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 9/18/2025 has been considered. No claims have been amended. Claims 1, 26, 29-33 and 43 are pending and are the subject of the present Official action. 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 and of PCT/US2018/22873 filed on 3/17/2017, 7/12/2017 and 3/16/2018, 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.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 9/15/2025 was received. The submission was in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement was considered by the examiner.
Maintained 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 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.
Claims 1, 26, 29-33 and 43 are rejected under 35 U.S.C. 103 as being unpatentable over Bance et al. US 2013/0095071, published 4/18/2013 (hereinafter Bance, reference of record) in view of Meyers et al. US 2007/0009433, published 1/11/2007 (hereinafter Meyers, reference of record) and Staecker et al. "Development of gene therapy for inner ear disease: Using bilateral vestibular hypofunction as a vehicle for translational research." Hearing research 276.1-2 (2011): 44-51 (hereinafter Staecker, reference of record). This rejection is maintained for the same reasons of record as outlined in the official action dated 3/18/2025. A reply to applicants’ traversal is found below.
Claims 1, 26 and 43: Bance describes an adeno-associated virus (AAV) expression vector for treating hearing loss (Bance, para 9). Bance discloses an AAV vector which has enhanced permeability across the round window membrane for improved targeted gene therapy into the inner ear (Bance, para 9, 24). Bance states that AAV vectors appear to be the best choice for inner ear gene therapy due to their long-lasting expression of transfected genes (Bance, para 7). Bance states that AAV vectors can achieve latent infection of a broad range of cell types, exhibiting the desired characteristics of persistent expression of a therapeutic gene in a patient (Bance, para 109). Bance states that “the discovery includes the use of any appropriate type of adeno-associated virus known in the art including but not limited to AAV1, AAV2, AAV3, AAV4, AAV5, AAV6 and AAV7” (Bance, para 109). Bance provides embodiments using a wild type AAV serotype 2 (AAV2) vector (Bance, para 52 and Fig 15 gene expression results into inner ear hair cells). Bance identifies TMPRSS3 as a gene target for treating hereditary hearing loss within the inner ear (Bance, para 32, 73 and claim 57). Bance describes expression constructs using hCMV promoters, corresponding to the elected promoter (Bance, para 215, 216). Although Bance describes the expression of TMPRSS3, Bance does not provide a sequence listing which is at least 90% identical to SEQ ID NO: 1 as described in claims 1, 26 and 43. Furthermore, Bance does not describe a hCMV promoter operably linked to a nucleic acid sequence consisting of SEQ ID NO: 1 or having at least 90% identical to SEQ ID NO: 1.
Claim 29: Bance describes viral vector titers of 7.5x1013 and 1-5x1013 (Bance, para 61, 109 and 193).
Claims 30-31: Bance describes administration via saline injection into the inner ear of a subject (Bance, para 141, 142, 150, 187, 194).
Claims 32: Bance describes more specific injection sites into the round window membrane of the inner ear (Bance, para 150, 182). Bance observed the targeted expression of genes in sensory hair cells and spiral ganglion of the cochlea and vestibular systems (Bance, para 194). Bance verified cell transfection using cochlear immunostaining (Bance, para 215 and 217).
Claims 1, 26 and 43: Meyers discloses an expression vector comprising a nucleic acid sequence which is 98.8% identical to instant SEQ ID NO: 1 (sequence search results shown below, TMPRSS3 gene described as “14094” nucleic acid throughout Meyers). The only difference between the sequences is a single nucleotide synonymous substitution with no impact on TMPRSS3 protein function. Meyers provides embodiments using adenoviral (AAV) gene therapy vectors, promoters derived from AAV2 serotypes including CMV promoters (Meyers, para 230, 231, 233, 237 and 471). Furthermore, it is noted that the preamble limitation of claim 26 describing “a method for treating hearing loss” is considered intended use language that does not carry patentable weight since there lacks a structural difference between the claimed invention and the prior art. If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction, see MPEP 2111.02. Meyers describes transfected cells expressing TMPRSS3 (Meyers, para 197). Although Meyers describes the use of CMV promoters, neither Meyers nor Bance describe the use of hCMV promoters operably linked to TMPRSS3 gene expression.
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Claims 1, 26 and 43: However, hCMV is a known promoter commonly used for inner ear gene delivery studies. For example, Staecker describes the use of adenoviral vectors for gene therapy within the inner ear (Staecker, pg 45 col 1). Staecker states that the bulk of inner ear gene delivery studies to date have used the hCMV promoter (Staecker, pg 48 col 2). Staecker states that both adenovector modifications and promoter selection can be used to increase gene delivery specificity (Staecker, pg 48 col 2).
It would have been prima facie obvious to one of ordinary skill in the art to transduce SEQ ID NO: 1 or a nucleic acid sequence having at least 90% identical to SEQ ID NO: 1 as disclosed by Meyers using the AAV2 expression system disclosed by Bance as a gene therapy treatment for hearing loss. It would have been a matter of combining prior art elements according to known methods to yield predictable results since TMPRSS3 is a known gene which Bance identifies as a target for treating hereditary hearing loss within the inner ear (Bance, para 32, 73 and claim 57). Meyers describes a similar AAV gene therapy vector for delivering TMPRSS3, which shares over 98% sequence similarity to instant SEQ ID NO: 1. One of ordinary skill in the art would have been motivated to make this combination since both Meyers and Bance describe AAV vectors for TMPRSS3 transduction into the inner ear. One would have a reasonable expectation of success given that the AAV2 expression system described by Bance appears to be the best choice for inner ear gene therapy due to their long-lasting expression of transfected genes as described by Bance (Bance, para 7).
Furthermore, it would have been prima facie obvious to one of ordinary skill in the art to use a hCMV promoter as described by Staecker to express the TMPRSS3 gene in the gene therapy system described by Bance in view of Meyers. It would have been a matter of combining prior art elements according to known methods to yield predictable results since Bance uses the same hCMV promoter for cochlear staining experiments (Bance, para 215 and 216) and Meyers uses the closely related CMV promoter for TMPRSS3 expression in COS cells (Meyers, example 5). One of ordinary skill in the art would have been motivated to use a hCMV promoter since this promoter is commonly used for inner ear gene delivery studies and offers increase gene delivery specificity (Staecker, pg 48 col 2). One would have a reasonable expectation of success given that the hCMV promoter is commonly used for inner ear gene delivery studies according to Staecker. Accordingly, in the absence of evidence to the contrary, one of ordinary skill in the art would have considered the claimed invention as a whole to have been prima facie obvious to at the time the invention was made.
Response to Traversal
Applicant argues that Bance discredits the use of wild type AAV2 expression vectors and refers to para 7 of Bance for support which describes the RWM not being permeable to AAV requiring the development of new methodologies. Applicant cites para 9 and 16 of Bance showing that tyrosine-mutations were made to AAV2 vectors to enhance transport across the round window membrane, allowing for the non-invasive delivery of the vectors to hair cells and spiral ganglion neurons. Applicant acknowledges Bance teaches the use of wild type AAV2 mutants but states that their expression is limited to inner hair cells. Applicant points to the declaration submitted by Dr. Staecker showing the ability of AAV2-hTMPRSS3 to restore hearing function after hearing loss.
This argument has been fully considered, but was not found persuasive. Although it is admitted that the disclosure of Bance largely focuses on AAV2 vectors which contain a mutation of one or more surface-exposed tyrosine residues, Bance nonetheless considers AAV2 wild type vectors (Bance, para 109-110). Nonpreferred and alternative embodiments constitute prior art. Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure, see MPEP 2123. In particular, Bance provides embodiments using a wild type AAV serotype 2 (AAV2) vector (Bance, para 52 and Fig 15 gene expression results into inner ear hair cells). Teaching away requires the prior art to criticize, discredit, or otherwise discourage the claimed solution, see MPEP § 2141.02(VI): “the prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed.” Since the prior art clearly does not do this, this argument is unconvincing.
Applicant further argues that none of Bance, Meyers and Staeker disclose or suggest enhanced expression of hTMPRSS3 resulting from administration of the claimed expression vector to the ear in spiral ganglion nerves as well as both OHC and IHC as described in the declaration from Dr. Staecker on 6/16/2022. Applicant summarizes the declaration and argues unexpected results regarding the ability of AAV2-hTMPRSS3 to restore hearing function after hearing loss. Applicant argues surprising and unexpected results in view of Landegger.
This argument has been fully considered, but was not found persuasive. Firstly, the present claims do not describe administration or expression of hTMPRSS3 into the spiral ganglion nerves, OHC and/or IHC using the claimed expression vector. Secondly, Bance states that “AAV vectors appear to be the best choice for inner ear gene therapy due to their long-lasting expression of transfected genes” (Bance, para 7). Bance provides embodiments using wildtype AAV serotype 2 (AAV2) vectors (Bance, para 52 and Fig 15 gene expression results into inner ear hair cells). Thus, according to Bance, AAV2 vectors provide a predictable vehicle for expressing genes like TMPRSS3 into inner ear hair cells for treating hearing loss.
Conclusion
THIS ACTION IS MADE FINAL. 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 ALEXANDER NICOL whose telephone number is (571)272-6383. The examiner can normally be reached on M-F 8-5 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria Leavitt can be reached on (571)272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Alexander Nicol
Patent Examiner
Art Unit 1634
/ALEXANDER W NICOL/Examiner, Art Unit 1634