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 .
Claims 1-2, 6, 16, 19, 37, 55, 80, 84-87, 95-98, 100-101, 103, and 123-134, of record 12/23/2025, are pending and subject to prosecution. Claims 1, 16, 37, 55, and 95-96 are amended. Claims 10 and 18 are cancelled. Claims 123-134 are newly added.
Declaration of Dr. Corey
A declaration under 37 CFR 1.130A was filed 12/23/2025 to disqualify the prior art reference Corey et al. (US 20220315948 A1) as being the work of an inventor of the instant application. Dr. Corey asserts that the subject matter disclosed in the publication, PCDH15 sequences, was conceived by and obtained directly or indirectly from him.
The declaration is sufficient to overcome the rejection of the pending claims based upon Corey et al. as set forth in the last Office action.
Status of Prior Rejections/Response to Arguments
RE: Rejection of claims 1-2, 6, 16, 19, 37, 55, 84-87, 95-98, and 100-101 under 35 U.S.C. 102(a)(1) and 102(a)(2) over Boye et al. (US 20190153050 A1):
RE: Rejection of claims 1-2, 6, 16, 19, 37, 55, 84-87, 95-98, 100-101, and 103 under 35 U.S.C. 103 over Boye et al. (US 20190153050 A1) in view of Ahmed et al. (American Journal of Human Genetics, 2001):
The applicant asserts that the amendments to claims 1, 16, 37, 55, and 95-96 to require a nucleotide sequence encoding the first portion of PCDH15 comprising a sequence at least 80% identical to SEQ ID NO 4 and/or a nucleotide sequence encoding the first portion of PCDH15 comprising a sequence at least 80% identical to one of SEQ ID NO 5-7 are effective to obviate the rejection.
This argument is not found persuasive because Boye et al. teach an exemplary PCDH15 protein sequence which is encoded by a nucleotide sequence comprising SEQ ID NOs 4-5. However, the rejections are withdrawn in favor of new rejections specifically addressing the amendments.
RE: Rejection of claims 1-2, 6, 10, 16, 18-19, 37, 55, 84-87, 95-98, 100-101, and 103 under 35 U.S.C. 103 over Boye et al. (US 20190153050 A1) in view of Ahmed et al. (American Journal of Human Genetics, 2001), further in view of Corey et al. (US 20220315948 A1):
The cancellation of claims 10 and 18 renders the rejection thereto moot.
The declaration submitted on 12/23/2025 by Dr. Corey to disqualify the teachings of the prior art reference Corey et al. (US 20220315948 A1) as obtained from an inventor of the instant application has been recorded. In light of the claim amendments and declaration, the rejection is withdrawn.
New/Modified Rejections
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.
Claims 1-2, 6, 16, 19, 37, 55, 80, 84-87, 95-98, 100-101, 123, 125, and 129-133 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Boye et al. (US 20190153050 A1), of record, evidenced by UniProt (Webpage capture, 2025) and NCBI (Webpage, 2025).
Boye et al. teach dual-vector systems for delivering large genes to mammalian cells using AAV (See Abstract).
Regarding claims 1-2, 6, 16, 19, 37, 55, 84-87, 95-98, 100-101, 123, 125, and 129-133: Boye et al. teach AAV dual-vector systems for delivering a split transgene for the treatment of disorders such as Usher syndrome (which reads on “hearing loss or vision loss”) (See Abstract and ¶0005-0006 and 0012-0016). The AAV can be of any serotype, and the capsid may comprise mutations (See ¶0092-0093). The polypeptide encoded by the split transgene can be PCDH15 (See ¶0086, 0095-0096, and 0098). Boye et al. teach that system can comprise a first AAV comprising a polynucleotide comprising ITRs, a promoter, an N-terminal portion of a full-length gene for a polypeptide, a splice donor site, and an intron (See ¶0087). A second AAV can comprise a polynucleotide comprising ITRs, a intron, a splice acceptor site, a C-terminal portion of a full-length gene for a polypeptide, and a polyadenylation signal (See ¶0087). The introns can comprise splice donor and acceptor sequences (which reads on “splice donor of an intron”) (See ¶0088). Recombination of the transgenes can occur via the AAV ITRs (which read on “recombinogenic sequences”, “second 5’ isolated nucleic acid”, and “second isolated 3’ nucleic acid”) (See ¶0144). An alkaline phosphatase intron sequence can also be used for concatemerization and recombination (See ¶0193). The polynucleotide can be delivered for expression of the polypeptide in a host cell (which reads on “host cell comprising the first 5’ isolated nucleic acid” and “method for expressing a full length PCDH15 in a cell”) (See ¶0027 and 0096). The vector system can be combined with a pharmaceutically acceptable carrier to form a pharmaceutical composition (See ¶0125).
Boye et al. do not expressly teach the polynucleotide encoding the first portion of PCDH15 as comprising a sequence with 80% identity to instant SEQ ID NO 4. However, Boye et al. teach the exemplary PCDH15 sequence as Q96QU1 (See ¶0086, 0095-0096, and 0098), which is encoded by nucleotide sequence NM_033056.3 (See https://www.ncbi.nlm.nih.gov/nuccore/NM_033056.3). This nucleotide sequence comprises a sequence having 97.4% identity to instant SEQ ID NO 4 (See alignment below, first 120 nt displayed).
PNG
media_image1.png
168
590
media_image1.png
Greyscale
The nucleotide sequence of NM_033056.3 also comprises a sequence having 99.1% identity to instant SEQ ID NO 5 (See alignment below, first 120 nt displayed).
PNG
media_image2.png
164
588
media_image2.png
Greyscale
The exemplary sequence taught by Boye et al. therefore reads on “comprises a sequence at least 80% identical to SEQ ID NO: 4”, “comprises a sequence at least 95% identical to SEQ ID NO: 4”, and “a sequence at least 80% identical to… SEQ ID NO… 5”.
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.
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 1-2, 6, 16, 19, 37, 55, 84-87, 95-98, 100-101, 103, 123, 125, and 129-134 are rejected under 35 U.S.C. 103 as being unpatentable over Boye et al. (US 20190153050 A1), of record, evidenced by UniProt (Webpage capture, 2025) and NCBI (Webpage, 2025), in view of Ahmed et al. (American Journal of Human Genetics, 2001), of record.
The teachings of Boye et al., UniProt, and NCBI are set forth in the rejection above and are incorporated herein in their entirety.
Regarding claims 103 and 134: Following the discussion of claims 1-2, 6, 16, 19, 37, 55, 84-87, 95-98, 100-101, 123, 125, and 129-133, Boye et al., evidenced by UniProt and NCBI, teach a method of treating Usher syndrome by delivery of a dual AAV system encoding PCDH15 but do not expressly teach the treatment of Usher syndrome type 1F.
Ahmed et al. teach that Usher syndrome type 1F is caused by mutations in PCDH15 (See Abstract).
It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of Boye et al. to comprise use of the dual vector system for treating Usher syndrome type 1F. One would be motivated to make this modification because Boye et al. teach that PCDH15 can be delivered for treating Usher syndrome (See ¶0005-0006) and because Ahmed et al. teach that Usher syndrome type 1F is specifically caused by mutations in native PCDH15 (See Abstract). There would be a reasonable expectation of success in doing so because the system of Boye et al. could be readily administered to cells of a subject with Usher syndrome type 1F.
Allowable Subject Matter
Claims 124 and 126-128 are 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.
The following is a statement of reasons for the indication of allowable subject matter:
A nucleic acid encoding a transgene comprising a portion of PCDH15 comprising a sequence at least 95% identical to instant SEQ ID NO 6 appears to be free of the prior art.
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 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 JENNIFER S SPENCE, whose telephone number is 571-272-8590. The examiner can normally be reached M-F 8:30-5:30.
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, Christopher M Babic, can be reached at 571-272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/J.S.S./Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633