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 .
Election/Restrictions
1. Applicant’s election without traverse of hybrid vectors in the reply filed on 04/21/2025 is acknowledged.
Upon further considerations, the species election requirement between hybrid, overlapping, and trans-splicing vectors is withdrawn.
In view of the above noted withdrawal of the restriction requirement, applicant is advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application.
Once a restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Claims 3-6, 10, 18, 21, 24, 26, 28, 29, 31-33, and 35-58 have been cancelled. Claims 2, 7-9, 11, 13-15, 19, 20, 22, 23, 25, 27, 30, and 34 have been amended.
Claims 13-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
Claims 1, 2, 7-9, 11, 12, 17, 19, 20, 22, 23, 25, 27, 30, and 34 are under examination.
Claim Objections
2. Claims 1 and 23 are objected to because of the recitation “a stereocilin protein”. Correction to “the stereocilin protein” is required.
3. Claim 2 is objected to because of the recitation “a full-length stereocilin protein”. Correction to “the full-length stereocilin protein” is required.
4. Claim 8 is objected to because of the recitation “a 3’ end”. Correction to “the 3’ end” is required.
5. Claim 23 is objected to because of the recitation “contacting a human OHC”. Correction to “contacting the human OHC” is required.
6. Claim 27 is objected to because of the recitation “STRC”. Correction to “stereocilin (STRC)” is required.
7. Claims 25, 27, 30, and 34 should recite “the inner ear” (lines 3 and 2, respectively).
8. Applicant is advised that should claims 25 and 30 be found allowable, claims 27 and 34 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Rejections - 35 USC § 112(a) – written description
9. 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.
10. Claims 1, 2, 7-9, 11, 12, 17, 19, 20, 22, 23, 25, 27, 30, and 34 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Adequate written description requires more than a mere statement that it is part of the invention. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC1993). The Guidelines for the Examination of Patent Application Under the 35 U.S.C.112, 1"Written Description Requirement" makes it clear that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species disclosures of relevant, identifying characteristics, i.e., structure or other physical and or chemical properties, functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the genus (Federal Register, Vol. 66, No. 4, pages 1099-1111, Friday January 5, 2001, see especially page 1106 3rd column). To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail such that the Artisan can reasonably conclude the inventors had possession of the claimed invention. Such possession may be demonstrated by describing the claimed invention with all its limitations using such descriptive means as words, structures, figures, diagrams, and/or formulae that fully set forth the claimed invention. Possession may be shown by an actual reduction to practice, showing that the invention was "ready for patenting", or by describing distinguishing identifying characteristics sufficient to show that the Applicants were in possession of the claimed invention (January 5, 2001, Fed. Reg., Vol. 66, No. 4, pp.1099-11). In analyzing whether the written description requirement is met for the genus claims, it is determined whether representative numbers of species have been described by their complete structure and functional characteristics.
The claims are drawn to a genus of OCM promoters having sequence at least 85% identical to SEQ ID NO: 1-3. With the exception of SEQ ID NO: 1-3, the specification fails to describe additional representative species of promoters having sequences at least 85% identical to SEQ ID NO: 1-3 and maintaining OCM promoter activity. The applicant is relying upon biological activity and the disclosure of three wild type nucleic acid sequence to support an entire genus. However, the claimed genus is very large; and a great deal of variability is encompassed by the claims. The claims encompass in their breadth any substitution, deletion, insertion, and any fragment having at least 85% identity to SEQ ID NO: 1-3. The fragment can be any sequence in SEQ ID NO: 1-3 or other unrelated molecule with the claimed percent identity, for example the fragment can have the claimed percent identity over a contiguous or non-contiguous portions of the claimed sequence and could be derived from the claimed sequences or from sequences that are distinct from the claimed sequence. It is well known that even minor structural differences can result in inactive promoters. For example, Sikder (Thesis, 2020) teaches that a single amino acid substitution in the SLC6A14 promoter inhibits its activity (see p. 111). Reijnen (PNAS, 1992, 89: 6300-6303) teaches that a single amino acid substitution in the fIX promoter inhibits its activity (see Abstract; p. 6300 column 1, second paragraph and column 2, first paragraph). Ludlow (JBC, 1996, 271: 22076-22080) teaches that a single amino acid substitution in the GpIbβ promoter inhibits its activity. One of skill in the art would know that a change of even one nucleotide in the claimed sequence could render an inactive OCM promoter or a promoter with reduced activity. Therefore, one of skill in the art would not recognize the applicant to be in possession of the entire claimed genus of OCM promoters having at least 85% identical to SEQ ID NO: 1-3.
Claim Rejections - 35 USC § 103
11. 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.
12. Claims 1, 2, 7-9, 12, 17, 19, 20, 22, 23, 25, 27, 30, and 34 are rejected under 35 U.S.C. 103 as being unpatentable over Simons (WO 20/014625), in view of both Athas et al. (Otolaryngology Head and Neck Surgery, 1999, 121: 64-65 ; cited on the IDS filed on 04/09/2025) and GenBank JN959272.1 (2011).
Simons teaches a two AAV1 vector system encoding human stereocilin (STRC) and using the system to transduce mouse or human outer hair cells (OHCs) in vitro; or to treat sensorineural hearing loss in a subject having a mutation in STRC via administering the system to the inner ear of the human subject. The AAV1 vector system comprises a first AAV1 vector comprising a promoter operably linked to a first nucleic acid encoding the N-terminal portion of STRC; and a second AAV1 vector comprising a promoter operably linked 5’ to a second nucleic acid encoding the C-terminal portion of STRC (claims 1, 12, 20, 22, 23, 25, 27, 30, and 34). Upon administration, the different portions generate a nucleic acid encoding the full-length STRC by one of the following mechanisms:
(1) homologous recombination, when the two nucleic acids encoding STRC N- and C-terminal portions partially overlap (claim 2);
(2) splicing, when the first nucleic acid comprises a splice donor at the 3' end of the first nucleic acid and the second nucleic acid comprises a splice acceptor at the 5' end of the second nucleotide (claims 7 and 9); or
(3) splicing/homologous recombination, when the first nucleic acid comprises in 5’ to 3’ order: the first nucleic acid, a splice donor, and a first recombinogenic region; and the second nucleic acid comprises in 5’ to 3’ order: a second recombinogenic region, a splice acceptor, and the second nucleic acid (claim 8).
See Simons, Abstract; p. 1, line 31, through p. 2, line 26; p. 3, lines 20-32; p. 4, lines 8-33; p. 5, lines 1-15; p. 6, first full paragraph; p. 10, lines 5-7; p. 134, lines 8-11; p. 135-136; p. 137, lines 15-30; p. 138, lines 2-7; p. 146, lines 6-11; p. 170, lines 13-17.
With respect to claims 1 and 17, Simons teaches that the promoter is the oncomodulin (OCM) promoter (p. 119, lines 18-21; p. 121, line 34 through p. 122, line 1). However, Simons does not specifically teach that the OCM promoter is set forth by SEQ ID NO: 1 (claims 1 and 17). Athas et al. teaches the mouse OCM promoter, useful for driving specific expression in OHCs (see p. 64, column 2). One of skill in the art would have found obvious to use the promoter identified by Athas et al. as the promoter in the first and second AAV1 vectors, to achieve the predictable result of specifically expressing the full-length STRC in outer hair cells in vitro and in vivo. The specification discloses that SEQ ID NO: 1 is the sequence of the mouse OCM promoter (see p. 77, line 42). Thus, it is reasonable to conclude that the mouse OCM promoter of Athas et al. is at least 85% to the mouse OCM promoter set forth by SEQ ID NO: 1.
While Athas et al. do not specifically teach SEQ ID NO: 1, Athas et al. teach that transcriptional analysis with a luciferase reporter gene could be used to identify the OCM promoter and determine the optimal size for clinical use (see p. 64, column 2). Furthermore, as evidenced by the attached Sequence alignment to GenBank JN959272.1, the sequence of the mouse OCM gene was known in the prior art; this gene comprises the region 13210-14249 which is identical to the claimed SEQ ID NO: 1. One of skill in the art would have found obvious to use transcriptional analysis on the gene identified as GenBank JN959272.1, to achieve the predictable result of identifying the optimal OCM promoter for clinical use. By doing so, one of skill in the art one of skill in the art would have identified and used the promoter set forth by SEQ ID NO: 1 and promoters at least 85% identical to SEQ ID NO: 1.
With respect to claim 19, Simons teaches that the amino acid sequence encoding the human STRC is set forth by SEQ ID NO: 1, while the encoding nucleic acid sequence is set forth by SEQ ID NO: 2 (see p. 41, lines 26-31; p. 42-43). As evidenced by the attached Sequence Alignments, SEQ ID NOs: 1 is 99.5% identical to the claimed SEQ ID NO: 4, while SEQ ID NO: 2 is 97.5% identical to the claimed SEQ ID NO: 6.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
13. Claims 1, 2, 7-9, 11, 12, 17, 19, 20, 22, 23, 25, 27, 30, and 34 are rejected under 35 U.S.C. 103 as being unpatentable over Simons taken with both Athas and GenBank JN959272.1, in further view of Colella et al. (WO 16/139321).
The teachings of Simons, Athas, and GenBank JN959272.1 are applied as above for claims 1, 2, 7-9, 12, 17, 19, 20, 22, 23, 25, 27, 30, and 34. Simons, Athas, and GenBank JN959272.1 do not teach a degradation signal (claim 11). Colella et al. teach that the production of truncated proteins from dual vector systems raises safety concerns and should be abolished. Colella et al. teach including degradation signals to mitigate the expression of truncated proteins; a degradation signal is included in the nucleic acid encoding the N-terminal portion (3’ to the recombinogenic region) and in the nucleic acid encoding the C-terminal portion (between the recombinogenic region and the splicing acceptor) (see p. 2, lines 2-4 and 17-23; p. 13, line 26 through p. 14, line 2; p. 31, lines 26-30; p. 50, lines 22-27; Fig. 1). One of skill in the art would have found obvious to introduce degradation signals as taught by Colella et al., to achieve the predictable result of eliminating the truncated proteins produced upon administration in vivo.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
14. No claim is allowed. No claim is free of prior art.
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/ILEANA POPA/Primary Examiner, Art Unit 1633
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