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
This Office Action is responsive to Applicant’s Amendment and Remarks, filed July 27, 2026. The amendment, filed July 27, 2026, is acknowledged, wherein claims 30 and 50 are amended, claims 1 – 28, 31 – 33, 39, 41 – 49, 51 – 69, 71 – 82, 84 – 142, and 144 – 253 are canceled.
Claims 29 – 30, 34 – 38, 40, 50, 70, 83, and 143 are pending in this application and are currently examined.
Priority
This application is a continuation application of PCT/US21/28486, filed April 21, 2021, which claims benefit of domestic applications 63/013,456 and 63/020,473, filed April 21, 2020 and May 5, 2020, respectively.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 07/27/2026 was filed after the mailing date of the previous Office Action on January 27, 2026. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Withdrawn Objections
The objection of claims 30 and 50 in the previous Office Action, dated January 27, 2026, has been considered and is withdrawn in view of the amended claims 30 and 50.
The following are maintained / modified grounds of rejection necessitated by Applicant’s Amendment, filed July 27, 2026, wherein claims 30 and 50 are amended.
Modified Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
i. Determining the scope and contents of the prior art.
ii. Ascertaining the differences between the prior art and the claims at issue.
iii. Resolving the level of ordinary skill in the pertinent art.
iv. Considering objective evidence present in the application indicating obviousness or
nonobviousness.
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.
Claims 29 – 30, 34 – 37, 50, 70, 83, and 143 are rejected under 35 U.S.C. 103 as being unpatentable over Yu et al. (US20190134184A1) in view of Rabideau et al. (WO2019/036682A1).
Yu et al. teach a self-replicating RNA molecule (also referred to as a self-amplifying mRNA, or SAM molecule) comprising the construct (para. [0012]), which is useful as components of immunogenic compositions (para. [0009]). The self-amplifying mRNA (SAM) background consists of VEE TC-83 replicon encoding the viral nonstructural proteins 1 – 4 (nsP1-4), followed by the subgenomic promotor, and either Zika prME or Zika CprME. Yu et al. disclose a SAM-Zika construct (Fig 5):
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wherein the construct is arranged from 5’ to 3’ and includes a 5’ cap, 5’ UTR, VEE TC-83 replicon sequences encoding nsP1 – nsP4, a subgenomic promoter operably linked to the Zika prME or CprME antigen sequence, and a 3’UTR (para. [0032]). The 5’ end of the RNA may be capped with a modified ribonucleotide with the structure m7G(5’) ppp(5’) N (cap 0 structure) or a derivative thereof, wherein the 5’cap of the RNA molecule may be further modified by a 2’-O-Methyltransferase which results in the generation of a cap 1 structure (m7Gppp[m2’-O] N) (para. [0079]). Modified nucleobases which can be incorporated into modified nucleosides and nucleotides and be present in the RNA molecules include m5U (5-methyluridine) and m6A (N6-methyladenosine) (para. [0081]). Non-naturally occurring forms of polypeptides may comprise one or more heterologous amino acid sequences (e.g. another antigen sequence, another signal sequence, a detectable tag, or the like) in addition to a Zika virus prME antigen sequences. For example, a polypeptide may be a fusion protein (para. [0071]). The nucleic acid may comprise one or more heterologous nucleic acid sequences (e.g. a sequence encoding another antigen and/or a control sequence such as a promotor or an internal ribosome entry site (para. [0077]). A self-replicating RNA molecule may have a 3’ poly-A tail (para. [0090]). The self-replicating RNA molecule may encode a single heterologous polypeptide antigen (i.e. a Zika virus prME antigen) (para. [0094]). In some embodiments, a method is provided for inducing an immune response against a Zika virus infection in a subject in need thereof comprising administering to the subject an immunologically effective amount of a composition comprising one or more of the constructs, vectors, or self-replicating RNA molecules (para. [0020]). Yu et al. further teach that the nucleic acid-based vaccine may be an RNA-based vaccine and that, in certain embodiments, the RNA-based vaccine comprises a self-replicating RNA molecule, also referred to as a self-amplifying mRNA or SAM molecule. Yu et al. teach that the self-replicating RNA molecule may be an alphavirus-derived RNA replicon (para. [0083]). Yu et al. also teach that self-replicating RNA molecules can be produced using replication elements derived from alphaviruses, with the structural viral proteins substituted by a nucleotide sequence encoding a protein of interest. Yu et al. teach that the self-replicating RNA molecule is typically a positive-strand RNA molecule that can be directly translated after delivery to a cell, where translation provides an RNA-dependent RNA polymerase that produces antisense and sense transcripts from the delivered RNA, resulting in amplification of the introduced replicon RNA and expression of the encoded antigen (para. [0084]). Yu et al. further teach that one suitable system for achieving self-replication is an alphavirus-based replicon, including replicons using a replicase from Venezuelan equine encephalitis virus, and that the attenuated TC83 mutant of VEEV has been used in replicons (para. [0085]). Yu et al. further teach that, in certain embodiments, the self-replicating RNA molecule encodes an RNA-dependent RNA polymerase that can transcribe RNA from the self-replicating RNA molecule and a Zika virus prME antigen, wherein the polymerase may be an alphavirus replicase comprising one or more of alphavirus proteins nsP1, nsP2, nsP3, and nsP4 (para. [0086]). Yu et al. also teach that the alphavirus structural proteins are absent from the self-replicating RNAs and are replaced by genes encoding the immunogen of interest, such that the subgenomic transcript encodes the immunogen rather than the structural alphavirus virion proteins (para. [0087]). Yu et al. further teach that, in certain embodiments, the self-replicating RNA molecule has a 5′ cap, such as 7-methylguanosine, and that the cap can enhance in vivo translation of the RNA. Importantly, Yu et al. teach that the 5′ sequence of the self-replicating RNA molecule must be selected to ensure compatibility with the encoded replicase (para. [0089]). Yu et al. also teach that the self-replicating RNA molecule may have a 3′ poly-A tail (para. [0090]). Yu et al. additionally teach that the self-replicating RNA can be prepared by in vitro transcription using a DNA template and a DNA-dependent RNA polymerase, such as T7, T3, or SP6 RNA polymerase. Yu et al. teach that appropriate capping and poly-A addition reactions can be used as required, and that these RNA polymerases can have stringent requirements for the transcribed 5′ nucleotide(s). Yu et al. further teach that, in some embodiments, these requirements must be matched with the requirements of the encoded replicase to ensure that the IVT-transcribed RNA can function efficiently as a substrate for its self-encoded replicase (para. [0092]).
However, Yu et al. do not explicitly teach that N1 is a modified adenosine, N2 is a uridine or modified uridine.
Rabideau et al. teach RNA polymerase variants, which increases transcription efficiency while reducing the number of double-stranded RNA contaminants and run-on transcripts produced during an in vitro transcription reaction (Abstract). Rabideau et al. disclose methods of capping a mRNA with cap analogs, such as trinucleotides, co-transcriptionally in an in vitro transcription assay using a T7 RNA polymerase variant described. In some embodiments, greater than 90% of the RNA produced includes a functional cap, and the RNA produced does not elicit a substantial cytokine response, even in the absence of post-IVT purification (page 3, para. 5; page 4, para. 1). The cap analog is m7GpppA2’OMepU (page 12, para. 3). Thus, Rabideau et al. is relied upon for its teaching of co-transcriptional capping of RNA using cap analogs, including trinucleotide cap analogs, during IVT. Rabideau et al. teach that, in the presence of trinucleotide cap analogs, RNA can be generated co-transcriptionally as capped RNA products (page 4, para. 1). Rabideau et al. further provide examples and lists of trinucleotide cap analogs, including modified trinucleotide cap analogs, for use in RNA capping (page 53 – 54).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the self-amplifying RNA constructs as taught by Yu et al., which encode antigens such as Zika prME or CprMe and incorporate elements like 5’ capping and m6A modifications with the capping methods using trinucleotide cap analogs in view of Rabideau et al. because Yu et al. disclose that modified nucleobases such as m6A and m5U may be incorporated into RNA, and that the 5’ end may include a cap structure to improve RNA function and immunogenicity and Rabideau et al. teach that co-transcriptional capping of RNA using trinucleotide cap analogs improves transcription efficiency and reduces undesirable double-stranded RNA byproducts. One would have been motivated to combine the self-amplifying RNA constructs as taught by Yu et al., which encode antigens such as Zika prME or CprMe and incorporate elements like 5’ capping and m6A modifications with the capping methods using trinucleotide cap analogs in view of Rabideau et al. because the combination will further enhance the transcription yield and capping efficiency of the SAM RNA product as disclosed by Rabideau et al. Therefore, one of the ordinary skill in the art would have had a reasonable expectation of success to combine the self-amplifying RNA constructs as taught by Yu et al., which encode antigens such as Zika prME or CprMe and incorporate elements like 5’ capping and m6A modifications with the capping methods using trinucleotide cap analogs in view of Rabideau et al. because Rabideau et al. disclose the trinucleotide capping approach that would improve the efficiency and quality of the RNA products disclosed by Yu et al., thereby rendering the claimed combination obvious.
Regarding the claimed N1 and N2 corresponding to endogenous 5’ viral nucleotides, it would have obvious for one of ordinary skill in the art to select the first and second transcribed nucleotides of the capped RNA so that they correspond to the first and second endogenous 5’ nucleotides of the self-replicating viral backbone. Yu et al. teach that the 5’ sequence of the self-replicating RNA molecule must be selected to ensure compatibility with the encoded replicase, and further teach that RNA polymerases used for IVT may have stringent requirements for the transcribed 5’ nucleotide(s), which must be matched with the requirements of the encoded replicase so that the IVT-transcribed RNA functions efficiently as a substrate for its self-encoded replicase. Rabideau et al. teach co-transcriptional capping using trinucleotide cap analogs during IVT. Therefore, one of ordinary skill in the art preparing the capped SAM/self-replicating RNA of Yu et al. using the trinucleotide capping method of Rabideau et al. would have been motivated to select N1 and N2 to correspond to and preserve the endogenous 5’ viral nucleotides for compatibility with the self-encoded replicase, thereby obtaining a capped self-replicating RNA having defined first and second 5’ nucleotides selected for replicase compatibility.
Claims 38 and 40 are rejected under 35 U.S.C. 103 as being unpatentable over Yu et al. (US20190134184A1) in view of Rabideau et al. (WO2019/036682A1) as applied to claims 29 – 30, 34 – 37, 50, 70, 83, and 143 above, and further in view of Brown (Wiley-Vch, Cop, 2012, cited in the PTO-892 on January 27, 2026).
The combined teachings of Yu et al. and Rabideau et al. teach the limitations discussed above.
However, Yu et al. and Rabideau et al. do not teach the elected species:
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Brown teaches that one of the most common monovalent isosteric replacements is the substitution of hydrogen with fluorine. These atoms have similar van der Waals radii but different electronic effects, fluorine being the most electronegative element in the periodic table. Due to the high strength of the C-F bond, fluorine is often introduced to achieve metabolic stability (page 17, 2.3.1 Monovalent Atoms and Groups, para. 1).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the known trinucleotide cap analog, m7GpppA2’OMepU, as taught by Rabideau et al. by substituting fluorine or a fluorinated group at the claimed position in view of Brown because Brown teaches fluorine substitution as a known and predictable chemical modification used to provide structurally similar analogs with altered or improved stability. The modification would have amounted to substitution of one known monovalent substituent for another on a known cap analog scaffold, with the expected result of a structurally similar modified cap analog suitable for use in the capping method of Rabideau et al. One would have been motivated to modify the known trinucleotide cap analog, m7GpppA2’OMepU, as taught by Rabideau et al. by substituting fluorine or a fluorinated group at the claimed position in view of Brown because Brown teaches that the introduction of F will lead to metabolic stability. Such substitution will yield predictable and improved results. Therefore, a person of ordinary skill in the art would have had a reasonable expectation of success to modify the known trinucleotide cap analog, m7GpppA2’OMepU, as taught by Rabideau et al. by substituting fluorine or a fluorinated group at the claimed position in view of Brown because Rabideau et al. teach modified trinucleotide cap analogs for RNA capping and Brown teaches fluorine substitution as a routine and predictable modification.
Responses to Applicant’s Remarks:
Applicant’s Remarks, filed July 27, 2026, have been considered and are found to be not persuasive.
Applicant argues that Yu et al. and Rabideau et al. do not teach or suggest that N1 is a first nucleotide of the self-amplifying backbone corresponding to a first endogenous 5′ nucleotide of the self-replicating RNA virus, and that N2 is a second nucleotide of the self-amplifying backbone corresponding to a second endogenous 5′ nucleotide of the self-replicating RNA virus. However, the argument is not persuasive. The rejection does not rely solely on the schematic depiction of “CAP” in Figure 5 of Yu et al. Instead, Yu et al. is relied upon for teaching a SAM/self-replicating RNA construct comprising a 5′ cap, 5′ UTR, VEE TC-83-derived replicon sequences encoding nsP1 – nsP4, a subgenomic promoter operably linked to a Zika prME or CprME antigen sequence, a 3′ UTR, and a poly(A) sequence. Yu et al. teach that the RNA-based vaccine may comprise a self-replicating RNA molecule, also referred to as a self-amplifying mRNA or SAM molecule, and that the self-replicating RNA molecule may be an alphavirus-derived RNA replicon. Yu et al. teach that self-replicating RNA molecules may be produced using alphavirus replication elements, with the structural viral proteins substituted by a nucleotide sequence encoding a protein of interest. Yu et al. also teach that a self-replicating RNA molecule is typically a positive-strand RNA molecule that may be translated after delivery to a cell, thereby providing an RNA-dependent RNA polymerase that produces antisense and sense transcripts and amplifies the introduced replicon RNA. Yu et al. teach that a suitable system is an alphavirus-based replicon, including replicons using a replicase from Venezuelan equine encephalitis virus, and that the attenuated TC-83 mutant of VEEV has been used in replicons. Yu et al. further teach that the self-replicating RNA molecule may encode an RNA dependent RNA polymerase and a Zika virus prME antigen, wherein the polymerase may be an alphavirus replicase comprising one or more of nsP1, nsP2, nsP3, and nsP4. Yu et al. also teach that alphavirus structural proteins are absent from the self-replicating RNA and replaced by genes encoding the immunogen of interest, such that the subgenomic transcript encodes the immunogen rather than structural alphavirus virion proteins. Importantly, Yu et al. teach that the self-replicating RNA molecule has a 5′ cap and that the 5′ sequence of the self-replicating RNA molecule must be selected to ensure compatibility with the encoded replicase. Yu et al. also teach that the self-replicating RNA may have a 3′ poly-A tail. Yu et al. additionally teach that the self-replicating RNA may be prepared by IVT using T7, T3, or SP6 RNA polymerase; that appropriate capping and poly-A addition reactions may be used; and that these RNA polymerases may have stringent requirements for the transcribed 5′ nucleotide(s). Yu et al. further teach that these requirements must be matched with the requirements of the encoded replicase so that the IVT-transcribed RNA can function efficiently as a substrate for its self-encoded replicase. Thus, Yu et al. explicitly recognize the importance of selecting and matching the 5′ sequence of the self-replicating RNA for compatibility with the encoded replicase. Rabideau et al. is relied upon for teaching a known co-transcriptional trinucleotide capping method during IVT. Accordingly, one of ordinary skill in the art preparing the capped SAM/self-replicating RNA of Yu et al. using the trinucleotide capping method of Rabideau et al. would have been motivated to select N1 and N2 to correspond to and preserve the endogenous first and second 5′ nucleotides of the self-replicating viral backbone for compatibility with the self-encoded replicase. Therefore, Applicant’s argument that the cited art fails to teach or suggest the claimed N1 and N2 limitations is not persuasive
Applicant argues that Rabideau et al. is directed to RNA polymerase variants and not explicitly to the claimed resulting RNA. However, the argument is not persuasive. Rabideau et al. is not relied upon for teaching the SAM backbone, the alphavirus/VEE replicase, or the biological function of the self-replicating RNA. Yu et al. is relied upon for those teachings. Rabideau et al. is relied upon for teaching co-transcriptional capping of RNA using cap analogs, including trinucleotide cap analogs, during IVT. Rabideau et al. teach that, in the presence of trinucleotide cap analogs, RNA may be generated co-transcriptionally as capped RNA products, and further provide examples and lists of trinucleotide cap analogs, including modified trinucleotide cap analogs, for use in RNA capping. Accordingly, the fact that Rabideau et al. also disclose RNA polymerase variants does not negate the teaching of co-transcriptional RNA capping using trinucleotide cap analogs. In the present rejection, Rabideau et al. supply the known IVT capping technique, while Yu et al. supply the SAM/self-replicating RNA construct and the teaching that the 5′ sequence must be selected/matched for replicase compatibility.
Applicant argues that there is no motivation to combine Yu et al. and Rabideau et al. to arrive at the claimed invention. However, the argument is not persuasive. Yu et al. teach capped SAM/self-replicating RNA constructs comprising alphavirus/VEE replicon sequences, nsP1–nsP4 replicase sequences, a subgenomic promoter, and an exogenous antigen-encoding cassette. Yu et al. further teach that the 5′ sequence of the self-replicating RNA molecule must be selected to ensure compatibility with the encoded replicase. Yu et al. also teach that the stringent 5′ nucleotide requirements of IVT RNA polymerases must be matched with the requirements of the encoded replicase so that the IVT-transcribed RNA functions efficiently as a substrate for the self-encoded replicase. Rabideau et al. teach co-transcriptional capping using trinucleotide cap analogs during IVT. Rabideau et al. further teach that such capping methods can improve capping efficiency and RNA product quality and reduce undesirable RNA byproducts, including double-stranded RNA contaminants and run-on transcripts. Therefore, one of ordinary skill in the art would have been motivated to apply the trinucleotide capping method of Rabideau et al. to capped SAM/self-replicating RNA construct of Yu et al. to obtain a capped RNA product having defined 5′ nucleotides. Further, because Yu et al. teach that the 5′ sequence must be selected/matched for replicase compatibility, one of ordinary skill would have been motivated to select N1 and N2 to correspond to the endogenous first and second 5′ nucleotides of the self-replicating viral backbone.
Applicant argues that one of ordinary skill in the art would not have had a reasonable expectation of success because Yu et al. allegedly use canonical RNA polymerase promoters that would introduce non-endogenous 5′ nucleotides. However, the argument is not persuasive. Yu et al. explicitly recognize that RNA polymerases used for IVT may have stringent requirements for the transcribed 5′ nucleotide(s), and that these requirements must be matched with the requirements of the encoded replicase so that the IVT-transcribed RNA functions efficiently as a substrate for the self-encoded replicase. Thus, Yu et al. identify the same technical consideration raised by Applicant, which is the 5′ nucleotide sequence of the IVT product must be compatible with the self-encoded replicase. Rabideau et al. teach a co-transcriptional capping method using trinucleotide cap analogs during IVT. The use of the trinucleotide cap analogs of Rabideau et al. provides a known method for producing capped RNA products having defined 5′ nucleotides. Therefore, one of ordinary skill in the art would have had a reasonable expectation of success in applying the known trinucleotide capping method of Rabideau et al. to the SAM/ self-replicating RNA constructs of Yu et al. while selecting N1 and N2 to correspond to the endogenous first and second 5′ nucleotides of the viral backbone for replicase compatibility.
Regarding Rabideau et al., Applicant argues that the experimental discussion relates to GAG trinucleotides and that the GAU trinucleotide listed on page 12 is not the GAG trinucleotide used in the examples. However, the argument is not persuasive. Rabideau et al. is not relied upon for showing that a particular GAG or GAU trinucleotide produces Applicant’s alleged biological result. Rabideau et al. is relied upon for teaching the general IVT-compatible technique of co-transcriptional capping using trinucleotide cap analogs, including modified trinucleotide cap analogs. The rejection relies on Yu et al. for the SAM/self-replicating RNA construct and for the teaching that the 5′ sequence must be selected/matched for replicase compatibility. Rabideau et al. provide the known trinucleotide capping method by which a capped RNA product with defined first and second transcribed nucleotides can be produced. Accordingly, Applicant’s distinction between GAG examples and other listed trinucleotide cap analogs of Rabideau et al. does not overcome the rejection.
Applicant argues that the application demonstrates unexpected results based on a comparison between AU-SAM and GG-SAM constructs. This argument is not persuasive because the alleged evidence is not commensurate in scope with claim 29. Claim 29 broadly recites a self-amplifying expression system comprising a self-amplifying backbone comprising one or more polynucleotide sequences of a self-replicating RNA virus and a cassette comprising at least one exogenous nucleic acid sequence for delivery. The claim is not limited to the specific AU-SAM construct tested in the specification, the specific VEEV embodiment tested, the particular antigen tested, the particular formulation, the particular dose, or the particular immune readout relied upon by Applicant. The cited comparison appears to be limited to a specific AU-SAM construct compared against a specific GG-SAM construct. Such evidence is insufficient to establish unexpected results across the full scope of claim 29, which encompasses broad self-replicating RNA viruses, broad viral backbones, broad exogenous cassettes, and broad N1/N2 embodiments. Accordingly, Applicant’s evidence does not outweigh the prima facie case of obviousness because it is not commensurate in scope with the pending claims.
Applicant argues that Brown does not cure the deficiencies of Yu et al. and Rabideau et al. with respect to claims 38 and 40. This argument is not persuasive for at least the reasons discussed above. Yu et al. and Rabideau et al. render obvious the capped SAM/self-replicating RNA system including the claimed endogenous N1/N2 selection and Brown is relied upon only for the additional chemical substituent features recited in claims 38 and 40. Brown teaches fluorine substitution as a known bioisosteric/stability-directed modification. Thus, one of ordinary skill in the art would have found it obvious to modify the known trinucleotide cap analog scaffold of Rabideau et al. using the fluorine-containing substituent teachings of Brown to obtain a structurally similar cap analog with the expected benefit of stability, while retaining the functionality of the capped RNA system taught by Yu et al. and Rabideau et al.
Maintained 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 29 – 30, 34, 50, 70, and 83 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2, 5, 50, 52, 70, and 75 of copending Application No. 18/658,604 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘604 anticipates the claimed invention.
‘604 teaches a composition for delivery of a self-expression system comprising a single-stranded RNA (ssRNA) vector, wherein the ssRNA vector comprises a m7G cap, a poly(A) tail, a self-amplifying backbone, and one or more modified nucleosides, wherein the self-amplifying backbone comprises a polynucleotide that is a self-replicating RNA virus, such as alphavirus; the ssRNA vector is produced by in vitro transcription, wherein the m7G cap analog comprises a trinucleotide m7G-ppp-A-U cap analog; the ssRNA vector comprises a cassette comprising at least one nucleic acid sequence for delivery, wherein the at least one nucleic acid sequence comprises a polypeptide-encoding nucleic acid sequence, wherein the polypeptide-encoding nucleic acid sequence is an antigen-encoding nucleic acid sequence, wherein the cassette is operably linked to or operably inserted into the self-amplifying backbone; the self-amplifying backbone comprises a polynucleotide that is a self-replicating RNA virus comprising at least one nucleic acid sequence from 5’ to 3’, described by the formula:
m7G-ppp-N1-N2-Nv,
wherein m7G is a 7-methylguanylate (m7G) cap, ppp is a triphosphate bridge, N1 is a first nucleotide of the self-amplifying backbone corresponding to a first endogenous 5’nucleotide of the self-replicating RNA virus, N2 is a second nucleotide of the self-amplifying backbone corresponding to a second endogenous 5’nucleotide of the self-replicating RNA virus, and Nv comprises (1) one or more additional nucleic acid sequence of the self-amplifying backbone, and (2) a cassette comprising at least one nucleic acid sequence for delivery, and wherein the cassette is operably linked to the self-amplifying backbone (claims 2, 50, and 52). The one or more modified nucleosides comprises m5C, m6A, 2’-O-Me, s2U, and m5U (claims 5 and 52). The composition for delivery of the self-amplifying expression system comprises the self-amplifying expression system, wherein the self-amplifying expression system comprises one or more self-amplifying mRNA (SAM) vectors, wherein the one or more SAM vectors comprise (a) the self-amplifying backbone, wherein the self-amplifying backbone comprises the nucleic acid sequence, wherein the self-amplifying backbone sequence comprises a subgenomic promoter nucleotide sequence and a poly(A) sequence, and the cassette comprises at least one antigen-encoding nucleic acid sequence comprising an epitope-encoding nucleic acid sequence (claim 70). The at least one nucleic acid sequence for delivery comprises the polypeptide-encoding nucleic acid sequence, wherein the polypeptide-encoding nucleic acid sequence encodes an epitope capable of stimulating a B cell response or the polypeptide-encoding nucleic acid sequence encodes a full-length protein or functional portion thereof (claim 75).
For these reasons above, ‘604 anticipates the claimed invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Responses to Applicant’s Remarks:
Applicant’s Remarks, filed July 27, 2026, have been fully considered and are found to be not persuasive.
Regarding ‘604, Applicant argue that ‘604 has a later patent term filing date. Therefore, the rejection should be withdrawn. However, the rejection is consistent with established practice for addressing nonstatutory double patenting. As explained in MPEP 804(II)(B)(5), a later-expiring patent may serve as a proper reference in a one-way obviousness-type double patenting rejection unless the applicant can show that the claims could not have been filed in a single application and that the Office was solely responsible for any delay that caused the reference patent to issue first. In the present case, Applicant does not provide evidence that the Office, rather than Applicant, is solely responsible for any prosecution delay, nor that the claims could not have been presented together. Courts have consistently held that applicant-driven prosecution choices, such as filing multiple applications or continuations, do not warrant application of the two-way test. Therefore, the one-way test applies, and the double patenting rejection over ‘604 remains proper.
Conclusion
No claim is found to be allowable.
Applicant's amendment necessitated the maintained / modified 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.
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/H.Y.L./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693
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