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 DNA virus for species 1, animal/human cells for species 2, and dehydroascorbic acid for species 3 in the reply filed on June 06, 2025 is acknowledged.
Priority
The present application is a 35 U.S.C. 371 national stage filing of International Application No. PCT/US20/67405, filed 12/30/2020.
Applicant’s claim for the benefit of a prior-filed parent provisional application 62/955,002, filed on 12/30/2019, under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Thus, the earliest possible priority for the instant application is 12/30/2019.
Claims Status
Claim 8 is canceled, claims 3 and 6-7 have been withdrawn from consideration as being drawn to non-elected subject matter, and claims 1-2, 4-5 and 9-15 have been considered on the merits. All arguments have been considered.
Withdrawn Objections & Rejections
Applicant's response filed 01/15/2026 has been considered. Rejections and/or objections not reiterated from the previous Office action mailed 08/26/2025 are hereby withdrawn.
The objections and rejections presented herein represent the full set of objections and rejections currently pending in the application.
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 9 is 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 9: The claim recites “an agent”. This is indefinite because it is unclear if the claim is referring to the agent of claim 1 or a different agent.
Because examples 1 and 2 in the instant specification recite the use of a single agent, and for purposes of compact prosecution, the claim is interpreted as referring to the agent as recited in Claim 1. Amending the claim to recite “the [
Claim Rejections - 35 USC § 103 (new)
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.
Claims 1, 2, 4, 5, 9-11 are rejected under 35 U.S.C. 103 as being unpatentable over Ferreira et al (Biotechol. Prog(2009)25(1)235-243; as cited in the IDS filed 06/28/2025; previously cited) in view of Bijur et al (Enviro. And Mol. Mut.(1999)33;1-9; previously cited).
Regarding claim 1, 2, 4, 5 and 10: Ferreira teach a vector production cell (293 cells) that are treated with an agent to induce an arrect of the cell cycle (cell cycle inhibitors) (p236 col1 para 4, Table 1). Ferreira teach use of hydroxyurea and Aphidicolin as cell cycle inhibitors which arrest the cell cycle in the S/G2 phase (Table 1).
Ferreira also teach transfecting a recombinant Adenovirus (AdV, a DNA virus) construct to produce viral particles, thus encoding genetic constructs coding for the vector genome and vector production information (p236 col2 para3).
Ferreira do not teach the cell cycle arrest agent is dehydroascorbic acid (DHA), the oxidized form of ascorbic acid (AA) or that the cell cycle arrest inhibitor arrests the cells in the S and G2 phases.
Bijur teach dehydroascorbic acid induces cell cycle arrest (abstract). It would have been prima facie obvious to substitute a cell cycle arrest agent in the method taught by Ferreira with the cell cycle arrest agent, dehydroascorbic acid, taught by Bijur because it would have been obvious to substitute one known element for another to obtain predictable results. There would have been a reasonable expectation that dehydroascorbic acid taught by Bijur would work equivalently to the cell cycle arrest agents taught by Ferreira because these agents are well known in the art to produce cell cycle arrest.
Substitution of one element for another known in the field, wherein the result of the substitution would have been predictable, is considered to be obvious. See KSR International Co. v Teleflex Inc 82 USPQ2d 1385 (US 2007) at page 1395.
While Bijur do not explicitly teach dehydroascorbic acid induces cell cycle arrest in the S and G2 stages, the method disclosed by the combination of Ferreria and Bijur comprises the identical active steps of the claimed methods and so is considered to produce the identical result as the claimed method.
Regarding claim 9: The teachings of Ferreira and Bijur are discussed supra. Ferreira also teaches one day after seeding cells, cells are incubated with a cell cycle inhibitor for 6, 12, 24, and 48h (p236 col2 para 4). This reads on the addition of the agent is timed.
Regarding claim 11: The teachings of Ferreira and Bijur are discussed supra. Ferreira also teach the cells are 293 cells, which are equivalent to HEK293 derived cells (p236 col2 para 4).
Claims 12-15 are rejected under 35 U.S.C. 103 as being unpatentable over Ferreira et al (Biotechol. Prog(2009)25(1)235-243; as cited in the IDS filed 06/28/2025) in view of Bijur et al (Enviro. And Mol. Mut.(1999)33; 1-9; previously cited) as applied to claims 1, 2, 4, 5, and 9-11 above, and further in view of Kovesdi et al (Viruses(2010)2;1-23; cited previously).
Regarding claims 12 and 13: The teachings of Ferreira and Bijur are discussed supra. Ferreira also teach the AdV expresses the GFP protein (p236 para3). Ferreira do not explicitly teach the Adv vector is a partially deleted adenoviral vector, or that the vector production cell is a cell that carries genes of an adenoviral E1 region.
Kovesdi teach therapeutic adenovirus vectors are non-replicating and the genome comprises a deletion in the E1 region or replacement of E1 with an expression cassette to produce a therapeutic gene product (p2 para1). Such vectors require a producer cell line containing the adenovirus E1 sequence to complement the E1 region to allow for production of the viral particles (p1 para1).
It would have been obvious for one of ordinary skill in the art at the time of the effective filing date to modify the method taught by Ferreira and Bijur, drawn to providing a vector production cell and transfecting genetic constructs for the vector genome and vector production into the cell, with the disclosure of Kovesdi, which teaches a producer cell line containing the adenovirus E1 sequence to complement the E1 region of an adenovirus vector which comprises a deletion of the E1 region to allow for production of the viral particles.
One would have been motivated to modify the method of Ferreira and Bijur by using the producer cells taught by Kovesdi because Kovesdi teach that therapeutic vectors are deleted in the E1 region to provide space for gene expression cassettes. Furthermore, the goal of Ferreira is to generate viral particles, thus it would be obvious to complement a deleted E1 gene with E1 genes in the producer line because it the E1 gene would be required for generation of viral particles.
One would have had a reasonable expectation of success because Kovesdi teach that is standard practice for Adv vectors and high capacity ADV vectors to have deleted E1 regions (Figure 1).
Regarding claim 14: The teachings of Ferreira and Bijur are discussed supra. Ferreira and Bijur do not explicitly teach the modified adenoviral genome is deleted of all adenoviral genes.
Kovesdi teach high capacity adenoviral vectors are deleted of all adenoviral genes and have a capacity of ~35kb (p2 fig1).
It would have been obvious to one of ordinary skill in the art to adapt the method of Ferreira and Bijur, drawn to generating Adv particles, by using a high capacity adenovirus vector deleted of all Adv genes as taught by Kovesdi, because Kovesdi teaches that the high capacity Adv vector can accommodate the largest transgene payload, and is therefore more flexible and efficient.
Accordingly, one of ordinary skill in the art would have been motivated to modify the Adv vector as taught by Ferreira with the disclosure of Kovesdi to for the purposes of having an AdV system that was flexible and efficient.
One would have had a reasonable expectation of success because Kovesdi teach the vectors can be used in vivo with long term, high level transgene expression with negligible toxicity (p11 ¶2).
Regarding claim 15: The teachings of Ferreira and Bijur are discussed supra. Ferreira and Bijur do not explicitly teach the modified adenoviral genome is deleted of all adenoviral genes and second constructs provide the packaging information for adenoviral genome.
Kovesdi teach HEK293 cells were developed to trans-complement the lack of E1 in AdV vectors through and insertion of E1A and E1B sequence (p2 para3).
Thus the use of HEK 293 derived cells by Ferreira, as discussed supra, and the generation of viral particles as disclosed by Ferreira, demonstrate second constructs providing the packaging information for the adenoviral genome are present.
Response to Arguments
The responses are directed to the Arguments filed 01/15/2026.
Regarding Arguments directed to 35 USC § 112:
Applicant submits the amendments presented in the claim set filed 01/15/2026 render moot the rejection as written.
This is found persuasive because Applicant amends the claims to recite “the agent comprises dehydroascorbic acid” which changes the claim limitations. The rejection is withdrawn.
Regarding Arguments directed to 35 USC § 102 and 103:
Applicant submits the amendments presented in the claim set filed 01/15/2026 overcome the rejections as written.
Specifically, claim 1 has been amended to recite “wherein: the agent comprises dehydroascorbic acid; and the cell cycle is arrested in the S and G2 stages”. This overcomes the rejections as written and the rejections are withdrawn.
Applicant argues that none of the cited references, alone or in combination, disclose, teach, or suggest the specific combination of: (1) using dehydroascorbic acid as the agent, and (2) arresting the cell cycle in the S and G2 stages for enhanced gene transfer vector production”. This is not found persuasive as discussed supra in the new rejection under 103.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDREA LYNNE MORRIS SPENCER whose telephone number is (571)272-3328. The examiner can normally be reached Monday-Friday 9:00-5:00.
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/ANDREA LYNNE MORRIS SPENCER/Examiner, Art Unit 1631
/JAMES D SCHULTZ/Supervisory Patent Examiner, Art Unit 1631
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