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 .
DETAILED ACTION
Claim Status
Applicant’s Amendment filed November 8, 2023 has been received and entered.
Claims 1-61 have been canceled.
Claims 62-81 have been added.
Claims 62-81 are pending and under examination.
Priority
Applicant's claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. This application is a 371 of PCT/US2021/055320 filed on October 15, 2021 which claims the benefit of U.S. Provisional Application 63/093,024 filed on October 16, 2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on November 8, 2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Interpretation
Claims 62, 65-67, 75, and 77 recite CDR regions for the VH and VL regions of the polypeptide that binds MUC18, wherein the CDR regions have at least 85% identity to the recited SEQ ID NOs. However, SEQ ID NO: 7, SEQ ID NO: 11, and SEQ ID NO: 14 are less than 8 amino acids long, which would make even a one amino acid substitution impossible. Therefore, the amino acid sequences of SEQ ID NO: 7, SEQ ID NO: 11, and SEQ ID NO: 14 are being interpreted as requiring 100% sequence identity.
Claim Rejections - 35 USC § 112(a)
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 62 and 69-81 are rejected under 35 U.S.C. 112(a) 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 at the time the application was filed, had possession of the claimed invention.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See MPEP § 2163.
The instant claims are directed to a polypeptide that specifically binds MUC18 comprising a variable heavy domain (VH) and a variable light chain (VL) with CDR regions having at least 85% identity to the SEQ ID NOs listed in the instant claims, further comprising a VH with an amino acid sequence at least 85% identical to SEQ ID NO: 20 and a VL with an amino acid sequence at least 85% identical to SEQ ID NO: 21.
Specifically, claims 62, 75, and 77 recite the anti-MUC18 comprises a CDR-H1 having at least 85% identity to SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3; a CDR-H2 having at least 85% identity to SEQ ID NO: 4, SEQ ID NO: 5, or SEQ ID NO: 6; and a CDR-H3 having at least 85% identity to SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, or SEQ ID NO: 10; further comprising a CDR-L1 having at least 85% identity to SEQ ID NO: 11, SEQ ID NO: 12, or SEQ ID NO: 13; a CDR-L2 having at least 85% identity to SEQ ID NO: 14, SEQ ID NO: 15, or SEQ ID NO: 16; a CDR-L3 having at least 85% identity to SEQ ID NO: 17, SEQ ID NO: 18, or SEQ ID NO: 19.
The claims encompass a large genus of structurally distinct polypeptides. Variability in the antigen binding site is achieved by V(D)J recombination, with the most diverse regions being the CDR regions. As taught by Janeway et al. (2001), the antibody repertoire in humans is at least 1011, with a large degree of diversity in both heavy and light chains. See also Rabia et al. (2018), which teaches that the maximal chemical diversity of antibody CDRs is unimaginably large and is extremely challenging to define the sequence determinant of antibody specificity (see pg. 4). The state of the art is such that antibody production is extremely complex and requires a deep understanding of protein-engineering techniques, mechanisms of action and resistance, and the interplay between the immune system. The development of candidate antibodies involves a complex process of clinical and preclinical evaluation that include identification of the physical and chemical properties of the antibody (Scott et al., 2012, p. 278-279). Antibodies have a wide range of pharmacokinetics, effector functions, size and immunogenicity, affinities and avidities, all of which effect the function of each antibody in vivo (Scott, p. 278).
The claims recite the anti-MUC18 comprises a CDR-H1 having at least 85% identity to SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3; a CDR-H2 having at least 85% identity to SEQ ID NO: 4, SEQ ID NO: 5, or SEQ ID NO: 6; and a CDR-H3 having at least 85% identity to SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, or SEQ ID NO: 10; further comprising a CDR-L1 having at least 85% identity to SEQ ID NO: 11, SEQ ID NO: 12, or SEQ ID NO: 13; a CDR-L2 having at least 85% identity to SEQ ID NO: 14, SEQ ID NO: 15, or SEQ ID NO: 16; a CDR-L3 having at least 85% identity to SEQ ID NO: 17, SEQ ID NO: 18, or SEQ ID NO: 19. Therefore, only considering a polypeptide comprising CDR amino acid sequences with 100% identity would allow for 36 different combinations of variable heavy chain CDR amino acid sequences and 27 possible combinations of variable light chain CDR amino acid sequences, for a total of 972 possible combinations. The possible combinations are further multiplied when considering a polypeptide comprising CDR amino acid sequences that are 85% identical to the recited SEQ ID NOs, which allows for one amino acid substitution for most CDRs (i.e., CDRs ≥ 8 amino acids long).
The instant specification recites that conservative modifications are introduced and typically no more than five residues within a CDR region are altered. The mutations may be amino acid substitutions, additions, or deletions [0122]. However, the instant claims do not specify what positions within the CDR that the substitutions occur. Furthermore, claim 69 recites the polypeptide comprises VH and VL amino acid sequences having at least 85% identity to SEQ ID NOs: 20 and 21, respectively. Therefore, it can be considered that the inventions defined by 62, 75, and 77 encompass an enormous number of possible variants.
The instant specification only provides the amino acid sequence of one anti-MUC18 antibody, JM1-24-3 mAb. However, which residues of the anti-MUC18 antibody are critical for binding is highly unpredictable, and the instant application has not provided any correlation between what specific structure is needed for binding to MUC18. For example, a polypeptide comprising a VL with a CDR-L1 of SEQ ID NO: 13, a CDR-L2 of SEQ ID NO: 16, and a CDR-L3 of SEQ ID NO: 19 is 100% identical to the VL CDRs of an anti-CD200 antibody previously described in the art (SEQ ID NO: 17 of WO 2019/126536), demonstrating the promiscuous nature of the combination of VL CDR sequences recited in the instant claims.
Therefore, the instant application has not provided a sufficient description showing possession of the necessary functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the genus of polypeptides encompassing various structures, specificities and functions. Further, the Court has interpreted 35 U.S.C. § 112, first paragraph, to require the patent specification to “describe the claimed invention so that one skilled in the art can recognize what is claimed. Enzo Biochem, Inc. v. Gen-Probe, Inc., 63 USPQ2d 1609 and 1618 (Fed. Cir. 2002). In evaluating whether a patentee has fulfilled this requirement, our standard is that the patent’s “disclosure must allow one skilled in the art ‘to visualize or recognize the identity of’ the subject matter purportedly described.” Id. (quoting Regents of Univ. of Cal. v. Eli Lilly & Co., 48 USPQ2d 1398 (Fed Cir. 1997)).
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "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. The invention is, for purposes of the 'written description’ inquiry, whatever is now
claimed." (See Vas-Cath, p. 1117). The specification does not "clearly allow persons of ordinary skill in
the art to recognize that [he or she] invented what is claimed." (See Vas-Cath, p. 1116). Also, it is noted that the Court has held that the disclosure of screening assays and general classes of compounds was not adequate to describe compounds having the desired activity: without disclosure of which peptides, polynucleotides, or small organic molecules have the desired characteristic, the claims failed to meet the description requirement of § 112. See University of Rochester v. G.D. Searle & Co., Inc., 69 USPQ2d 1886,1895 (Fed. Cir. 2004).
Meeting the written description threshold requires showing that the applicant was in “possession” of the claimed invention at the time of filing. Vas-Cath, 935 F.2d at 1563-1564. Support need not describe the claimed subject matter in exactly the same terms as used in the claims. Eiselstein v. Frank, 52 F.3d 1035, 1038 (Fed. Cir. 1995). This support cannot be based on obviousness reasoning —i.e., what the written description and knowledge in the art would lead one to speculate as to modifications the inventor might have envisioned, but failed to disclose. Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572 (Fed. Cir. 1997). Ariad points out, the written description requirement also ensures that when a patent claims a genus by function, the specification recites sufficient materials to accomplish that function - a problem that is particularly acute in biological arts." Ariad, 598 F.3d at 1352-3. Given the broadly claimed class of anti-MUC18 polypeptides, in the absence of sufficient disclosure of relevant identifying characteristics, the patentee must establish “a reasonable structure-function correlation” either within the specification or by reference to the knowledge of one skilled in the art with functional claims. There is insufficient written description of the required kind of structure-identifying information about the corresponding makeup of the claimed polypeptides to demonstrate possession. Also, see Amgen Inc. v. Sanofi, Aventisub LLC, No. 2017-1480 (Fed. Cir. 2017). Thus, one of skill in the art would conclude that the specification fails to provide adequate written description to demonstrate that Applicant was in possession of the claimed genus. See Eli Lilly, 119 F. 3d 1559, 43, USPQ2d 1398.
Claims 70-74, 76, and 78-81 are included in the rejection because they depend from or otherwise require all the limitations of a rejected independent claim.
Allowable Subject Matter
Claims 63-68 are objected to as being dependent upon a rejected independent claim, but would be allowable if rewritten in independent form including all of the limitations of the independent claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter:
Claims 63-68 are drawn to a polypeptide that binds to MUC18 comprising a CDR-H1 of SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3; a CDR-H2 of SEQ ID NO: 4, SEQ ID NO: 5, or SEQ ID NO: 6; and a CDR-H3 of SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, or SEQ ID NO: 10; further comprising a CDR-L1 of SEQ ID NO: 11, SEQ ID NO: 12, or SEQ ID NO: 13; a CDR-L2 of SEQ ID NO: 14, SEQ ID NO: 15, or SEQ ID NO: 16; and a CDR-L3 of SEQ ID NO: 17, SEQ ID NO: 18, or SEQ ID NO: 19.
There is no prior art that teaches or suggests an anti-MUC18 polypeptide comprising any of SEQ ID NOs: 1-19. In addition to the individual CDR sequences, the following VH CDR amino acid sequence combinations were searched and found to be free of prior art:
CDRH1-CDRH3 – SEQ ID NO: 1, SEQ ID NO: 4, SEQ ID NO: 7
CDRH1-CDRH3 – SEQ ID NO: 2, SEQ ID NO: 5, SEQ ID NO: 8
CDRH1-CDRH3 – SEQ ID NO: 3, SEQ ID NO: 6, SEQ ID NO: 9
CDRH1-CDRH3 – SEQ ID NO: 3, SEQ ID NO: 6, SEQ ID NO: 10
The closest prior art, WO 2019/126536, is directed towards an anti-CD200 antibody, however, does not teach or suggest the presently claimed method with specific sequences.
Conclusion
No claim is allowed.
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/MAUREEN VARINA DRISCOLL/ Examiner, Art Unit 1644
/DANIEL E KOLKER/Supervisory Patent Examiner, Art Unit 1644