DETAILED ACTION
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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on September 22, 2025 has been entered.
Applicant’s amendments to the claims and reply have overcome the objections to the claims.
Claim Rejections - 35 USC § 112
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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 31, 33-37, 39-46, and 48-50 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. This is a written description rejection.
Instant claims 31, 35, and 37 are drawn to an RNA or DNA nucleic acid encoding at least one Merkel Cell Polyomavirus (MCV) T antigen that comprises a mutation that disrupts at least one oncogenic feature of a native MCV Large or Small T antigen (LTAg) and (STAg), respectively, selected from CR1 binding, DnaJ binding, phosphatase pp2A-binding, Rb binding, ATPase activity, helicase activity, chaperone protein binding, hVam6p binding, Fbxw7 binding, origin binding, and transformation. The nucleic acid molecule comprises at least 85% identity to the entire length of SEQ ID NOs: 1, 3, or 5; variants and fragments thereof comprising at least 85% identity over at least 70% of SEQ ID NOs: 1, 3, or 5; and/or a fragment comprising at least 70% identity to SEQ ID NOs: 1, 3, or 5. Claim 41 states that these nucleic acid sequences are operably linked to SEQ ID NO: 7. Specific residue mutations encoded by the nucleic acid are listed in instant claims 33 and 34. In instant claim 36, the amino acid sequence encoded by the instant nucleic acid is selected from an amino acid sequence comprising at least 90% identity over the entire length of SEQ ID NOs: 2, 4, or 6; a fragment comprising at least 90% identity over at least 70% of SEQ ID NOs: 2, 4, or 6; an amino acid sequence selected from SEQ ID NOs: 2, 4, or 6; or a fragment comprising at least 70% of SEQ ID NOs: 2, 4, or 6. Claim 40 states that these amino acid sequences are operably linked to SEQ ID NO: 7. Claim 39 requires a regulatory sequence operable linked to the MCV antigens; claim 42 states that the nucleic acid is an expression vector; claim 43 states that the nucleic acid is a viral particle; and claim 44 states that the nucleic acid and MCV peptide, respectively, are comprised within an immunogenic composition and claim 45 states that the composition further comprises a pharmaceutically acceptable excipient and an adjuvant. Instant claims 46, 49, and 50 are drawn to inducing an immune response (claim 48) or treating or preventing MCV-associated infection or carcinoma pathology in a subject (claims 46, 49 and 50) upon administration of the instant nucleic acids to a subject.
There is no disclosure of sufficient characteristics of the claimed genus of MCV LTAg and STAg nucleic acids and corresponding amino acid sequences claimed. The skilled artisan would not recognize a nucleic acid and corresponding amino acid encompassed by the instant claims due to the lack of description of the claimed genus. For example, 15% variation of 2451 nucleic acids (length of instant SEQ ID NO: 1, where the percent identity is at least 85% recited in claim 31(ii)(a)) is approximately 368 nucleic acids in instant SEQ ID NO: 1. There is no indication that the genus of nucleic acids possessing up to approximately 368 nucleic acids in variation disrupts at least one oncogenic feature of a native MCV antigen possessing only 90% identity to the amino acid sequence selected from SEQ ID NOs: 2, 4, or 6; or 90% identity over at least 70% of the amino acid sequence selected from SEQ ID NOs: 2, 4, or 6; or an amino acid fragment that comprises at least 70% identity to SEQ ID NOs: 2, 4, or 6, as recited. In another example, a 30% variation of SEQ ID NO: 1 of 2451 nucleic acids (length of instant SEQ ID NO: 1, where the percent identity is at least 70% of SEQ ID NOs: 1, 3, or 5 recited in claim 31(ii)(c)) is approximately 1716 residues. There is no indication that the genus of nucleic acids possessing up to approximately 1716 nucleic acids of SEQ ID NO: 1, 3, or 5 disrupts at least one oncogenic feature of a native MCV antigen possessing only 90% identity to the amino acid sequence selected from SEQ ID NOs: 2, 4, or 6; or 90% identity over at least 70% of the amino acid sequence selected from SEQ ID NOs: 2, 4, or 6; or an amino acid fragment that comprises at least 70% identity to SEQ ID NOs: 2, 4, or 6, as recited. There is also no evidence of written description for the exponential number of species of nucleic acids encompassed by claim 31(ii)(b). Therefore, the claims encompass nucleic and amino acid sequences with no defined structure and the specification does not reasonably convey possession of these undefined nucleotides and corresponding amino acids. Similarly, there is no written description for the genus of amino acid sequences recited in claim 46 comprising 97.5% identity to the amino acid sequence selected from SEQ ID NO: 4; or 85% identity of the amino acid sequence selected from SEQ ID NO: 6; or an immunogenic fragment comprising at least about 95.7% identity over at least 75% of SEQ ID NO: 6, as recited. In the latest updated sequence search of the instantly claimed sequences (completed Sept 30, 2025), there was not a single species of SEQ ID NOs: 4 or 6 that shares less than 100% identity in the instant application.
The skilled artisan would not to recognize that applicants were in possession of the claimed genus of MCV LTAg and STAg nucleic acid and peptide sequences claimed. Instant Figures 4, 12, and 13 depict responses in mice administered numbered LTAg Pools, implying that there are various collections of LTAg antigens within each pool administered, but there is no description provided for what is contained within any of the pools administered. Figure 5 depicts responses in mice administered LTAg and STAg 10-mer peptides and corresponding immunodominant epitopes. However, none of the 10-mer peptides depicted in Figure 5 meet the requirements of the instant amino acid sequences, i.e., comprising at least about 70% or 90%; or 90% identity over at least 70% of the amino acid sequence selected from SEQ ID NOs: 2, 4, or 6, as recited., or 100% sequence identity to the amino acid sequence selected from SEQ ID NOs: 2, 4, or 6 since the peptides only comprise 10 residues.
The applicable standard for the written description requirement can be found in MPEP 2163; University of California v. Eli Lilly, 43 USPQ2d 1398 at 1407; PTO Written Description Guidelines; Enzo Biochem Inc. v. Gen-Probe Inc., 63 USPQ2d 1609; Vas- Cath Inc. v. Mahurkar, 19 USPQ2d 1111; and University of Rochester v. G.D. Searle & Co., 69 USPQ2d 1886 (CAFC 2004). To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. In this case, the only factor present in the specification are MCV LTAg and STAg nucleic acids of SEQ ID NOs: 1, 3, and 5, which are non-naturally-occurring codon-optimized synthetic consensus MCV T antigen sequences (discussed in Example 1 of the instant disclosure) and corresponding amino acid sequences SEQ ID NOs: 2, 4, and 6.
Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus. A definition by function alone is not sufficient because it is only an indication of what a thing does, rather than what it is. Eli Lily, 119 F.3 at 1568, 43 USPQ2d at 1406. Further, a vague functional description (“plants with reducing power”) and an invitation for further research by testing to determine which plant or plant materials possess the requisite characteristics does not satisfy written description requirement. Ariad Pharmaceuticals, Inc. v. Eli Lilly and Co., 598 F.3d 1336, 1341 (Fed. Cir. 2010) (en banc.)
The court clearly states in Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, 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 page 1117.) The specification does not clearly allow persons of ordinary skill in the art to recognize that the inventors invented what is claimed. As discussed above, the skilled artisan cannot envision the distinguishing, identifying characteristics of the encompassed genus of MCV LTAg and STAg nucleic acids and peptides claimed. Given that the specification has only described SEQ ID NOs: 1-6, the full breadth of the claims does not meet the written description provision of 35 U.S.C. 112, first paragraph.
Response to Arguments
In reply to the rejection of record, applicant cites case law discussing that the claimed subject matter is not required to have literal support. Applicant summarizes the instantly presented claim amendments and asserts that the claimed genus of variants is supported by SEQ ID NOs: 1-6 in Example 1 and Figures 1 and 4.
Applicant’s arguments and a review of the claim amendments have been fully considered, but are found unpersuasive. The case law discussed by applicant is in agreement with the instant written description rejection since the rejection does not mention or imply that the claimed genus of variants be literally supported in the instant disclosure. There is no disclosure of sufficient characteristics of the claimed genus of MCV LTAg and STAg nucleic acids and corresponding amino acids claimed. the claims encompass nucleic and amino acid sequences with no defined structure and the specification does not reasonably convey possession of these undefined nucleotides and corresponding amino acids. The skilled artisan would not to recognize that applicants were in possession of the claimed genus of MCV LTAg and STAg nucleic acid and peptide sequences claimed. Instant Figures 4, 12, and 13 depict responses in mice administered numbered LTAg Pools, implying that there are various collections of LTAg antigens within each pool administered, but there is no description provided for what is contained within any of the pools administered. Figure 5 depicts responses in mice administered LTAg and STAg 10-mer peptides and corresponding immunodominant epitopes. However, none of the 10-mer peptides depicted in Figure 5 meet the requirements of the instant amino acid sequences claimed. The only disclosure present in the specification are MCV LTAg and STAg nucleic acids of SEQ ID NOs: 1, 3, and 5, which are non-naturally-occurring codon-optimized synthetic consensus MCV T antigen sequences (discussed in Example 1 of the instant disclosure) and corresponding amino acid sequences SEQ ID NOs: 2, 4, and 6. Therefore, the claims encompass nucleic and amino acid sequences with no defined structure and the specification does not reasonably convey possession of these undefined nucleotides and corresponding amino acids.
In Hologic, Inc. v. Smith & Nephew Inc., No. 2017-1389 (Fed. Cir. Mar. 14, 2018), the Federal Circuit concluded that disclosure of a species provides written descriptive support for a claimed genus where the invention was in a predicable field of art, the species was a well-known member of the genus, and other members of the genus were also well known. In contrast to Hologic, the instant disclosure does not provide adequate support in a predictable field of art. The broad number of species claimed is not a well-known member of the genus of nucleic acids encoding an antigen that disrupts at least one oncogenic feature selected from CR1 binding, DnaJ binding, phosphatase pp2A-binding, Rb binding, ATPase activity, helicase activity, chaperone protein binding, hVam6p binding, Fbxw7 binding, origin binding, and transformation. The skilled artisan would not predict requisite function from the scope of nucleic acids claimed.
Similar to Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200 (Fed. Cir. 1991), the dispute centered on whether the description in the application relied on by Amgen to demonstrate possession of the full scope of DNA claims, particularly those generically claiming any sequence encoding a polypeptide “sufficiently duplicative” of EPO to exhibit its biological activity, sufficiently supported the claims. The Federal Circuit invalidated claims drawn to generic DNA sequences not sufficiently supported by the disclosure, which described only a limited number of EPO analogs. Although the specification asserted that numerous analogs could be created, the court found that Amgen had provided insufficient examples and technical guidance for producing DNA sequences other than the few disclosed. The court emphasized that the claims require a broad genus of DNA sequences, yet the specification only described and enabled a small subset. In the instant case, nucleic acid SEQ ID NOs: 1, 3, and 5, are adequately described.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim 46 is rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Barrett et al. (WO 2016/073595), of record.
Geneseq database accession number BCQ39883 of Barrett et al.(of record) shares (rounded to the nearest whole number) shares 97% identity with at least 75% (encompassing up to 100%) of instant SEQ ID NO: 4, as required. On page 29, line 4 to page 32, line 27, Barrett et al. teach that these peptides are used to treat polyomavirus-associated disease, i.e., MCC, upon administration, as required. Also see page 32, line 28 to page 34, line 25.
Response to Arguments
Applicant argues that treating and preventing an MCV-associated pathology is not taught or suggested by Barrett et al. by administering an amino acid sequence comprising the percent identity claimed.
Applicant’s arguments and a review of the claimed invention have been fully considered, but are found unpersuasive. The sequence alignment of instant SEQ ID NO: 4 with the nucleic acid encoding Geneseq database accession number BCQ39883 of Barrett et al. shares (rounded to the nearest whole number) 97% identity with at least 75% (encompassing up to 100%), as required. Beginning on page 17, line 26 to page 18, line 14, Barrett et al. describe transducing dendritic cells (DCs) with nucleic acids encoding MCV antigens corresponding to SEQ ID NO: SEQ ID NO: 38. On page 29, line 4 to page 34, line 25, Barrett et al. describe administering modified DCs expressing SEQ ID NO: 38 to subjects to treat or inhibit polyomavirus infection and/or “polyomavirus-associated disease (such as PVAN, PML, hemorrhagic cystitis, TS, or MCC)” – quoted from page 29, lines 5-6.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 31, 33-37, 39-46, and 48-50 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 11,524,065, of record. Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1, 6, 7, and 9, of ‘065 anticipate a nucleic acid encoding at least one modified Merkel Cell Polyomavirus (MCV) T antigen that disrupts at least one oncogenic feature of a native MCV T antigen selected from the group consisting of CR1 binding, DnaJ binding, phosphatase pp2A binding, Rb binding, ATPase activity, helicase activity, chaperone protein binding, hVam6p binding, Fbxw7 binding, origin binding, and transformation; wherein the nucleic acid molecule comprises a sequence selected from the group consisting of: SEQ ID NOs: 1, 3, and 5, which are identical to the instant SEQ ID NOs: 1, 3, and 5, operably linked to an IgE leader sequence, SEQ ID NO: 7, as required by instant claims 31, 39, and 41. Claims 2 and 3 of ‘065 anticipate the mutations recited in instant claims 33 and 34. Claim 4 of ‘065 anticipates the MCV T antigens of instant claim 35 and claim 5 of ‘065 anticipates the nucleic acid types recited in instant claim 37. In claim 8, the nucleotide sequence of ‘065 encodes an amino acid sequence comprising at least 98% identity to SEQ ID NO:4; b) a nucleotide sequence encoding an amino acid sequence comprising at least 90% identity to SEQ ID NO:6; c) a nucleotide sequence encoding an amino acid sequence selected from the group consisting of SEQ ID NO:4 and SEQ ID NO:6; d) a nucleotide sequence having at least about 90% identity over an entire length of a nucleotide sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:3 and SEQ ID NO:5; and e) a nucleotide sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:3 and SEQ ID NO:5 in an immunogenic composition, anticipating instant claims 36 and 40. Claims 10-13 of ‘065 anticipate the components and formulations recited in instant claims 42-45, respectively. Claims 14-16 of ‘065 anticipate the instant method of inducing an immune response and treating and preventing MCV-associated pathology in a subject by administering the immunogenic composition encoding at least one modified MCV T antigen, as instantly claimed in 46 and 48-50.
In reply to the rejection of record, applicant argues that the claims of ‘065 are distinct from the instant claims because the claims of ‘065 do not recite the instant limitations. Applicant requests withdrawal of the provisional obvious-type double patenting rejection and at least held in abeyance until allowable subject matter has been indicated.
Applicant’s arguments have been fully considered, but are found unpersuasive because the nucleic acid sequences, SEQ ID NOs: 1-3 of ‘065 encoding SEQ ID NOs: 2, 4, and 6, of ‘065 are indistinguishable from the instant sequences claimed. The instant rejection is not provisional since US 11,524,065 is patented. Applicant’s request for abeyance has been considered, but is unsupported. Only objections or requirements as to form not necessary to further consideration may be held in abeyance, not rejections. With regard to overcoming all types of non-statutory double patenting, MPEP § 804, subsection I.B.1 states that these rejections can be overcome by 1) amending the claims so that the rejection is no longer applicable, or 2) filing a terminal disclaimer. Applicant’s amendments to the instant claims do not obviate the rejection. Applicant is encouraged to file a terminal disclaimer.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SHANON A FOLEY whose telephone number is (571)272-0898. The examiner can normally be reached M-F, generally 5:30 AM-5 PM, flexible.
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/Shanon A. Foley/ Primary Examiner, Art Unit 1671