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/RCE under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e) was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114 and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicants’ submission filed on 10/13/2025 has been considered.
Claims 5 and 10 have been amended. Claims 5 and 9-11 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, 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.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/13/2025 was received. The submissions were in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements were considered by the examiner.
Withdrawn Rejections
The objection to claim 10 has been withdrawn in light of applicant’s amendments changing the last “or” to “and” to recite proper Markush language.
The 35 U.S.C. 103 rejection of claims 5 and 9-11 has been re-applied in modified form in light of applicant’s amendments which specify that the expression vector is administered to the inner hair cells, outer hair cells and spiral ganglion cells of the subject.
Claim Rejections - 35 USC § 112b
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.
Claim 10 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claim 10 describes the injection method being selected from the group consisting of cochleostomy, round window membrane, endolymphatic sac, among other inner ear anatomical structures. While cochleostomy is a surgical procedure in which an opening is made in the bony wall of the cochlea which may read on an “injection method”, the other elements recited in the Markush group are inner ear anatomical structures and not “injection methods”. Please note that the language of a claim must make it clear what subject matter the claim encompasses to adequately delineate its "metes and bounds", see MPEP 2173.
Claim Interpretation
It is emphasized that claim 5 describes administration of an expression vector to the inner hair cells, outer hair cells and spiral ganglion cells of a subject. The claims do not necessarily require that the nucleic acid sequence is expressed exclusively in those cells or to what extent expression is achieved.
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 5 and 9-11 stand rejected in modified form 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 applied in modified form to address applicants claim amendments on 10/13/2025. A reply to applicants’ traversal is found below.
Claim 5: 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 provides embodiments using a wild type AAV serotype 2 (AAV2) vector and found 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). The cochlea is an anatomical structure of the inner ear which comprises inner hair cells, outer hair cells and spiral ganglion cells (Bance, para 140). As stated in the claim interpretation section it is emphasized that claim 5 describes administration of an expression vector to the inner hair cells, outer hair cells and spiral ganglion cells of a subject. The claims do not necessarily require that the nucleic acid sequence is expressed exclusively in those cells or to what extent expression is achieved. Bance identifies TMPRSS3 as a gene target for treating hereditary hearing loss within the inner ear, which is the gene encoded by the nucleic acid sequence of SEQ ID NO: 1 (Bance, para 32, 73 and claims 44 and 57). 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). Bance describes expression constructs using rAAV2 vectors and human cytomegalovirus (hCMV) promoters (Bance, para 215, 216). Although these constructs are for the expression of EGFP for cochlear staining, it is argued that hCMV promoters are commonly used in the art for driving expressing of transgenes within the inner ear.
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).
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 independent claim 5.
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, described as “14094” gene throughout Meyers). 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). Meyers describes transfected cells expressing TMPRSS3 (Meyers, para 197).
PNG
media_image1.png
88
579
media_image1.png
Greyscale
Claims 9-10: Bance describes administration via saline injection into the inner ear of a subject (Bance, para 141, 142, 150, 187, 194). Bance describes viral vector titers of 7.5x1013 and 1-5x1013 (Bance, para 61, 109 and 193). Bance describes more specific injection sites into the round window membrane of the inner ear (Bance, para 150, 182).
Claim 11: Bance treating subjects which have one or more genetic risk factors associated with hearing loss (Bance, para 30, 35 and 101).
It would have been prima facie obvious to one of ordinary skill in the art to deliver a TMPRSS3 nucleic acid sequence at least 90% identical to instant SEQ ID NO: 1 as disclosed by Meyers using the wildtype AAV2 gene therapy expression vector and hCMV promoter described by Bance as a method for treating hearing loss. Bance provides embodiments showing the expression of TMPRSS3 using AAV2 viral vectors and Meyers shows that nucleic acid sequences at least 90% identical to SEQ ID NO: 1 can be expressed using AAV vectors. Therefore, it would have been a matter of simply substituting the TMPRSS3 sequence disclosed by Meyers into the AAV2 gene therapy vector construct described by Bance as a suitable treatment for hearing loss. Furthermore, both Bance and Staecker show that hCMV promoters drive strong transgene expression within the inner ear. Therefore, one of ordinary skill in the art would have been motivated make this substitution in order to restore the activity of TMPRSS3 to promote inner ear hair cell survival and restore hearing to patients suffering from hearing loss or deafness as described by Bance. One would have a reasonable expectation of success given that AAV2 type vectors appear 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 repeats previous arguments that Bance teaches away from the administration of wild type AAV2 expression vectors and refers to Fig 15 of Bance for support which describes wild type AAV2 expression vectors unable to penetrate outer hair cells. Applicant cites para 9 and 16 of Bance showing that tyrosine-mutations were made to AAV2 vectors to enhance transport across the OHC, IHC and spiral ganglion cells, 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.
This argument has been fully considered, but was not found persuasive since Bance provides embodiments using a wild type AAV serotype 2 (AAV2) vector and found 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). The cochlea is an anatomical structure of the inner ear which comprises inner hair cells, outer hair cells and spiral ganglion cells (Bance, para 140). As stated in the claim interpretation section it is emphasized that claim 5 describes administration of an expression vector to the inner hair cells, outer hair cells and spiral ganglion cells of a subject. The claims do not necessarily require that the nucleic acid sequence is expressed exclusively in those cells or to what extent expression is achieved. Furthermore, 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 points to the affidavit submitted by Dr. Hinrich Staecker submitted on 4/15/2024 and 6/16/2022 to argue unexpected results. Dr. Staecker describes 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. 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 delivering genes like TMPRSS3 to the cochlea (which is inclusive of inner hair cells, outer hair cells and spiral ganglion cells) for robust expression in at least the inner ear hair cells for treating hearing loss.
Nonstatutory 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 Langi, 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 706.02(1)(1) - 706.02(1)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 5 and 9-11 stand provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 26, 29-33 and 43 of copending Application No: 16/488,103 (US Patent Application Publication Number US2020/0248203). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims broadly embrace the patented claims. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. This rejection is applied in modified form to address applicants claim amendments on 10/13/2025. A reply to applicants’ traversal is found below.
Claim 5: The co-pending claims are drawn to a pharmaceutical composition for treating hearing loss comprising an expression vector encoding SEQ ID NO: 1 (which encodes for the TMPRSS3 gene). The co-pending claims describe the use of AAV2 vectors and HCMV promoters (claims 1, 26 and 43). The co-pending claims describe injection into the inner ear which is inclusive of inner hair cells, outer hair cells and spiral ganglion cells) (claim 31).
Claims 9-10: The co-pending claims describe injection methods into the inner ear and round window membrane for treating hearing loss (claims 1, 32 and 43).
Claims 11: The co-pending claims describe treating subjects which have one or more genetic risk factors associated with hearing loss (claim 43).
Response to Traversal
Applicant traverses the instant rejection by requesting that the rejection be held in abeyance until allowable subject matter has been identified.
Applicant request to hold the nonstatutory double patenting rejection in abeyance until allowable subject matter is technically non-responsive, see MPEP 804. Only objections and matters of form may be held in abeyance, see MPEP 714.02. Rather than pause prosecution to engage in mailings that outline the consequences of non-responsive submissions, the foregoing is set forth as a warning that future such non-responsive submissions will require a pause in prosecution and the issuance of a notice of non-compliance, along with the attendant delay and potential for loss of patent term extension, should allowable subject matter be reached. In the lack of a proper response, the rejection is therefore maintained accordingly.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Dr. ALEXANDER NICOL whose telephone number is (571)272-6383. The examiner can normally be reached on M-F 8-5 EST.
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, 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.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see https://ppair-my.uspto.gov/pair/PrivatePair. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
Alexander Nicol
Patent Examiner
Art Unit 1633
/ALEXANDER W NICOL/Examiner, Art Unit 1634