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 amendment and Declaration under 37 CFR 1.130(A) submitted on 8/4/2025 are acknowledged.
Applicant’s election of the required species in the reply filed on 2/27/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Applicant elected the following species:
Flavivirus nucleic acid sequence (claim 6): SEQ ID NO: 13. Due to SEQ ID NO: 13 being free of the prior art of record, the examiner has withdrawn the election of species requirement.
Flavivirus encoded polyprotein (claim 7): SEQ ID NO: 14. Due to SEQ ID NO: 14 being free of the prior art of record, the examiner has withdrawn the election of species requirement.
Amended claims 1-9 are under examination on the merits.
Declaration under 37 CFR 1.130
The declaration under 37 CFR 1.130(A) filed on 8/4/2025 is sufficient to overcome the rejection of claims 1-2 & 4-9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Baker, et al. (EBioMedicine. 2020 Jul;57:102838. doi: 10.1016/j.ebiom.2020.102838. Epub 2020 Jun 20. PMID: 32574959; hereinafter referred to as “Baker”) as evidenced by GenBank accession MT505350 (7/7/2020; hereinafter referred to as “MT505350”), and the rejection of claim 3 under 35 U.S.C. 103 as being unpatentable over Baker (supra) as applied to claims 1-2 & 4-9 above, and further in view of Liu, et al. (Sci Rep. 2017 May 19;7(1):2193. doi: 10.1038/s41598-017-02460-2. PMID: 28526819; hereinafter referred to as “Liu”). The declaration demonstrates that 102(b)(1) is applicable, since the cited Baker publication was published 1 year or less before the effective filing date of a claimed invention, and the Baker publication was the work of the inventors.
Priority
The petition under 37 CFR 1.78(b) and (c) that was granted on 1/30/2026 is acknowledged. The instant application’s effective filing date is 8/25/2020, due to the benefit of provisional Application No. 63/069,853.
Claim Interpretation
The examiner is interpreting the claim limitation “stable” to mean that the AAV were still capable of replication and detectable expression of the encoded reporter after ten rounds of cell culture passaging, as indicated by the specification (para. [0006]).
Response to Arguments
Applicant’s arguments, see pp. 1-4, filed 8/4/2025, with respect to objections to the specification and claims, and rejections under 35 U.S.C. §§102-103 and 112(b) have been fully considered and are persuasive. The objections and rejections have been withdrawn.
Applicant’s arguments with respect to claims 1-9 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Objections Removed
The previous objections are hereby withdrawn due to Applicant’s amendment and Declaration under 37 CFR filed 8/4/2025:
Specification.
Claim objections: Claims 1, 2, 5, and 8 for minor informalities.
Rejections Removed
The previous rejections are hereby withdrawn due to Applicant’s amendment and Declaration under 37 CFR 1.130 filed on 8/4/2025:
35 U.S.C. §102: claims 1-2 and 4-9 as being anticipated by Baker, et al. (EBioMedicine. 2020 Jul;57:102838. doi: 10.1016/j.ebiom.2020.102838. Epub 2020 Jun 20. PMID: 32574959; hereinafter referred to as “Baker”) as evidenced by GenBank accession MT505350 (7/7/2020; hereinafter referred to as “MT505350”).
35 U.S.C. §103: claim 3 as being unpatentable over Baker (supra) as applied to claims 1-2 & 4-9 above, and further in view of Liu, et al. (Sci Rep. 2017 May 19;7(1):2193. doi: 10.1038/s41598-017-02460-2. PMID: 28526819; hereinafter referred to as “Liu”).
New Objections
Claims 6 and 7 are 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.
New Rejections
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.
(New Rejection) Claims 1-2, 4-5 & 8-9 are rejected under 35 U.S.C. 102(a)(1)as being anticipated by Kinney (WO 2019036617 A1, published 2/21/2019).
The claimed invention encompasses a recombinant flavivirus comprising: a heterologous reporter cassette, the heterologous reporter cassette having a 5’ end, a nucleotide segment encoding a reporter, and a 3’ end; the 5’ end of the reporter cassette encoding 25 to 38 amino acids of an amino terminus of a flavivirus capsid protein; the 3’ end of the reporter cassette encoding 25 to 38 amino acids of an amino terminus of the flavivirus capsid protein, wherein the flavivirus is stable, as recited in claim 1. In one embodiment, the flavivirus further comprises a nucleic acid segment encoding a 2A self-cleaving sequence positioned immediately 3’ of the reporter and immediately 5’ of the nucleotide segment encoding a second 25 to 38 amino acids of a flavivirus capsid protein, as recited in claim 2. In a particular embodiment, the flavivirus is a Zika virus, as recited in claim 4. In a different embodiment, the reporter is a luciferase, EGFP, mCherry, mScarlet, mNeonGreen, or Renilla luciferase reporter, as recited in claim 5. In other embodiments, the flavivirus has a nucleic acid sequence that is at least 98% identical to SEQ ID NO: 13, as recited in claim 6, or encodes a polyprotein that is at least 95% identical to the amino acid sequence of SEQ ID NO: 14, as recited in claim 7.
Another embodiment of the claimed invention encompasses a recombinant flavivirus polyprotein comprising an amino terminal segment comprising a heterologous reporter, the reporter being flanked by an amino terminal first capsid segment corresponding to a capsid sequence comprising 25 to 38 amino acid terminal amino acids of the flavivirus capsid protein and a carboxy terminal second capsid segment corresponding to a capsid segment comprising 25 to 38 amino acids of the amino terminus of the flavivirus capsid protein, as recited in claim 8. In a specific embodiment, the polyprotein further comprises a 2A self-cleaving segment between the reporter and the second capsid segment, as recited in claim 9.
The Prior Art
Kinney discloses chimeric flaviviruses engineered to contain a reporter gene, and chimeric nucleic acid molecules encoding the chimeric flaviviruses (Abstract). Kinney also discloses a chimeric flavivirus nucleic acid molecule comprising in the 5’ to 3’ direction: (i) a 5’ non-coding region from a West Nile virus (WNV) genome; (ii) a nucleic acid encoding amino acid residues 1-35 of a capsid (C) protein of the WNV; (iii) a reporter gene; (iv) a nucleic acid encoding a 2A proteolytic site; (v) a nucleic acid encoding a flavivirus C protein, comprising (a) a 5’ portion encoding amino acid residues 1-35 of a C protein of the WNV, wherein the 5’ portion comprises at least one silent mutation; and (b) a 3’ portion encoding amino acid residue 36 to the C-terminal most amino acid residue of the flavivirus C protein, wherein the 3’ portion comprises a WNV prM signal sequence, a DENV prM signal sequence or a chimeric WNV/DENV prM signal sequence, (vi) a nucleic acid encoding a prM and an E protein from the DENV; (vii) a nucleic acid encoding non-structural proteins NS1, NS2A, NS2B, NS3, NS4A, and NS5 from the WNV; and (viii) a 3’ non-coding region from the WNV genome (Kinney claim 1). Kinney also discloses configurations of the chimeric reporter West Nile/dengue viruses, which include ZsGreen and P2A peptide encoding sequences (Fig. 2). Kinney discloses that in some embodiments, the reporter gene encodes a light-emitting protein, such as a green, blue, cyan, yellow, orange, or red fluorescent protein, and otherwise may be a bioluminescent protein, such as luciferase (pp. 19-20, bridging para; pp. 21-22 printout). The examiner is interpreting the WNV/DENV chimera disclosed by Kinney to read on the instant claim 4’s limitation of “wherein the flavivirus is a Dengue virus”.
Therefore, Kinney anticipates claims 1-2, 4-5 & 8-9.
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.
(New Rejection) Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Kinney (WO 2019036617 A1, published 2/21/2019), as applied to claims 1-2, 4-5 & 8-9 above, and further in view of Liu, et al. (Sci Rep. 2017 May 19;7(1):2193. doi: 10.1038/s41598-017-02460-2. PMID: 28526819; hereinafter referred to as “Liu”).
In another embodiment of the claimed invention, the 2A self-cleaving sequence is a T2A sequence, as recited in claim 3.
The Prior Art
The teachings of Kinney are described above. However, it does not teach a flavivirus with a 2A self-cleaving sequence that is specifically a T2A sequence.
Liu teaches that 2A “self-cleaving” peptides facilitate cloning of multiple genes in a single vector that requires co-expression of multiple factors due to their polycistronic nature, small size, and high “cleavage” efficiency (Abstract). Liu further teaches that T2A leads to the highest level of protein expression at the second gene position for bicistronic 2A constructs, compared to other 2As. (Page 4, para. 1).
It would have been obvious to one of ordinary skill in the art to modify Kinney to utilize a T2A sequence as a self-cleaving sequence. Liu teaches that T2A leads to the highest level of protein expression at the second gene position for bicistronic 2A constructs, compared to other 2As. Kinney teaches use of other 2A self-cleaving sequences, including P2A. One of ordinary skill in the art would be motivated to use T2A because Liu demonstrates that it leads to the highest level of protein expression in certain constructs, including bicistronic 2A constructs. Therefore, claim 3 was prima facie obvious to one of ordinary skill in the art before the priority date of the instant application.
Allowable Subject Matter
SEQ ID NOs: 13-32 are free of the prior art of record, and the prior art of record does not teach sequences that are at least 98% identical to SEQ ID NO: 13, 15, 17, 19, 21, 23, 25, 27, 29, or 31, or 95% identical to SEQ ID NO: 14, 16, 18, 20, 22, 24, 26, 28, 30, or 32.
Conclusion
No claim is allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEFFREY MARK SIFFORD whose telephone number is (571)272-7289. The examiner can normally be reached 8:30 a.m. - 5:30 p.m. ET with alternating Fridays off.
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/JEFFREY MARK SIFFORD/Examiner, Art Unit 1671
/BENJAMIN P BLUMEL/Primary Examiner, Art Unit 1671
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