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 .
Amendments
In the reply filed 8/13/2026, Applicant has amended Claims 1, and cancelled claims 2 and 4.
Claims 12-20 are pending but withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.
Claims 1, 3, 5-11 are under consideration.
Priority
The instant application was filed 8/11/2023 and is a CON of PCT/JP2022/005335 filed 2/10/2022 and claims foreign priority to application JP2021-020868, filed 2/12/2021.
Applicant is advised of possible benefits under 35 U.S.C. 119(a)-(d) and (f), wherein an application for patent filed in the United States may be entitled to claim priority to an application filed in a foreign country.
However, Applicant cannot rely upon the certified copy of the foreign priority application to overcome this rejection because a translation of said application has not been made of record in accordance with 37 CFR 1.55. See MPEP §§ 215 and 216.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a) -(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action, 37 CFR 41.154(b) and 41.202(e).
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Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Withdrawn 35 USC § 112(b)
The prior rejection of Claims 3, 5-11 under 35 U.S.C. § 112(b) pre-AIA 2nd paragraph as being indefinite is withdrawn in light of Applicant’s amendments of instant claims to describe the “one or more virus helper genes”, "the promoter capable of regulating expression", and the “one or more adeno-associated virus genes”.
New Claim Rejections - 35 USC § 112(b)
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.
Claims 1, 3, 5-11 are 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 pre-AIA the applicant regards as the invention.
Claim 1 recites “at least one” of the virus helper genes is under control of a promoter capable of regulating expression directed to the first vector, and again recites in a wherein clause directed to the first vector that “one or more” virus helper genes are under control of a promoter capable of regulating expression, thereby indicating that the scope of the claim encompasses “one” virus helper gene, yet the claim goes on to recite that two of the virus helper gene (E4 and VA RNA) are under the control of the promoter capable of regulating expression, which on its face appears to contradict the recited limitation of “one” virus helper gene under the control of the promoter capable of regulating expression. The claim is indefinite due to this apparent contradiction in terms, and should be revised to indicate that “two or more” of the virus helper genes are under the control of a promoter capable of regulating expression. Dependent claims 3 and 5-11 do not resolve this contradiction and should be amended accordingly.
Claim 6 recites the limitations "an E4 gene, and a VA-RNA gene" in regard to Claim 1. There is insufficient antecedent basis for this limitation in the claim because Claim 1 already recites an E4 gene and VA-RNA gene, thereby rendering Claim 6 indefinite as to which of the E4 and VA-RNA genes the claim refers. Appropriate correction is required.
Withdrawn 35 USC § 102
The prior rejection of Claims 1, 3, 5-11 under 35 U.S.C. 102(a)(1) as being anticipated by Agilent (AAV Helper-Free System, Instruction Manual, rev. D0-2015, pgs 1-48, on-line 3/21/2016), as evidenced by Colosi et al., (US 7,037,713, filed 2/11/2002, patented 5/02/2006) is withdrawn in light of Applicant’s amendment of Claim 1 to include the limitations of claim 2, which Agilent does not anticipate.
Withdrawn 35 USC § 103
The prior rejection of Claims 1, 3, 5, and 9-11 under 35 U.S.C. 103 as being unpatentable over Gao US 6,953,690, filed 9/20/2000, patented 10/11/2005), in view of Orberger et al., (WO 2002/38782, filed 11/13/2001, published 5/16/2002) is withdrawn in light of Applicant’s amendment of Claim 1 to include the limitations of Claim 4, which neither Gao nor Orberger make obvious.
New 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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 1, 3, 6-11 are rejected under 35 U.S.C. 103 as being unpatentable over Colosi (US 6,004,797, filed 11/07/1996, patented 12/21/1999), in view of Liu et al. (WO2003/039459, filed 10/31/2002, published 5/15/2003), Goepfert et al. (US 2022/0135954, filed 10/31/2021, published 5/05/2022, with priority to EP 20202010, filed 10/15/2020) and Agilent (AAV Helper-Free System, Instruction Manual, rev. D0-2015, pgs 1-48, on-line 3/21/2016, prior art of record).
In regard to claim 1, Colosi teaches a composition comprising:
A first vector containing adenovirus genes comprising an E2 gene, an E4 gene, and VA-RNA gene (col 5, Summary of the Invention, 2nd para., col 13, 3rd para., Example 9, col 30, last para., see Fig. 3 “pladeno5”), and in regard to the promoter of the first vector, Colosi teaches the adenoviral gene regions are operably linked to heterologous promoters such as the inducible metallothionein promoter (col 14, 2nd para.); and
A second vector containing the AAV rep and cap genes with an AAV p5 promoter (Example 9, col 31, “plasmid pW1909”, see also “Plasmid Construction”, col 19, 3rd & 5th para.).
However, in regard to the E4 gene of the first vector of claim 1, Colosi is silent to at least the E4 adenoviral gene under the control of an inducible metallothionein promoter.
Liu (WO2003) teaches compositions and methods for making both adenoviral and AAV vectors [0008, 0034], wherein at least one of the adenoviral genes (i.e., E4orf6) is under the control of the inducible metallothionein promoter and explains that doing so can reduce any potential toxicity associated with overexpression of the adenoviral genes in cells [0073-0074, 00332-00333, 00337]. Furthermore, Liu teaches concentrations of zinc to be used to induce the E4 gene, which the Examiner has interpreted as a “drug” based on the fact that there is no special definition of “drug” in Applicant’s specification, zinc is used clinically, and Applicant’s specification explicitly recites the use of the metallothionein promoter.
According, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to prepare the composition comprising a first vector comprising at least one of the adenoviral genes under an inducible metallothionein promoter as suggested by Colosi, and choose the E4 gene under the inducible promoter as taught by Liu with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so not only because Colosi suggests do so from a limited genus of adenoviral genes and promoters to choose from, but because Liu teaches that the induction of the adenoviral E4 gene limits toxicity to the cell.
However, in regard to the VA RNA of the first vector of claim 1, Colosi is silent to at least the VA-RNA adenoviral genes under the control of an inducible promoter.
Goepfert (US2022) teaches compositions and methods for AAV vectors, wherein at least one of the adenoviral genes (i.e., VA-RNA) is under the control of an inducible promoter and explains that doing so can improve control of VA RNA transcription and thereby AAV particle production ([001] of US2022, and see also p. 5, Summary of the Invention, para. 6, pgs. 45-46, Exemplary Compounds and Compositions According to the Current Invention of priority document). Furthermore, Goepfert teaches that well-known drug inducible promoters can be used to regulate the adenoviral VA RNA (p. 46, 2nd para. of priority document). Furthermore, Goepfert cites the prior patent of Colosi “6,004,797” as a method to be used for generating AAV vectors licensing agreement (p. 58, Exemplary uses and methods comprising the nuclei acid and the DNA according to the current invention of priority document).
According, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to prepare the composition comprising a first vector comprising at least two of the adenoviral genes under an inducible promoter as suggested by Colosi, and choose the VA RNA under the inducible promoter as taught by Goepfert with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so not only because Colosi suggests the general concept of inducible promoters for limited genus of adenoviral genes, but because Goepfert teaches that the controlled induction of the VA RNA improves AAV production.
However, in regard to the composition of claim 1, Colosi is silent with respect to a kit comprising the vectors.
With respect to claim 1, Agilent teaches a kit comprising:
a first plasmid vector containing adenoviral genes E2A, E4 and VA RNA; and
a second plasmid vector containing AAV genes Rep and Cap (see entire document, note Fig. 1). Furthermore, the Agilent kit manual cites the prior patent of Colosi “6,004,797” in their licensing agreement (p. 2, para. #1).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to prepare the composition of plasmid vectors as taught by Colosi for the production of rAAV and to combine them into a kit as taught by Agilent with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so not only for matters of convenience and commercial applicability, but also because Agilent indicates that the subject matter of Colosi was to be licensed as a kit.
In regard to claim 3, as stated supra, the E2, E4, and VA-RNA are derived from adenovirus.
In regard to claim 6, as stated supra, Colosi teaches the E2, E4, and VA-RNA are in the first vector.
In regard to claim 7, Colosi teaches that an E4 region of about 3 kb can be used in the first vector, which comprises the E4ORF6 gene (col 15, 4th para.). Furthermore, Liu teaches the drug inducible promoter operably linked to the E4ORF6 gene [00332], thereby establishing that this was a predictably obvious choice.
In regard to claim 8, Colosi teaches that a VA RNA region of about 700 bp can be used in the first vector, which comprises the VA-I RNAs (col 15, 4th para.). Furthermore, Goepfert teaches the drug inducible promoter operably linked to the VA-I RNA (p. 5, 3rd para. of priority document), thereby establishing that this was a predictably obvious choice.
In regard to claims 9-10, as stated supra, the AAV Rep and Cap genes are operably linked to promoters naturally carried by AAV (e.g., p5).
In regard to claim 11, as stated supra, the AAV genes include Rep and Cap genes.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Colosi (US 6,004,797, filed 11/07/1996, patented 12/21/1999), in view of Liu et al. (WO2003/039459, filed 10/31/2002, published 5/15/2003), Goepfert et al. (US 2022/0135954, filed 10/31/2021, published 5/05/2022, with priority to EP 20202010, filed 10/15/2020) and Agilent (AAV Helper-Free System, Instruction Manual, rev. D0-2015, pgs 1-48, on-line 3/21/2016, prior art of record), as applied to claim 1, in further view of Zhou et al., (Virology, 2000, 275:348-357)
As stated supra, Colosi teaches a first vector comprising the adenoviral gene regions (which include E2, E4, and VA RNA) that are operably linked to heterologous promoters, and Colosi and Liu make obvious that the E4 gene is under an inducible promoter, and Colosi and Goepfert make obvious that the VA RNA gene is under an inducible promoter.
However in regard to claim 5, Colosi et al. are silent to the adenoviral E2 gene under the control of a drug inducible promoter.
Zhou teaches compositions and methods for making both adenoviral and helper-dependent AAV vectors (Abstract, Discussion, p.354, col 2, 2nd para.), wherein the adenoviral gene (i.e., E2a) is under the control of a drug inducible promoter and explains that doing so can reduce any potential toxicity associated with overexpression of the adenoviral E2 genes in cells (Results, p. 349, 1st para., Discussion, p. 354, col 1, 3rd para.).
According, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to prepare the composition comprising a first vector comprising at least two of the adenoviral genes under inducible promoters as suggested by Colosi et al., and combine the E2a gene under the inducible promoter as taught by Zhou with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so not only because Colosi suggests do so from a limited genus of adenoviral genes, but because Zhou teaches that the induction of the adenoviral E2a gene limits toxicity to the cell.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
RESPONSE TO ARGUMENTS
Applicant's arguments filed on 8/13/2026 are acknowledged but are considered moot in light of the new rejection as necessitated by amendment.
Applicant's arguments have been fully considered but they are not persuasive.
Conclusion
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 extension fee 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 date of this final action.
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARTHUR S LEONARD whose telephone number is (571)270-3073. The examiner can normally be reached on Mon-Fri 9am-5pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Doug Schultz can be reached on 571-272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ARTHUR S LEONARD/Examiner, Art Unit 1631
