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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 3/1/2024 has been considered by the examiner.
Specification
The incorporation of essential material in the specification by reference to an unpublished U.S. application, foreign application or patent, or to a publication is improper, see paragraph [0001] of the instant published application, USPgPub 2024/0197862. Applicant is required to amend the disclosure to include the material incorporated by reference, if the material is relied upon to overcome any objection, rejection, or other requirement imposed by the Office. The amendment must be accompanied by a statement executed by the applicant, or a practitioner representing the applicant, stating that the material being inserted is the material previously incorporated by reference and that the amendment contains no new matter. 37 CFR 1.57(g).
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code in paragraphs [0082-0093+] of the instant published application. 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.
The specification is objected to for failing to adhere to the requirements of the sequence rules, see paragraphs [0006, 0011, 0012+], of the instant published disclosure. Applicant must append SEQ ID NOs. to all mentions of specific sequences comprising four or more amino acids and ten or more nucleic acids in the specification applicable to the rule. See 37 CFR § 1.821 (a)-(d) and MPEP § 2422. Appropriate correction is required.
Claim Objections
Claim 1 is objected to because of the following informalities: “GSAS” is not compliant with the sequence requirements set forth in 37 CFR § 1.821 (a)-(d) and MPEP § 2422.
Claims 11-18 recite, “derived from SARS-CoV-2…strain”, which is ungrammatical.
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.
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 1-20 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 states the antigenic recombinant protein “substantially consists of” residues 14-1205 of the SARS-CoV-2 Beta variant spike protein with proline substitutions at residues 983 and 984 and a “GSAS” substitution at residues 679 - 682 and a C-terminal T4 fibritin trimerization domain. The metes and bounds of “substantially consists of” is not defined by the claims or the specification. It cannot be determined whether the fragment in the claim may contain additional sequences, which would “substantially” encompass the entire SARS-CoV-2 Beta variant spike protein or if applicant intends to claim only the fragment recited, “consisting of” residues 14-1205 with proline substitutions at residues 983 and 984 and a “GSAS” substitution at residues 679 - 682. However, if only the recited fragment residue positions are intended, it is unclear what other residues are “consisting of” within the spike protein Beta variant. This rejection affects all dependent claims. In the interest of compact prosecution, “substantially consists of” is interpreted as equivalent to “consisting essentially of”. Since there is an absence of a clear indication of what the basic and novel characteristics actually are, "consisting essentially of" will be construed as equivalent to “comprising”. See the MPEP § 2111.03.
Claim 1 states that the SARS-CoV-2 type is a “Beta variant”, but no structural features defining Beta or Beta variant viruses are recited. Given the quantity of spike substitutions shared between Beta, Delta, Omicron BA.1, Omicron BA.2, and Omicron BA.5 lineages, as evidenced in Table 1 of Zeng et al. (Viruses. 2023 Dec 8; 15 (12): 2394), the “SARS-CoV-2 Beta variant”, is indeterminable. This rejection affects all claims.
Claims 9-11, 13, 15, and 17 require a “suitable interval between doses”. Paragraph [0154] of the instant published disclosure, USPgPub 20240197862, mentions that days between prime and boost administrations range between 223.3 to 294.5 days and 120.9 to 128.0 days, but there is no indication that any point in time between these interval ranges is “suitable”, as required. The requisite degree of “suitable interval between doses” is indeterminable. This rejection affects all depend claims.
Claims 11, 13, 15, and 17 recite, “a polynucleotide sequence encoding a polypeptide sequence at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 5 or 6 or a polypeptide sequence at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 5 or 6. 11.” It is not clear whether the polynucleotide from a SARS-CoV2 wild type strain encoding a polypeptide is intended to be administered as a first dose or whether the polynucleotide encoding a polypeptide is derived from a circulating SARS-CoV2 wild type strain the claimed method is inducing an immune response against. An additional confusion arises since the SARS-CoV-2 strain comprises a polynucleotide sequence expressing nucleic acids encoding polypeptides, it is unclear how a SARS-CoV-2 nucleic acid alternatively comprises, “a polypeptide sequence at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 5 or 6”. These issues also affect all dependent claims. The only mention of a polynucleotide sequence encoding a spike polypeptide in the instant disclosure occurs in paragraph [0107], constructing the recombinant spike protein. There is no suggestion or antecedent basis for priming with a polynucleotide sequence encoding a spike polypeptide and boosting with a spike polypeptide and the claims do not clearly articulate this concept, if intended. Therefore, in the interest of compact prosecution, the first, second, and third doses recited in claims 11-18 are interpreted as all doses comprising an antigenic SARS-CoV-2 spike recombinant protein, commensurate with the teachings and discussions throughout the instant disclosure.
Claim 19 states that the SARS-CoV-2 is a WT strain or a variant. Since SARS-CoV-2 variants are also WT, it is not clear what the difference is between WT or variant alternatives.
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 1-20 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.
Claim 1 states that the SARS-CoV-2 type is a “Beta variant”, but no structural features defining Beta or Beta variant viruses are recited. Given the quantity of spike substitutions shared between Beta, Delta, Omicron BA.1, Omicron BA.2, and Omicron BA.5 lineages, as evidenced in Table 1 of Zeng et al. (Viruses. 2023 Dec 8; 15 (12): 2394), the “SARS-CoV-2 Beta variant”, is indeterminable and the skilled artisan would not recognize the Beta variant required. For example, N501Y is present in Beta, Omicron BA.1, Omicron BA.2, and Omicron BA.5 lineages and D614G is also present in Beta, Delta, Omicron BA.1, Omicron BA.2, and Omicron BA.5 lineages, according to Table 1 of Zeng et al. There are no structural motifs or patterns provided in the instant disclosure that would identify the Beta variant required. The skilled artisan would not predict that a SARS-CoV-2 spike protein is specific to any Beta variant.
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 amino acid sequences comprising at least 95% identity to SEQ ID NOs: 5, 6, 14, and 15.
There is no disclosure of sufficient characteristics of the SARS-CoV-2 spike protein Beta variants claimed to allow persons of ordinary skill in the art to recognize that applicants were in possession of the exponential quantity encompassed by claims. The specification does not provide adequate written description of SARS-CoV-2 spike proteins attributed as derived from a Beta variant. The specification does not clearly allow persons of ordinary skill in the art to recognize that the inventors invented what is claimed. The claims do not meet the written description provision of 35 U.S.C. 112, first paragraph.
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.
Claims 1, 3, 5, 8-10, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Gobeil et al. (Cell Reports. 2021 Jan 12; 34 (2)), Kirchdoerfer et al. (Scientific Reports. 2018 Oct 24; 8 (1): 15701), and Su et al. (bioRxiv. 2021 May 17: 2021-05).
Su et al. teach administering a modified SARS-CoV-2 Beta variant, B.1.351 spike protein with CpG 1018 (comprising 100% sequence identity to instant SEQ ID NO: 7), and alum hydroxide on day zero and boosting on day 21, a suitable interval, as required by instant claims 1, 3, 5, 8, 9 and 19. See “Immunogenicity analysis of Prototype S-Trimer and modified B.1.351 S-Trimer in mice”. Under “Booster doses following two doses of prototype vaccine could strengthen broad neutralization”, Su et al. teach administering a third dose at a suitable interval, as required by instant claim 10.
Su et al. do not teach the B.1.351 spike protein administered substantially consists of residues 14-1205 of spike protein of SARS-CoV-2 Beta variant with proline substitutions at residues 983 and 984 and a “GSAS” substitution at residues 679 – 682, as required by instant claim 1.
The “S-GSAS/PP” template of Gobeil et al. comprises ectodomain residues 1-1208, GSAS at the S2 furin cleavage site (corresponding to residues 679-682), and K986P-V987P mutations in “Plasmids” and Figure 1A.
One of ordinary skill in the art prior to the instant effective filing date would have been motivated to have administered the “S-GSAS/PP” of Gobeil et al. as the SARS-CoV-2 spike protein of Su et al. because of Gobeil et al. teach the two consecutive proline substitutions at the junction of the HR1 and CH regions stabilize the pre-fusion conformation, increase protein expression, and improves immunogenicity of spike proteins and “GSAS” inhibits furin cleavage and maintaining protein stability, see the paragraph bridging the columns on page 2, the paragraph bridging the pages 2-3, and Figures 3-5. One of ordinary skill in the art prior to the instant effective filing date would have had a reasonable expectation of success to have administered the “S-GSAS/PP” of Gobeil et al. as the SARS-CoV-2 spike protein of Su et al. because protein stability mutations taught by Gobeil et al. enhance immunogenicity.
Neither Su et al. nor Gobeil et al. mention a C-terminal T4 fibritin trimerization domain.
Kirchdoerfer et al. do, see “Plasmid construction, Protein expression and purification”.
One of ordinary skill in the art prior to the instant effective filing date would have been motivated to have C-terminally attached the T4 fibritin trimerization domain of Kirchdoerfer et al. to the “S-GSAS/PP” of Su et al. and Gobeil et al. because Kirchdoerfer et al. demonstrate that attachment of the C-terminal T4 fibritin trimerization domain to a recombinant SARS-CoV-2 spike protein promotes assembly of a soluble spike in its native trimeric conformation and more homogeneous material as vaccine immunogens, see Figure 4 and “Plasmid construction, Protein expression and purification”. One of ordinary skill in the art prior to the instant effective filing date would have had a reasonable expectation of success to have C-terminally attached the T4 fibritin trimerization domain of Kirchdoerfer et al. to the “S-GSAS/PP” of Su et al. and Gobeil et al. because the spike protein of Kirchdoerfer et al. also possesses a prefusion-stabilized SARS-CoV spike comprising K968P and V969P, see “Trypsin-cleaved SARS-CoV spike” and Kirchdoerfer et al. teach recombinant strategies taught stabilize equivalent regions in other coronaviruses in Figure 2 and HIV in the Introduction and the paragraph under Figure 6.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Gobeil et al., Kirchdoerfer et al., and Su et al. as applied to claims 1, 3, 5, 8-10, and 19 above, and further in view of SEQ 14 alignment with UniProt db access no A0A6M6D937_SARS2 Oct 2020.
See the teachings of Gobeil et al., Kirchdoerfer et al., and Su et al. above. None of the references teach a sequence comprising at least 95% identity to instant SEQ ID NO: 14, as required.
UniProt db access no A0A6M6D937 shares 95.6% (rounds to 96%) identity with instant SEQ ID NO: 14, see the alignment provided.
It would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to have used the UniProt db access no A0A6M6D937 sequence as the SARS-CoV-2 spike of Gobeil et al., Kirchdoerfer et al., and Su et al. because UniProt db access no A0A6M6D937 possesses all of the requisite sequence structures to induce an immune response against SARS-CoV-2, taught by Su et al., and implement all of the recombinant modifications of Gobeil et al., Kirchdoerfer et al.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Gobeil et al., Kirchdoerfer et al., and Su et al. as applied to claims 1, 3, 5, 8-10, and 19 above, and further in view of Gupta (Advanced Drug Delivery Reviews. 1998; 32: 155 –172).
See the teachings of Gobeil et al., Kirchdoerfer et al., and Su et al. above. None of the references teach the immunogenic composition comprises from about 250 to about 1500 µg Al3+, as required.
Gupta teaches, “The usual dose of aluminum used for human fore, potency tests in animals based on dilution of vaccines is around 0.5 mg” in section 5.2, i.e., 500 µg.
Absent evidence of criticality, the ml and µg quantity of dose and Al3+, respectively, are adjustable in the prior art. Therefore, it would have been prima facie obvious for a person having ordinary skill in the art prior to the effective filing date to optimize the ml and µg Al3+ quantities per dose . MPEP 2144.05 states, “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine optimization.”
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Gobeil et al., Kirchdoerfer et al., and Su et al. as applied to claims 1, 3, 5, 8-10, and 19 above, and further in view of Kuo et al. (Scientific Reports. 2020 Nov 18; 10 (1):20085).
See the teachings of Gobeil et al., Kirchdoerfer et al., and Su et al. above. None of the references teach the immunogenic composition comprises from about 750-1500 μg CpG, as required.
Kuo et al. teach 1500 μg CpG 1018 or 750 μg CpG 1018 administered with recombinant SARS-CoV-2 spike, see “S‑2P did not result in systemic adverse effects in rats”, which is the same CpG administered by Su et al.
Absent evidence of criticality, the μg quantity of CpG is adjustable in the prior art. Therefore, it would have been prima facie obvious for a person having ordinary skill in the art prior to the effective filing date to optimize the μg quantity of CpG per dose . MPEP 2144.05 states, “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine optimization.”
Claims 7 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Gobeil et al., Kirchdoerfer et al., and Su et al. as applied to claims 1, 3, 5, 8-10, and 19 above, and further in view of Malladi et al. (ACS infectious diseases. 2021 Jul 14; 7 (8): 2546-2564).
See the teachings of Gobeil et al., Kirchdoerfer et al., and Su et al. above. None of the references teach the immunogenic composition can be stored at 40°C to 42°C for 3 to 7 days, as required by claim 7 or intramuscular administration, required by claim 20.
Malladi et al. teach a highly thermotolerant SARS-CoV‑2 spike protein maintaining functional stability under transient thermal stress of up to 100 °C and stability during storage of over 4 weeks at 37 °C in the abstract, Figures 1, 2, and the first paragraph of the Discussion.
One of ordinary skill in the art prior to the instant effective filing date would have been motivated to have lyophilized the recombinant spike protein of Gobeil et al., Kirchdoerfer et al., and Su et al., as taught by Malladi et al., because it eliminates the requirement for cold-chain in the Introduction and Conclusion sections. One of ordinary skill in the art prior to the instant effective filing date would have had a reasonable expectation of success to have lyophilized the recombinant spike protein of Gobeil et al., Kirchdoerfer et al., and Su et al., as taught by Malladi et al., because the recombinant spike proteins of Gobeil et al., Kirchdoerfer et al., Su et al., and Malladi et al., are in trimeric conformation, see the previous citations of Gobeil et al., Kirchdoerfer et al., and Su et al and “Trimeric mRBD Elicits High Titers of Neutralizing Antibodies in Mice and Guinea Pigs and Protects Hamsters from Viral Challenge” by Malladi et al.
Malladi et al. teach intramuscular administration of the recombinant spike protein in “Mice and Guinea Pig Immunizations”.
It would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to have administered the recombinant spike protein of Gobeil et al., Kirchdoerfer et al., and Su et al. intramuscularly, as taught by Malladi et al. with a reasonable expectation of success because both Su et al. and Malladi et al. teach prophylactic efficacy with prime-boost administrations, see the previous citations of Gobeil et al., Kirchdoerfer et al., and Su et al and the abstract and “Trimeric mRBD Elicits High Titers of Neutralizing Antibodies in Mice and Guinea Pigs and Protects Hamsters from Viral Challenge”.
Claims 11-18 are rejected under 35 U.S.C. 103 as being unpatentable over Gobeil et al., Kirchdoerfer et al., and Su et al. as applied to claims 1, 3, 5, 8-10, and 19 above, and further in view of SEQ 5 alignment with Geneseq db access no BJU94406 August 2021.
See the teachings of Gobeil et al., Kirchdoerfer et al., and Su et al. above. None of the references teach a sequence comprising at least 90% identity to instant SEQ ID NO: 5, as required.
Geneseq db access no BJU94406 shares 100% identity with instant SEQ ID NO: 5, see the alignment provided.
It would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to have used the Geneseq db access no BJU94406 sequence as the SARS-CoV-2 spike of Gobeil et al., Kirchdoerfer et al., and Su et al. because Geneseq db access no BJU94406 possesses all of the requisite sequence structures to induce an immune response against SARS-CoV-2, taught by Su et al., and implement all of the recombinant modifications of Gobeil et al., Kirchdoerfer et al.
Instant claims 15 and 16 additionally require a fourth dose, not taught by any of the references. However, it would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to have boosted the recombinant spike protein multiple times, i.e., more than three, to boost and maintain immune recognition.
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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claims 1 and 4-6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, and 5 of U.S. Patent No. 12,296,002. Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1, 4, and 5 of ‘002 anticipate the immunogenic composition against a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), comprising an antigenic recombinant protein and an adjuvant selected from the group consisting of an aluminum-containing adjuvant, an unmethylated cytosine-phosphate-guanosine (CpG) motif, and a combination thereof, wherein the antigenic recombinant protein substantially consists of residues 14-1205 of spike protein of SARS-CoV-2 Beta variant with proline substitutions at residues 983 and 984 and a “GSAS” substitution at residues 679 - 682 and a C-terminal T4 fibritin trimerization domain of instant claim 1. Claim 4 of ‘002 requires a 0.5 ml dose of the immunogenic composition comprises from about 250 to about 1500 µg Al3+, or about 375 µg Al3+ or about 750 µg Al3+, recited in instant claim 4. Claim 1 of ‘002 requires the unmethylated CpG motif as a synthetic oligodeoxynucleotide (ODN) of SEQ ID NO: 8, identical to SEQ ID NO: 8, recited in instant claim 5. Claim 5 of ‘002 anticipates a 0.5 ml dose of the immunogenic composition comprises from about 750 to about 3000 μg of the unmethylated CpG motif, or about 750 μg, 1500 μg, or 3000 μg of the unmethylated CpG motif, recited in instant claim 6.
Claims 8, 11-18, and 20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, , 3-6, 8, and 14 of U.S. Patent No. 12,296,002 in view of Su et al. (bioRxiv. 2021 May 17: 2021-05).
See claims 1, 4, and 5 of ‘0002. Claims 3 and 8 of ‘0002 recite SEQ ID NOs: 5 and 6, which are identical to instant SEQ ID NOs: 5 and 6 recited in instant claims 11-18. Claim 6 of ‘0002 is drawn to a method of eliciting an immune response against a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a subject in need thereof, comprising administering to the subject an effective amount of the SARS-CoV-2 spike, corresponding to instant claim 8. Claim 14 of ‘0002 states that the administration is intramuscular, as required by instant claim 20. The claims of ‘002 do not mention that the effective amount of the SARS-CoV-2 spike is accomplished by a prime-boost regimen.
Su et al. teach administering a modified SARS-CoV-2 Beta variant, B.1.351 spike protein and boosting on day 21, see “Immunogenicity analysis of Prototype S-Trimer and modified B.1.351 S-Trimer in mice”. Under “Booster doses following two doses of prototype vaccine could strengthen broad neutralization”, Su et al. teach administering a third booster dose.
One of ordinary skill in the art prior to the instant effective filing date would have been motivated to have administered the SARS-CoV-2 spike of ‘002 in a prime-boost regimen, as taught by Su et al. to induce significant neutralizing antibody titers an and an optimal immune response, see “Immunogenicity of Prototype or B.1.351 S-Trimer booster doses (dose 3) in mice” and “Booster doses following two doses of prototype vaccine could strengthen broad neutralization”. One of ordinary skill in the art prior to the instant effective filing date would have had a reasonable expectation of success to have administered the SARS-CoV-2 spike of ‘002 in a prime-boost regimen, as taught by Su et al. because both ‘002 and Su et al. administer the recombinant spike protein with CpG and alum adjuvants.
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Allen 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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Shanon A. Foley/ Primary Examiner, Art Unit 1671
Prosecution Insights