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/US2022/040272, filed on August 13, 2022, which claims priority to U.S. Provisional Application No. 63/233,320, filed on August 15, 2021 that is hereby acknowledged by the Examiner.
Status of the Claims
The amendment dated 02/15/2024 is acknowledged. Claims 16-35 are pending and under examination.
Information Disclosure Statement
There was no information disclosure statement (IDS) submitted at the time of this Office action.
Specification
The disclosure is objected to because of the following informalities: The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see pages 12, 16 and 17). 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. Appropriate correction is required.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 16-31 and 34-35 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Stewart-Jones (WO2021/159040).
The claims are directed to a method of making an mRNA vaccine comprising:
(a) providing a parent nucleic acid sequence, wherein the parent nucleic acid sequence encodes a surface protein of an infection-causing agent or a cancer cell;
(b) performing undirected mutagenesis on the parent nucleic acid sequence to produce a variant population of undirected mutated sequences;
(c) transcribing the variant population of undirected mutated sequences to produce a variant population of undirected mutated mRNA sequences, wherein the variant population of undirected mutated mRNA sequences comprises at least one sequence that is not a known disease sequence; and
(d) formulating the variant population of undirected mutated mRNA sequences into a vaccine active against an unknown disease variant.
Regarding claims 16-19, 30-31 and 35, Stewart-Jones discloses an mRNA vaccine (are compositions (e.g., vaccines) that comprise one or more messenger ribonucleic acid (mRNA) molecules; pg. 2, lines 2-3) designed to induce an immune response against cancer cells or an infection causing agent (the mRNA molecules described herein are used to express key neutralizing domains of the SARS-CoV-2 coronavirus spike (S) protein that are efficient at inducing protective immunity; pg. 2, lines 5-6), wherein the mRNA vaccine is comprised of: at least one undirected mutated mRNA (polynucleotides encoding peptides or polypeptides containing substitutions, insertions and/or additions, deletions and covalent modifications with respect to reference sequences; pg. 87, lines 16-18; pg. 91, lines 10-15) wherein the undirected mutated mRNA is derived from at least a portion of a surface protein of the cancer cells or wherein the undirected mutated mRNA is derived from the parent infection-causing agent (mRNAs of the invention are designed to produce SARS-CoV-2 Spike proteins; pg. 22, line 24), wherein the infection-causing agent is a virus, a bacteria or a fungus (mRNAs of the invention are designed to produce SARS-CoV-2 Spike proteins; pg. 22, line 24), wherein the undirected mutated mRNA is generated using undirected mutagenesis (Codon optimization tools, algorithms and services are known in the art - nonlimiting examples include services from GeneArt (Life Technologies), DNA2.0 (Menlo ParkCA) and/or proprietary methods; pg. 91, lines 22-25); and wherein the undirected mutated mRNA contains at least 1 undirected mutation (polynucleotides encoding peptides or polypeptides containing substitutions, insertions and/or additions, deletions and covalent modifications with respect to reference sequences; pg, 87, lines16-18; pg. 91, lines 10-15).
Regarding claims 20-22, Stewart-Jones discloses the mRNA vaccine of claim 1. Stewart-Jones further discloses wherein the mRNA vaccine is designed to induce an immune response to a viral infection (The mRNA molecules described herein are used to express key neutralizing domains of the SARS-CoV-2 coronavirus spike (S) protein that are efficient at inducing protective immunity; pg. 2, lines 5-6); and wherein the undirected mutated mRNA sequences are in a receptor binding domain virus (an mRNA comprising an open reading frame (ORF) that encodes a receptor binding domain (RBD) of a SARS-CoV-2 Spike protein; pg. 4, lines 3-4; pg. 13, lines 11-12; pg. 24, lines 24-28).
Regarding claim 23, Stewart-Jones discloses the nucleic acid sequence is incorporated in a plasmid (see Example 2).
Regarding claim 24, Stewart-Jones discloses the method utilizing error-prone RNA polymerases (pg. 102, lines 1-13).
Regarding claim 25, Stewart-Jones discloses the mRNA sequences is formulated using lipid nanoparticles (pg. 104, lines 25-28).
Regarding claims 26-27, Stewart-Jones discloses wherein the undirected mutated mRNA contains at least 50 undirected mutations (an encoded Spike protein antigen, has no greater than 100 ... or no greater than 5 amino acid substitutions and/or deletions; pg. 23, lines 5-8).
Regarding claim 28, Stewart-Jones discloses the undirected mutated mRNA vaccine of claim 1. Stewart-Jones further discloses wherein the undirected mutations in the mRNA have a density and wherein the density is not uniform across the undirected mutated mRNA (minor truncation, e.g., of one to a few, possibly up to 5 or up to 10 amino acids from the N- or C-terminus of the encoded Spike protein; pg. 22, lines 31-33).
Regarding claim 29, Stewart-Jones discloses the undirected mutated mRNA vaccine of claim 1. Stewart-Jones further discloses wherein the vaccine is comprised of a mixture of mRNAs (compositions that comprise a mixture of mRNAs encoding SARS-CoV-2 S protein subdomains; pg. 68, lines 3-4) and wherein at least one of the mRNAs is an undirected mutant variant of the parent mRNA (encoded SI or S2 protein antigens, may be tolerated without changing the antigenic properties of the protein. Likewise, variation (e.g., conservative substitution) of one to a few, possibly up to 4, 5, 6, 7, 8, 9 or 10 amino acids (or more) of the encoded Spike protein subunits, e.g., encoded S1 or S2 protein antigen; p. 24, lines 7-10).
Regarding claim 34, Stewart-Jones discloses wherein· the mRNA vaccine is designed to induce an immune response to a viral infection (the mRNA molecules described herein are used to express key neutralizing domains of the SARS-CoV-2 coronavirus spike (S) protein that are efficient at inducing protective immunity; pg. 2, lines 5-6), wherein the receptor binding domain is conserved (Likewise, variation (e.g., conservative substitution); p. 24, line 8); and wherein the undirected mutated mRNA
sequences are present in other parts of the viral genome (i.e. none of the mutations in a receptor binding domain) (minor truncation, e.g., of one to a few, possibly up to 4, 5, 6, 7, 8, 9 or 10 amino acids from the N- or C-terminus of the encoded subunit, e.g., encoded SI or S2 protein antigens, such as the NTD region; pg. 24, lines 5-7, page 35, lines 24-26).
Therefore, the cited prior art anticipates the claimed invention.
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 32-33 are rejected under 35 U.S.C. 103(a) as being unpatentable over Stewart-Jones (WO2021/159040) as applied to claims 16 and 30 above, in view of Sahin et al. “Sahin” (US2016/0058853). The teachings of Stewart-Jones are outlined above and incorporated herein.
Regarding claims 32-33, Stewart-Jones discloses an mRNA vaccine by the method of claim 16, but does not explicitly teach wherein the mRNA vaccine is designed to induce an immune response to a cancer cell.
Sahin, however, discloses the mRNA vaccine designed to induce an immune response to a bacterial infection, a fungal infection or a cancer cell (methods for inducing an efficient and specific immune response in a cancer patient by administering cancer vaccines targeting individual expression patterns of tumor antigens: paragraph [0014]), and wherein the undirected mutations are contained in mRNA coding for a surface protein of the bacteria. fungus or cancer cell (a vaccine for inducing a second immune response, when administered to a patent, preferably provides a collection of MHC presented epitopes ... incorporating sequence changes based on the identified mutations or sequence differences ... presentation of these epitopes by cells of a patient, in particular antigen presenting cells, preferably results in T cells targeting the epitopes when bound to MHC; paragraph [0057] and [0014]).
Accordingly, it would have been obvious to a person of ordinary skill in the art, at the time of the invention, to have modified the mRNA vaccine, as previously disclosed by Stewart-Jones, with a mRNA vaccine that is designed to induce an immune response to a bacterial infection, a fungal infection or a cancer cell; and wherein the undirected mutations are contained in mRNA coding for a surface protein of the bacteria, fungus or cancer cell, as previously disclosed by Sahin. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success for the benefit of a superior mRNA vaccine that can provide personalized therapy (Sahin reference; paragraph [0008]).
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
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