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 .
Response to Amendment
The amendment filed 11 March 2026 in which claim 21 was amended and claim 35 was added has been entered.
Claims 21-35 are under examination on the merits.
Claim Rejections - 35 USC § 112
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.
(Previous rejections, withdrawn as to claims 21-34). Claims 21-34 were 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Applicant’s amendments to claim 21 have overcome the previous rejection to the instant claims.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
(New rejection, necessitated by amendment as to claims 21 and addition of claim 35). Claims 21-35 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for some embodiments, does not reasonably provide enablement for all embodiments. The Specification does not enable any person skilled in the area to which it pertains, or which it is most nearly connected, to use the invention commensurate in scope with these claims.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.” These factors include, but are not limited to:
• (A) The breadth of the claims;
• (B) The nature of the invention;
• (C) The state of the prior art;
• (D) The level of one of ordinary skill;
• (E) The level of predictability in the art;
• (F) The amount of direction provided by the inventor;
• (G) The existence of working examples; and
• (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
The breadth of claims 21-35 broadly encompasses a single-plasmid method for producing a recombinant adeno-associated virus in a host cell. Embodiments that comprise a modified adenovirus E4 coding region comprising SEQ ID NO: 17 or SEQ ID NO: 18, a modified adenovirus E2a coding region comprising SEQ ID NO: 4, a sequence that encodes adenovirus VAI RNA coding region comprising SEQ ID NO: 16, a regulatory region comprising SEQ ID NO: 19, an AAV Rep coding region comprising SEQ ID NO: 20, an AAV Cap coding region comprising SEQ ID NO: 21, and a sequence encoding a recombinant AAV genome are enabled as a single-plasmid method for producing a recombinant adeno-associated virus in a host cell wherein the single expression construct is the only exogenous expression construct required for producing the recombinant AAV in the host cell.
Embodiments that do not comprise a modified adenovirus E4 coding region comprising SEQ ID NO: 17 or SEQ ID NO: 18, a modified adenovirus E2a coding region comprising SEQ ID NO: 4, a sequence that encodes adenovirus VAI RNA coding region comprising SEQ ID NO: 16, a regulatory region comprising SEQ ID NO: 19, an AAV Rep coding region comprising SEQ ID NO: 20, an AAV Cap coding region comprising SEQ ID NO: 21, and a sequence encoding a recombinant AAV genome are not enabled as a single-plasmid method for producing a recombinant adeno-associated virus in a host cell wherein the single expression construct is the only exogenous expression construct required for producing the recombinant AAV in the host cell.
The level of skill in the art is high and would include e.g. PhD level scientists. The Specification provides a working example of a single-plasmid that is used for producing a recombinant adeno-associated virus in a host cell without another exogenous plasmid but does not provide any working examples or reasonable direction in any other single-plasmid systems (¶0158 and Table 1).
Tang, et al. (Biores Open Access. 2020 Oct 16;9(1):219-228., hereinafter “Tang”) provides a review in the state of the art in plasmid systems for producing recombinant AAVs. Triple and dual plasmid systems are the most common in the art, with triple plasmid systems (1. ITR flanked vector plasmid, 2. Rep/cap plasmid, and 3. Adenoviral gene helper plasmid) has been used in producing AAV since 1998 and the dual plasmid system (1. ITR flanked vector plasmid and 2. Combined Rep/cap and adenoviral gene plasmid) since 2003 (Introduction ¶1). The triple plasmid system is used frequently for clinical manufacturing while the dual plasmid system is still currently under improvement (Introduction ¶1 and 3). Tang evidences that ability to produce recombinant AAV using a triple or dual plasmid system is not reasonably predictive of the ability to create and use a functional single plasmid system to produce recombinant AAV.
In view of the breadth of the claims, the limited teachings of the Specification and the examples regarding the single working example of a single-plasmid method for producing a recombinant adeno-associated virus in a host cell, the state of the art, and the low predictability with regard to the ability of producing recombinant AAVs in a host cell with another single-plasmid system than the one described in ¶0158, it would require undue experimentation to practice the claimed method.
Accordingly, the Specification does not enable any person skilled in the area to which it pertains, or which it is most nearly connected, to use the invention commensurate in scope with these claims.
Claim Rejections - 35 USC § 102
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.
(Previous rejection, withdrawn as to claim 21). Claim 21 was rejected under 35 U.S.C. 102(a)(2) as being anticipated by Clark. This rejection is withdrawn due to Applicant’s amendment to claim 21 submitted on 11 March 2026.
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.
(Previous rejections, withdrawn as to claims 22-24, 26, 28-30, and 32-34). Claims 22-24, 26, 28-30, and 32-34 were rejected under 35 U.S.C. as being prima facie obvious over Clark and Huang. This rejection is withdrawn due to Applicant’s amendment to claim 21 submitted on 11 March 2026.
(Previous rejection, withdrawn as to claim 25). Claim 25 was rejected under 35 U.S.C. as being prima facie obvious over Clark, Sonntag, and Gray. This rejection is withdrawn due to Applicant’s amendment to claim 21 submitted on 11 March 2026.
(Previous rejection, withdrawn as to claim 27). Claim 27 was rejected under 35 U.S.C. as being prima facie obvious over Clark, Hörer, and Gray. This rejection is withdrawn due to Applicant’s amendment to claim 21 submitted on 11 March 2026.
(Previous rejection, withdrawn as to claim 31). Claim 31 was rejected under 35 U.S.C. as being prima facie obvious over Clark, Huang, and Brimble. This rejection is withdrawn due to Applicant’s amendment to claim 21 submitted on 11 March 2026.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
(Previous rejection, maintained as to claims 21-22 and 24-33). Claims 21-22 and 24-33 were provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4, 6-7, 10, and 18 of copending Application No. 18/181,952. This rejection is maintained because the claims of the copending application could reasonably encompass the amended claims of the instant application.
(Previous rejection, maintained as to claim 23). Claim 23 was provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 10 of copending Application No. 18/181,952 in view of Clark and further in view of Grifman. This rejection is maintained because the claims of the copending application could reasonably encompass the amended claims of the instant application.
(New rejection, necessitated by the addition of claim 35). Claim 35 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 10 of copending Application No. 18/181,952 (reference application) and in further view of Kovesdi, et al. (Viruses. 2010 Aug;2(8):1681-1703., hereinafter “Kovesdi”). Although the claims at issue are not identical, they are not patentably distinct from each other because they are drawn to an expression contrast for transforming rAAVs.
Regarding claim 35, conflicting claim 10 recites a method of producing recombinant parvovirus, comprising the steps of: introducing the expression construct of claim 1 into a host cell; incubating the host cell harboring the expression construct for a desired period of time to produce recombinant parvovirus particles; and harvesting the recombinant parvovirus particles after the incubation period and conflicting claim 1 recites an expression construct comprising: (1) a modified adenovirus E4 coding region that encodes E4 open reading frame 6/7; (2) a modified adenovirus E2a coding region that encodes an E2a protein; (3) an adenovirus VA RNA coding region that encodes adenovirus VAI RNA and VAII RNA;(4) a parvovirus protein coding region that encodes parvovirus proteins necessary for the production of the recombinant parvovirus; (5) a recombinant parvovirus sequence comprising (i) an expression cassette comprising a nucleotide sequence encoding a transgene and a regulatory element operably linked to the nucleotide sequence, and (ii) at least one ITR at one end of the expression cassette; and (6) one or more regulatory elements that allow expression of the E4 open reading frame 6/7, the E2a protein, the adenovirus VAI RNA and VAII RNA, and the parvovirus proteins necessary for the production of the recombinant parvovirus in a host cell. The conflicting claims do not recite that the host cell expresses adenovirus E1a and E1b proteins. However, Kovesdi teaches that when the adenoviral vector is non-replicating (i.e. the E1 gene is deleted for the gene of interest) a producer cell line containing adenovirus E1 sequences in require for adenoviral production (pg. 1682 ¶1).
Arguments
Applicant’s arguments filed 11 March 2026 have been fully considered are discussed to the extent they apply to the current grounds of rejection set forth above.
Applicant contends on page 9 of the Remarks submitted on 11 March 2026:
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In response: Since Applicant did not file a terminal disclaimer with the Response, the double patenting rejections of record are maintained for the reasons set forth above.
Conclusion
NO CLAIMS ARE ALLOWED
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Cassandra Senn Grizer whose telephone number is (571)272-2292. The examiner can normally be reached M-Th 0630 - 1700 ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Thomas J. Visone can be reached at 571-270-0684. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CASSANDRA SENN GRIZER/ Examiner, Art Unit 1672
/THOMAS J. VISONE/ Supervisory Patent Examiner, Art Unit 1672
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