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 .
Application Status
The Amendments and Remarks filed 20 August 2025 are acknowledged and have been entered. The Amendment and Remarks filed 11 March 2024 did not comply with 37 C.F.R. 1.126 because the claims were not numbered consecutively. Consequently, the newly amended claims corrected this issue. Claims 1, 16, 17, 25, 85, 87, 164, 171, and 172 are amended. Claims 2, 7, 10-13, 18, 21, 23, 24, 26-81, 84, 89-91 and 96-163 are cancelled. Claims 1, 3-6, 8-9, 14-17, 19-20, 22, 25, 82-83, 85-87, 92-95, and 164-172 are under examination on the merits.
Any objection or rejection not reiterated herein has been overcome by applicant’s claim amendments. All 103 and NSDP rejections in this office action has been maintained.
Priority
This application is a divisional of application 15/831,230 filed 12/04/2017 which claims priority to 62/587,954 filed 11/17/2017, 62/486,361 filed 4/17/2017, and 62/430,250 filed 12/02/2016.
Information Disclosure Statement
The information disclosure statements filed 8/20/2025 and 10/01/2025 have been considered.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. 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 1, 3-6, 8-9, 16-17, 22, 25, 92-94, 164, 170-172 are rejected under 35 U.S.C. 103 as being obvious over Frolov 2014 (US 2014/0079734 A1) in view of Johnston (US 2008/0279891 A1).
Regarding claim 1, 9 and 164, Frolov 2014 teaches alphavirus RNA replicons and methods of their use in vaccines and producing heterologous proteins [0003, 0013, abstract]. Frolov 2014 teaches Sindbis- and Semliki Forest virus-based vectors (nucleic acid molecule) with modifications in the beginning of the capsid-coding sequence, a sequence that encodes a viral capsid that contains a translational enhancer (i.e., a first nucleic acid sequence) derived from an Old-World alphavirus such as, e.g., Sindbis, Semliki Forest, Ross River or other Old-World alphavirus [0008, 0041, 0129]. Frolov 2014 teaches the translational enhancer is folded into a stable stem-loop structure (i.e., DLP loop motif) [0047]. Frolov 2014 also teaches these modifications to be a part of a recombinant replicon (i.e., modified viral RNA replicon) acid that also includes a 5” UTR and a nucleic acid sequence encoding alphavirus (e.g., VEEV) nonstructural proteins nsP1, nsP2, nsP3 and nsP4, a heterologous protein (GOI) (i.e., second nucleic acid sequence) downstream from the nonstructural proteins and a 3’UTR [0041, Figs. 1-3]. Frolov 2014 teaches these nonstructural proteins nsP1, nsP2, nsP3 and nsP4 form the replicative enzyme complex, which amplifies the viral genome and synthesizes additional subgenomic RNA that is a template for synthesis of viral structural proteins [0026]. Frolov 2014 teaches that these RNA modified structures increase expression of heterologous nucleotide sequences of interest [0131]. Frolov also teaches that the present invention provides a method eliciting an immune response to a heterologous protein in a subject, comprising administering to the subject an immunogenic amount of a recombinant replicon nucleic acid of this invention, thereby eliciting an immune response to the heterologous protein encoded by the recombinant replicon nucleic acid [0010].
Frolov 2014 does not teach wherein the first nucleic acid sequence is operably linked upstream to the second nucleic acid sequence.
Johnston teaches alphavirus adjuvants or Venezuelan Equine Encephalitis viral adjuvants, i.e., modified alphavirus genomic nucleic acids, for enhancing an immune response to an immunogen [abstract]. Johnston teaches that replicon vectors that comprise a capsid translational enhancer region of the alphavirus capsid protein can operably associate with the sequences encoding the non-structural proteins to enhance expression thereof [0140].
It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to modify the replicon of Frolov 2014 by placing the sequence encoding the viral capsid enhancer upstream of the second nucleic acid sequence encoding the nonstructural viral proteins and heterologous sequence of interest. One of ordinary skill would be motivated to make this modification for the advantage of enhancing expression of the non-structural proteins for the purpose of amplifying the viral genome and synthesizing additional subgenomic RNA.
Regarding claim 3, while Frolov 2014 teaches that a promoter can be used to direct transcription of a subgenomic messenger RNA as part of the alphavirus replication process [0048], Frolov or Johnston do not teach where the nucleic acid molecule comprises a promoter operably linked upstream to the first nucleic acid sequence. It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to modify the nucleic acid molecule as taught and suggested by Frolov 2014 and Johnston where the molecule comprises a promoter operably linked upstream to the first nucleic acid sequence. One of ordinary skill would be motivated with a reasonable expectation of success to make the modification for the advantage of directing the expression of the viral capsid enhancer and thereby enhancing expression of the non-structural proteins for the purpose of amplifying the viral genome and synthesizing additional subgenomic RNA.
Regarding claim 4, Frolov 2014 teaches a 5' UTR sequence operably linked upstream to the first nucleic acid sequence [0041, Figs 1-3].
Regarding claim 5, although Frolov 2014 teaches a 5' UTR sequence operably linked upstream to the first nucleic acid sequence [0041, Figs 1-2], Frolov 2014 does not teach where the 5' UTR sequence is operably linked downstream to the promoter and upstream to the first nucleic acid sequence. Frolov 2014 does teach a 5’UTR operably linked downstream of a promoter in the DI RNA-encoding alphavirus replicon [Fig. 1-3]. Frolov 2014 teaches that the 5’ UTR has a strong positive effect on replication of these RNAs. It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to modify the nucleic acid molecule as taught and suggested by Frolov 2014 and Johnston where the molecule comprises a 5' UTR sequence operably linked downstream to the promoter and upstream to the first nucleic acid sequence. One of ordinary skill would be motivated to make the modification for the advantage of directing the strong expression/replication of the viral capsid enhancer and thereby enhancing expression of the non-structural proteins for the purpose of amplifying the viral genome and synthesizing additional subgenomic RNA. One of ordinary skill would have an expectation of success since Frolov 2014 already teaches replicons that comprise a 5' UTR sequence is operably linked downstream of a promoter.
Regarding claim 6, Frolov 2014 teaches the recombinant replicon nucleic acids comprising a nucleic acid sequence encoding a protease [0041]. Frolov 2014 teaches the capsid-coding sequence, which contains a translational enhancer is fused in frame (i.e., operably linked downstream to the first nucleic acid sequence) with a nucleotide sequence encoding a protease (e.g., FMDV-2A protease) [0129]. Frolov 2014 teaches that the protease is included for polyprotein processing [0120]. Frolov 2014 also teaches that the viral genome is translated into the polyprotein precursor of the nonstructural proteins which is sequentially self-processed by the encoded protease [0026]. Frolov 2014 does not teach wherein the coding sequence for an autoprotease peptide is operably linked upstream to the second nucleic acid sequence and downstream to the first nucleic acid sequence. It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to further modify the nucleic acid molecule as taught and suggested by Frolov 2014 and Johnston wherein the coding sequence for an autoprotease peptide is operably linked between the first and second nucleic acid sequence. One of ordinary skill would be motivated to make this modification with a reasonable expectation of success for the advantage of cleaving the nonstructural proteins from the viral capsid enhancer aiding in the polyprotein processing of the nonstructural proteins.
Regarding claim 8, Frolov teaches a nucleotide sequence encoding a F2A protease [0129].
Regarding claim 16, Frolov 2014 teaches the recombinant replicon nucleic acid comprising a promoter operably linked to and a nucleic acid sequence encoding a heterologous protein (i.e., GOI encoding a polypeptide) [0008, Fig. 1-3].
Regarding claim 17, Frolov teaches that the heterologous protein can be a therapeutic protein [0011, claim 20]. Frolov 2014 teaches that the heterologous nucleic acid of this invention can encode a protein or peptide, which can be, but is not limited to, an antigen, an immunogen or immunogenic polypeptide or peptide, a fusion protein, a fusion peptide, a cancer antigen, etc. [0088].
Regarding claim 22, Frolov teaches that the modified vectors are expression vectors [0133].
Regarding claim 25, Frolov 2014 teaches that the DI RNA-encoding replicons can be cloned into plasmids under control of RNA Pol II promoters [0132].
Regarding claims 92, 170 and 172, Frolov 2014 teaches a modified VEEV RNA replicon [0055, 0120, Fig. 1].
Regarding claims 93 and 171, the combination of Frolov 2014 teaches where the second nucleic acid sequence encodes nonstructural proteins nsp 1-4 [Figs 1-2].
Regarding claim 94, Frolov 2014 teaches that nonlimiting examples of an alphavirus of this invention include eastern equine encephalitis virus (EEEV) [0055].
Claims 14-15 and 165-166 are rejected under 35 U.S.C. 103 as being unpatentable over Frolov 2014 (US 2014/0079734 A1) and Johnston (US 2008/0279891 A1) as applied above to claim 1 and 164 and further in view of Regts (US 2004/0005711 A1).
The teachings of Frolov 2014 and Johnston are discussed above as applied to claim 1 and 164. Frolov nor Johnston teach wherein the viral capsid enhancer comprises a nucleic acid sequence of one of SEQ ID NOs: 1 and 46-52.
Regts teaches alphavirus vector systems used for vaccine purposes [abstract]. Regts teach that the alphavirus vector system comprises a translational enhancer element which helps overcome lower expression or improves expression of heterologous proteins [0019]. Regts teach that the translational enhancer element comprises a viral capsid gene segment, such as from an alphavirus (e.g., Semliki Forest virus (SFV)) [0019]. Regts teaches that this enhancer element is termed SFV-enh6,7 and has a sequence (SEQ ID NO:4) which is 100% identical to SEQ ID NO: 50 of the instant application [0040, Fig. 9 and 19].
It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to modify the nucleic acid molecule as taught and suggested by Frolov 2013 and Johnston with the sequence of the SFV-enh6,7 enhancer of Regts. This modification would amount as a simple substitution of one alphavirus capsid translation enhancer for another, both known to improve expression of heterologous proteins. The combination of prior art elements according to known methods to yield predictable results supports can support a conclusion of obviousness. See MPEP 2143(I). One of ordinary skill in the art would have a reasonable expectation of success since both Frolov and Regts teach modified alphavirus replicons used for heterologous protein expression.
Claims 19-20 and 95 are rejected under 35 U.S.C. 103 as being unpatentable over Frolov 2014 (US 2014/0079734 A1) and Johnston (US 2008/0279891 A1) as applied above to claim 1 and further in view of Mir (Mir et. al. 2009. Clinical and Vaccine Immunology Vol. 16, No. 10 p. 1467-1475).
The teachings of Frolov 2014 are discussed above as applied to claim 1 and similarly apply to claim 19-20 and 95.
Frolov 2014 or Johnston do not teach a nucleic acid molecule further comprising a third nucleic acid sequence encoding one or more RNA stem-loops of a second viral capsid enhancer or a variant thereof; and a fourth nucleic acid sequence operably linked to the third nucleic acid sequence, wherein the fourth nucleic acid sequence comprises a coding sequence for a second gene of interest (GOI) or at least two, three, four, five, or six expression cassettes, and wherein the a second autoprotease peptide is operably linked downstream to the third nucleic acid sequence and upstream to the fourth nucleic acid sequence.
Frolov does teach that the replicon comprises a promoter upstream of a heterologous protein of interest [0041, Figs. 1-3].
Mir teaches the ability to exploited self-splicing 2A sequences of the foot-and-mouth disease virus (FMDV) to generate a DNA vaccine construct expressing multiple full-length antigens from a single open reading frame (ORF). Mir teaches that is possible to coexpress up to four full-length antigens joined by 2A sequences in a single ORF under the control of a single promoter thereby generating a DNA vaccine construct (V-2A) that expresses high levels of full-length and functional antigens which are secreted at different stages of disease development and which induce strong immune responses [pg. 1467, col. 1, para 2].
Therefore, it would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to modify the nucleic acid of Frolov 2014 to additionally contain a third nucleic acid sequence encoding one or more RNA stem-loops of a second viral capsid enhancer or a variant thereof; a fourth nucleic acid sequence operably linked to the third nucleic acid sequence, wherein the fourth nucleic acid sequence comprises a coding sequence for a second gene of interest (GOI) and wherein a coding sequence for a second F2A peptide is between the third and fourth sequences, or two or more expression cassettes. One of ordinary skill would be motivated to make this modification for the advantage of coexpressing multiple genes of interest in coordinated manner and/or where the posttranslational modification due to FMDV 2A leads to the segmentation of the long-translated polypeptide into individual proteins. This modification would simply amount to a duplication of parts of the nucleic acid molecule of the current claim 1 and of the expression cassette as disclosed by Frolov 2014.
Claims 82-83, 85-86 and 167-168 are rejected under 35 U.S.C. 103 as being unpatentable over Frolov 2014 (US 2014/0079734 A1) and Johnston (US 2008/0279891 A1) as applied above to claim 1 and 164 and further in view of Lee (US20080131459A1).
Regarding claims 82-83 and 167-168, the teachings of Frolov 2014 and Johnston are discussed above as applied to claim 1 and 164. Frolov does not teach wherein the modified viral replicon is derived from an arterivirus virus species of Porcine respiratory and reproductive syndrome virus (PRRSV). Frolov or Johnston do not teach where the second nucleic acid sequence encodes the entire pp lab nonstructural protein of the modified arterivirus RNA replicon.
Johnston teaches that the viral adjuvants of the invention can be derived from any suitable virus such as a nidovirus [0098-0099] where the nidovirus includes equine arteritis
virus, lactate dehydrogenase-elevating virus, porcine respiratory and reproductive syndrome virus, and simian hemorrhagic fever virus of the family Arteriviridae [0089].
Lee teaches a luciferase (LUC)-expressing PRRSV viral replicons [0066; Fig. 10] and the use of a PRRSV vector for the expression of a heterologous gene or a genetic vaccine. Lee teaches that two overlapping ORFs, ORF1a and 1b, are expressed from the genomic RNA, processed into 13 mature nonstructural proteins (i.e., the entire pp lab nonstructural protein of the modified arterivirus RNA Replicon), and known to be involved in viral replication [0003].
It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to modify the nucleic acid molecule as taught and suggested by Frolov 2014 and Johnston where the modified viral replicon is derived from PRRSV the second nucleic acid sequence encodes the entire pp lab nonstructural protein of the modified arterivirus RNA replicon. This modification would amount as a simple substitution of one modified viral replicon for another, where the replicons are both shown to be used for expression of heterologous proteins. Additionally, one of ordinary skill would be motivated to use the entire pp lab nonstructural protein of the modified arterivirus RNA replicon as the second nucleic acid because Frolov 2014 uses the all 4 non-structural proteins from the alphavirus genome in its viral replicon for the purpose of amplifying the viral genome and synthesizing additional subgenomic RNA. The combination of prior art elements according to known methods to yield predictable results supports can support a conclusion of obviousness. See MPEP 2143(I). One of ordinary skill in the art would have a reasonable expectation of success since both Frolov and Regts teach modified viral replicons for expression of heterologous proteins.
Regarding claim 85, Frolov 2014 teaches where the replicon can comprise nucleotide sequences encoding one or more proteins of interest [0120]. Frolov also teach that the replicon comprises a promoter upstream of a heterologous protein of interest [0041, Figs. 1-3]. However, Frolov2014 or Johnston do not teach that the replicon comprises one or more genes of interest are each operably linked to a promoter, thereby comprising one or more expression cassettes. Frolov 2014 teaches that a promoter can be used to direct transcription of a subgenomic messenger RNA as part of the alphavirus replication process [0048]. It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to modify the nucleic acid molecule as taught and suggested by Frolov 2014 and Johnston where the molecule comprises at least one to six expression cassettes. One of ordinary skill would be motivated with a reasonable expectation of success to make the modification for the advantage of directing the expression of multiple genes of interest individually.
Regarding claim 86, Frolov teaches a replicon that comprises of an expression cassette (promoter operably linked to a GOI) downstream of the second nucleic acid sequence (comprising the non-structural proteins) [041, Figs. 1-3].
Claims 87 and 169 is rejected under 35 U.S.C. 103 as being unpatentable over Frolov 2014 (US 2014/0079734 A1), Johnston (US 2008/0279891 A1), and Lee (US 20080131459 A1) as applied to claims 1, 82, and 83 and further in view of Stein (US 20050171044 A1) and Sanches (US 2009/0202588 A1).
The teachings of Frolov 2014, Johnston, and Lee are discussed above as applied to claims 1, 82, and 83. Frolov, Johnston or Lee do not teach where at least one of the one or more expression cassettes is operably positioned downstream to a transcriptional regulatory sequence (TRS) of the modified arterivirus RNA replicon, wherein the TRS is selected from the group consisting of TRS1, TRS2, TRS3, TRS4, TRS5, TRS6, and TRS7.
Stein teaches that nidoviruses, such as Porcine reproductive and respiratory syndrome virus [table 1], comprise a TRS that appear to play a critical role in viral transcription by bringing into close proximity the minus strand body TRS and positive-strand leader TRS in order to complete synthesis of the negative-sense sg RNA templates [0101, Fig. 2B, Table 3]. Stein teaches TRS-1 and TRS-2 [0176, Fig. 6].
Sanches teaches vectors and virus particles comprising sequences encoding at least one neutralizing epitope of ORF5 of porcine reproductive and respiratory syndrome virus (PRRSV) for the preparation of vaccines [abstract]. Sanches teaches that TRS is a sequence or a fragment of a sequence capable of driving the synthesis of subgenomic viral RNAs [0046]. Sanches teaches that protein coding sequences within the nucleic acids of the present invention are preferably linked to sequences controlling the expression of these genes in the host cells or organisms [0078]. Sanches teaches the genes encoding the epitopes or further polypeptides may for example be flanked by transcription regulatory sequences (TRS) to increase transcription and/or translation of the protein coding sequences [0078].
It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to modify the nucleic acid molecule as taught and suggested by Frolov 2014 and Johnston where the molecule comprises TRS1 or TRS1 positioned upstream of the expression cassette. One of ordinary skill would be motivated to make the modification with a reasonable expectation of success for the advantage of aiding in transcription of the expression cassette because Stein teaches that TRSs pay a viral role in viral transcription and Sanches teaches that polypeptides are linked to TRS sequences to increase the transcription and/or translation of the protein coding sequences.
Response to Arguments
Applicant's arguments filed 8/20/2025 have been fully considered but they are not persuasive. Applicants argue that Frolov 2014 fails to provide a capsid enhancer upstream of a first nucleic acid comprising nucleic acid encoding for nonstructural protein and a gene of interest. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). The rejection relies on the combination of Frolov and Johnston and Johnston provides a rationale for placing a capsid enhancer upstream of a sequence encoding a nonstructural protein and/or a GOI.
Applicants argue that Johnston, speculates on the possible placement of capsid translation enhancers in different locations, without providing for a configuration described in the claims. Applicants argue that this teaching does not specifically direct one of ordinary skill to the configuration provided in the claims of comprising an enhancer upstream of nonstructural protein encoding sequences, where the gene of interest is downstream from the nonstructural protein encoding sequences. Applicants’ arguments are unpersuasive because a skilled artisan equipped with the teachings of Frolov (as shown in Fig.3) and Johnston [0140] would rationally conclude that the capsid enhancer would necessarily need to be placed upstream of the heterologous sequence or the sequences encoding the non-structural protein in order to enhance expression.
Applicants argue that Johnston fails provide any data supporting a likelihood of success in modifying a region 5' of the nonstructural encoding sequence of the alphavirus replicon and obtaining successful expression and that 5’ sequences are less tolerant to change. Applicant’s arguments are unpersuasive because the rejection as stated above is the combination of Frolov and Johnston. Frolov positively teaches that the 51 nucleotide long conserved sequence element (51-nt CSE), which is located in the first 200 5'-terminal nucleotides of the genome serves as a strong enhancer of RNA replication. This provides evidence that the 200 nucleotides of the 5’ end of a viral replicon upstream of the nonstructural proteins can handle being modified to comprise a needed sequence. Additionally, Frolov already teaches the use of an enhancer to aid in the expression of a GOI. Therefore, a skilled artisan would have a reasonable expectation of success with modifying a region 5' of the nonstructural encoding sequence of the alphavirus replicon and obtaining successful expression.
Applicants argue that that the present application provides data illustrating the benefit to modifying the region upstream from the nonstructural encoding sequence, with a capsid enhancer encoding sequence. Applicants argue that such data demonstrate alphavirus replicons, exemplified by the VEEV replicon and the EAV replicon, are flexible enough to accept incorporation of a stem loop structure (the DLP) in the 5' end of their RNAs. This statement does not provide or demonstrate the unexpected benefits of modifying the region upstream from the nonstructural encoding sequence, with a capsid enhancer encoding sequence; nor did applicant’s point to any part of the specification that reveals such benefit. A review of the specification did not reveal any benefits to modifying the region upstream from the nonstructural encoding sequence, with a capsid enhancer encoding sequence that would not have been obvious over the combination of the cited art.
Applicants argue that not of the cited references describe such a configuration comprising a capsid enhancer upstream of a nucleic acid encoding nonstructural protein, and a gene of interest downstream of the nonstructural protein encoding sequence or provide a reasonable expectation of success for such a configuration. Applicants’ arguments are unpersuasive as Frolov and Johnston in combination provides a reasonable rationale to configure such configuration and a reasonable expectation of success for such a configuration. Furthermore, the argument that Mir does not appear to describe the use of a single capsid enhancer, let alone multiple capsid enhancers is unpersuasive in view of the teachings of Johnston who provides a rationale to operably link a capsid enhancer to a GOI.
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 1, 2-6, 8-9, 14-17, 19-20, 22, 25, 82-83, 85-87, 92-95, and 164-172 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 8-10, 13, 16, 43 and 48 of U.S. Patent No. US11845939B2 in view of Frolov 2014 (US 2014/0079734 A1), Johnston (US 2008/0279891 A1), Regts (US 2004/0005711 A1), Lee (US 20080131459 A1), Stein (US 20050171044 A1), and Sanches (US 2009/0202588 A1).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claim 8 of the patented claims teach a nucleic acid molecule, comprising a modified viral RNA replicon, wherein the modified viral RNA replicon comprises: a first nucleic acid sequence encoding one or more structural elements of a viral capsid enhancer comprising one or more RNA stem-loops, wherein the viral capsid enhancer is heterologous to the viral RNA replicon; and a second nucleic acid sequence comprising a sequence encoding for at least one viral nonstructural protein of a corresponding unmodified viral RNA replicon, wherein the first nucleic acid sequence is operably linked upstream to the second nucleic acid sequence, wherein the modified viral RNA replicon further comprises one or more expression cassettes, wherein at least one of the one or more expression cassettes comprises a promoter operably linked to a sequence for a gene of interest (GOI). Claim 11 further teaches wherein the native viral nonstructural proteins of the corresponding unmodified viral RNA replicon is from an alphavirus or arterivirus.
The patented claims do not teach that the expression cassette comprising the GOI is a component/operably linked of the second nucleotide sequence.
The teachings of Frolov 2014 are discussed above and provides for a replicon where an expression cassette is operably linked to a second nucleic acid sequence comprising nonstructural proteins [0041, Figs. 1-3].
It would have been to one ordinary skilled in the art before the effective filing date of the claimed invention to combine the teaching of the patented claims and modify the replicon where the expression cassette comprising the GOI is a component/operably linked of the second nucleotide sequence. One of ordinary skill would be motivated for the advantage of GOI expression. The combination of prior art elements according to known methods to yield predictable results supports can support a conclusion of obviousness. See MPEP 2143(I). One of ordinary skill in the art would have a reasonable expectation of success since both the patented claims and Frolov 2014 teach the use of modified viral RNA replicon for gene expression.
For additional limitations of the instant claims, see the additional teachings of the patented claims. To the extent that there are limitations that are not provided for by the patented claims, the teachings of Frolov 2014, Johnston, Regts, Lee, Stein and Sanches are discussed above. It would have been obvious to have modified the subject matter of the patented claims to arrive at the subject matter of the instant claims for substantially the same reasons as discussed above in view of the teachings of these references.
Response to Arguments
Applicant's arguments filed 8/20/2025 have been fully considered but they are not persuasive in view of the response as discussed above.
Conclusion
No claims allowed.
THIS ACTION IS MADE FINAL. 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 TIFFANY N GROOMS whose telephone number is (571)272-3771. The examiner can normally be reached on M-F 830-530.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jennifer Dunston can be reached on 571-272-2916. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see https://ppair-my.uspto.gov/pair/PrivatePair. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/T.N.G./Examiner, Art Unit 1637
/Jennifer Dunston/Supervisory Patent Examiner, Art Unit 1637