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
Acknowledgement is hereby made of receipt and entry of the communication filed on Sep. 11, 2024. Claims 1-19 are pending and are currently examined.
Claim Rejections - 35 USC § 112 (b)
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-19 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.
Claims 1-3 and 14-19 recites the term “variants” that renders the claims indefinite. It is not clear what kind of “variant” of SARS-COV-2 is included in the claims. For example, claim 2 recites that “the immune response comprises the generation of antibodies that bind to the Delta, Wuhan, Alpha, Epsilon, Gamma, and Beta variants of SARS-CoV2”, where it does not provide a reference Beta and does not define how much amino acids difference being considered as a variant of the Beta that can be target by the immune responses.
Accordingly, one of ordinary skill in the art will not know the metes and bounds of
the claim.
The base claim 14 recites a phrase “self-amplifying self-adjuvant RNA vaccine” that renders the claim indefinite. It is not clear what the self-amplifying self-adjuvant RNA vaccine mean in the invention. The instant specification discloses that “ Exemplary RNA vaccine prime vaccination may be self-amplifying self-adjuvant RNA vaccines (that preferably comprise an RNA encoding a coronavirus S protein and/or a coronavirus N protein)” (See [0017]), however, it is unclear if the self-amplifying self-adjuvant RNA vaccines is the RNA encoding a coronavirus S protein and/or a coronavirus N protein or this is just an example.
For purposes of compact prosecution and applying prior art, the phrase “self-amplifying self-adjuvant RNA vaccine” was interpreted herein as the RNA encoding a coronavirus S protein and/or a coronavirus N protein in the vaccine.
It is noted any interpretation of the claims set forth above does not relieve Applicant of the responsibility of responding to this rejection. If the actual interpretation of the claims is different than that posited by the Examiner, additional rejections and art may be readily applied in a subsequent final Office action
Note: In claims 1 and 6-7, applicant claims the sequences (amino acids sequences or nucleotide sequences) as “having 90% identity to…”.
However, the instant specification discloses that “the N-ETSD may have an amino acid sequence that has at least 90% identity to amino acid sequence SEQ ID NO: 1” (See [0012]); “… the CoV-2 nucleocapsid protein or variant thereof comprises a sequence with at least 80% identity to SEQ ID NO: 1 or SEQ ID NO:7…In still other embodiments, the identity value is at least 90%...” (See [0047]); “With regard to the S protein it is contemplated that the S protein may have an amino acid sequence that has at least 90% identity to amino acid sequence SEQ ID NO:3 or SEQ ID NO:4” (See [0014]); “The nucleic acid encoding the CoV-2 spike fusion protein has at least 85% identity to SEQ ID NO: 6 …In some embodiments, the identity value is at least 90%...” (See [0045]); and “The nucleic acid encoding the CoV-2 spike protein has at least 85% identity to SEQ ID NO:5…In some embodiments, the identity value is at least 90%...” (See 0044]).
For purposes of compact prosecution and applying prior art, the phrase “having 90% identity to…” was interpreted herein to “having at least 90% identity to…”.
It is noted any interpretation of the claims set forth above does not relieve Applicant of the responsibility of responding to this rejection. If the actual interpretation of the claims is different than that posited by the Examiner, additional rejections and art may be readily applied in a subsequent final Office action.
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 1-13 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.
The base claim 1 is directed to a kit for use in eliciting in a subject an immune response against a SARS-COV-2 variant, the kit comprising a recombinant vaccine composition having a first portion encoding a coronavirus N protein comprises a nucleic acid encoding an amino acid sequence having at least 90% identity to SEQ ID NO: 1 or SEQ ID NO:7.
Claims 6 and 7 are directed to S protein has an amino acid sequence having at least 90% identity to SEQ ID NO:3 or SEQ ID NO:4, and the second portion comprises a nucleotide sequence having at least 90% identity to SEQ ID NO:5 or SEQ ID NO:6, respectively.
The written description rejection is made because the claims are interpreted as being drawn to a sequence recited as being “at least 90% identity” to the instant claimed SEQ ID NOs 1, 3-4, 5-6 and 7, respectively. This means that up to 10% amino acids sequences/ nucleotide sequence of N-ETSD protein and S protein can vary. However, the specification does not indicate which portions of the claimed SEQ ID NOs are essential to retain the ability to be a functional composition in the kit to elicit an immune response against a SARS-COV-2 variant or altered up to 10% and still retain the ability of eliciting the claimed immune responses.
This can be evidenced by the studies of Rak et al. Vaccines (Basel). 2023 Dec 3;11(12):1810) and Rees-Spear et al. (The effect of spike mutations on SARS-CoV-2 neutralization. Cell Rep. 2021 Mar 23;34(12):108890). Rak et al. teaches that at least 12 mutations have arisen in the N sequence, affecting more than 40 known immunogenic T-cell epitopes, so the antigenicity of the N protein of recent SARS-CoV-2 variants may be altered. This fact should be taken into account as a limitation in the development of cross-reactive vaccines based on N-protein (See Abstract). Rees-Spear et al. teaches that a single substitution of S494D toward the end of the RBM destroys neutralization activity by COVA2-29 (cluster I) and COVA1-12 (cluster VI), and the double mutations of LF455-6YL reduce neutralization by RBD-specific mAbs from different clusters (See page 4, left column, paragraph 1-4).
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).
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.).
As discussed above, the specification does not clearly disclose to the skilled artisan that the inventor was in possession of the claimed invention at “having at least 90% identity” to the claimed SEQ ID NOs. Therefore, the full breadth of the claims does not meet the written description provision of 35 U.S.C. 112, first paragraph.
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.
Note: Soon-shiong is the first inventor in the prior art of WO2021183665A1 and the single inventor in the instant application, however, there are eight more inventors in WO2021183665A1 who are not inventors in the instant application.
Claims 1-12, and 14-19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Soon-shiong et al. (WO2021183665A1, published on Sept. 16, 2021, submitted in the IDS filed on 12/17/2024, hereinafter, “Soon”).
Regarding the base claim 1, Soon teaches a vaccine composition to induce immunity against a coronavirus in a subject comprises a recombinant nucleic acid that encodes N-ETSD, a modified nucleocapsid protein that includes an endosomal targeting sequence, and/or that encodes S-Fusion, a modified spike protein that has improved surface expression (See Abstract and Fig. 25 below), and the vaccine compositions and methods to generate immunity against coronaviruses, and particularly as it relates to SARS-Co V-2 (See [0003]). Fig. 25 teaches that the two portions of N-ETSD and spike protein (See [0046]), where the N-ESTD can be considered as the first portion and the spike portion can be considered as the second portion that teaches claim 1 for the gene portions.
As for the SEQ ID NO: 1 or Seq ID NO: 2, Soon’s SEQ ID NO: 1 and NO: 7 teaches an identical sequence of the SEQ ID NO: 1 (See Table A below) SEQ ID NO: 7 as claimed. For example, Soon’s claim 6 teaches that the recombinant nucleic acid of claim 3, wherein the N-ETSD has an amino acid sequence that has at least 90% identity to amino acid sequence SEQ ID NO: 1.
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624
950
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794
849
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Soon also teaches a kit for include at least one dose of the vaccine composition as claimed (See [00318). Here Soon teaches the claim 1.
Regarding the base claim 14, Soon teaches that the vaccine may be formulated as a recombinant nucleic acid, recombinant yeast, and/or recombinant vims such as an adenovirus and can be administered via rejection and/or mucosal delivery (See Abstract). Based on the description above, Soon teaches the kit for use in eliciting in a subject an immune response against a SARS-COV-2, teaches the two portions of N-ETSD and spike protein, and teaches the SEQ ID NOs: 1 and 7 as claimed. Fig. 25 also teaches that the human adenovirus serotype 5 vaccine platform with El, E2b, and E3
regions delete (See [0046]). Here Soon teaches the base claim 14-1).
Soon also teaches that in particular embodiments, the initial prime vaccine can
be a lipid nanoparticle vaccine containing mRNA encoding the S protein, such as those vaccines currently being tested by Modema and by Pfizer (See [00260]). Based on the interpretation of the self-amplifying self-adjuvant RNA vaccines described above, the paragraph [00260] above of Soon teaches the base claim 14-2). Soon teaches claim 14-3) of directions for use by stating that “direct administration of the pharmaceutical composition or drug is typically performed by a health care professional (e.g., physician, nurse, etc.), and wherein indirect administration includes a step of providing or making available the pharmaceutical composition or drug to the health care professional for direct administration (e.g., via injection, infusion, oral delivery, topical delivery,
etc.)”(See [00327]).
Based on the description above, Soon also teaches the based claim 17-1) at a kit for eliciting in a subject an immune response against a SARS-COV-2 comprising the recombinant adenoviral vaccine composition with E1 gene and E2b gene deletion (See [00269]) and the two portions of (N-ETSD) and spike protein with SEQ ID NO: 1 or 7 (See Table A above), and teaches claim 17-3) by stating the use of the vaccine kit being performed by the health care professional direction. For the claim 17-2), Soon teaches that numerous candidate anti-SARS-CoV2 vaccine compositions target one or more proteins of the virus, for example, Novamax produced a protein subunit-based vaccine.([0007]).
Regarding claim 4, Soon teaches that the COVID-19 vaccine disclosed herein generates long-term T and B cell memory (See [00102]).
Regarding claim 5, Soon teaches that in some embodiments, the SARS virus is SARS-Co V-2, and/or the endosomal targeting sequence of the N-ETSD is encoded at a 5'-end and/or a 3'-end of the first portion.
Regarding claim 6, Soon teaches the S protein has an amino acid sequence that has at least 90% identity to amino acid sequence SEQ ID N0:3 or SEQ ID N0:4 (See claim 9, page 93), where the SEQ ID NO: 3 is identical to the SEQ ID NO: 3 as claimed (See Table B below).
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Regarding claim 7, Soon teaches that the second portion has nucleotide sequence SEQ ID NO:5 (See claim 12, page 94), where the SEQ ID NO: 5 is identical to the claimed SEQ ID NO: 5 as claimed (See Table C below).
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Regarding claims 8-9, Soon teaches that the vaccine may be formulated as a recombinant nucleic acid, recombinant yeast, and/or recombinant vims such as an adenovirus and can be administered via rejection and/or mucosal delivery (See Abstract), where the recombinant virus is an adenovirus with an E1 gene region deletion and an E2b gene region deletion (See [0014]).
Regarding claims 10-12, Soon teaches that numerous candidate anti-SARS-CoV2 vaccine compositions target one or more proteins of the virus, such as a protein subunit-based vaccine (teaches claim 12), RNA-based vaccines (teaches claim 10), and a non-replicating adenoviral vector that encodes one or more viral proteins (teaches claim 11).
As for the claims 2-3, 15-16 and 18-19, although Soon does not explicitly list the antibody to bind to Delta, Wuhan, Alpha, Epsilon, Gamma, and Beta variants of SARS-CoV2 (See claims 2, 15 and 18), and does not discloses the cytotoxicity against different cells harboring Delta, Omicron, Wuhan, Alpha, Epsilon, Gamma, or Beta variants of SARS-CoV2 (See claims 3, 16 and 19), these claims do not add a structural component to the kit of the base claim 1. Soon’s teaching on the claimed kit containing the claimed gene portions with the identical SEQ ID NOs: 1 and 7 will to generate antibodies that bind to the viruses of claims 2, 15 and 18 and generate cytotoxic T cells against the viruses in claims 3, 16 and 19.
Accordingly, Soon teaches each and every aspect of claims 1-12 and 14-19.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Soon as applied to claims 1, 4-12, 14 and 17 and in view of Shin et al. (Nat Nanotechnol. 2020 Aug;15(8):646-655).
Claim 13 requires a heat-inactivated coronavirus vaccine composition.
Soon teaches the vaccine may be formulated as a recombinant nucleic acid, recombinant yeast, and/or recombinant vims such as an adenovirus and can be administered via injection and/or mucosal delivery (See Abstract), where the yeast is a whole, heat-inactivated yeast from Saccharomyces cerevisiae (See [00134]. Because the heat-inactivated yeast carrying the N antigen of SARS-COV-2 for a vaccine composition, it is reasonably to consider this can teach a comparable heat-inactivated coronavirus vaccine composition as claimed.
Nevertheless, Shin teaches inactivated vaccines (IVs) are heat or chemically inactivated pathogens or fractions thereof. These vaccine formulations are incapable of replication and safer than LAVs (Live attenuated vaccines). Several COVID-19 IVs are in development, with the first clinical trial approved recently for Sinovac (See page 647, right column).
It would have been prima facie obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to introduce the teaching of the heat inactivated SARS-COV-2 of Shin into Soon’s design to develop an invention as claimed. Because the heat-inactivated vaccine can offer a safe, stable and straightforward approach for the immunization, one of skill in the art would be motivated to use a heat-inactivated coronavirus for the vaccine development. There would be a reasonable expectation of success to develop such a kit for eliciting an immune response using the heat-inactivated vaccine.
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 1-11, 15-16 and 18-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6, 9-14, 18 and 20 of US 12,016,916 B2 (referred to as “patent”).
Although the conflicting claims are not identical, they are not patentably distinct from each other.
The patent claims teach the instant claims as the following:
Patent claims 1 teaches the instant claims 1. Although the patent base claim 1 is directed to a method claim and the instant base claim 1 is directed to a kit, they contain same portions of the sequences with same function as “eliciting in a subject an immune response against a SARS-COV-2 variant”. Also, the SEQ ID NOs: 1 and 7 in the patent claim1 teaches the at least “ 90% identity to SEQ ID NO: 1 or SEQ ID NO:7” in the instant claim 1.
In addition, this rejection is necessitated by the decision of the Court of Appeals for the Federal Circuit in Pfizer Inc. v Teva pharmaceuticals USA Inc., 86 USPQ2d 1001, at page 1008 (March 2008), which indicates that there is no patentable distinction between claims to a product and a method of using that product disclosed in the specification of the application and that the preclusion of such a double patenting rejection under 35 USC 121 does not apply where the present application is other than a divisional application of the patent application containing such patentably indistinct claims.
Patent claims 2-3, 18 and 20 teach the instant claims 2-3, 15-16 and 18-19.
Patent claim 4 teaches the instant claim 4.
Patent claim 6 teaches the instant claim 5.
Patent claims 9 and 10 teach the instant claims 6 and 7.
Patent claim 11 teaches the instant claim 8.
Patent claim 12 teaches the instant claim 9.
Patent claims 13 and 14 teach instant claim 10 and 11.
Accordingly, claims 1-11, 15-16 and 18-19 of the instant application are unpatentable over claims 1-4, 6, 9-14, 18 and 20 of US patent 12,016,916 B2
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RUIXUE WANG whose telephone number is (571)272-7960. The examiner can normally be reached Monday-Friday 8:00 am..
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Thomas J. 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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/RUIXUE WANG/Examiner, Art Unit 1672
/NICOLE KINSEY WHITE/ Primary Examiner, Art Unit 1672
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