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 .
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1, 2, 4, 5, 9, 12-14 and 27-29), and the species SEQ ID NO.4 in the reply filed on 04/12/2026 is acknowledged.
Claims 17, 20-22 and 30-31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 04/12/2026.
Claims 1, 2, 4, 5, 9, 12-14 and 27-29 are under examination.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) was filed before the mailing date of the non-final first action on the merits. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on pages 25,26,29,52, and 73. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.821 - 1.825 because the application does not contain a statement that the CRF is identical to the "Sequence Listing" part of the disclosure, as described above in item 1), as required by 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii).
Required response - Applicant must provide such statement.
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
The sequence identifiers ”SEQ ID NO:” next to each occurrence within the
disclosure, for example:
1. Place sequence identifiers ”SEQ ID NO:” on pages 65,69,82,86,91 to identify the DNA sequence of CMV +T7_Cov2_SA ( page 65), CMV+T7_Cov2_SA_GFP (page 69), DNA sequence of CMV+T7_VEE_SA_GFP (page 82), DNA sequence of CMV+T7_VEE_SA_GFP (page 86), DNA Sequence of Vector CMV+ T7 VEE_SA_GFP (page 91), CBA+T7 VEE GFP (page 95), CBA+T7-Fu11Covid-GFP ( page 101), CBA+T7-RedCovid-GFP ( page 113), etc.
The sequence identifiers must be present every time any sequence amino acid/nucleic acid is recited.
Claim Interpretation
It should be noted that the optional recitations in claims 13 and 14 are not given
patentable weight as they are not required by the subject claim.
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.
Claim 29 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.
Regarding claim 29, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-2, and 27 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhang et al ( Journal of Virology Methods, 2020).
Regarding claims 1-2, and 27, Zhang et al disclose an expression vector to express a full-length cDNA clone of the wild type Senecavirus (SVA), a positive stranded RNA virus from the Picornaviridae family. It should be noted that the expression vector of Zhang et al contains the full-length SVA genome, which reads on a self-amplifying DNA plasmid encoding all replicon proteins from a positive- stranded RNA virus (i.e. claims 1-2). Zhang et al teach that the expression vector comprises of a dual promoter that includes the CMV and T7 promoters to allow for eukaryotic-cell transcription and in vitro transcription, respectively, this reads on claim 27. Specifically, Zhang et al demonstrate how to clone the entire genome of SVA strain CH/HeN-2018 onto a plasmid called pcDNA-rSVAuni and use Gibson assembly to produce a dual-promoter expression vector. Zhang et al demonstrate that transfecting mammalian cells (i.e. PK-15) directly with the plasmid DNA successfully produced infectious recombinant virus. Zhang et al ,on the other hand, show that transfecting mammalian cells (i.e. PK-15) with RNA transcripts, generated by in vitro transcribing the plasmid DNA using the T7 RNA polymerase, also produced infectious recombinant virus. ( See Fig.1, and section 3.3. on page 4).
Taken together, Zhang et al teach an expression vector that encodes all replicons proteins from a positive stranded RNA virus, wherein the vector comprises of prokaryotic and eukaryotic promoters.
Claims 1-2, 5, 9, 13-14, 28-29 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Shattock et al (WO 2020/254804 A1).
Regarding claims 1-2,5,9, Shattock et al teach a self-amplifying RNA (saRNA) construct derived from a positive stranded RNA virus, wherein the RNA construct comprises a sequence encoding at least one therapeutic biomolecule (i.e. a payload). ( See claims 1-3). Shattock et al teach that the self-amplifying RNA can be used in therapy, for example in treating diseases and/or in vaccine delivery. (See abstract). Specifically, Shattock et al teach a saRNA construct that is derived from Venezuelan Equine Encephalitis Virus (VEEV), this reads on claim 5. (See claim 5). Shattock et al also teach that the saRNA construct maybe made using DNA plasmid. ( See page 63 lines 9-10, and Figs.7-8). In one of the embodiments, Shattock et al state that the “saRNA construct comprises, preferably 5' to 3', a promoter, a sequence encoding at least one non-structural protein, a sub genomic promoter, a sequence encoding at least one therapeutic biomolecule, a spacer sequence, and at least one sequence encoding an innate inhibitor protein”. ( See Fig.1 (i.e. IIP VEEV Replicon), and page 40-lines 1-4). It should be noted that the sequence encoding at least one non-structural proteins reads on a portion of replicon proteins. It should also be noted that the sequence encoding one therapeutic biomolecule and the sequence encoding an innate inhibitor protein reads on one or more payload, and thus Shattock et al construct also anticipates claim 9.
Regarding claims 13-14, Shattock et al teach a pharmaceutical composition comprising of the saRNA construct and a pharmaceutically acceptable vehicle (i.e. carrier), this reads on claim 13. ( See claim 26). According to Shattock et al “ the composition may be in the form of Lipid nanoparticles (with RNA on the surface or encapsulated) or any other suitable form
that may be administered to a person or animal in need of treatment or vaccination”, this reads on claim 14. ( See page 69 lines 16- 23).
Regarding claims 28-29, Shattock et al teach a saRNA construct encoding multiple payloads including a therapeutic biomolecule and an innate inhibitor protein. In a preferred embodiments, Shattock et al teach that the therapeutic protein is a cytokine. ( See page 10 lines 29-30).
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.
Claims 4 are rejected under 35 U.S.C. 103 as being unpatentable over Shattock et al (WO 2020/254804 A1) in view of Zhang et al ( Journal of Virology Methods, 2020), and Yi et al ( Molecular Biology Reports, 2020).
The teachings of Shattock et al and Zhang et al are set forth above.
Regarding claim 4, Shattock et al teach a saRNA construct comprising a promoter, such as T7 promoter, to drive the expression of replicon proteins (i.e. the nonstructural proteins Nsp1-Nsp4), and a sub-genomic promoter that drives the expression of the gene of interest GOI (i.e. the payload/therapeutic biomolecule). (See Figs 7-8). It is noted that Shattock et al do not teach a saRNA construct comprising two promoters, such as T7 and CMV promoters.
Zhang et al supplement the teachings of Shattock et al by teaching a self-amplifying DNA construct derived from a positive strand RNA virus comprising a dual promoter that includes the CMV and T7 promoters. Zhang et al demonstrate that the inclusion of the two promoters would permit eukaryotic-cell transcription, and in vitro transcription, respectively. Zhang et al also teach that the dual promoter constructs can be applied in antiviral therapies and vaccine development. ( See abstract). Thus, providing an ordinary skill in the art with some teachings and motivation to modify the construct of Shattock to further include the eukaryotic promoter CMV to drive the expression of the saRNA construct in eukaryotic cell.
Another prior art by Yi et al further supplements the teachings of Shattock et al by teaching a dual promoter expression vector for expressing recombinant proteins in prokaryotic and eukaryotic cells from the T7 and CMV promoters, respectively. ( See Fig.1). Yi et al teach that an expression vector comprising a prokaryotic-eukaryotic double promoter has the potential applications in rapid cloning and expression of recombinant proteins in both prokaryotic and eukaryotic expression systems. ( See abstract). It is noted that the expression constructs of Yi et al is not a self-amplifying construct. However, Yi et al state that “ To produce the same protein in both prokaryotic and eukaryotic systems, different vectors need to be designed and transfected in different cells, which is time consuming and laborious”. To address this issue, Yi et al developed a dual promoter expression vector that combines all of the essential elements for recombinant protein expression into a single vector in both prokaryotic and eukaryotic systems. Thus, providing an ordinary skill in the art with the teachings and motivation to modify the self-amplifying RNA constructs of Shattock et al to further include the CMV promoter to drive its expression in a eukaryotic cell.
Taken together, claim 4 would have been obvious to one of ordinary skill in the art, as there was some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. Because Shattock et al teach a self-amplifying RNA construct comprising a T7 promoter driving the expression of the replicon proteins, and a sub-genomic promoter driving the expression of the payload, but fail to teach a self-amplifying RNA construct comprising both T7 and CMV to drive the expression of the viral replicon in eukaryotic and prokaryotic systems. Zhang et al supplements the teachings of Shattock et al by teaching a self-amplifying DNA comprising T7 and CMV promoters, demonstrating that the presence of the two promoters allows for eukaryotic-cell transcription, and in vitro transcription. Yi et al teach an expression vector comprising of dual promoter, namely the T7 and CMV promoters, to drive the expression of the recombinant proteins in prokaryotic and eukaryotic cells, and clearly suggest that prokaryotic-eukaryotic double expression vector has the potential applications in rapid cloning and expression of recombinant proteins in both prokaryotic and eukaryotic expression systems. Thus, Zhang and Yi provide teachings and motivation to ordinary skill in the art to modify the construct of Shattock et al to further include the CMV promoter in addition to the T7 promoter because doing so would permit the expression of the viral construct in prokaryotic and eukaryotic cells. There is a reasonable expectation of success, when building a self-amplifying vector, that taking the vector described in Shattock et al, and inserting a second promoter to drive the expression of the replicon proteins, that the vector of claim 4 could be successfully synthesized.
Allowable Subject Matter
Claim 12 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. It should be noted that SEQ ID NO:4, the elected species is free of art. For this reason, sequence search was extended to include all of the SEQ ID NOs recited in claim 12. Sequence search did not find any prior art with 100% identity to the claimed SEQ ID NOs: 1-12. Therefore, SEQ ID No: 1-12 are free of art.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to FATIMAH KHALAF MATALKAH whose telephone number is (703)756-5652. The examiner can normally be reached Monday-Friday,7:30 am-4:30 pm EST.
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/FATIMAH KHALAF MATALKAH/Examiner, Art Unit 1638
/PETER PARAS JR/Supervisory Patent Examiner, Art Unit 1632
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