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 .
Applicant’s reply has cured the objection to the instant specification, claim objections, the previous rejections under 35 USC § 112(b), and the rejection under 35 USC § 103 regarding SEQ ID NO: 33.
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, 2, 4, 8-10, 14-19, 21, 27, 29-31, and 34 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.
Amended claim 1 requires a “mutated spike glycoprotein”. Since Portelli et al. (Nature Genetics. 2020 Oct; 52 (10): 999-1001) describe genomic variations of SARS-CoV-2 spike glycoproteins across many isolates, averaging two variants per month (second paragraph), it is unclear what is encompassed by the instant “mutated spike glycoprotein”. One spike protein compared with any other would be mutated, as evidenced by Portelli et al. Is the mutation claimed acquired by recombinant techniques?
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, 2, 4, 8-10, 14-19, 21, 27, 29-31, and 34 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 claim 1 requires an antigen from an infectious disease-causing bacteria and an antigen from a betacoronavirus. While the claim amendments have removed the term, “derived”, the claims still encompass any antigen from any disease-causing bacteria and any betacoronavirus. Claim 17 requires polysaccharides from N. meningitidis. The instant disclosure provides discussions for the full length SARS-CoV-2 spike glycoprotein, i.e., SEQ ID NOs: 1 and 2, specific Neisseria meningitidis polypeptides, SEQ ID NOs: 3 and 4, Neisseria meningitidis capsular polysaccharides, MenA, MenC, MenW, and MenY, Clostridium difficile toxin A or C and c-terminal portions thereof, and S. pneumoniae capsular polysaccharides in paragraphs [0031, 0125, 0165, 0172, 0216, 0217, 0245, 0815, and 0816 of the instant published disclosure, USPgPub 2025/0281601, of record. Therefore, while the instant disclosure provides written support for whole, specific antigens obtained from Neisseria meningitidis, Clostridium difficile, S. pneumoniae, and SARS-CoV-2, there is no written description for any antigen from any infectious disease-causing bacteria and any antigen from any betacoronavirus, encompassed by the instant claims.
The skilled artisan would not recognize any antigen from any bacteria, administered at an effective dose to a human to elicit an immune response against an infectious disease-causing bacterium, as asserted. Cavaillon (Toxicon. 2018; 149: 45-53, of record) review exotoxins and endotoxins from various bacteria, including Neisseria meningitidis, Clostridium difficile, and S. pneumoniae, leading to the production of IFNγ and chemokines, resulting in a cytokine storm, sepsis, toxic shock syndrome, and mortality. See the abstract, Table 1, Sections 2, 4, and Figures 1 and 2, depicting enhanced release of cytokines upon first contact with an endotoxin and/or exotoxin superantigen.
Amended claim 1 requires a “mutated spike glycoprotein”. Since Portelli et al. (Nature Genetics. 2020 Oct; 52 (10): 999-1001) describe genomic variations of SARS-CoV-2 spike glycoproteins across many isolates, averaging two variants per month (second paragraph), it is unclear what is encompassed by the instant “mutated spike glycoprotein”. One spike protein compared with any other would be mutated, as evidenced by Portelli et al.
The instant disclosure provides no written support for any and all antigens from the broad genus of betacoronavirus spike glycoproteins. Llanos et al. (International Journal of Molecular Sciences. June 2020; 21: 4546, of record) review betacoronavirus genomes, divided into five subgenera by the International Committee on Taxonomy of Viruses (ICTV): Embecovirus, Sarbecovirus, Merbecovirus, Nobecovirus and Hibecovirus, see Table 1 and Figure 1. The skilled artisan would not recognize a mutated spike glycoproteins from any betacoronavirus, administered at an effective dose to a human to elicit an immune response against a betacoronavirus, as asserted. Hurtado-Tamayo et al. (Frontiers in Cellular and Infection Microbiology. 2023; 13: 1166839, of record) describe accessory proteins encoded by betacoronaviruses associated with virulence, see "Interference of deadly HCoV accessory proteins with the inflammatory response". Therefore, while accessory proteins of betacoronaviruses are antigenic, expression promotes pathogenesis.
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 factors present in the specification are SARS-CoV-2 mRNA sequences SEQ ID NOs: 1 or 2, specific Neisseria meningitidis polypeptides, SEQ ID NOs: 3 and 4, Neisseria meningitidis capsular polysaccharides, MenA, MenC, MenW, and MenY, Clostridium difficile toxin A or C and c-terminal portions thereof, and S. pneumoniae capsular polysaccharides. There is no disclosure of sufficient characteristics of the claimed genus of betacoronavirus and bacteria antigens allowing persons skilled in the art to recognize that applicants were in possession of the claimed genus of betacoronavirus and bacteria antigens claimed. In the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of betacoronavirus and bacteria antigens. 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.
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 betacoronavirus and bacteria antigens. 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, 2, 4, 8, 15, 30, 31, and 34 are rejected under 35 U.S.C. 103 as being unpatentable over Maeda et al. (PNAS. 15 April 2021; 118 (18): e2025622118), Polack et al. (New England journal of medicine. 2020 Dec 31; 383 (27):2603-2615), and Dubensky et al. (USPgPub 2013/0315950), as evidenced by Vogel et al. (BioRxiv. 2020 Sep 8: 2020-09). All references of record.
In response to the rejection of record, applicant points out that Maeda et al. utilizes a bacteria with a large number of the surface proteins deleted. Applicant concludes that Maeda et al. do not teach or suggest co-administration of an antigen from an infectious disease-causing bacterium.
Applicant’s arguments and a review of Maeda et al. have been fully considered, but are found unpersuasive. Claim 1 requires co-administration of an antigen from a disease-causing bacteria, not the disease-causing bacteria itself. In the paragraph bridging the columns on page 1, Maeda et al. teach:
One of the oldest vaccine technologies is the killed whole-cell vaccine (KWCV) or bacterin. Many developing countries produce KWCVs (for example, pertussis) indigenously. KWCVs are currently licensed to prevent deadly diseases, for example cholera (5), and are produced at large industrial scale for agricultural animals. Several KWCVs have been developed against pathogenic Escherichia coli (reviewed in ref. 6)….Vaccination specifically with conserved E. coli antigens did not alter the gastrointestinal (GI) microbiome (6, 9). In human studies, volunteers were immunized orally with a KWCV against ETEC (10) with no adverse effects. An ETEC oral KWCV along with a cholera B toxin subunit adjuvant was studied in children and found to be safe (11).
Therefore, the E. coli KWCV of Maeda et al. express at least one antigen in common with a disease-causing E. coli. The mentions of E coli in the instant disclosure found in paragraphs [0014, 0026-0029, 0047, 0319, and 0759] do not distinguish sources of the instant bacterial antigens. The instant disclosure provides as much description of the E. coli antigens encompassed by the claims as those remaining in the E. coli KWCV of Maeda et al.
Regarding the teachings of Polack et al., applicant points out that this reference does not teach the addition of a bacterial antigen.
Applicant’s arguments and a review of Polack et al. have been fully considered, but are found unpersuasive. The teachings of Polack et al. are relevant to the required limitations of an mRNA encoded SARS-CoV-2 antigen, recited in claim 1.
Applicant argues that Dubensky et al. do not teach or suggest any co-administration of an antigen from a disease-causing bacteria and an mRNA encoding a betacoronavirus antigen.
Applicant’ arguments have been fully considered, but are found unpersuasive because Dubensky et al. is not required to re-teach limitations that have been taught in other references. Contrary to applicant’s assertion, paragraph [0089] of Dubensky et al. discuss one dose of a composition comprising nucleic acids and bacterial antigens of paragraphs [0055, 0068, 0120, 0133], and Figures 1 and 2.
Claims 9, 10, 14, 16, 17, and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Maeda et al., Polack et al., and Dubensky et al., as evidenced by Vogel et al. as applied to claims 1, 2, 4, 8, 15, 30, 31, and 34 above, and further in view of Jansen et al. (USPgPub 2018/0214532), instant SEQ ID NO: 3 alignment with Geneseq db access no BAT08834 Sept 2013, and instant SEQ ID NO: 4 alignment with Geneseq db access no ADE44816 Jan 2004. All references of record.
In reply to the rejection of record, applicant argues that Jansen et al. fail to teach co-administration of an antigen from a disease-causing bacteria and an mRNA encoding a betacoronavirus antigen.
Applicant’ arguments have been fully considered, but are found unpersuasive because the combined teachings of Maeda et al., Polack et al., and Dubensky et al. would have provided inspiration to one of ordinary skill in the art prior to the instant effective filing date to have combined all of the requisite limitations of teach co-administration of an antigen from a disease-causing bacteria and an mRNA encoding a betacoronavirus antigen, with a reasonable expectation of success, absent evidence to the contrary.
Claims 19, 21, 27, and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Maeda et al., Polack et al., and Dubensky et al., as evidenced by Vogel et al. as applied to claims 1, 2, 4, 8, 15, 30, 31, and 34 above, and further in view of Tussey et al. (USPgPub 2016/0166671). All references of record.
In reply to the rejection of record, applicant argues that Tussey et al. fail to teach co-administration of an antigen from a disease-causing bacteria and an mRNA encoding a betacoronavirus antigen.
Applicant’ arguments have been fully considered, but are found unpersuasive because the combined teachings of Maeda et al., Polack et al., and Dubensky et al. would have provided inspiration to one of ordinary skill in the art prior to the instant effective filing date to have combined all of the requisite limitations of teach co-administration of an antigen from a disease-causing bacteria and an mRNA encoding a betacoronavirus antigen, with a reasonable expectation of success, absent evidence to the contrary.
Allowable Subject Matter
Claim 33 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. The prior art does not teach or suggest an mRNA comprising a sequence having residues 1-102 and 3880-4284 of SEQ ID NO: 1 and wherein residues 103-3879 of SEQ ID NO: 1 are replaced with a variant SARS-CoV-2 antigen.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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
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