DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, 18285829, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-13 are pending.
Priority
The filing receipt, mailed , states that this application is a 371 of PCT/JP2021/01641, filed 4/21/2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 10/05/2023, 1/4/2024, and 6/20/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Figures 1A, IB, IC, ID, 5A, 5B, depict nucleic acid sequences but are identified by SEQ ID NOs in the figures, themselves, or in the Brief Description of the Drawings section in the specification.
Drawings
1. 37 C.F.R. states: “The Office will accept and record non-English language documents only if accompanied by an English translation signed by the individual making the translation.””
The drawings are objected to as failing to comply with 37 CFR 1.84(p)(5) because they include the following reference character(s) not mentioned in the description: All Figures contain foreign language (Japanese) characters.
Corrected drawing sheets in compliance with 37 CFR 1.121(d), or amendment to the specification to add the reference character(s) in the description in compliance with 37 CFR 1.121(b) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
2. The set of Figures contain two subsets with conflicting numbering systems, which are” A. Figures 1A, IB, IC, ID, 2A, 2B, 2C, 3A, 3B, 4K, 5A, 5B, 6, 7, 8, and B. #01, #02, #03, #04, #05, #06, #07, #08. #09, #09. This incongruity must be corrected, (compare to above instruction in para 1 of this section, regarding correction of drawings).
Specification
The disclosure is objected to because of the following informalities: The Brief Description of Drawings lists Figures 1A, IB, IC, ID, 2A, 2B, 2C, 3A, 3B, 4K, 5A, 5B, 6, 7, 8, but does not list . #01, #02, #03, #04, #05, #06, #07, #08. #09, #09.
Appropriate correction is required.
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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 8 recites the broad recitation a liver-specific transcription factor, and the claim also immediately recites (HNF-1, HNF-2, HNF-3, HNF-6, C/ERP or DBP) which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
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.
Claim(s) 1, 4, 7, 8, 10-13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wilson, WO 2018/200419, Chivukula, WO 2021178510, and Asokan, US 20190048041, (of record, IDS).
Wilson, WO 2018/200419, throughout the publication and abstract and teach adeno-associated capsids for targeting primate and human cells. Wilson, at p. 10, lines 9-26, teaches mutated AAV capsids; at p. 20, lines 11-18, teaches hypervariable regions within the AAV capsid, including the loci in claim 1, at p. line 30-pr. 21, line 8, teaches hypervariable (HVR IX), including aa 706. Wilson teaches, at SEQ ID NO: 21, ASN at aa 706 is changed to TYR, and p. 31, line 11; at SEQ ID NO: 25, SER at aa 587 is changed to GLN, and p. 31, lines 15-16; at SEQ 136, at 706: S YTSNYLKSVN, at p. 31, lines 14-18; p.35, lines 5-17; SEQ 137, ASN (N) at 706: S YTSNY[Y]KSVN; SEQ 138, ASN (N) at 706: S YTSNY[Y]KSVN; at SEQ 139, ASN (N) at 706: S YTSNY[Y]KSVN.
Wilson at p. 18, line 32-p. 19, line 2, teaches serotypes to AAV capsid distinct from other AAV serotypes; at p. 19, lines 25-28, teaches AAV8 capsid and AAV3 capsid; at p. 47, lines 9-19, teaches serotypes including AAV3 and AAV8; at p. 37, lines 13-22, teaches different serotypes, including AAV 8, AAV2 and serotypes to chimeric AAV.
Wilson at p. 58, line 18-p. 59, line 12, teaches expression in liver is desirable, as in claims 7, 8 11, and the availability of liver-specific promoters, and at p. 58, line 31, the TBG promoter, as in claim 11.
Wilson at p. 62, lines 10-line 28, line 12, teaches, as in claims 11, 12 and p. 65, lines 19-30, teaches treatment of ornithine transcarbamylase deficiency, as in claim 13.
Wilson does not teach a protein with at least 90% identity to SEQ ID NO: 11. Wilson does not teach neutralizing antibody against AAV2.
Chivukula, WO 2021178510, teaches throughout the publication and abstract, ornithine transcarbamylase (OTC) deficiency, and e.g., disclose therapeutic nucleic acid encoding OTC, at reference SEQ ID NO: 3, which reads on instant SEQ ID NO: 11, as in instant claim 1.
Asokan, US 20190048041, teaches throughout the publication and abstract, and at para [0003], teaches the present invention relates to modified capsid proteins from adeno-associated virus (AAV) and virus capsids and virus vectors comprising the same. In particular, the invention relates to modified AAV capsid proteins and capsids comprising the same that can be incorporated into virus vectors to confer a phenotype of evasion of neutralizing antibodies without decreased transduction efficiency.
[0006] The present invention overcomes previous shortcomings in the art by providing methods and compositions comprising an adeno-associated virus (AAV) capsid protein, comprising one or more amino acid substitutions, wherein the substitutions introduce into an AAV vector comprising these modified capsid proteins the ability to evade host antibodies.
Asokan at para 6.
[0004] Host-derived pre-existing antibodies generated upon natural encounter of AAV or recombinant AAV vectors prevent first time as well as repeat administration of AAV vectors as vaccines and/or for gene therapy. Serological studies reveal a high prevalence of antibodies in the human population worldwide with about 67% of people having antibodies against AAV1, 72% against AAV2, and about 40% against AAV5 through AAV9.
Asokan at para 4.
It would have been prima facie obvious before the filing date of the instant application for one of ordinary skill in the art to have combined a protein with at least 90% identity to SEQ ID NO: 11, as taught by Chivukula and neutralizing antibody against AAV2, as taught by Asokan, with the mutated capsid AAV as taught by Wilson.
One of ordinary skill in the art would have motivated to have combined SEQ ID NO: 11, as taught by Chivukula, because Chivukula teaches therapeutic nucleic acid encoding ornithine transcarbamylase (OTC) deficiency and Wilson contemplates the OTC gene therapy of liver disease. One of ordinary skill in the art would have motivated to have combined neutralizing antibody technology as directed towards AAV2, as taught by Asokan, because Wilson teaches AAV2 serotypes and Asokan teaches the evasion of humoral inhibition by avoiding neutralizing antibody against genetically engineered AAV vector therapy.
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.
Claims 1-13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7-12 of copending Application No. 17624927 in view of Wilson, WO 2018/200419, Chivukula, WO 2021178510, and Asokan, US 20190048041, (of record, IDS).
Reference claims 1, 7-12 of copending Application No. 17624927, currently recites:
1. (Currently Amended) An adeno-associated virus vector (AAV) comprising a mutated AAV3B capsid protein having an amino acid sequence of SEQ ID NO: 4 or an amino acid sequence in which 1-3 amino acid residues at other than position 472, position 587 and position 706 in the sequence of SEQ ID NO: 4 are deleted, substituted, inserted or added, wherein the AAV vector is not cross-reactive with a neutralizing antibody against AAV serotype 2 present in a serum.
Application No. 17624927, at reference claim 1.
Wilson, WO 2018/200419, throughout the publication and abstract and teach adeno-associated capsids for targeting primate and human cells. Wilson, at p. 10, lines 9-26, teaches mutated AAV capsids; at p. 20, lines 11-18, teaches hypervariable regions within the AAV capsid, including the loci in claim 1, at p. line 30-pr. 21, line 8, teaches hypervariable (HVR IX), including aa 706. Wilson teaches, at SEQ ID NO: 21, ASN at aa 706 is changed to TYR, and p. 31, line 11; at SEQ ID NO: 25, SER at aa 587 is changed to GLN, and p. 31, lines 15-16; at SEQ 136, at 706: S YTSNYLKSVN, at p. 31, lines 14-18; p.35, lines 5-17; SEQ 137, ASN (N) at 706: S YTSNY[Y]KSVN; SEQ 138, ASN (N) at 706: S YTSNY[Y]KSVN; at SEQ 139, ASN (N) at 706: S YTSNY[Y]KSVN.
Wilson at p. 18, line 32-p. 19, line 2, teaches serotypes to AAV capsid distinct from other AAV serotypes; at p. 19, lines 25-28, teaches AAV8 capsid and AAV3 capsid; at p. 47, lines 9-19, teaches serotypes including AAV3 and AAV8; at p. 37, lines 13-22, teaches different serotypes, including AAV 8, AAV2 and serotypes to chimeric AAV.
Wilson at p. 58, line 18-p. 59, line 12, teaches expression in liver is desirable, as in claims 7, 8 11, and the availability of liver-specific promoters, and at p. 58, line 31, the TBG promoter, as in claim 11.
Wilson at p. 62, lines 10-line 28, line 12, teaches, as in claims 11, 12 and p. 65, lines 19-30, teaches treatment of ornithine transcarbamylase deficiency, as in claim 13.
Wilson does not teach a protein with at least 90% identity to SEQ ID NO: 11. Wilson does not teach neutralizing antibody against AAV2.
Chivukula, WO 2021178510, teaches throughout the publication and abstract, ornithine transcarbamylase (OTC) deficiency, and e.g., disclose therapeutic nucleic acid encoding OTC, at reference SEQ ID NO: 3, which reads on instant SEQ ID NO: 11, as in instant claim 1.
Asokan, US 20190048041, teaches throughout the publication and abstract, and at para [0003], teaches the present invention relates to modified capsid proteins from adeno-associated virus (AAV) and virus capsids and virus vectors comprising the same. In particular, the invention relates to modified AAV capsid proteins and capsids comprising the same that can be incorporated into virus vectors to confer a phenotype of evasion of neutralizing antibodies without decreased transduction efficiency.
[0006] The present invention overcomes previous shortcomings in the art by providing methods and compositions comprising an adeno-associated virus (AAV) capsid protein, comprising one or more amino acid substitutions, wherein the substitutions introduce into an AAV vector comprising these modified capsid proteins the ability to evade host antibodies.
Asokan at para 6.
[0004] Host-derived pre-existing antibodies generated upon natural encounter of AAV or recombinant AAV vectors prevent first time as well as repeat administration of AAV vectors as vaccines and/or for gene therapy. Serological studies reveal a high prevalence of antibodies in the human population worldwide with about 67% of people having antibodies against AAV1, 72% against AAV2, and about 40% against AAV5 through AAV9.
Asokan at para 4.
It would have been prima facie obvious before the filing date of the instant application for one of ordinary skill in the art to have combined the claimed invention of Application No. 17624927, comprising a protein that is a mutated AAV3B capsid protein having an amino acid sequence of SEQ ID NO: 4 or an amino acid sequence in which 1-3 amino acid residues at other than position 472, position 587 and position 706 and neutralizing antibody against AAV2, as taught by Asokan, with the mutated capsid AAV as taught by Wilson.
a mutated AAV3B capsid protein having an amino acid sequence of SEQ ID NO: 4 or an amino acid sequence in which 1-3 amino acid residues at other than position 472, position 587 and position 706
One of ordinary skill in the art would have motivated to have combined the claimed invention of Application No. 17624927, comprising a protein that is a mutated AAV3B capsid protein having an amino acid sequence of SEQ ID NO: 4 or an amino acid sequence in which 1-3 amino acid residues at other than position 472, position 587 and position 706 and neutralizing antibody against AAV2, as taught by Asokan, with the mutated capsid AAV as taught by Wilson in order to evade humoral inhibition by avoiding neutralizing antibody against genetically engineered AAV vector therapy, as taught by Asokan.
This is a provisional nonstatutory double patenting rejection.
Conclusion
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James (Doug) Schultz, can be reached at (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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MARK L. SHIBUYA
Primary Patent Examiner
Art Unit 1631
/MARK L SHIBUYA/Primary Patent Examiner, Art Unit 1631
Prosecution Insights