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
Priority
This Application is a national phase application filed under 35 U.S.C. § 371 claiming priority to International Application No. PCT/JP2022/011707, filed on March 15, 2022, which claims benefit to Japanese Patent Application No. 2021/042666, filed March 16, 2021 that is hereby acknowledged by the Examiner.
Status of the Claims
The amendment dated 08/12/2024 is acknowledged. Claims 43-62 are pending and under examination.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/29/2023 and 05/30/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement(s) is/are being considered by the Examiner.
Drawings
The drawing filed on 09/15/2023 are acknowledged and accepted by the Examiner.
Specification
The disclosure is objected to because of the following informalities: The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (pages 30-31, 65, 69, 84-86). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claim 47 and 59-62 are rejected under 35 U.S.C. 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claim 47 recites “preferentially”. The term "preferentially" is a relative term which renders the claim indefinite. The term "preferentially" is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Thus, the claim is rendered indefinite.
Claims 59-62 recite “administering a follicular T cell reactive with SARS-CoV-2”. It is not clear as to what the administration step encompasses, e.g. an in vitro assay. Note: Applicant’s disclosure does not outline administering follicular T cells to a test subject (i.e. mice challenge). Since the claims do not set forth any steps involved in the method/process, it is unclear what method/process applicant is intending to encompass. A claim is indefinite where it merely recites a use without any active, positive steps delimiting how this use is actually practiced.
The following is a quotation 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 43-49 and 54 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
MPEP 2163.11.A.2.(a).i) states, "Whether the specification shows that applicant was in
possession of the claimed invention is not a single, simple determination, but rather is a factual
determination reached by considering a number of factors. Factors to be considered in
determining whether there is sufficient evidence of possession include the level of skill and
knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention".
For claims drawn to a genus, MPEP § 2163 states 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 Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at
1406.
The claims are directed a method for inducing a follicular T cell reactive with SARS-CoV-2,
comprising a step of administering SARS-CoV-2 protein or a part thereof, or a functional equivalent thereof to a test subject.
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.
The grounds for the written description rejection are as follows: (1) Claims 43-49 recite “a part thereof, or a functional equivalent thereof” without guidance on what encompasses “a part thereof” or a “functional equivalent thereof”; (2) Claim 54 recites “comprises up to 20 amino acids” that can be interpreted as claiming a single amino acid up to 20 amino acids. The claims are rejected because the specification does not satisfy the written description requirement for the genus of the claimed proteins.
The “part thereof” or “functional equivalent” can have any type of mutation (e.g., deletion, insertion, substitution), anywhere along the SARS-CoV-2 protein sequence. The specification only sets forth the functional equivalent or part thereof “includes one that is not the SARS-CoV-2 virus protein or a part thereof itself, but a mutant or variant (e.g., amino acid sequence variant, etc.) of the SARS-CoV-2 virus protein or a part thereof, which has the biological action of the sARS-CoV-2 virus protein or a part thereof, and one that, at the time of action, can be transformed into the SARS-CoV-2 virus protein or a part thereof itself, or a mutant or variant of the SARS-CoV-2 virus protein or a part thereof (e.g., nucleic acids encoding the SARS-CoV-2 virus protein or a part thereof itself or a mutant or variant of the SARS-CoV-2 virus protein or a part thereof, and vectors, cells, and the like containing nucleic acids)” and that “functional equivalents can be found by searching databases and the like”, for example, “BLAST” (see disclosure page 36 lines 5-28); however, as Applicant has disclosed, “a functional equivalent” or “part thereof” is “a mutant or variant” that can be found in electronic searches.
There is some general teaching in the art that some amino acid variations are tolerated without losing a protein' s tertiary structure, but conservation of structure is not necessarily a surrogate for conservation of function. While one of skill in the art could, with the aid of a computer as suggested, could identify all the protein and nucleic acid sequences, this would not tell one the structure of the polypeptides having the recited functional activity of inducing a follicular T cell reactive with SARS-CoV-2.
Applicant has not provided a structure-function nexus for claiming “a functional equivalent” or “part thereof” nor “up to 20 amino acids”. The instant claims encompass a genus of peptides having alterations of any portion (i.e. part thereof) of the SARS-CoV-2 protein. For example, SEQ ID NO: 6, it is 19 amino acids (AA) long, so a peptide can vary up to 19 AA along the sequence, so, for substitutions alone (i.e., each position could be any one of the 20 canonical amino acids) would encompass 2019 = 5,242,880,000,000,000,000,000,000 peptide species, which also need to have the ability to induce a follicular T cell reactive with SARS-CoV-2. This reasoning would also apply to the fragments (i.e. up to 20 amino acids), which encompass any two, any three, and any four, etc. (e.g., 1-3, 13-19, etc.) stretches along any part of the sequence, which need to retain function, so it appears to permutate into an equally large genus.
Accordingly, it does not appear applicants were in possession of the claimed sequences having “a functional equivalent” or “part thereof” at the time of filing. Given that there is no identification of any particular portion of the structure that must be conserved, and in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus. While it is possible to make antigenic polypeptides, the specification must provide an adequate description of the genus. The provision of a partial structure and a function without a nexus between the two does not put one in possession of the large genus of variants encompassed by the claims. Vas-Cath Inc. V. Mahurkar, 19 USPQ2d 1111, clearly states 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 [he or she] invented what is claimed." (See Vas-Cath at page 1116).
Thus, the Applicant has not shown, otherwise, which mutations would retain the functional limitation. The Applicant has not provided adequate written description to support the claimed genus of the construct limited by the function of inducing a follicular T cell reactive with SARS-CoV-2. Therefore, the written description is not commensurate in scope with the claims drawn to “a functional equivalent thereof” a “part thereof” and “up to” 20 amino acids, wherein the parts or variants induce a follicular T cell reactive with SARS-CoV-2. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics of the claimed genus, the claims are rejected as lacking adequate descriptive support for the claimed invention.
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.
Claims 43-53, 55 and 58 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bettini et al. “Bettini” (Vaccines, February 12, 2021, 9(147):1-18, IDS of record dated 12/29/2023).
The claims are directed to a method for inducing a follicular T cell reactive with SARS-CoV-2,
comprising a step of administering SARS-CoV-2 protein or a part thereof, or a functional equivalent thereof to a test subject.
Note: It is understood by the Office that the full-length spike protein encompasses the various protein sequences of the present application, thus, it is considered that a variety of follicular T cells are induced thereby, including cells that “are responsive to coronavirus other than SARS-CoV-2” and “cells that are specific to SARS-CoV-2”. Additionally, claim 58 is written in the alternative, thus, the TCRαβ pair is not required and the prior art needs only to be a follicular T cell that is reactive with SARS-CoV-2.
Regarding claims 43-53, 55 and 58, Bettini discloses an overview of the results from pre-clinical studies in animal models as well as clinical studies in humans that assessed the efficacy of SARS-CoV-2 mRNA vaccines, with a primary focus on adaptive immune responses post vaccination (Abstract). Bettini teaches that “Tfh cells, a specialized type of CD4 T cells shaping GC reactions, are of particular interest to vaccine developers because of their crucial importance for the development of GC-derived B cell responses. By delivering co-stimulatory molecules and cytokines to B cells, Tfh cells mediate the formation of GCs and the selection of affinity-matured GC B cells, which can further differentiate into LLPCs or MBCs… and To verify that this observation could be extended to SARS-CoV-2 mRNA vaccines, we evaluated the induction of Tfh cells after the immunization of BALB/c mice with SARS-CoV-2 mRNA vaccines or with rRBD-AddaVax. As anticipated, the mRNA-LNP platform was a potent inducer of Tfh cells also in the context of a SARS-CoV-2 vaccine, whereas rRBD-AddaVax only induced a more modest Tfh cell population in comparison to SARS-CoV-2 mRNA” (section 3.2.1 T Follicular Helper Cell Response). Bettini discloses the administration of a SARS-CoV-2 mRNA vaccine composition induced T follicular helper (Tfh) cells that are responsive to SARS-CoV-2, and that the full-length SARS-CoV-2 spike protein or a part thereof was used as the polypeptide encoded by the mRNA (see fig. 1, S1 and section 2.2 and 3.2.1). With respect to claims 50-53, Bettini’s disclosure of the full-length SARS-CoV-2 spike glycoprotein encompasses SEQ ID NOs. 6-12 outlined in the claims.
Therefore, the cited prior art anticipates the claimed invention.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
Claim 54 and 56-57 are rejected under 35 U.S.C. 103(a) as being unpatentable over Bettini et al. “Bettini” (Vaccines, February 12, 2021, 9(147):1-18, IDS of record dated 12/29/2023) as applied to claim 46 above, in view of Sahin et al. “Sahin” (Nature, 2020, 586, October 2020:594-599).
The teachings of Bettini are outlined above and incorporated herein.
The claim is directed to the method of claim 46, wherein said SARS-CoV-2 protein or a part thereof comprises up to 20 amino acids.
Regarding claims 54 and 56-57, Bettini discloses the use of the full-length SARS-CoV-2 Spike glycoprotein or receptor binding domain (RBD) using constructs such as BNT162b1, but does not explicitly disclose the SARS-CoV-2 protein is up to 20 amino acids.
Sahin, however, discloses antibody and T cell responses after vaccination with BNT162b1 from a second, non-randomized open-label phase I/II trial in healthy adults (Abstract); and the use of mRNA that encodes the receptor binding domain (RBD) of the SARS-CoV-2 spike protein utilizing BNT162b1, whereby they constructed a “pool of 15-mer peptides that overlapped by 11 amino acids and covered the whole sequence of the BNT162b1-encoded SARS-CoV-2 RBD” (Methods: Clinical Trial Designs). With respect to claims 56 and 57, Sahin’s 15mer peptides of the entire SARS-CoV-2 RBD encompasses the SEQ ID NOs. recited in the claims. Sahin discloses that “Two doses of 1–50 μg of BNT162b1 elicited robust CD4+ and CD8+ T cell responses and strong antibody responses, with RBD-binding IgG concentrations clearly above those seen in serum from a cohort of individuals who had recovered from COVID-19” (Abstract).
Accordingly, it would have been obvious to one of ordinary skill in the art to generate a method for inducing a follicular T cell reactive with SARS-CoV-2 protein comprising administering said protein to a test subject as disclosed by Bettini, whereby the protein can be the full-length Spike protein or fragments thereof comprising up to 20 amino acids such as the 15mer RBDs disclosed by Sahin. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success given the fact that the sequences for the SARS-CoV-2 virus was known in the prior art and given the knowledge from Bettini that the protein was a potent inducer of Tfh cells also in the context of a SARS-CoV-2 vaccine (section 3.2.1 T Follicular Helper Cell Response) and Sahin that administration of said proteins from their pool of “15-mer peptides that overlapped by 11 amino acids and covered the whole sequence of the BNT162b1-encoded SARS-CoV-2 RBD” (Methods: Clinical Trial Designs) of BNT162b1 “elicited robust CD4+ and CD8+ T cell responses and strong antibody responses, with RBD-binding IgG concentrations clearly above those seen in serum from a cohort of individuals who had recovered from COVID-19” (Abstract). Therefore, the claimed invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Barry Chestnut whose telephone number is (571)270-3546. The examiner can normally be reached on M-Th 8:00 to 4:00.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Thomas Visone can be reached on 571-270-0684. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BARRY A CHESTNUT/Primary Examiner, Art Unit 1672