DETAILED ACTION
Claims 1-8 are currently pending.
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
Acknowledgement is made of the instant application being a national stage entry under 35 USC 371 of international application PCT/US2021/033826, filed May 24, 2021, which claims the benefit of provisional application No. 63/029,839, filed May 26, 2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/20/2022 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1 and 5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Murphy et al., (Journal of Virology, Apr 2007, p 3721-3730; see PTO-892) (“Murphy”).
Murphy is directed to sequence manipulations of the p5 promoter, specifically the core structure: TATA/RBE/YY1+, and the effect on the adeno-associated virus type 2 (AAV2) life cycle. Murphy teaches transfection in HeLa cells (Abstract).
Murphy’s FIG. 4A illustrates the following p5 promoter constructs:
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Murphy teaches the recombinant promoter constructs were used in assays assessing function in transcription, integration and Rep-dependent replication. Murphy teaches the recombinant promoter constructs p5RBEfix and p5pacRBE comprising exogenous spacer sequence “ttaa” inserted between YY1-60 and the REP binding element (RBE) (i.e., REP binding site) in order to generate a PacI restriction site. Murphy further teaches the insertion of a single nucleotide between the RBE and YY1+1 site in the p5RBEfix construct to generate a ClaI restriction site (FIG 4; and page 3725 at p5IEE RBE requirements for transcription, replication and integration). Thus, Murphy’s p5RBEfix and p5pacRBE constructs anticipate claim 1.
Regarding claim 5, Murphy teaches transfection in HeLa host cells (Abstract), thus anticipating claim 5.
Claim(s) 8 is rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Hermonat et al., (US 2002/0001580; see PTO-892) (“US ‘580”), as evidenced by Zhan et al., (The Journal of Biological Chemistry, Vol 274, No. 44, Issue of October 29, pp. 31619-31624; see PTO-892) (“Zhan”) and Lace et al., (Journal of General Virology, Vol 90, Iss. 10, Abstract; see PTO-892) (“Lace”).
US ‘580 is directed to utilization of AAV vectors to transfect epithelial cells with an AAV/heterologous gene containing/Neo vector, to form a heterologous protein secreting culture of epithelial cells to prepare recombinant skin useful in skin gene therapy (Abstract and [0002], [0006]-[0009]).
Regarding claim 8, US ‘580 at Experiment 6 ([0118]-[0119]) teaches construction of second generation recombinant AAV vectors wherein the p5 promoter has been replaced with the suprabasal promoter, P97 (HPV-P97), that is driving AP, LacZ, and GM-CSF. Thus, US ‘580 teaches a recombinant AAV harboring the HPV P97 promoter.
Zhan teaches Rep78 binds a 44-base pair region within the HPV-P97 promoter (Abstract, page 31619). Thus, Zhan evidences that the P97 promoter comprises a REP binding site (i.e., Rep78).
Furthermore, Lace evidences the P97 promoter comprises a YY1 binding site (Abstract).
Thus, US ‘580, as evidenced by Zhan and Lace, anticipates claim 8.
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.
Claim(s) 2 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Murphy, as applied to claims 1 and 5 above.
The teaching of Murphy is set forth above, and anticipates claims 1 and 5.
Regarding claim 2, Murphy teaches the spacer sequence comprises 4 nucleotides (FIG 4A) in order to create a PacI restriction site. Murphy does not further teach the spacer is 5-100 nucleotides. However, it would be obvious to the skilled artisan to include additional spacer sequence providing additional restriction sites to provide further optimization of the plasmid constructs.
The instantly claimed range of spacer nucleotides, are so close to Murphy that the fact pattern is similar to the one in In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) or Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) where despite a “slight” difference in the ranges the court held that such a difference did not "render the claims patentable" or, alternatively, that "a prima facie case of obviousness exists where the claimed ranges and prior art ranges do not overlap but are close enough so that one skilled in the art would have expected them to have the same properties”.
In light of the case law cited above and given that there is only a "slight” difference between the range disclosed by Murphy, and the ranges disclosed in the present claim, it therefore would have been obvious to one of ordinary skill in the art that the component ranges disclosed in the present claim is but an obvious variant of the amounts disclosed in Murphy, and thereby one of ordinary skill in the art would have arrived at the claimed invention.
Regarding claim 7, it is noted that Murphy does not comment on reduction of DNA contamination. However, Murphy’s FIG. 4B illustrates the insertion mutations, p5RBEfix and p5pacRBE, result in reduction of CAT expression as compared to wild type p5 promoter.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to employ Murphy’s disclosed insertion mutations for the predictable result of reducing undesired DNA contamination since doing so would reduce deleterious immune response in therapeutic use.
Claim(s) 3-4 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Murphy, as applied to claims 1 and 5 above, and further in view of Wang et al., (Nat Rev Drug Discov 18, 358–378 (2019); see PTO-892) (“Wang”).
The teaching of Murphy is set forth above.
Regarding claims 3-4 and 6 and the limitations directed to an AAV comprising the recombinant p5 promoter construct of claim 1 (claim 3), wherein the AAV is selected from AAV1-AAV9 (claim 4), and a host cell further comprises the AAV vector of claim 3 (claim 6), it is noted that, although Murphy teaches assessing the AAV2 p5 promoter using plasmid constructs and further transfection into HeLa cells in order to assess function in transcription, integration and Rep-dependent replication, Murphy does not further teach AAV1-AAV9 comprising the modified p5 promoter constructs. However, Wang teaches that AAV2 has been successfully cloned into plasmid constructs, enabling genetic studies and complete sequencing of the AAV2 genome, thus providing fundamental knowledge leading to the use of AAV technology as a gene delivery vehicle for human gene therapy. Preclinical and clinical successes in AAV-mediated gene replacement, gene silencing and gene editing have helped AAV gain popularity as the ideal therapeutic vector and Wang teaches the advent of AAV vectors, and their use as a biotherapy, has also advanced the understanding of virus–host interactions that govern the transduction pathway of AAV (Abstract; Fig. 1; Fig. 2).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare an AAV2 vector comprising the recombinant p5 promoter construct disclosed by Murphy since doing so would permit further analysis of transcription, integration and Rep-dependent replication in the host HeLa cells disclosed by Murphy thus further advancing the understanding of virus–host interactions that govern the transduction pathway.
The person of ordinary skill in the art would have been motivated to modify the teachings of Murphy to prepare an AAV2 vector and host cell comprising the AAV2 recombinant p5 promoter construct, for the predictable result of successfully further analysis of transcription, integration and Rep-dependent replication in the host HeLa cells disclosed by Murphy, thus meeting the limitations of claims 3-5.
The skilled artisan would have had a reasonable expectation of success in combining the teachings of Murphy and Wang because each of these teachings are directed at adeno-associated virus (AAV) therapeutic uses.
Conclusion
No claim is allowed. No claim is free of prior art.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to E. YVONNE PYLA whose telephone number is (571)270-7366. The examiner can normally be reached M-F 9am - 6pm.
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E. YVONNE PYLA
Primary Examiner
Art Unit 1633
/EVELYN Y PYLA/ Primary Examiner, Art Unit 1633