DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Claims Status
Claims 1-20 are under examination on their merits.
Priority
For claims 1-20 in this application, a priority date of 27 April 2022 is applicable because the subject matter of each of said claims is found in 63/335,519 filed 04/27/2022.
Drawings
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color (see drawings 1A, 1B, 2A and 2B filed on 4/27/2023). Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Claim Objections
Claims 1 and 2 are objected to because the citation of “SARS-Cov-2” is inconsistent with other claims. For example, claims 4, 8 and 12 recite “SARS-CoV-2.” The examiner recommends the use of “SARS-CoV-2” in claims 1 and 2.
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.
Claims 1-20 are 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 1 recites, “…a mutant SARS-Cov-2 spike protein comprising D614G mutation (SEQ ID NO: 1) or a portion thereof…” However, because of the use of parenthesis, it is unclear if SEQ ID NO: 1 is required for this claim or if it is an optional limitation. Claims 2-20 are also rejected because they depend from claim 1, but do not remedy this deficiency.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 1 recites the broad recitation “a mutant SARS-Cov-2 spike protein comprising D614G mutation”, and the claim also recites “(SEQ ID NO: 1)” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Claims 2-20 are also rejected because they depend from claim 1, but do not remedy this deficiency.
For claims 14 and 18, “immune response” to SARS-CoV-2 vaccination is said to either last “for longer than six months from the time of administration” (claim 14) or “longer than about 12 months from the time of administration” (claim 18). Since “the vaccine of claim 1” is given “at least two times” (claim 15) that are “at least two weeks” (claim 16) or “between about two and about three weeks” (claim 17), it is unclear if claims 14 and 18 refer to the first or second dose as the baseline for calculating the relapsed time after “administration,” rendering both claims indefinite. The applicant needs to clarify this issue. For the purpose of compact prosecution, it is assumed that the second dose of vaccination is the baseline for both claims, as antibody response after the priming (first) dose appears to be negligible (FIG. 2A and FIG. 2B).
Claim 14 recites “a method of eliciting a long-term immune response against SARS-CoV-2…”. However, the metes and bounds of “long-term immune response” and the dosage or vaccination regimens required for such an endpoint are unclear. While the specification on page 12, lines 4-13, provides examples of how long an immune response may last, these examples are not a binding definition that would provide a clear boundary to one of ordinary skill in the art as to what constitutes long-term and what would not be considered long-term as it relates to an immune response. The only example (Figure 2A) refers to antibody response in vaccinated B57BL/6 mice (page 12, lines 21-25) at day 7 and day 15 after each dose of vaccination (Figure 2A), which does not allow a meaningful extrapolation for the actual duration of antibody response. Moreover, it is unclear if “long-term” also implies that a memory immune response is achieved or that circulating antibodies or virus-specific T cells are above a minimum threshold for a period of time in order to qualify as long-term. In addition, the claim recites that the effective amount administered is defined by how long an immune response is elicited (longer than 6 months-claim 14 and longer than 12 months-claim 18). However, applicants have not established what the metes and bounds are of an effective amount of their vaccine that can achieve this duration of immune response. The specification or the claims provide any guidance or specific examples as to how one of ordinary skill in the art would know how to formulate their vaccine in order to achieve an immune response that lasts longer than 6 months or longer than 12 months.
Claims 15-20 are also rejected since they descend from claim 14, but do not remedy the deficiency in claim 14. If applicants amend claim 14 to recite “A method of eliciting an immune response against SARS-CoV-2…”, the rejection of claim 14 and its dependent claims under 35 U.S.C. 112(b) would be overcome.
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.
Claims 1-3 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wu et al. 2021 (bioRxiv, epub date of 01/25/2021, PMID: 33501442).
The claimed invention is drawn to a vaccine composition capable of eliciting an immune response in a subject against SARS-CoV-2. The vaccine comprises a mutant SARS-CoV-2 spike protein carrying a D614G mutation or a portion thereof or the vaccine comprises an mRNA encoding the mutant SARS-CoV-2 spike protein or a portion thereof [claim 1]. The portion of the mutant spike protein is SEQ ID NO: 6 [claim 2]. The vaccine also requires a nanoparticle [claim 3].
The specification states that a vaccine refers to a composition that includes an antigen or a nucleotide encoding an antigen. [see page 6, lines 21-22] The specification also states that a nanoparticle is a nanomaterial used as a transport module for another substance, such as a polynucleotide or protein. [see page 6, lines 8-9] Therefore, the broadest reasonable interpretation of vaccine and nanoparticle in view of the claimed limitations is a composition comprising a mutant SARS-CoV-2 spike protein with the mutation D614G and a virus or viral vectors (which is a nanoparticle) that contains this spike protein.
Wu et al. teach two engineered viral vectors expressing the spike protein of SARS-CoV-2 with the D614G mutation. Specifically, the engineered viral vectors are lentivirus and VSV. [see table 2 and methods section] Since the engineered viral vectors of Wu et al. are identical to that claimed, those viral vectors of Wu et al. would inherently (See MPEP 2112 III.) be capable of inducing an immune response in a subject against SARS-CoV-2. Therefore, Wu et al. anticipates the claimed invention.
Claims 1-5 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Tang et al 2022 (PGPub US 2022/0040292 A1, published 02/10/2022).
The claimed invention is drawn to a vaccine composition capable of eliciting an immune response in a subject against SARS-CoV-2. The vaccine comprises a mutant SARS-CoV-2 spike protein comprising a D614G mutation or a portion thereof or the vaccine comprises an mRNA encoding the mutant SARS-CoV-2 spike protein or a portion thereof [claim 1]. The portion of the mutant spike protein is SEQ ID NO: 6 [claim 2]. The vaccine also requires a nanoparticle [claim 3], such as a lipid nanoparticle [claim 5], which encapsulates the protein or mRNA [claim 4].
Tang et al 2022 teaches the composition of an mRNA-based vaccine (Figure 1) encoding SARS-CoV-2 spike (S) protein or spike subunit (claim 2), “including mutated epitopes” in “a pharmaceutically acceptable polymeric nanoparticle carriers and liposomal nanoparticle carriers… for stimulating system immune responses” (Abstract), and their SEQ ID NO: 11 (Figure 5C and pp. 15-18) is 100% identical with SEQ ID NO: 1 of this instant application, while their SEQ ID NO: 11 also has amino acid residues 612-617 as Tyr-Gln-Gly-Val-Asn-Cys (Pg. 17), being 100% identical to SEQ ID NO: 6 (YQGVNC) of this instant application. Moreover, Tang et al 2022 discloses multiple mRNA vaccines that specifically target SARS-CoV-2 viruses with the “D614G” mutation (¶[0039]), as well as viruses with other natural variants in the S protein (¶[0041]).
Therefore, Tang et al anticipate claims 1-5.
Claims 1 and 6-20 are also rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Tang et al 2022 (supra).
As dependents of claim 1, claims 6-13 refer to a method “of eliciting an immune response to a SARS-CoV-2 spike protein in a subject” by “administering to the subject the vaccine composition of claim 1 in an amount effective to elicit the immune response” (claim 6), wherein “the immune response is a humoral immune response” (claim 7) that can be assessed by “an increase in the antibody titers against SARS-CoV-2 spike protein” (claim 8), and wherein the vaccine is given “at least two times” (claim 9) “intramuscularly” (claim 12), and the time interval between first and second dose is “at least about two weeks” (claim 10) or “between about two and about three weeks” (claim 11) when “the subject is a human” (claim 13).
Claims 14-20 then recite the utility of an mRNA-based SARS-CoV-2 vaccine (from claim 1) capable of inducing “a long-term immune response” that is “longer than six months from the time of administration” (claim 14), with methods and limitations that are almost identical to claims 9-13 in terms of delivery route (intramuscular) (claim 19) and dosing schedule (“at least two times,” separated by “at least about two weeks” or “between about two and about three weeks”), except that “the immune response” may also last “longer than 12 months from the time of administration” (claim 18).
In view of the 35 USC 112(b) rejections pertaining to claims 14 and 18 above, the invention of claims 14-20 is interpreted as a method of eliciting an immune response to a SARS-CoV-2 spike protein in a subject, by administering to the subject the vaccine composition of claim 1 in an amount effective to elicit the immune response.
Tang et al 2022 teach the composition of mRNA-based vaccines (Figure 1) encoding SARS-CoV-2 S proteinor its subunit (claim 2), being formulated in “a pharmaceutically acceptable polymeric nanoparticle carriers and liposomal nanoparticle carriers… for stimulating system immune responses” (Abstract). SEQ ID NO: 10 of Tang et al 2022 represents a nucleic aicd sequence encoding the coronavirus spike protein of SEQ ID NO: 11. Tang et al 2022 provide a coronavirus spike protein which is SEQ ID NO 11 and it has has a 100% match with SEQ ID NO: 1 and SEQ ID NO: 6 in this instant application (identical vaccine targets), and their vaccine “compositions… can be formulated for inhalation, intramuscular, oral, sublingual, buccal, parenteral, nasal, subcutaneous, intradermal or topical administration” (¶[0071]) and “may be administered to a subject in an amount effective to induce a specific immune response against 2019-nCoV in the subject” (¶[0036]); “the vaccine formulations... may be administered to subjects, including human subjects, by any mode of administration... used to administer vaccines.” (¶[0071]). Moreover, “an initial measurement of an immune response to the vaccine may be made by measuring production of antibodies in the subject receiving the vaccine” (¶[0073]). In one example, adult mice receive a priming dose on day 1 (¶[0088]) and a boosting dose on “day 28,” with “antibody titer” measured by ELISA on “day 35” (¶[0089]), which meet the limitations of administering the first and second administrations apart by at least two weeks or about two to about three weeks. Moreover, because 2019-nCoV is an early name for SARS-CoV-2, Tang et al 2022 not only taught the composition of mRNA vaccines against SARS-CoV-2 variants but also provided a detailed guidance for preferred route of administration, dosing intervals (at least 2-3 weeks) and the measurement of antibody titer after the second dose.
Thus, Tang et al 2022 anticipates claims 1 and 6-20.
Conclusion
No claim is allowed.
Additional Prior Art Cited but Not Applied
McFadden et al 2021 (US 2021/0025535 A1. COVID-19 vaccine based on the myxoma virus platform, published 10/07/2021). McFadden et al taught the use of “synthetic nucleic acid sequence of modified spike protein,” including a spike protein (SEQ ID NO 14) encoded by their DNA SEQ ID NO 15 that has a 97.7% match with SEQ ID NO 2 of this instant application; they also disclosed that their amino acid sequence can be SEQ ID NO 14 “or a sequence at least 95% identical to SEQ ID 14 “ (claim 6), which effectively encompasses SEQ ID NO 2 and other D614G-related forms in this instant application.
King et al 2021 (WO 2021/163438 A1, Polypeptides, compositions, and their use to treat or limit development of an infection. Published 08/19/2021). This prior art taught that potent vaccine formulations for inducing SARS-CoV-2-specific immune protection can be made of polypeptides and nanoparticles: pertinent to an optional (alternative) composition in claim 1 of this instant application.
Pardi & Weissman 2021 (WO 2022/011092 A1, Nucleoside-modified RNA for inducing an immune response against SARS-CoV-2, published 01/13/2022). This prior art disclosed “compositions and methods for inducing an adaptive immune response against SARS-CoV-2 in a subject” (Abstract), noting that “antigen-encoding RNA” sequences can be modified to “induce a significantly more robust adaptive immune response as compared with an unmodified… RNA molecule of the same sequence” (Pg. 47), with a factor ranging from 2-fold (Pg. 47) to 2000-fold (Pg. 47, last para.). As a result, their method “provides sustained protection against SARS-CoV-2 for 6 months or more” or “for 1 year or more” (Pg. 107, 1st para).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JIANMING TANG whose telephone number is (571) 272-0081. The examiner can normally be reached M-F 8:00-5:30 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Michael Allen (SPE) can be reached at (571) 270-3497. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JIANMING TANG/Examiner, Art Unit 1671
/BENJAMIN P BLUMEL/Primary Examiner, Art Unit 1671