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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 7/23/26 has been entered.
Election/Restrictions
Applicant’s election without traverse of invention I in the reply filed on 8/25/25 is acknowledged.
Claim 39 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 8/25/25.
Claims 21-38 and 40 are examined on the merits. Claim 40 is newly presented.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 7/30/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63/265,634, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. The amendment of claim 21 to recite, “substantially 100% of cytidines in the polynucleotide are 5-methyl-cytidines” is not supported by ‘634. The provisional application 63/393,400 does provide support for this limitation. Therefore, the claimed invention has the earliest effective priority date of 7/29/2022, which is the submission date of ‘400.
Claim Objections
(New Objection) Claims 22-34, 37, 38 and 40 are objected to because of the following informalities: these claims recite, “The polynucleotide” or “the polynucleotide”, however, these claims depend from claim 21 which refers to the polynucleotide as “isolated polynucleotide”. Therefore, it is suggested that claims 22-34, 37, 38 and 40 be amended to also recite “isolated” in order to place these claims in a form commensurate with claim 21. Appropriate correction is required.
Terminal Disclaimer
The terminal disclaimer filed on 7/23/26 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of any patent issued to 18/751,109 has been reviewed and is accepted. The terminal disclaimer has been recorded.
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.
(Prior Rejection withdrawn in view of filing of Terminal Disclaimer) Claims 21-33 and 35-38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 15 of copending Application No. 18/751,109 in view of Muik et al. (infra).
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.
(Prior Rejection Maintained) Claims 21-38 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.
The term “substantially 100% of cytidines in the polynucleotide are 5-methyl-cytidines” in claim 21 is a relative term which renders the claim indefinite. The term “substantially” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Furthermore, it is unclear if the limitation of “substantially 100%” includes 100% or 99% or less of the cytidines are 5-methyl-cytidines. Claims 22-38 are also rejected because they depend from claim 21, but do not remedy this deficiency.
Response to arguments:
Applicant presents the following arguments in traversal of the rejection:
Applicants argue that in view of paragraph 50 of the published specification (see below), a skilled person in the art would understand the meaning of what “substantially 100%” means.
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This argument is not convincing. Paragraph 50 provides two examples (50% and 100%) of what the metes and bounds of “substantially 100% of cytidines in the polynucleotide are 5-methyl-cytidines” are. However, this guidance is not sufficient to inform one of ordinary skill in the art as to what constitutes substantially 100% since the amount of cytidines being replace are either all of them (100%) or half (50%). This rejection can be overcome by claiming either 50% of the cytidines are replaced with 5-methyl-cytidines or 100% (see new claim 40).
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)(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.
(Prior Rejection Maintained and extended to new claim 40 and new limitations) Claim(s) 21-33, 35-38 and 40 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Muik et al. (US PGPub 2023/0338512).
The claimed invention is drawn to an isolated RNA polynucleotide, which encodes Venezuelan Equine Encephalitis Virus (VEEV) non-structural proteins (nsp) nsp1-4, and a polypeptide comprising an antigenic peptide, wherein the polynucleotide comprises a 5-methyl-cytidine. The antigen peptide is a protein derived from a virus, which includes a receptor binding domain and CD8+ T cell epitopes. The virus is COVID-19 (a coronavirus) and the antigenic peptide can be derived from a coronavirus or the antigenic peptide can be derived from an influenza hemagglutinin (HA), which would include the transmembrane domain of the HA. In addition, the antigenic peptide comprises a receptor binding domain, transmembrane domain and CD4+ T cell epitopes and CD8+ T cell epitopes. The polynucleotide can also be part of a vector, which can be combined with a pharmaceutically acceptable vehicle. The vector possesses a promoter, a 5’UTR, a polynucleotide encoding alphavirus nsp1-4, a subgenomic (SG) promoter, a gene of interest encoding an antigenic peptide, a 3’ UTR and a poly A tail. The claimed vaccine composition (polynucleotide or vector) is combined with another one or more vaccine composition.
Muik et al. largely focuses on developing RNA based compositions against SARS-CoV-2 viruses. [see abstract] These compositions can be formulated with pharmaceutically acceptable carriers and different RNA sequences can be complexed together or separately with proteins and/or lipids to generate RNA particles for administration, which would anticipate the combination of another one or more vaccine composition [instant invention’s claim 38]. [see paragraphs 75-77 and 28] Muik et al. teach the generation of an VEEV alphavirus RNA replicon that contains nucleic acid sequences encoding nsp1-4 and an immunogen. [see paragraph 605] The general structure of such a replicon can be found in Figure 5 and summarized in paragraph 321.
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In addition to figure 5, paragraphs 683-691 further teach the structure of an alphavirus RNA sequence which possesses a 5’ UTR, nsp1-4 coding sequences from VEEV linked to a promoter, a subgenomic promoter which is part the UTR region seen in figure 5. Figure 5 also reaches the encoding of a COVID-19 spike protein, which would inherently possess a S1 portion, a receptor binding domain, and a transmembrane domain. The spike protein would also inherently possess CD4+ and CD8+ T cells epitopes.
Muik et al. also teach that a transmembrane domain of an influenza hemagglutinin can be encoded by their RNA polynucleotide sequences. [see paragraph 492]
The RNA sequences of Muik et al. can possess modified nucleobases, such as 5-methylcytidine. More specifically, Muik teach at paragraph 606 that “In one embodiment, the RNA described herein may have modified nucleosides” and that 5-methylcytidine is substituted partially or completely, preferably completely, for cytidine, which thereby teach the claimed limitation of amended claim 21 of “substantially 100% of cytidines in the polynucleotides are 5-methyl-cytidines”. [see paragraph 621] The RNA can also be part of a vector. [see paragraph 650]
Therefore, Muik et al. anticipates the instant invention.
Response to arguments:
Applicant presents the following arguments in traversal of the rejection:
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., self-amplifying alphavirus replicon in which substantially all cytidines are replaced by 5-methylcytidines) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
The 35 USC 102 rejection based on Muik et al. is based on picking and choosing and combining various parts of Muik et al. to state that the claimed invention is anticipated. For example, Muik identifies saRNA as one possible RNA platform; separately lists various nucleoside modifications, including 5-methyl-cytidine; does not disclose the presently claimed specific combination of features a polynucleotide encoding VEEV non-structural proteins nsp1-nsp4 and replacement of cytidines in the polynucleotide with 5-methyl-cytidine. Moreover, Muik et al. provides a generalized list of possible nucleoside modifications in paragraph 621 and Muik et al. do not provide any working examples of experimental data demonstrating the generation of a polynucleotide encoding VEEV nsps1-4 and containing 5-methyl-cytidine. Lastly, Muik et al. expressly teaches that in some embodiments, “the saRNA preferably contains uridine” (see paragraphs 733-734). Thus, Muik et al. does not direct the skilled artisan toward a substantially or fully 5-methyl-cytidine-substituted isolated polynucleotide encoding VEEV NSP1-3.
In response, in figure 5, Muik et al. teach polynucleotides containing VEEV nsps1-4 and an antigenic sequences encoding the spike protein of SARS-CoV-2, which possess CD4+ and CD8+ T cells epitopes. With regard to modifications of an RNA sequence in which substantially 100% or 100% of the cytidines are replaced with 5-methyl-cytidine, Muik et al. teach at paragraph 606:
“In one embodiment, the RNA described herein may have modified nucleosides. In some embodiments, the RNA comprises a modified nucleoside in place of at least one (e.g., every) uridine.”
; and at paragraph 621:
“In one embodiment, the RNA comprises other modified nucleosides or comprises further modified nucleosides, e.g., modified cytidine. For example, in one embodiment, in the RNA 5-methylcytidine is substituted partially or completely, preferably completely, for cytidine. In one embodiment, the RNA comprises 5-methylcytidine and one or more selected from pseudouridine (ψ), N1-methyl-pseudouridine (m1ψ), and 5-methyl-uridine (m5U). In one embodiment, the RNA comprises 5-methylcytidine and N1-methyl-pseudouridine (m1ψ). In some embodiments, the RNA comprises 5-methylcytidine in place of each cytidine and N1-methyl-pseudouridine (m1ψ)) in place of each uridine.” .
Therefore, the teachings of Muik et al. specifically teach that their RNA sequences can be modified in the same manner as applicant’s claimed invention. With regard to no working examples or experimental data, such information is not required by the prior art since the prior art is presumed enabled, absent evidence to the contrary.
Therefore, Muik et al. anticipate the instant invention.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
(Prior Rejection Maintained) Claim(s) 34 is rejected under 35 U.S.C. 103 as being unpatentable over Muik et al. as applied to claims 21-33 and 35-38 above, and further in view of Gaiha et al. (US PGPub 20230302083).
The claimed invention also requires that the CD4+ T cell epitope is a Pan-DR epitope (PADRE).
The teachings of Muik et al. are summarized above, however, they do not teach the use of a CD4+ T cell epitope that is Pan-DR (PADRE).
Gaiha et al. immunogenic compositions focused on treating SARS-CoV-2 viruses. One example is nucleic acid sequences which encode SARS-CoV-2 spike proteins, with a focus on CTL epitopes. [see paragraphs 11 and 105] Gaiha et al. also teach the use of immune-enhancer elements, such as the universal T-helper epitope pan HLA-DR (PADRE). [see paragraph 58]
It would have been obvious to one of ordinary skill in the art to modify the compositions taught by Muik et al. in order to employ immune-enhancers, such as PADRE, with their immunogenic compositions. One would have been motivated to do so, given the suggestion by Muik et al. that inducing immune responses against an immunogen of interest is an important focus of their teachings [see paragraph 25]. There would have been a reasonable expectation of success, given the knowledge that PADRE functions as a T-helper epitope and can aid in inducting immune responses, as taught by Gaiha et al. Thus the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Response to arguments:
Applicant presents the following arguments in traversal of the rejection:
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., “self-amplifying alphavirus replicon in which substantially all cytidines are replaced by 5-methylcytidines” and “self-amplifying RNA”) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Therefore, arguments pertaining to these limitations are rendered moot.
Furthermore, Maruggi et al. teach that mRNA possessing modified nucleotides, such as 1-methylpseudouridine, can increase protein expression. [see page 760, left column, last paragraph] Lastly, Muik et al. do teach in paragraph 734, that: “In some embodiments, the saRNA comprises one or more nucleoside modifications as described herein.” and as stated above, Muik et al. teach the claimed polynucleotide that possesses VEEV nsps1-4, antigenic sequences and 5-methyl-cytidine substitutions. The additional teachings of Gaiha et al. establish why one of ordinary skill in the art would also include a PADRE sequence with a SARS-CoV-2 spike protein.
Thus the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BENJAMIN P BLUMEL whose telephone number is (571)272-4960. The examiner can normally be reached M-F 8-5 EST.
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/BENJAMIN P BLUMEL/Primary Examiner, Art Unit 1671
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