Notice of Pre-AIA or AIA Status
The present application, 17766646, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1, 2,7, 11, 15-16, 20-21, 23-25, 27, 32-35, 38-40, 42 are pending.
Priority
The filing receipt, mailed 2/21/2023, states that this application, filed 4/5/2022, claims benefit Domestic Priority data as a 371 of PCT/KR2020/014585, filed 10/23/2020 which claims benefit of 62/924,711, filed 10/23/2019.
Compliance with the Nucleotide and Amino Acid Sequence Rules
Because of applicant’s amendments to the specification, filed 9/30/2025, the application appears to satisfy the Nucleotide and Amino Acid Sequence Rules and is now considered to comply with these rules.
Drawings
The corrected drawings, filed 9/30/2025, are acceptable and acknowledged.
Withdrawal and Modification of Claim Rejections
1. The rejection of Claims 7, 16, and 32, 35 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in view of applicant’s amendments to the claims and arguments, filed 9/30/2025.
2. The rejection of Claims 1, 2, 7, 20, 23-25, 27, 32, 38-40 and 42 is/are rejected under 35 U.S.C. 102 (a)(1) 2. and (a)(2) as being anticipated by Danthinne, US 8,709,778, (of record, IDS filed 3/24/2023) , is withdrawn in view of applicant’s amendments to the claims and arguments, filed 9/30/2025. This rejection is modified in the obviousness rejection below.
Claim Rejections - 35 USC § 103
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.
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.
1. Claim(s) 1, 2, 7, 11, 15-16, 20, 42 is/are rejected under 35 U.S.C. 103 as being unpatentable over Danthinne, US 8,709,778, (of record, IDS filed 3/24/2023); Fisher, 20030082140; Baurin 2001, Molecular Therapy, abstract 11, vol 3, number 5, part 2 of 2 parts, S5-S8; Aldabe, US 20210180084, filing date 5/14/2019.
Danthinne discloses a method for preparing a gutless adenovirus vector, the method comprising a step for transfecting a gutless plasmid and a helper plasmid into 293 cells, reading on a virus packaging cell strain, in which the gutless plasmid includes 3' ITR, a packaging signal, a cassette expressing B-galactosidase under the control of a CMV promoter, reading on a genome plasmid, and SV40 poly-adenylation signal, a stuffer DNA, and 5' ITR (see column 24, line 42 - column 25, line 67), describing instant Claims 1, 2 and 23.
Danthinne, at Fig. 11, teach a plasmid, including an Ori replication origin, which reads on the gutless adenovirus genome plasmid of instant claim 7. Danthinne at col. 13, lines 38-45, describes E1 region of adenovirus as in instant Claims 20 and 38. Danthinne, at col. 5, line 4; col. 10, lines 5-9, teach linearization of a final genome plasmid by a restriction enzyme, as in instant Claim 24.
Danthinne, at col. 25, lines 52-67, teach transfection by calcium phosphate precipitation, as in instant Claim 25. Claim 25 states elements in the alternative ("or") so that elements (a) to (e) are considered to be members of a Markush group.
Danthinne, at col. 38, lines 38-44, teach a final genome plasmid, as in instant Claims 32 and 42. Danthinne, at col. 2, lines 29-38, teach a GLAd that is free of a contaminant virus species, such as replication-competent adenovirus, as in instant Claims 39 and 40.
Danthinne does not teach a cloning shuttle plasmid in a gutless adenovirus system and does not teacher a stuffer DNA (sDNA) comprising a scaffold/matrix attachment element (SMAR).
Fisher, 20030082140, throughout the publication and abstract an at para [0054] teach the use of cloning shuttle plasmids in order to allow recombination to occur between homologous adenovirus sequences contained in the adenovirus shuttle for expression, e.g. of a foreign gene. These recombinant adenovirus vector genomes can replicate and be packaged into fully-infectious adenovirus particles. The recombinant vector can then be isolated from contaminating virus particles by one or more rounds of plaque, and the vector can be further purified and concentrated by density ultracentrifugation. Fisher states:
In preferred, non-limiting embodiments of the invention, the expression vector is an E1-deleted human adenovirus vector of serotype 5. To prepare such a vector, an expression cassette comprising a transcriptional promoter element operatively linked to an MDA-7 coding region and a polyadenylation signal sequence may be inserted into the multiple cloning region of an adenovirus vector shuttle plasmid, for example pXCJL.1. In the context of this plasmid, the expression cassette may be inserted into the DNA sequence homologous to the 5' end of the genome of the human serotype 5 adenovirus, disrupting the adenovirus E1 gene region. Transfection of this shuttle plasmid into the El-transcomplementing 293 cell line, or another suitable cell line known in the art, in combination with either an adenovirus vector helper plasmid such as pJM17 or pBHG10 or a ClaI-digested fragment isolated from the adenovirus 5 genome, allows recombination to occur between homologous adenovirus sequences contained in the adenovirus shuttle plasmid and either the helper plasmid or the adenovirus genomic fragment. This recombination event gives rise to a recombinant adenovirus genome in which the cassette for the expression of the foreign gene has been inserted in place of a functional E1 gene. When transcomplemented by the protein products of the human adenovirus type 5 E1 gene (for example, as expressed in 293 cells), these recombinant adenovirus vector genomes can replicate and be packaged into fully-infectious adenovirus particles. The recombinant vector can then be isolated from contaminating virus particles by one or more rounds of plaque, and the vector can be further purified and concentrated by density ultracentrifugation.
Fisher, at para [0054], citations omitted.
Baurin 2001, Molecular Therapy, abstract 11, vol 3, number 5, part 2 of 2 parts, S5-S8, teaches that a “gutless” adenovirus vector is a fully-deleted adenovirus vector. Furthermore these vectors are less toxic, less immunogenic and more persistent that previous generations of adenovirus vectors.
Aldabe, US 20210180084, filing date 5/14/2019, teaches throughout the publication and abstract and at, e.g., para [0006], which states:
[0006] In the genome of eukaryotic cells exist sequences in their chromosomes that interact with the nuclear matrix and mediate structural organization of the chromatin into loops or domains within the nucleus. These sequences are known as Scaffold/Matrix Attachment Region (hereafter referred as “S/MAR”) and play an important role in chromatin organization, transcription and replication. These abilities of S/MAR elements have led to investigate their role in different non-integrating expression cassettes to assist in the establishment of episomes over cell division. In non-viral plasmids, S/MAR elements are used to establish long-term gene expression through the interaction with the nuclear matrix maintaining episomal transgene expression over hundreds of cell generations after an initial phase of antibiotic selection. The episomal replication is due to a stable association with early replication foci by the binding of S/MAR elements to the nuclear matrix protein scaffold attachment factor A (SAF-A).
Aldabe at para [0006].
Furthermore, Aldabe, at para [008]-[0011], teaches subcloning S/MAR elements into AAV vectors which are designed to persist predominantly as episomes. Aldabe, at para [0075], teaches that these expression vectors can be gutless adenovirus.
It would have been prima facie obvious before the application was filed, for one of ordinary skill in the art to have combined into a gutless adenovirus system, as taught by Danthinne, a cloning shuttle plasmid, as taught by Fisher and Baurin and a scaffold/matrix attachment element (SMAR) in stuffer DNA (sDNA), as taught by Aldabe.
One of ordinary skill in the art would have been motivated to have combined shuttle plasmids to have genes, as taught by Fisher, in order to express those genes in gutless adenovirus vectors. One of ordinary skill in art would have been motivated to use gutless adenovirus vector, as they represent a further refinement of deleted adenoviruses, as taught by Baurin. One of ordinary skill in the art would have been motivated to have combined scaffold/matrix attachment element (SMAR) in stuffer DNA (sDNA) in gutless adenovirus vectors, as taught by Aldabe, in order to establish long-term gene expression through the interaction with the nuclear matrix to maintain episomal transgene expression over hundreds of cell generations.
Conclusion
1. Claims 21, 23-25, 27, 32, 35, 38-40 are free of the examined prior art, which does not teach or suggest the pAd5pTP expression plasmid.
2. Claims 23-25, 27, 32-35, 38-40 are therefore allowed.
3. Claim 21 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.
4. 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.
5. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Mark L Shibuya whose telephone number is (571)272-0806. The examiner can normally be reached M-F, 9AM-4:30PM.
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MARK L. SHIBUYA
Primary Patent Examiner
Art Unit 1631
/MARK L SHIBUYA/Primary Patent Examiner, Art Unit 1631