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/US2022/020218, filed on 03/14/2022, which claims priority to U.S. Provisional Application No. 63/281,021, filed on 11/18/2021, which claims priority to U.S. Provisional Application No. 63/161,429, filed on 03/15/2021 that is hereby acknowledged by the Examiner.
Status of the Claims
The amendment dated 10/07/2024 is acknowledged. Claims 46-65 are pending and under examination.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/14/2023 and 10/07/2024 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 09/14/2023 are acknowledged and accepted by the Examiner.
Claim Objections
Claims 48 and 63 are objected to for the following informalities:
Claims 48 and 63 are 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.
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).
Claims 46-47, 49, 51, 53-62 and 64 are rejected under 35 U.S.C. 103(a) as being unpatentable over Vogel et al. “Vogel” (BNT162b vaccine protect rhesus macaques from SARS-CoV-2, Nature, 592(7853):283-289, IDS of record dated 12/14/2023).
The claims are directed to a method of eliciting an immune response in a human subject, the method comprising intramuscularly administering to the human subject a dose of a vaccine comprising: a messenger ribonucleic acid (mRNA) comprising an open reading frame (ORF) that encodes a fusion protein comprising, from N-terminus to C-terminus, an N-terminal domain (NTD) of a SARS-CoV-2 Spike (S) protein linked to a receptor-binding domain (RBD) of the SARS-CoV-2 S protein, wherein the mRNA is formulated in a lipid nanoparticle (LNP); wherein the ORF comprises nucleosides consisting of 1-methyl-pseudouridine, adenosine, guanosine, and cytidine; and wherein the dose comprises from 2.5 ug-15 ug of the mRNA.
Regarding claims 46-47, 49, 51, 62 and 64, Vogel discloses the preclinical development of two vaccine candidates (BNT162b1 and BNT162b2) that contain nucleoside-modified messenger RNA that encodes immunogens derived from the spike glycoprotein (S) of SARS-CoV-2, formulated in lipid nanoparticles. BNT162b1 encodes a soluble, secreted trimerized receptor-binding domain (known as the RBD–foldon). BNT162b2 encodes the full-length transmembrane S glycoprotein, locked in its prefusion conformation by the substitution of two residues with proline (S(K986P/V987P); hereafter, S(P2) (also known as P2 S)) (Abstract). Vogel discloses the administration to rhesus macaques of two doses of BNT162b1 encoding the RBD domain of the SARS-Cov-2 spike protein fused to the signal peptide (page 283 second column second para. - page 284 first column fourth para.). Vogel discloses “BNT162b1 and BNT162b2 DNA templates were cloned into a plasmid vector with backbone sequence elements (T7 promoter, 5′ and 3′ UTR, 100 nucleotide poly(A) tail) interrupted by a linker (A30LA70, 10 nucleotides) for improved RNA stability and translational efficiency. The DNA was purified, spectrophotometrically quantified and in vitro-transcribed by T7 RNA polymerase in the presence of a trinucleotide cap1 analogue ((m2 7,3′-O)Gppp(m2’-O)ApG) (TriLink) and with N1-methylpseudouridine-5′-triphosphate (m1ΨTP) (Thermo Fisher Scientific) replacing uridine-5′-triphosphate (UTP)” (Methods second column second para.). Vogel discloses the vaccine is administered to mice in a single dose of 0.2, 1 or 5 ug to mice (page 285 first column last para. – second column first para.) and to macaques in two doses 21 days apart of 30 or 100 ug (page 287), resulting in GMT of 285 that occurs 28 days after the second dose (page 287 first column second para.); and the nanoparticles comprise a ionizable cationic lipid, a pegylated lipid, DSPC and cholesterol and the vaccine has a concentration of 0.5mg/ml; and (Methods second column fourth para.). Vogel discloses one intramuscular dose of either candidate vaccine elicits a dose-dependent antibody response with high virus-entry inhibition titers and strong T-helper-1 CD4+ and IFNγ+CD8+ T cell responses (Abstract). With respect to the method being administered to a human subject, Vogel discloses the vaccine candidates are being evaluated in phase I trials in Germany and the USA1–3, and BNT162b2 is being evaluated in an ongoing global phase II/III trial (NCT04380701 and NCT04368728) (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.
Regarding claims 53 and 54, Vogel discloses intramuscular injections to mice in a single dose of 0.2, 1 or 5 ug to mice (page 285 first column last para. – second column first para.) and to macaques in two doses 21 days apart of 30 or 100 ug (page 287 and Figure 3) which encompasses the claimed 10 ug of mRNA. The dose comprising 10 ug of the mRNA is not inventive and considered routine and obvious to one of ordinary skill in the art. It has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value of a result effective variable. According to section 2144.05 of the M.P.E.P., "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation." Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). "No invention is involved in discovering optimum ranges of a process by routine experimentation." Id. at 458, 105 USPQ at 236-237. The "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Application of Boesch, 617 F.2d 272, 276, 205 USPQ 215, 218-219 (C.C.P.A. 1980). See MPEP § 2144.05 (II) (“Generally, differences in concentration … will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration … is critical.”). Accordingly, it would have been obvious for one of ordinary skill to determine the appropriate concentration of the mRNA dosage in the methods disclosed by the prior art by routine experimentation procedures known in the art in order to optimize the amount of vaccine dosage to arrive at the currently claimed amount.
Regarding claims 55-61, with respect to the subject’s patient parameters/indicators such as age, being immunocompromised, having a chronic pulmonary disease, COPD, asthma, an underlying comorbid condition (e.g. obesity, heart disease, diabetes, or lung disease), the limitation is not considered an inventive step and would be considered routine and obvious to one of ordinary skill in the art to use a cohort of subjects whereby the subjects of varying age have one or more of said conditions in order to assess the efficacy of the vaccine against the virus. In the absence of any unexpected results of eliciting an immune response against SARS-CoV-2 recited in these claims, the selections defined therein only can be seen as routine and obvious selections which does not involve an inventive step in view of Vogel.
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.
Claims 50, 52 and 65 are rejected under 35 U.S.C. 103(a) as being unpatentable over Vogel et al. “Vogel” (BNT162b vaccine protect rhesus macaques from SARS-CoV-2, Nature, 592(7853):283-289, IDS of record dated 12/14/2023) as applied to claims 46-47, 51, 62 and 64 above, in view of Joyce et al. “Joyce” (WO2021/178971, filing date March 8, 2021, IDS of record dated 12/14/2023). The teachings of Vogel are outlined above and incorporated herein.
Regarding claims 50, 52 and 65, Vogel does not disclose that the non-cleavable linker is a glycine-serine (GS) linker.
Joyce, however, disclose vaccines against SARS-CoV-2 comprising a nanoparticle comprising a fusion protein comprising a nanoparticle-forming peptide and at least one antigenic coronavirus peptide selected from: a. a receptor-binding domain (RBD) of a coronavirus, or a fragment or variant thereof, b. an N-terminal domain (NTD) of a coronavirus, or a fragment or variant thereof, c. an SI domain of a coronavirus, or a fragment or variant thereof, d. a stabilized extracellular spike S-2P domain of a coronavirus, or a fragment or variant thereof, e. a stabilized extracellular spike S domain of a coronavirus, or a fragment or variant thereof, or f. a stabilized extracellular spike S-trimer of a coronavirus, or a fragment or variant thereof (claim 1 of Joyce); and whereby the fusion protein comprises a flexible amino acid linker such as a glycine-serine linker (para. [0114 and Table 1). Joyce states “In some embodiments, the antigenic coronavirus peptide may comprise 1, 2, or 3 or more distinct domains of a coronavirus spike protein connected together in sequence, and in such embodiments, a linker may optionally separate the distinct domains (paragraph [0117]).
It would have been obvious to one of ordinary skill in the art to generate an mRNA comprising an open reading frame (ORF) that encodes a fusion protein comprising, from N-terminus to C-terminus, an N-terminal domain (NTD) of a SARS-CoV-2 Spike (S) protein linked to a receptor-binding domain (RBD) of the SARS-CoV-2 S protein, wherein the mRNA is formulated in a lipid nanoparticle (LNP) as disclosed by Vogel, whereby a non-cleavable linker is a glycine-serine (GS) linker as disclosed by Joyce. One of ordinary skill in the art would be motivated to do so with a reasonable expectation of success given the fact the GS linker are known in the art and Joyce demonstrates generating a SARS-CoV-2 fusion protein comprising a GS linker (Figure 1) for the advantage of stabilizing the fusion protein. 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