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 .
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119
(a)-(d). Acknowledgment is made of Applicants’ claim for benefit to foreign applications CN202011419528.4 and CN202011418490.9 filed 12/07/2020.
This application claims the benefit of priority to Patent Application PCT/CN2021/135817. Acknowledgement is made of Applicants’ claim for benefit to prior filed to Patent Application Number PCT/CN2021/135817, filed on 12/06/2021.
Information Disclosure Statement
The IDS filed 06/27/2023 has been considered by the Examiner.
Status of Claims
Claims 1-2 and 6-16 are under examination.
Claim Rejections - 35 USC § 102
Rejection to claims 1-3, 6-9, and 11-16 under 35 U.S.C. 102(a)(1) as being anticipated by Maunder et al. (Nature Communications, 2016) have been withdrawn in view of applicant’s amendments filed 01/26/2026.
Claim Rejections - 35 USC § 103
Rejection of claim 4 under 35 U.S.C. 103 as being unpatentable over Maunder et al. (Nature Communications, 2016) as applied to claims 1-3 above, and further in view of Mullick et al. (BMC Biotechnology, 2006) has been withdrawn in view of the applicant’s amendments filed 01/26/2026.
Rejection of claims 3 and 5 under 35 U.S.C. 103 as being unpatentable over Maunder et al. (Nature Communications, 2016) as applied to claims 1-2 and 7 above, and further in view of Cawood et al. (WO 2020/161484 A1) have been withdrawn in view of the applicant’s amendments filed 01/26/2026.
Rejection of claim 10 under 35 U.S.C. 103 as being unpatentable over Maunder et al. (Nature Communications, 2016) as applied to claims 1 and 7 above, and further in view of Sriram et al. (Circulation, 2001) has been withdrawn in view of the applicant’s amendments filed 01/26/2026.
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:
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.
New Rejections:
Claims 1-2, 6-9, and 11-16 is rejected under 35 U.S.C. 103 as being unpatentable over Maunder et al. (Nature Communications, 2016) in view of Mullick et al. (BMC Biotechnology, 2006) and Cawood et al. (WO 2020/161484 A1).
Regarding claim 1, Maunder et al. teach a viral vector production system (TRiP) (page 1, abstract). Maunder et al. teach the system has two ITR fragments and a gene expression cassette inserted between the two ITR fragments. Maunder et al. further teach the gene expression cassette comprises a CMV promoter (page 2, paragraph 3), a TBS repressor operator (page 2, paragraph 4), an internal ribosome entry site (page 4, paragraph 2), a target gene and a polyadenylation signal which are linked in sequence (page 4, figure 3). Maunder et al. teach a viral vector where the translation is inhibited by combining a tryptophan RNA-binding attenuation protein (TRAP) of Bacillus subtilis and a TRAP-binding sequence (tbs) (a repressible operon) inserted upstream of a transgenic open-reading frame (ORF) (page 2, paragraph 4).
Maunder et al. teach a translational block of one or more transgenes, but does not teach a transcriptional block.
Mullick et al. teach a regulatory system that would be more versatile in its application, generating a configuration of the switch that would be relatively independent of cellular transcription factors (page 11, right column).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to have combined the teachings of Maunder et al. for a viral vector production system (TRiP) with the teachings of Mullick et al. for regulating transcription. Mullick et al. provide motivation by teaching that repressor configurations have demonstrated tight control of gene expression. One of skill in the art would have had a reasonable expectation of success at combining Mauder et al. and Mullick et al. because both teach regulation within mammalian cells.
Maunder and Mullick et al. teach a Cumate-Cuo regulable system, but do not teach specific locations and details of the features.
Cawood et al. teach the CuO element of a Cumate-Cuo regulable system and a TATA BOX are inserted into the gene expression cassette (page 12, lines 15-16). Cawood et al. teach the addition of up to 10 CuO sites which would require engineering the vector for the placement of these elements in the vector (page 12, lines 3-6). Furthermore, one of the CuO elements could be 40-50 nucleotides away from the TATA box as routine experimentation would be required to design and add the number of elements taught by Cawood et al. Cawood et al. teach a system with a minimal promoter which comprises one or more cumate operator sites that provide a high level of control over AAV gene transcription (page 3, lines 22-26). Cawood et al. teach expression regulation of the Rep and Cap proteins. Cawood et al. further teach the system can regulate the expression of Adenoviral proteins in the packaging or producer cell lines, and which may have cytotoxic or cytostatic effects. Cawood et al. teach nucleic acid constructs for use in cell packaging and producer cell lines (page 6, lines 4- 10). Cawood et al. teach cumate-based system has particular advantages over antibiotics-based systems including removal of contaminating antibiotics carried over to final AAV preparations. Cawood et al. teach the system allows for a genetic-based induction system in the packaging cell line and a chemical-based induction system in the producer cell line. Cawood et al. teach these processes can be used in a Good Manufacturing Process (GMP) which reduces safety concerns. Cawood et al. teach the systems provide a high level of control over AAV gene transcription, with reduced 'off' state expression levels and high 'on' state expression levels (page 6, lines 11-24).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to have combined the teachings of Maunder et al. and Mullick et al. for the viral packaging vector containing an operon for expression in cells with the teachings of Cawood et al. for the cumate gene-switch system for regulated expression in mammalian cells. Cawood et al. provide motivation by teaching that the cumate system allows enhanced control and reduced safety concerns. One of skill in the art would have had a reasonable expectation of success at combining Maunder et al., Mullick et al., and Cawood et al. because they teach cell lines with packaging vectors for regulated expression in mammalian cells.
Regarding claim 2, Maunder et al. teach a TRiP-Adeno system which produces adenoviral vectors with an Ad5 packaging backbone (page 7, left column).
Regarding claim 6, Maunder et al. teach the promoter is CMV or PGK (page 2, left column).
Regarding claim 7, Maunder et al. teach a viral vector where the translation is inhibited by combining a tryptophan RNA-binding attenuation protein (TRAP) of Bacillus subtilis and a TRAP-binding sequence (tbs) (repressible operon) inserted upstream of a transgenic open-reading frame (ORF) (page 2, paragraph 4). Maunder et al. further teach when the gene of interest (Bax) is expressed within cells Bax produced a strong inhibitory effect on global gene expression as consequence of induction of apoptosis (page 7, right column). The specification of the present applications teaches "a negative effect on viral packaging" refers to directly killing the cells for packaging (page 9, paragraph 0055). Induction of apoptosis reads on a negative effect on viral packaging, because it is an induction of cell death.
Regarding claim 8, Maunder et al. teach a vector where the gene of interest (Bax) has cytotoxicity to the cells for packaging (page 7, Recovery of DNA-based vectors expressing an apoptotic gene).
Regarding claim 9, Maunder et al. teach a vector expressing an apoptotic gene (page 7, Recovery of DNA-based vectors expressing an apoptotic gene).
Regarding claim 11, Maunder et al. further teach a vector expressing Factor-VIII which is known to inhibit VSV-G envelope incorporation (page 6, paragraph 2), directly inhibiting assembly of the virus.
Regarding claim 12, Maunder et al. teach the vector for viral packaging which can include a reporter (page 4, Enhanced lentiviral vector titers using the TRiPLenti system), an internal ribosome entry site (IRES) (page 4, left column paragraph 2), and a polyadenylation signal (page 4, figure 3).
Regarding claim 13, Maunder et al. teach a viral vector packaging system (TRiP) comprising the vector for viral packaging and a backbone vector (page 11, Adenoviral vector production).
Regarding claim 14, Maunder et al. teach a method for packaging a virus comprising transferring a viral vector packaging system (TRiP) into host cells (page 11, Lentiviral vector production) and packaging in the presence of a TRAP-binding sequence (tbs), which acts to repress translation (page 2, paragraph 4).
Regarding claim 15, Maunder et al. teach the host cell is a HEK-293 cell. Maunder et al. teach the host cell is specifically a HEK-293T cell capable of providing the E1 region of an adenovirus (page 11, Cell lines).
Regarding claim 16, Maunder et al. teach the host cell derivative is a HEK-293T cell (page 4, left column).
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Maunder et al. (Nature Communications, 2016) in view of Mullick et al. (BMC Biotechnology, 2006) and Cawood et al. (WO 2020/161484 A1) as applied to claims 1 and 7 above, and further in view of Sriram et al. (Circulation, 2001).
Regarding claim 10, Maunder, Mullick, and Cawood et al. teach a viral vector production system (TRiP) (page 1, abstract). Maunder, Mullick, and Cawood et al. teach a gene of interest in the gene cassette, however does not specifically teach the gene is a cell cycle-associated gene.
Cell cycle associated gene therapy methods are well known in the art. Sriram et al. teach gene therapy methods including inhibition of cell cycle-associated genes for treatment of vasculo-proliferative disorders (page 2414, abstract). Sriram et al. teach endogenous gene expression can be downregulated using antisense techniques. Sriram et al further teach gene activity can also be regulated negatively using transcription factor decoy techniques. Sriram et al. teach adenoviral delivery of ribozymes targeting c-myb inhibit neointimal formation and local delivery of a proliferating cell nuclear antigen ribozyme inhibits stenosis (page 2416, paragraph 3).
It would have been obvious to one of ordinary skill in the art to combine the teachings of Maunder, Mullick, and Cawood et al. for a viral vector for packaging and Sriram et al. for the gene of interest as a cell cycle-associated gene. Sriram et al. provide motivation to combine the cell cycle, target-regulating mechanisms, and possible interventions in vasculo-proliferative diseases. The results would have been predictable because Sriram et al. teach viral vectors where the gene of interest is a cell-cycle associated gene. One of skill in the art would have had a reasonable expectation of success at combining Maunder, Mullick, Cawood and Sriram et al. because they teach vectors for regulated expression in mammalian cells.
Response to Arguments
Rejections under 35 U.S.C. 103 have been withdrawn in view of the applicant’s amendments filed 01/26/2026.
Applicant’s Argument: Applicant Argues Maunder explicitly warn that transcriptional repressor systems have inherent limitations (see Maunder et al., page 10, left column, last paragraph).
Examiner’s Response: Mauder et al. explain that transcriptional repression may be more limited than a translational block, however there is no teaching that transcriptional repression would not work.
Applicant’s Arguments: Applicant argues Cawood does not disclose a distance of 40-50 nucleotides.
Examiner’s Response: Cawood et al. teach the addition of up to 10 CuO sites which would require engineering the vector for the placement of these elements in the vector (page 12, lines 3-6). Furthermore, one of the CuO element would be 40-50 nucleotides away from the TATA box as routine experimentation would be required to design and add the number of elements taught by Cawood et al. Cawood et al. would be required experimentation to move around elements in order to fit the up to 10 CuO sites. Cawood et al. teach the CuO site or sites in the promoter are placed upstream of both the TATA box and the +1 site (page 12, lines 11-12).
Conclusion
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.
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/C.L.M./Examiner, Art Unit 1638
/Anna Skibinsky/
Primary Examiner, AU 1635
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