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 Claims
Claims 2, 5, 18-20 are cancelled. Claims 1, 6-7,10, 17, 21-24 are pending and under examination.
MAINTAINED REJECTIONS
Double Patenting
Claims 1-2, 6-7, 10, 17, and 21-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 7-9, 11-17, 19-20, 22-23, 25, 27, 30 and 34 of copending Application No. 18/289,028 (Hereinafter '028 application) (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claims 1, 17: Claim 20 of ‘028 application disclosed an AAV vector comprising instant SEQ ID NO: 1 (see alignment below)
Regarding claims 6, 7, 10, and 21-23: Claim 20 of ‘028 application teaches operably linking the promoter of instant SEQ ID NO: 1 to stereocilin protein. This reads on a heterologous protein transgene as required by claims 6-7, 10, and 21-23.
Regarding claim 24: Claims of ‘028 application did not teach a cell comprising an AAV vector comprising SEQ ID NO: 1. However, claim 22 of ‘028 application disclosed an OHC comprising the a two-vector system comprising: a) a first nucleic acid vector comprising an oncomodulin (OCM) promoter having at least 85% sequence identity to any one of SEQ ID NOs: 1-3 operably linked to a first polynucleotide encoding an N- terminal portion of a stereocilin protein; and b) a second nucleic acid vector comprising a second polynucleotide encoding a C-terminal portion of a stereocilin protein. Further, as indicated above, claim 20 taught an AAV vector comprising the oncomodulin promoter linked to stereocilin protein encoding gene. Claim 25 of ‘028 application taught a method of administering an effective amount of the nucleic acid construct of claim 1 of ‘028 application. As such, person of ordinary skill in the art would have been motivated to administer the AAV vector of claim 20 to treat the sensorineural loss as required by claim 25 of ‘028 application as required by the instant claim.
Response to Arguments: Applicants argued that the present application has an effective filing date of November 4, 2019, which is earlier than the effective filing date of May 5, 2021, for the 18/289,028 Application. Consequently, pursuant to M.P.E.P. § 1490(VI)(D) this rejection should be withdrawn.
It is submitted that according to MPEP 804(I)(B)(1)(b)(i) and MPEP 1490(VI)(D)(2)(a), a provisional nonstatutory double patenting rejection is only withdrawn when it is the only rejection remaining in an application having the earliest effective U.S. filing date (taking into account any benefit under 35 U.S.C. 120, 121, 365(c), or 386(c) ) with respect to the conflicting claims); at which point the "provisional" nonstatutory double patenting rejection in the other (later filed) application(s) will be converted into a nonstatutory double patenting rejection when the application with the earliest U.S. effective filing date issues as a patent.
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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 (i.e., changing from AIA to pre-AIA ) 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 6 and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Athas (Otolaryngology Head and Neck Surgery. 1999, See IDS filed 7/31/2023) and Liu et al (Mol Ther. 2005 Oct; Hereinafter "Liu"; See PTO-892) in view of GenBank AC121917.2 (See IDS filed 3/17/2025)) .
Regarding claim 1 and 6: Athas is directed to In vitro analysis of the Oncomodulin promoter for targeting gene expression to the ear. As indicated in the Office Action of Apr 9, 2025 Athas performed transcriptional analysis of taught characterization and determination of an oncomodulin promoter by transcriptional assays of the mouse oncomodulin promoter using a luciferase reporter system. Athas noted that they found a oncomodulin promoter is transcriptionally active in a cell line that contains it and by analogy will be active in OHC. (See Athas conclusion). As such, Athas taught that a method of determining an oncomodulin promoter in mouse. It is noted that Athas did not teach a promoter comprising a nucleotide sequence of SEQ ID NO: 1 as required by the claim 1. However, it would have been obvious for a person of ordinary skill in the art to arrive at the SEQ ID NO:1 as a potential promoter for oncomodulin gene, using the methods taught by Athas in view of GenBank. The Oncomodulin gene locus in chromosome 5 of mice (Mus musculus) was already known (See GenBank AC121917.2). It is also pointed out that Athas used a Luciferase to detect a promoter, which in itself is a (heterologous) transgene (which encodes a protein, as required by claims 6).
A person of ordinary skill in the art would have been able to use the methods taught by Athas to arrive at a nucleotide sequence of SEQ ID NO: 1 as an oncomodulin promoter. The person would have been motivated to arrive at the promoter of SEQ ID NO: 1 promoter due to the teachings of Athas that use of an oncomodulin promoter can prevent unwanted expression of a gene in cells other than were it is desired (i.e. tissue specific expression). Furthermore, the person would have been motivated to arrive at an AAV comprising an oncomodulin promoter of SEQ ID NO: 1 and a transgene. It is noted that Liu taught use of rAAV3 for delivery of nucleic acids to cochlear inner hair cells. (See Liu Abstract). Liu taught CBA (Chicken β Actin) driven EGFP expression in inner hair cells of the ear. A person of ordinary skill in the art would have found it obvious to replace CBA promoter taught by Liu with the oncomodulin promoter taught by Athas. The person would have recognized this as a simple substitution (oncomodulin promoter in place of CBA) for the same purpose. ((KSR Int’l Co. v. Teleflex, Inc., 550 U.S. 398 (2007) pg 14 and 12).
Regarding claim 24: Liu taught a cochlear inner hair cells transduced with AAV3. (See Liu Abstract)
Claims 7 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Athas (Otolaryngology Head and Neck Surgery. 1999, See IDS filed 7/31/2023) and Liu et al (Mol Ther. 2005 Oct; Hereinafter "Liu"; See PTO-892) in view of GenBank AC121917.2 (See IDS filed 3/17/2025)), and further in view of Izumikawa et al (Nat Med. 2005 Mar, hereinafter " Izumikawa", See PTO-892 of Apr 9, 2025).
Regarding claim 7 and 10: The teachings of Liu and Athas in view of GenBank GenBank AC121917.2 are set forth above. It is noted that neither reference taught the claimed transgenes or therapeutic proteins. As pointed out above, Athas taught expression of luciferase. Athas taught that the system could be used to express proteins in OHCs. A person of ordinary skill, in reading Athas would have recognized the desirability of expression of any known or useful protein that can cure genetic diseases of the ear. As an example, Izumikawa taught that ATOH1 gene expression is useful in treatment of deafness. (See Izumikawa Abstract). Thus, it would have been obvious to a person of ordinary skill in the art to try ATOH1 or any of the claimed proteins for therapeutic purposes as indicated in Athas. It has been held that "a person with ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense." See KSR International Co. v Teleflex, Inc. 82 USPQ2d 1385 at 1390.
Claim 17 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Athas (Otolaryngology Head and Neck Surgery. 1999, See IDS filed 7/31/2023) in view of GenBank AC121917.2 (See IDS filed 3/17/2025)) .
Regarding claims 17 and 21: The teachings of Athas are set forth above. As such it is clear that Athas envisioned a transgene expression, where the transgene is under the control of the oncomodulin promoter, as required by claims 17. It is also pointed out that Athas used a Luciferase to detect a promoter, which in itself is a (heterologous) as required by claim 21.
Claims 22 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Athas (Otolaryngology Head and Neck Surgery. 1999, See IDS filed 7/31/2023) in view of GenBank AC121917.2 (See IDS filed 3/17/2025)) and further in view of Izumikawa et al (Nat Med. 2005 Mar, hereinafter " Izumikawa", See PTO-892 of Apr 9, 202.
Regarding claims 22-23: The teachings of Athas and Izumikawa in view of GenBank AC121917.2 are set forth above. It is noted that neither reference taught the claimed transgenes or therapeutic proteins. It would have been obvious to a person of ordinary skill in the art to try ATOH1 or any of the claimed proteins for therapeutic purposes as indicated in Athas and Izumikawa for the reasons indicated above for claims 7 and 10. It has been held that "a person with ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense." See KSR International Co. v Teleflex, Inc. 82 USPQ2d 1385 at 1390.
Response to Arguments: Applicants argued that the activity of oncomodulin promoter in BeWo cell lines is not automatically applicable for outer hair cells as “[g]ene expression is highly context-dependent and depends not only on promoter presence, but also on the interplay of factors such as chromatin structure, transcriptional factor availability, and epigenetic regulation.” Applicants cited Li which taught that cis regulatory elements are highly complex and dependent on cellular state. Further Applicants pointed out that Li taught that each cell type has a unique combination of cis-regulatory element. Applicants further stated that “[g]ene expression is highly diverse and cell-type specific, depending not only on promoters but also transcription factors, chromatin accessibility, and epigenic modifications present in the cell type.” In view of this, Applicants argued that placental cells are vastly different from the specialized OHCs of the inner ear, and the skilled artisan would expect them to have vastly different regulatory networks for gene expression. Applicant’s arguments have been fully considered but are not found persuasive.
It is submitted that the sequence of promoter such as that recited in SEQ ID NO: 1, can be readily derived using routine methods, such as those described by Athas. The claims are not limited to any particular cell type, such as outer hair cells and therefor encompass expression in any cell type. A person of ordinary skill in the art would have had a reasonable expectation that a promoter identified using the methods of Athas would drive gene expression in at least some mammalian cells. Applicant’s cited references do not provide evidence specific to the oncomodulin promoter or any teaching that it would be inactive in BeWo cells or other cell types. Express teachings of Athas establish that the promoter obtained by their method “by analogy will be active in OHC”. Therefore, the Applicants’ assertions are unsupported and not persuasive.
Conclusion
No claim is allowed.
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 JAGAMYA VIJAYARAGHAVAN whose telephone number is (703)756-5934. The examiner can normally be reached 9:00a-5:00p.
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/JAGAMYA NMN VIJAYARAGHAVAN/ Examiner, Art Unit 1633
/EVELYN Y PYLA/Primary Examiner, Art Unit 1633