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 .
Status of Application/Amendments/Claims
Applicant’s response filed on 5/28/2026 has been considered. Claims 5 and 10 have been amended. Claims 5 and 9-11 are pending and are the present Official action. The terminal disclaimer over US 16/488,103 submitted on 5/28/2026 was received. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Priority
Applicant’s claim for the benefit of a prior-filed application PRO 62/472,790, PRO 62/531,522, PCT/US2018/22873 and CIP of 16/488,103 filed on 3/17/2017, 7/12/2017, 3/16/2018 and 8/22/2019, respectively, under 35 U.S.C 119(e) or under 35 U.S.C 120, 121 or 365(c) is acknowledged.
Accordingly, the effective priority date of the instant application is granted as 3/17/2017.
Withdrawn Rejections
The 35 U.S.C. 112(b) rejection of claim 10 has been withdrawing in light of applicants claim amendments which delete the ear anatomical structures.
The 35 U.S.C. 103 rejection of 5 and 9-11 has been withdrawn in light of applicants claim amendments describing the expression in the inner hair cells, outer hair cells and spiral ganglion cells.
The terminal disclaimer over US 16/488,103 submitted on 5/28/2026 was received. Accordingly, the provisional nonstatutory double patenting rejection of claims 5 and 9-11 has been withdrawn.
Claim Rejections - 35 USC § 112a, Written Description – New Matter
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.
Claims 5 and 9-11 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 for introducing new matter. This rejection us supported by Bance et al. US 2013/0095071, published 4/18/2013 (hereinafter Bance, reference of record). This rejection is newly applied to address applicants claim amendments filed on 5/28/2026.
MPEP § 2163.II.A.3.(b) states, “when filing an amendment an applicant should show support in the original disclosure for new or amended claims” and “[i]f the originally filed disclosure does not provide support for each claim limitation, or if an element which applicant describes as essential or critical is not claimed, a new or amended claim must be rejected under 35 U.S.C. 112, para. 1, as lacking adequate written description”. According to MPEP § 2163.I.B, “While there is no in haec verba requirement, newly added claim limitations must be supported in the specification through express, implicit, or inherent disclosure” and “The fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc., 935 F.2d at 1563-64, 19 USPQ2d at 1117”.
Claim 5 has been amended to describe a method for treating or preventing hearing loss comprising administering an expression vector comprising a nucleic acid sequence having at least 90% sequence identity to the nucleic acid of SEQ ID NO: 1 and a HCMV promoter to inner hair cells, outer hair cells, and spiral ganglion cells of a subject, wherein the expression vector is expressed in the inner hair cells, outer hair cells and spiral ganglion cells.
The specific anatomical structures wherein expression is claimed (inner hair cells, outer hair cells and spiral ganglion cells) refers to specific locations within the cochlea that is not supported by the generic disclosure and specific examples of the instant specification.
The response dated 5/28/2026 indicates that support for these amendments could be found at paragraphs 92 and 113-114 of the published specification, US 2020/0114023. A review of the Specification at paragraph 92 states:
“Two weeks after injection, mouse cochleae will be harvested to examine if the GFP signals are confined to hair cells. In our previous studies, we observed strong GFP expression in 100% inner hair cells and moderated expression in over 95% of outer hair cells. We thus expect to observe a similar expression pattern with the TMPRSS3 gene. [emphasis added]”
Paragraphs [0113] and [0114] present results of “The WAVE 1 test is an additional measurement provided by the ABR test” and “the auditory evoked potential as a result of acoustic stimulation, measured in millivolts, as a function of time, measured in milliseconds” (Fig.8), respectively.
While the Specification teaches neuronal responses after injection into Tmprss3−/−cochlea by cochleostomy (inner ear) of the construct AAV/Anc80-TMPRSS3-GFP (e.g, a wild -type AAV2 comprising a a cDNA sequence encoding wild-type human TMPRSS3) , there is nothing more to lead to one of lead one of skill in the art to appreciate that after injection by cochleostomy there was expression of GFP protein in all inner hair cells, outer hair cells, and spiral ganglion cells of a mouse, let alone a human subject. Therefore, the instant specification provides no examples to support amending claim 5 to include the expression of SEQ ID NO: 1 in inner hair cells, outer hair cells and spiral ganglion cells of the cochlea. As mentioned above, the applicant points to para 92 and 113-114 for support in adding these amendments. However, a closer examination of these sections of the specification does not describe the expression of SEQ ID NO: 1 using a wild type AAV2 vector, promoter and HCMV promoter in the inner hair cells, outer hair cells and spiral ganglion cells. At best, para 92 describes the expression of GFP (not SEQ ID NO: 1) in 100% of inner hair cells and moderate expression of 95% in outer hair cells, and that applicant “expects” similar expression patterns with the TMPRSS3 (SEQ ID NO: 1) gene. Importantly, the specification does not describe expression in the spiral ganglion cells.
It is noted that to establish inherency, the extrinsic evidence ‘must make clear that the missing descriptive matter is necessarily present in the thing described in the reference, and that it would be so recognized by persons of ordinary skill. Inherency, however, may not be established by probabilities or possibilities. The mere fact that a certain thing may result from a given set of circumstances is not sufficient’, see MPEP 2163.07(a). Thus, it would be unpersuasive to argue that the given vector would inherently be expressed in all three cell types without any peer reviewed data or work to properly establish that a skilled artisan would understand this to be true.
In fact, the prior art as evidenced by Bance shows that embodiments using a wild type AAV serotype 2 (AAV2) vectors have limited expression in the inner hair cells (IHCs) upon administration into the cochlea (Bance, para 52 and Fig 15 gene expression results into inner ear hair cells). Bance further states that the round window membrane is not permeable to AAV vectors (Bance, para 46). Furthermore, the applicant is on record as stating that these prior art attempts to use wildtype AAV2 (i.e., an AAV without a tyrosine mutation) for expression of a vector in inner hair cells (IHC), outer hair cells (OHC), and spiral ganglion were ineffective for expression in outer hair cells (page 4 of Applicants’ remarks) supporting unpredictable transduction efficiency of the wild type- AAV2 vectors by injecting viral vectors using the canalostomy (Injection through semicircular canals) approach in mice .
Thus, given the breadth of applicants claimed expression into the inner hair cells, outer hair cells and spiral ganglion cells of the cochlea in relation to the narrowly supported embodiments and examples of the specification, which are largely directed to expression into only hair cells, the instant specification not provide sufficient written description to support the claim to all cell types described. Claims 9-11 are rejected for their dependency on claim 5 for similar reasons. Thus, the amended claims include impermissible New Matter.
Conclusion
No claims 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 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 mailing date of this final action.
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Alexander Nicol
Patent Examiner
Art Unit 1634
/ALEXANDER W NICOL/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
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