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 .
This action is in response to the papers filed May 01, 2026.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on May 01, 2026 has been entered.
Claims 1-3 and 6-25 are currently pending in the application. Claims 2, 6, and 7 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 09/05/2024. Claims 9-25 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 09/05/2024.
Claim 1 is amended, no claims are newly added and claims 4-5 are canceled in the claim set filed May 01, 2026.
Claims 1, 3, and 8 are examined on the merits.
Priority
This application is a 371 of PCT/US2019/068070 filed 12/20/2019. Applicant’s claim for the benefit of a prior-filed provisional application 62/784,306 filed on 12/21/2018 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Thus, the earliest possible priority for the instant application is December 21, 2018.
Response to arguments
Maintained objections/ Rejections in response to Applicants’ arguments or amendments
Claim Rejections - 35 USC § 103
Claims 1, 3 and 8 remain rejected under 35 U.S.C. 103 as being unpatentable over Iizuka (Human Molecular Genetics, 2015, Vol. 24, No. 13) in view of Dalkara (In Vivo–Directed Evolution of a New Adeno-Associated Virus for Therapeutic Outer Retinal Gene Delivery from the Vitreous. Sci. Transl. Med. 5,189ra76-189ra76 (2013); IDS Reference) and Suzuki (Scientific Reports volume 7, Article number: 45524 (2017); IDS Reference).
This rejection has been modified as necessitated by Applicant’s amendment and arguments filed 05/01/2026.
Regarding claims 1 and 3, Iizuka teaches administering an AAV vector serotype 1 with a CMV promoter encoding Connexin26 protein (GJB2) (i.e. a heterologous nucleic acid encoding an expression product which as a polypeptide which reduces hearing loss) to drive expression of GJB2 through the inner ear (p. 3651, bridging paragraph; p. 3652, 2nd column; p. 3658, 1st column). Through administration of the AAV delivering GJB2 to neonatal GJB2-deficient mice, the Cx26 expression was rescued in cochleae (p. 3654, bridging paragraph). In non-rescued cochleae, organs of Corti collapsed and hair cells degenerated (p. 3655, 1st column).
However, Iizuka does not teach that the AAV capsid is an AAV2.7m8 capsid protein.
Dalkara teaches an insertion of a peptide comprising the amino acid sequence of SEQ ID NO: 1 into a AAV2 major capsid protein at position 588 (p. 2-3, bridging paragraph; p. 3 “the AAV2 seven–amino acid library, and 67% of all clones (32 of 48) contained the same 7mer motif (LGETTRP)” p. 3 , legend Fig 2.). Dalkara teaches that the 588LALGETTRP insertion disrupted AAV2 binding to its primary receptor heparan sulfate proteoglycan (HSPG) and further altered virus tropism (p 3, col.2). This vector is known as AAV2.7m8. Dalkara further teaches the AAV2.7m8 showed >10- to 100-fold more infectious than AAV2 in Chinese hamster ovary (CHO) cell lines (p. 3 last paragraph). Dalkara further teaches the AAV2.7m8 vector is utilized in gene therapy (p. 5, 2nd column). Dalkara further teaches the high infectivity of the 7m8 capsid compared to previous vectors may enable the use of relatively low dosages, thereby reducing the chance of immune response to vector capsid protein (p. 8).
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date to utilize AAV2.7m8 in place of AAV1 of Iizuka to deliver GJB2 expression with a reasonable expectation of success as they are both known AAV serotypes utilized for gene therapy and gene transfer. Furthermore, an artisan would be motivated to utilize AAV2.7m8 as the AAV2.7m8 capsid has been shown to have high infectivity compared to previous vectors (Dalkara; p. 8) that may enable the use of relatively low dosages (p. 8). Regarding the limitation wherein wherein the virion infects inner hair cells and outer hair cells, Suzuki teaches that AAV2 variants transduce inner hair cells and outer hair cells (Fig 3, p. 3). Therefore, an artisan would have a reasonable expectation of success that this limitation would be met by the AAV capsid and expression product claimed.
Regarding claim 8, Iizuka teaches that the hearing loss associated with GJB2 mutations is genetic/hereditary hearing loss (p. 3651, 2nd column, Abstract).
Therefore the invention would have been prima facie obvious to one of ordinary skill in the art at the time of the effective filing date.
In response to Applicant’s arguments filed 05/01/2026 regarding the 103 rejection,
Applicant’s arguments filed 05/01/2026 have been considered, however they are not persuasive.
Applicant argues that AAV tropism is a highly complex issue in transducing the appropriate target cells which based on the references cited does not have a reasonable expectation of success. Moreover, the present invention of AAV2.7m8 is the only reference demonstrating that AAV2.7m8 is capable of infecting both cochlear IHCs and OHCs with high efficiency. Applicant further utilizes post and prior art references to support their argument. Namely, Applicant points to Suzuki to demonstrate the difficultly in transducing hair cells and that to the date of Suzuki (published in 2017) “no AAV serotype has been shown to target hair cells throughout the entire cochlear spiral.” Applicant additionally points to Isgrig (2017) to say that AAV serotypes have sharply different behavior and can transduce different cell subtypes within the ear with particular biases.
The examiner disagrees. First, there is a motivation to combine which would lead one of ordinary skill in the art with a reasonable expectation of success to administer AAV2.7m8 to the ear. As shown above in the obviousness rejection, an artisan would be motivated to utilize AAV2.7m8 as the capsid has been shown to have high infectivity compared to previous vectors including at least Chinese hamster ovary (CHO) cell lines (p. 3, col.2), RGCs and Müller cells, amacrine cells, bipolar cells, rods, cones, and RPE (Fig 1, Fg. 3 E and F) (Dalkara; p. 8). Therefore, there is a motivation to improve upon a vector known in the art with the capsid described within in the invention to have high infectivity to enable the use of relatively low dosages, thereby reducing the chance of immune response to vector capsid protein. Second, Applicant cites Suzuki, which does state that “to date, no AAV serotype has been shown” however, Suzuki states this fact in their background portion of the document and their data shows that AAV2 variants do transduce inner hair cells and outer hair cells (Fig 3, p. 3). As Suzuki is prior art, an artisan would have a reasonable expectation of success in utilizing a variant of AAV2 such as AAV2.7m8 to transduce hair cells in the cochlear spiral. While AAV vector serotypes do have biases as stated in Isgrig, it indicates that transduction in cell subtypes is a characteristic of the AAV vector and not something provided externally. Therefore, an artisan would have expected transduction of the claimed cells with a reasonable expectation of success.
Conclusion
No claims are allowed.
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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 ALEXANDRA CONNORS whose telephone number is (571)272-7010. The examiner can normally be reached Monday - Friday (9AM-5PM).
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 at (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 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.
/ALEXANDRA F CONNORS/ Examiner, Art Unit 1634
/MARIA G LEAVITT/ Supervisory Patent Examiner, Art Unit 1634
Prosecution Insights