section 101 for lack
of utility when there is a complete absence of data supporting the
statements which set forth the desired results of the claimed
invention. ... In the context of determining whether sufficient
utility as a drug, medicament, and the like in human therapy has
been alleged, it is proper for the examiner to ask for
substantiating evidence unless one with ordinary skill in the art
would accept the allegations as obviously correct.
[Wjhere there is no indication that one skilled in [[the]] art would
accept without question statements [[as to the effects of the
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Application 11/625,202
claimed drug products]] and no evidence has been presented to
demonstrate that the claimed products do have those effects, an
applicant has failed to demonstrate sufficient utility and therefore
cannot establish enablement.
Id. at 1323 (internal citations and quotation marks omitted; text within
double brackets in original).)
Applying these principles to the facts here, we agree with the
Examiner that Appellant’s Specification fails to enable the broad scope of
the claims. The Specification lacks material guidance, and no working
examples are provided related to the disclosed use, which Appellant admits
is an unpredictable art. Appellant contends “[a] use of the invention as
disclosed in Claim 1 for preventing induction of the second signal necessary
for T cell activation is clearly described in the specification.” (App. Br. 8.)
We agree with Appellant that the Specification generically discloses this use.
But, as the Examiner points out, not only is there insufficient evidence and
no data in support, the disclosures as written are merely prophetic. (Ans. 8.)
Moreover, the Examiner provided evidence-based reasons that call into
doubt those prophetic statements. For example, Cammarota suggests that
amino acids of the P2 domain, which are included in an unmodified form in
constructs encompassed by claim 1, are directly involved in CD4 binding.
(Ans. 6—7; see Cammarota 801 (note residues NGQE (134—137) at the N-
terminus of the peptide that exhibited 3-fold more potent binding to CD4).)
Appellant did not rebut the Examiner’s findings concerning Cammarota.
Furthermore, we note that the claimed constructs include unmodified
residues at positions 134—137, which the Examiner explained are residues
that Cammarota teaches are directly involved in peptide binding to CD4.
(Ans. 6—7.) If such unmodified residues that direct potent binding are
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included in the claimed constructs, we are unpersuaded the ordinarily skilled
person would accept without reasonably questioning or doubting that
deletions or substitutions at other residue locations according to the claims
(e.g., single substitution at 140) would induce suppression rather than
activation of an immune response. (Id.)
Appellant further argues information of record shows that an
ordinarily skilled person could make and use the invention. (App. Br. 9.)10
Appellant cites “non-patent literature” of Konig and Clayton.11 According
to Appellant, “Konig teaches that changes to the HLA Class II molecule will
cause peptides [to be] unable to interact with the TCBL receptor on the CD4
T-cells.” (Id. at 10 (citing Konig 396 [sic 796] and Fig. 1).) And Appellant
contends Clayton “teaches that mutations to the Class II molecules result in
the inability to bind to CD4 receptors.” (Id.) Konig does provide some
support for Appellant’s position inasmuch as it suggests that specific
modifications (e.g., single alanine substitutions) at or about residues 137—
143 decreased function with CD4. As the unmodified residues appear to be
10 Regarding the Appellant’s descriptions of immunological signaling, along
with the structure of the claimed P1-X-P3 (or reverse) constructs and the
intended interaction or lack thereof of the various components (e.g., Pi and
P3 with the TCR and TCBL respectively) (see, e.g., App. Br. 9-10 and 11),
the Examiner appears to agree on the background immunological principles
and the intended use that is recited in the Specification (see Ans. 3—4). The
issue remains, however, whether Appellant’s Specification enables the
peptide constructs to be used as intended when, among other things, the
claims are broad, the art unpredictable, and there is no data or working
examples in the Specification.
11 L.K. Clayton et al., Identification of human CD4 residues affecting class
IIMHC versus HIV-1 gpl20 binding, 339 Nature 548—51 (1989) (Abstract
of record).
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largely conserved across species, we are unpersuaded by the Examiner’s
attempt to distinguish Konig as relating to murine versus human MHC II.
(Ans. 5—6; Reply Br. 10.) Nevertheless, as explained above, the Examiner’s
findings regarding Cammarota are unrebutted and raise doubts about
whether the broad range of modifications encompassed by the claims would
activate or inhibit an immune response such that the claimed peptides could
be used as envisioned. Clayton does not help Appellant’s argument.
Contrary to Appellant’s contention, Clayton “teaches mutations in CD4, not
in MHC class II” like the claims. (Ans. 6.) If anything, Clayton reinforces
the unpredictability in the art. (See, e.g., Clayton Abstract (“the CD4
residues important in MHC class II interaction have not been characterized.
. . . [T]he CD4 binding site for class II MHC is more complex than the
gpl20 binding site, possibly reflecting a broader area of contact with the
former ligand and a requirement for appropriate juxtaposition of the two N-
terminal domains.”).)
Appellant next turns to a declaration from the inventor.12 (App. Br.
11; Reply Br. 8—9.) The declaration provides background on the invention
and T-cell activation and signaling, similar to what is described in the
Specification. (See Talor Deck Tflf 7—10 and 12—15; see, e.g., Spec. 3:2—25
and 8:1—27.) On the key issues of enablement and whether the claimed
conjugated peptides suppress an immune response, however, the declaration
gives conclusory opinions with no data or other sufficiently persuasive
factual evidence. (See, e.g., id. Tflf 5, 11, 16—17.)13 For example, the
12 Declaration of Eyal Talor, Ph.D., dated Aug. 29, 2006 (“Talor Decl.”).
13 In re Am. Acad. ofSci. Tech Ctr., 367 F.3d 1359, 1368 (Fed. Cir. 2004)
(“[T]he Board is entitled to weigh the declarations and conclude that the lack
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inventor asserts “[t]he specifically modified MHC-derived peptides do not
react with the intended ligand on target T cells specific for autoantigens,
transplantation antigens, asthma and allergy that would otherwise cause or
contribute to autoimmune disease.” {Id. 111; see also id. 116
(“modifications to the MHC-derived peptide made only in specifically
selected sites . . . render the claimed modified MHC derived sequences
(described as P3 in the present invention) unable to interact with the intended
T cell ligand”).) The inventor tells but does not show that any of the peptide
conjugates encompassed by the claims inhibit an immune response in an
antigen specific manner. On the present record, and without data or other
persuasive corroborating evidence, the declaration is insufficient to convince
us that the Examiner’s enablement rejection is in error. (Ans. 8.)
In Appellant’s Reply Brief, Appellant again argues the skilled person
would be able to make and use the claimed peptide conjugates, and
Appellant contends the Examiner “vastly overstates the unpredictability of
the claimed peptides in reducing binding to CD4.” (Reply Br. 6.) These
contentions are unpersuasive for the reasons already explained. Appellant
also previously admitted the art was unpredictable. (App. Br. 10-11.)
Insofar as the Appellant is contending the art is generally unpredictable, but
predictable as to the interaction between peptides with a modified P2 domain
and CD4, we are unpersuaded for the reasons discussed above concerning at
least Cammarota.
of factual corroborations warrants discounting the opinions expressed in the
declarations.”); In re Wright, 999 F.2d at 1563 (“[W]e note that each of
these affidavits fails in its purpose because each merely contains
unsupported conclusory statements as to the ultimate legal question.”)
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Appellant’s mention of “CASP” and “tools” that could have been used
to predict peptide structures and interactions comes too late. (Reply Br. 5,
7.) Appellant did not cite any such tools in the Appeal Brief, and the
Examiner thus had no opportunity to respond. We thus decline to consider
whether, through the use of such “tools,” the skilled person could have used
the full scope of the claims without undue experimentation. 37 C.F.R.
§ 41.41(b)(1) & (2); See Ex parte Borden, 93 USPQ2d 1473, 1477 (BPAI
2010) (informative) (“Properly interpreted, the Rules do not require the
Board to take up a belated argument that has not been addressed by the
Examiner, absent a showing of good cause”).
For the above reasons, the preponderance of the evidence supports the
Examiner’s conclusion that claims 1 and 9 are nonenabled. Claims 4—7, 15,
and 16 were not argued separately and fall with claims 1 and 9.
SUMMARY
We affirm the rejection of the claims for lack of enablement.
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
14