Ex Parte TalorDownload PDFPatent Trial and Appeal BoardOct 11, 201711625202 (P.T.A.B. Oct. 11, 2017) Copy Citation 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.) Appeal 2016-005456 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 2 Appeal 2016-005456 Application 11/625,202 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). 3 Appeal 2016-005456 Application 11/625,202 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”).) 4 Appeal 2016-005456 Application 11/625,202 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). 5 Appeal 2016-005456 Application 11/625,202 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.”).) 6 Appeal 2016-005456 Application 11/625,202 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 7 Appeal 2016-005456 Application 11/625,202 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. 8 Appeal 2016-005456 Application 11/625,202 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 9 Appeal 2016-005456 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 10 Appeal 2016-005456 Application 11/625,202 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). 11 Appeal 2016-005456 Application 11/625,202 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 12 Appeal 2016-005456 Application 11/625,202 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.”) 13 Appeal 2016-005456 Application 11/625,202 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 Copy with citationCopy as parenthetical citation