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 .
DETAILED ACTION
Applicant's amendments and remarks filed on March 16, 2026 are acknowledged. Claims 2-12 and 14-25 have been canceled. Claims 1, 13, and 26 were amended. Claims 1, 13, and 26-29 are pending and are examined on the merits herein.
Continued Examination 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on March 16, 2026 has been entered.
Withdrawn Rejections
In view of Applicant’s amendments and response, the 35 U.S.C 112(a) written description rejection is withdrawn.
Priority
This application claims priority to PCT/US2021/014788 filed on January 22, 2021 which claims priority to U.S. provisional application 62/965,783, filed on January 24, 2020.
Claim Rejections - 35 USC § 112
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.
Enablement
Claims 1, 13, and 26-29 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is "undue". These factors include, but are not limited to: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Breadth of claims and nature of the invention:
Claims 1, 13, and 27 are drawn to a method of treating a subject having vestibular dysfunction comprising administering to the subject an effective amount of a Sox2 inhibitor wherein the Sox2 inhibitor is an inhibitory RNA molecule targeting Sox2 wherein the inhibitory RNA molecule is a siRNA comprising a sense strand and an antisense strand selected from the following pairs: SEQ ID NO: 35 and 36; SEQ ID NO: 37 and 38; SEQ ID NO: 39 and 40; and SEQ ID NO: 41 and 42.
Claims 26, 28, and 29 are drawn to a method of generating Type I vestibular hair cells in a human subject in need thereof comprising administering to the subject an effective amount of a Sox2 inhibitor wherein the Sox2 inhibitor is an inhibitory RNA molecule targeting Sox2 wherein the inhibitory RNA molecule is a siRNA comprising a sense strand and an antisense strand selected from the following pairs: SEQ ID NO: 35 and 36; SEQ ID NO: 37 and 38; SEQ ID NO: 39 and 40; and SEQ ID NO: 41 and 42.
State of the prior art, level of predictability in the art, and level of one of
ordinary skill:
A review of the prior art shows that the state of the art of treating a subject having vestibular dysfunction comprising administering to the subject an effective amount of a Sox2 inhibitor is immature and nascent.
Staecker et al. (Hearing Research 2011) discloses that there are currently no pharmaceuticals designed specifically for the inner ear. Development of therapies to treat hearing loss and balance disorders is complicated by the diversity of disease processes leading to functional loss. Further, part of the challenge in developing drugs for the inner ear is physical because it is separated for the general circular by a blood cochlea barrier with similar properties as the blood brain barrier making systemic delivery less efficient [page 44, left column, first paragraph].
Sayyid et al. (Curr Opin Otolaryngol Head Neck Surg 2018) discloses that vestibular dysfunction is a significant clinical problem with limited therapeutic options warranting research on biological strategies to repair/regenerate the vestibular organs to restore function [abstract]. Sayyid et al. also discloses that while combination therapies to stimulate vestibular hair cell regeneration may be promising, whether they are effective in the mature organ is currently unclear and warrants further examination. Moreover, understanding the genetic landscape of the regenerating utricles from nonmammalian to mammalian species is an area of active investigation [page 3, third paragraph]. Further, Sayyid et al. discloses that although the studies provide strong evidence that biological therapies to treat genetic causes of human deafness and balance disorders are highly feasible, most have found significantly reduced efficacy of gene therapy in both the auditory and vestibular systems of adult mice [page 5, third full paragraph].
A review of the prior art shows that the state of the art of generating Type I vestibular hair cells in a human subject in need thereof comprising administering to the subject an effective amount of any Sox2 inhibitor is immature and nascent.
Although post-filing, Zhang et al. (Am J Stem Cells 2020) discloses that sensorineural hearing loss, one of the most common health problems around the world, is mainly caused by cochlear hair cell (HC) damage or loss. In non-mammalian vertebrates, such as birds and fish, HCs can be spontaneously regenerated from supporting cells after damage. However, HCs in the adult mammalian cochlea cannot be spontaneously regenerated, and only neonatal cochlear HCs have a limited capacity for regeneration [page 25, left column]. Zhang et al. further discloses that HCs cannot be regenerated in the adult mammalian cochlea and current technologies are still quite far from restoring hearing functions in the HC-damaged mammalian cochlea. Thus, further research is needed to find ways to induce HC regeneration in both the neonatal and adult mammalian cochlea [page 29, right column, first paragraph].
Although post-filing, Berlingeri et al. (Hearing Research 2022) discloses that Sox2 is a transcription factor that is necessary in the mammalian inner ear for development of sensory hair cells and supporting cells. Sox2 is expressed in supporting cells of adult mammals, but its function in this context is poorly understood. Berlingeri et al. further determined that Sox2 is required in supporting cells for normal levels of vestibular hair cell regeneration but found no other major requirements for Sox2 in adult supporting cells [abstract].
Although post-filing, Yang et al. (Neuroscience 2026) discloses that the limited regenerative capacity of vestibular hair cells (HCs) in mammals is one of the causes of permanent balance disorders. The transcription factor Atoh1 has been identified as a potential candidate for inducing HC regeneration. However, regulation of Atoh1 alone has proven insufficient to achieve functional recovery of the mammalian vestibule. Endogenous Sox2 is required for Atoh1-associated HC formation during embryonic development, yet its role in Atoh1 overexpression-induced HC formation after birth remains unclear. Yang et al. demonstrated that endogenous Sox2 expression is essential for Atoh1-induced HC addition and regeneration in the mouse utricle [abstract].
Amount of direction provided by the inventor and existence of working
examples:
The specification envisions in example 9 that the methods disclosed can treat a human patient with vestibular dysfunction by improving or restoring vestibular function comprising locally administering to the inner ear a composition containing a Sox2 inhibitor. However, the specification does not disclose any working examples of treating a subject having vestibular dysfunction.
The specification envisions methods of generating Type I vestibular hair cells by reducing Sox2 activity or expression in Type II hair cells, regenerated or regenerating hair cells, or supporting cells that are then regenerated into hair cells based on the use of Sox2 inhibitors [page 22, last paragraph]. Working example 2 discloses that AAV8 virus was delivered by IL injection into adult mice and the results indicate that AAV8 transduces vestibular type II but not type I hair cells in the adult mouse in vivo. However, the specification does not disclose any working examples of generating Type I vestibular hair cells comprising administering an effective amount of a Sox2 inhibitor.
Quantity of experimentation:
In view of the breadth of the claims which embrace treating a subject having vestibular dysfunction comprising administering to the subject an effective amount of a Sox2 inhibitor wherein the Sox2 inhibitor is an inhibitory RNA molecule targeting Sox2 and generating Type I vestibular hair cells in a human subject in need thereof comprising administering to the subject an effective amount of a Sox2 inhibitor wherein the Sox2 inhibitor is an inhibitory RNA molecule targeting Sox2, the state and level of predictability in the art, the lack of working examples, and the failure to provide adequate guidance to overcome the state and level of predictability of the art, one of skill would have to perform undue experimentation in order to practice the invention commensurate in scope with the claims.
Response to Arguments
Applicant's arguments filed March 16, 2026 have been fully considered but they are not persuasive.
Applicant’s remarks did not address the 35 U.S.C. 112(a) enablement rejection; therefore, the Examiner is maintaining the rejection.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINA TRAN whose telephone number is (571)270-0550. The examiner can normally be reached M-F 7:30 - 5:00pm.
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, Jennifer Dunston can be reached at (571) 272-2916. 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.
/C.T./
Examiner, Art Unit 1637
/Jennifer Dunston/Supervisory Patent Examiner, Art Unit 1637
Prosecution Insights