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 CN202010826899.8 and CN202011004197.8 filed 08/17/2020 and 09/22/2020 respectively.
This application claims the benefit of priority to Patent Application PCT/CN2021/121350.
Acknowledgement is made of Applicants’ claim for benefit to prior filed to Patent Application
Number PCT/CN2021/121350, filed on 09/28/2021.
Information Disclosure Statement
The Information Disclosure Statements filed 05/11/2023, 09/23/2024, 02/27/2025, and 08/18/2025 have been considered by the Examiner.
Status of Claims
Claims 1, and 3-20 are under examination.
Claim Objections
Claim 9 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.
Claim Rejections - 35 USC § 103
Rejection to claim 2 has been withdrawn in view of the applicant canceling the claim in the reply filed 12/30/2025.
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.
Rejections maintained:
Claims 1, 3-8 and 10-20 are rejected under 35 U.S.C. 103 as being unpatentable over Wu et al. (Molecular Therapy: Methods & Clinical Development, 2018) in view of Aslanidi et al. (PNAS, 2009).
Regarding claim 1, Wu et al. teach a nucleic acid construct, wherein the nucleic acid construct comprises: AAV elements comprising a polynucleotide encoding Cap proteins and a polynucleotide encoding Rep proteins (page 38, abstract). Wu et al. teach the nucleic acid construct further comprises: inverted terminal repeats (ITRs), which reads on AAV cis-acting elements (page 38, introduction).
Wu et al. do not teach the construct further comprises a nucleotide sequence encoding IE protein.
Aslanidi et al. teach the inclusion of a nucleotide sequence encoding IE protein (page 5059, abstract). Aslanidi et al. teach after an IE-1 binding target sequence, homologous region 2 (HR2), is inserted into an expression cassette for producing rAAV, the production of rAAV can be increased (page 5059, abstract).
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 Wu et al. for a nucleic acid construct with the teachings of Aslanidi et al. for enhancing expression by adding a nucleotide sequence encoding IE protein and HR2 region for insertion. Aslanidi et al. provide motivation by teaching adding IE-1 to the nucleic acid expression cassette increases expression of the rAAV vector (page 5059, abstract). One of skill in the art would have had a reasonable expectation of success at combining Wu et al. and Aslanidi et al. because both teach production of rAAV in Sf9 cells following infection with a recombinant baculovirus.
Regarding claim 3, Wu et al. and Aslanidi et al. make obvious the nucleic acid construct according to claim 2. Aslanidi et al. further teach the IE protein is encoded by Autographa californica IE-1 (Acie01) gene and the recombination homologous region is hr2 (page 5059, abstract). Regarding claim 4, Wu et al. and Aslanidi et al. make obvious the nucleic acid construct of claim 1. Wu et al. further teach the nucleic acid construct further comprises a promoter of an IE protein coding gene, where the promoters are PH and P10 promoters (page 42, discussion).
Regarding claim 5, Wu et al. and Aslanidi et al. make obvious the nucleic acid construct of claim 1. Wu et al. further teach optimal expression of AAV Rep and Cap proteins downstream of the PH and P10 promoters (page 42, discussion). Aslanidi et al. teach homologous region 2 (HR2), is inserted into an expression cassette for producing rAAV (page 5059, abstract).
Regarding claim 6, Wu et al. and Aslanidi et al. make obvious the nucleic acid construct of claim 1. Wu et al. teach the nucleic acid construct further comprises: inverted terminal repeats (ITRs) which reads on AAV cis-acting elements (page 38, introduction).
Regarding claim 7, Wu et al. and Aslanidi et al. make obvious the nucleic acid construct of claim 1. Wu et al. further teach the genome of the rAAV vector includes the exogenous gene of interest (GOI) flanked by inverted terminal repeats (ITRs), with the AAV Rep and Cap proteins being supplied in trans (page 38, introduction). The gene of interest (GOI) is placed between AAV elements which are the Cap and REP elements.
Regarding claim 8, Wu et al. and Aslanidi et al. make obvious the nucleic acid construct of claim 7. Wu et al. further teach the genome of the rAAV vector includes the exogenous gene of interest (GOI) flanked by inverted terminal repeats (ITRs), with the AAV Rep and Cap proteins being supplied in trans (page 38, introduction). The gene of interest (GOI) is placed between the AAV Cap and REP elements. Aslanidi et al. teach the addition of a sequence for the IE protein as the gene of interest (page 5059, abstract). Furthermore, Wu et al. and Aslanidi et al. make obvious the following nucleic acid construct IE gene expression cassette-Cap gene expression cassette-ITR-exogenous gene of interest expression cassette-ITR- Rep gene expression cassette.
Regarding claim 10, Wu et al. and Aslanidi et al. make obvious the nucleic acid construct of claim 1. Wu et al. teach the construct is a recombinant baculovirus vector-and the recombinant baculovirus vector is a recombinant baculovirus shuttle vector (page 42, discussion).
Regarding claim 11, Wu et al.. teach a recombinant baculovirus (page 38, abstract). Wu et al. teach the recombinant baculovirus is obtained by constructing a nucleic acid through the baculovirus system (page 38, abstract). Wu et al. and Aslanidi et al. teach the nucleic acid is the nucleic acid as described above in regard to claim 1.
Regarding claim 12, Wu et al. teach an adeno-associated virus is obtained by infecting cells with the recombinant baculovirus of claim 11 and further packaging (page 43, discussion).
Regarding claim 13, Wu et al. teach a cell line (Sf9) where the cell line is infected with a recombinant baculovirus (page 42, discussion). Wu et al. and Aslanidi et al. make obvious the recombinant baculovirus is the recombinant baculovirus as described in regard to claim 11.
Regarding claim 14, Wu et al. and Aslanidi et al. make obvious an adeno-associated virus vector system and the nucleic acid construct described above in regards to claim 1. Wu et al. teach the = adeno-associated virus vector system comprises a baculovirus system (page 42, discussion).
Regarding claim 15, Wu et al. and Aslanidi et al. make obvious a method for constructing the nucleic acid construct of claim 1. Wu et al. teach the method comprises integrating AAV elements carrying an exogenous gene of interest (page 36, introduction). Aslanidi et al. teach a polynucleotide encoding an IE protein (page 5059, abstract). Aslanidi further teaches nucleic acid construct comprises a polynucleotide encoding hr2 (page 5059, abstract), and a recombination homologous region of baculovirus.
Regarding claim 16, Wu et al. and Aslanidi et al. make obvious the method according to claim 15. Wu et al. teach the wherein the method includes 1) AAV elements including a polynucleotide encoding Cap proteins and a polynucleotide encoding Rep proteins (page 38, abstract). 2) Aslanidi et al teach and AAV cis-acting elements where the AAV cis-acting elements are ITR sequences (page 5059, abstract). Aslanidi et al. further teaches the protein IE is encoded by Autographa californica IE-1 (Acie01) genes and hr2 (page 5059, abstract). 3) Wu et al. teach the backbone of the baculovirus vector is the pFast.Bac.Dual (pFD) (page 39, Generation of rAAVs from Single Novel BEV-Infected Sf9 Cells). 4) Aslanidi further teaches nucleic acid construct further comprises a polynucleotide encoding hr2 (page 5059, abstract), a recombination homologous region of baculovirus.
Regarding claim 17, Wu et al. and Aslanidi et al. make obvious a method for producing adeno-associated virus. Wu et al. teach the method comprises the step of infecting an insect cell line (page 42, discussion) with a recombinant baculovirus. Wu et al. and Aslanidi et al. make obvious the recombinant baculovirus is the recombinant baculovirus described above in regard to claim 11.
Regarding claim 18, Wu et al. and Aslanidi et al. make obvious the nucleic acid construct of claim 5. Wu et al. further teach the nucleic acid construct further comprises baculovirus promoters which are PH and P10 (page 42, discussion).
Regarding claim 19, Wu et al. and Aslanidi et al. make obvious the nucleic acid construct of claim 10. Wu et al. teach the construct is a recombinant baculovirus vector which is a shuttle vector (page 42, discussion).
Regarding claim 20, Wu et al. and Aslanidi et al. make obvious the method according to claim 16. Wu et al. teach the nucleic acid construct comprises inverted terminal repeats (ITRs), which reads on AAV cis-acting elements are ITR sequences (page 38, introduction).
Response to Arguments
Applicant's arguments filed 12/30/2025 have been fully considered but they are not persuasive.
Applicant’s Arguments: Claims 1-8 and 10-20 are rejected under 35 U.S.C. §103 as allegedly being unpatentable over Wu in view of Aslanidi. Applicant amends claim 1 herein to define that the nucleic acid construct comprises a polynucleotide encoding a recombination homologous region of baculovirus.
Examiner’s response: Aslanidi et al. teach the integration cassette includes a homologous region 2 (hr2) cloned from WT AcMNPV (page 5059, Results).
Applicant Argues: The skilled artisan would not have had a motivation to combine Wu and Aslanidi to arrive at the invention as claimed.
Examiner’s response: Aslanidi et al. provide motivation by teaching adding IE-1 to the nucleic acid expression cassette increases expression of the rAAV vector (page 5059, abstract).
Applicant Argues: Based on Wu and Aslanidi, there is simply no reason to combine all the nucleotide elements recited in the claims into one nucleic acid construct.
Examiner’s response: As stated above 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 Wu et al. for a nucleic acid construct with the teachings of Aslanidi et al. for enhancing expression by adding a nucleotide sequence encoding IE protein. Aslanidi et al. provide motivation by teaching adding IE-1 to the nucleic acid expression cassette increases expression of the rAAV vector (page 5059, abstract).
Applicant Argues: Wu would have led the skilled artisan to believe that including additional elements may negatively impact the function of the individual elements on the construct. Given the teachings of Wu, Applicant submits that the skilled artisan would not have had a reasonable expectation of success in combining Wu and Aslanidi to arrive at a single nucleic acid construct comprising all the recited nucleic acid elements.
Examiner Response: Wu et al teach since the cited study in 2002 further improvements have been made in two key aspects to improve genetic stability of the BEVs and to reduce the complexity of the Bac system (page 42, Discussion). Wu et al. teach AAV Cap and Rep helper genes were incorporated into a single BEV or integrated into Sf9 packaging cell lines, and the two-Bac systems and Sf9 packaging cell line-based OneBac systems were generated. Wu et al. further teach the current Bac systems still remain complicated and cost-intensive, and they lack versatility and flexibility (page 42, Discussion). Wu et al. teach the ideal solution is developing an efficient BEV integrating all the necessary packaging elements for rAAV production (page 42, Discussion). While Wu et al. teach improvements on the vector from 2002 and careful construction of the vector they do not teach away from all elements included in one vector. Wu et al. further does not teach away from additional packaging elements which as taught by Aslanidi increase expression of the rAAV vector. One of skill in the art would have had a reasonable expectation of success at combining Wu et al. and Aslanidi et al. because both teach production of rAAV in Sf9 cells following infection with a recombinant baculovirus. Wu et al. teach a more streamlined solution to rAAV production than the method of Aslanidi et al.
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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