Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The Applicants’ Amendment to the Claims filed on 07/01/2026 is entered.
The Applicants’ Amendment to the Specification filed on 06/18/2026 is entered.
Claims 6, 8-10, 14-15, 20-22, 24-25, 27, and 29-44 are cancelled.
Claims 48-49 are new.
Claims 1-5, 7, 11-13, 16-19, 23, 26, 28, 45-49 are pending and under examination.
Allowable Subject Matter
New claim 49 is allowed.
Rejoinder of Species - necessitated by amendment
In view of allowable subject matter, the species of A thru F are REJOINED and examined. The Species Election requirement mailed on 09/12/2025 is withdrawn.
Response to Amendment
The Response to the Sequence Listing deficiency is sufficient in view of the Applicants’ Amendment to the Specification filed on 06/18/2026.
The Objection to the Specification is withdrawn in view of the Applicants’ Amendment to the Specification filed on 06/18/2026.
The Objections to the Claims is withdrawn in view of the Applicants’ Amendment to the Claims filed on 07/01/2026.
The rejection of claims 1-7, 12-13, 16-19, 23, 26, 28, and 45-47 under 35 U.S.C. 103 as being unpatentable over Lavinder et al (WO2013/078455), in view of US 2010/0143949 to Petricoin et al in further view of Eggena et al (J. Immunol. 1996, Vol 156: pages 4005-4011) is withdrawn in view of the Applicants’ Amendment to the Claims filed on 07/01/2026 in combination with the applicants’ persuasive argument.
Priority
This US 18/009,304 filed on 12/08/2022 which is a 371 of PCT/CA2021/050791 filed on 06/10/2021 claims US Priority benefit of US Provisional 63/038,069 filed on 06/11/2020.
Claim Rejections - 35 USC § 112- new grounds necessitated by amendment
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Newly added claim 48 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 48 recites the limitation "the reagents used for endoprotease digestion" in line 2. There is insufficient antecedent basis for this limitation in the claim because claim 48 depends from claim 1 which does not recite reagents used for endoprotease digestion.
Written Description – update for amendment
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 1-5, 7, 11-13, 16-19, 23, 26, 28, and 45-48 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Presently amended claims require the critically essential element of “an antibody or antigen-binding fragment thereof that specifically binds to the target sequence thereby forming complexes of the antibody and the peptides present in the sample”.
While showing possession for the monoclonal antibody specific for the exact target consisting of SEQ ID NO: 1, such antibody comprising the combination of exact CDR sequences recited in present claim 11 and new claim 49, applicants have not shown possession for the specific antibodies targeting the peptide targets consisting of presently REJOINED species of target sequences: SSASTK (SEQ ID NO:21), TVSSAK (SEQ ID NO:23), TVSAAK (SEQ ID NO:24), STTPPK (SEQ ID NO:25), GPSVFPLAP (SEQ ID NO:2), SVFPLA (SEQ ID NO:3) or AST(KMe2)GPSVFP (SEQ ID NO:4).
Vas-Cath, Inc. v Mahurkar, 19 USPQ2d 1111, makes clear that "to satisfy the written description requirement, an applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention, and that the invention, in that context, is whatever is now claimed". For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California V. Ell Lilly, 43 USPQ2d 1398 (CAFC 1997). The recitation of a functional property alone, which must be shared by the members of the genus, is merely descriptive of what the members of the genus must be capable of doing, not of the substance and structure of the members. The Federal Circuit has cautioned that, for claims reciting a genus of antibodies with particular functional properties (e.g., binding to antigen, high affinity, neutralization activity, competing with a reference antibody for binding), "[claiming antibodies with specific properties, e.g., an antibody that binds to human TNF-a with A2 specificity, can result in a claim that does not meet written description even if the human TNF-a protein is disclosed because antibodies with those properties have not been adequately described." Centocor Ortho Biotech Inc. V. Abbott Labs., 97 USPQ2d 1870, 1875, 1877-78 (Fed. Cir. 2011).
On 22 February 2018, the USPTO provided a Memorandum clarifying the Written Description Guidelines for claims drawn to antibodies, which can be found at www.uspto.gov/sites/default/files/documents/amgen 22feb2018.pdf. That Memorandum indicates that, in compliance with recent legal decisions, the disclosure of a fully characterized antigen no longer is sufficient written description of an antibody to that antigen. Accordingly, the instant claims have been evaluated in view of that guidance.
Both the instant specification and the state of the art have been considered.
A review of the state of the art provides evidence that minor amino acid modifications within the CDR regions on an antibody can abolish the binding activity of said antibody. As was well-known in the antibody art, antibodies as a class share an overall structure generally comprising two heavy chain polypeptides that each comprises a heavy chain variable region (VH) and a heavy chain constant region made up of several domain (CHI, hinge, CH2, CH3, and for some antibodies, a CH4). Each of the heavy chains pairs with a light chain polypeptide that comprises a light chain variable region (VL) and a constant region. But while this overall structure is shared amongst antibodies from a wide variety of sources (human, rat, mouse, rabbit), the structure each antibody uses to bind its particular epitope on an antigen is structurally distinct and is formed by a recombination event that results in high variability at the amino acid sequence level. By the time the invention was made, it is well established in the art that the formation of an intact antigen-binding site in an antibody usually required the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three "complementarity determining regions" ("CDRs") which provide the majority of the contact residues for the binding of the antibody to its target epitope (Almagro & Fransson, Frontiers in Bioscience 2008; 13: 1619-33; see Section 3; of record) "Antibody Structure and the Antigen Binding Site" and Figure I). The state of the prior art is such that it involves testing antibodies both in vitro and in vivo to determine which antibody exhibits the desired binding activity/specificity and therapeutic activities, because even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function as evidenced by Rudikoff (Rudikoff et al., Proc Natl Acad Sci USA 1982, 79(6) 1979-1983, Publication Year: 1982; of record). Rudikoff teach that the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding. Even if the antibody is limited to antibody which can bind to tumor associated antigens, Riemer (Riemer et al. Mol Immunol, 2005 42(9): 1121-1124, Publication Date: 2005-01-08; of record) teaches that antibodies binding the same antigens have been shown to both ameliorate and aggravate disease symptoms (entire document, particular page 1123, column 1), indicating unpredictability of therapeutic outcomes.
MPEP § 2163 states that a "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
The instant specification provides only two examples of the presently claimed anti-target peptide antibody (specifically against target peptide of elected species of SEQ ID NO:1) but do not provide support for the critically essential antibodies directed against the presently REJOINED target peptides encompassed by the claims. Specifically, the present specification provides an antibody or antigen-binding portion thereof that specifically binds to the epitope of the sequence VTVSSASTK (instant target peptide SEQ ID NO:1). For example, antibodies PD030 r1 and PD030 r3 with their complete 6 CDRs, as defined by SEQ ID NOs: 5-10 and 11-16, respectively, specifically binds to the epitope of the sequence VTVSSASTK.
While having written description of the two types of anti-target peptide antibodies of claim 11 and 49 directed against target peptide SEQ ID NO:1, the specification does not provide sufficient descriptive support for the presently REJOINED embodiments embraced by the claims. In view of the state of the art and the instant specification it is considered that applicants were not in possession of an antibody or antigen-binding fragment thereof as defined in the presently amended claims. Specifically, the specification does not provide any such specific antibody against the presently REJOINED species of target sequences: SSASTK (SEQ ID NO:21), TVSSAK (SEQ ID NO:23), TVSAAK (SEQ ID NO:24), STTPPK (SEQ ID NO:25), GPSVFPLAP (SEQ ID NO:2), SVFPLA (SEQ ID NO:3) or AST(KMe2)GPSVFP (SEQ ID NO:4).
The Court of Appeals for the Federal Circuit has recently held that a "written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as be structure, formula [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." University of California v. Eli Lilly and Co., 1997 U.S. App. LEXlS 18221, at *23, quoting Fiers v. Revel, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993) (bracketed material in original).
Thus, the specification does not sufficiently describe the claimed invention in such full, clear, concise, and exact terms that a skilled artisan would recognize that applicants were in possession of the entire scope of the claimed invention.
For inventions in an unpredictable art, adequate written description of a genus, which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly. Description of a representative number of species does not require the description to be of such specificity that it would provide individual support for each species that the genus embraces. If a representative number of adequately described species are not disclosed for a genus, the claim to that genus must be rejected as lacking adequate written description under 35 U.S.C. 112, first paragraph. In the instant case, the unpredictability of the art is evidenced by the cited references, above. Adequate written description requires more than a mere statement that a compound is part of the invention and reference to a potential method of isolating a compound. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
Response to Argument: The Applicants’ response filed on 06/18/2026 and 07/01/2026 has been fully considered but is unpersuasive for reasons provided in the body of the rejection and here. The applicant argue that amendment to remove the language “or a variant thereof having one mutation” renders the rejection moot. However, the argument is unpersuasive because, as discussed above, claim amendment has necessitated rejoinder of species. While having written description of the two types of anti-target peptide antibodies of claim 11 and 49 directed against target peptide SEQ ID NO:1, the specification does not provide sufficient descriptive support for the presently REJOINED embodiments embraced by the claims. In view of the state of the art and the instant specification it is considered that applicants were not in possession of an antibody or antigen-binding fragment thereof as defined in the presently amended claims. Specifically, the specification does not provide any such specific antibody against the presently REJOINED species of target sequences: SSASTK (SEQ ID NO:21), TVSSAK (SEQ ID NO:23), TVSAAK (SEQ ID NO:24), STTPPK (SEQ ID NO:25), GPSVFPLAP (SEQ ID NO:2), SVFPLA (SEQ ID NO:3) or AST(KMe2)GPSVFP (SEQ ID NO:4).
Conclusion
Reasons for Allowability of present claim 49: The closest prior art is Lavinder et al (of record). However, Lavinder et al does not suggest the exact target sequence of instant SEQ ID NO:1 (VTVSSASTK) in the context of the present claim 49. The prior art does not teach or suggest the combination of elements of the present claim 49 invention as a whole.
Related prior art which may be applied in a future office action if appropriate:
Chhabra et al (WO-2018-083087, published May 11, 2018). Chhabra et al discloses the exact epitope of instant SEQ ID NO:1 and suggest making an antibody against such but does not actually disclose possession of such antibody against the epitope target consisting of instant SEQ ID NO:1.
Vasquez et al (WO2010-105256, published 03/15/2010 as shown in ScV report). Vasquez et al discloses instant SEQ 21: SSASTK.
Durr et al (WO2020-123268 as shown in ScV report). Durr et al discloses instant SEQ 21 which is called BHW56778 in ScV report).
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CATHERINE S HIBBERT whose telephone number is (571)270-3053. The examiner can normally be reached M-F 8:00-5:00.
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CATHERINE S. HIBBERT
Primary Examiner
Art Unit 1658
/CATHERINE S HIBBERT/Primary Examiner, Art Unit 1658
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