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 the Claims
Applicant’s submission filed 05 November 2025 has been entered. Claims 1-2, 4, 6-7, 9-10, 13, 31, and 38 are pending. Claim 31 has been amended. Therefore, prosecution on the merits continues for claims 31 and 38 as being drawn to the elected invention, with claims 1-2, 4, 6-7, 9-10, and 13 withdrawn for reading on non-elected invention(s). All arguments have been fully considered with the status of each prior ground of rejection set forth below.
Status of Prior Rejections/Response to Arguments
RE: Rejection of claims 31 and 38 under 35 USC 112(a)
Applicant has amended independent claim 31 to i) remove the limitation requiring the miR-184 to be encoded by an expression vector, ii) revert the claim language back to include “miR-184 or an miR-184 mimic” within the composition (emphasis added), and iii) further define within a new limitation that the store-operated calcium entry modulator is selected from the group consisting of BTP2, GD3+, cyclosporin A, and ORAI1 siRNA. With these amendments, Applicant has provided the ordinary artisan with sufficient information to generate and utilize the claimed invention, as well as written description support for the store-operated calcium entry modulators.
Therefore, the rejections are withdrawn.
New Grounds of Rejection
Claim Objections
Claim 38 is objected to because of the following informalities:
Regarding claim 38: The instant claim is objected to for reciting “where the composition further comprises…” instead of “wherein the composition further comprises…”, or the like.
Appropriate correction is required.
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 31 and 38 are rejected under 35 U.S.C. 103 as being unpatentable over Nagosa et al (Stem Cell Reports, 2017, of record) in view of Numaga-Tomita et al (J Cell Sci, 2013, of record on IDS filed 12 July 2024).
Nagosa et al and Numaga-Tomita et al are considered prior art under 35 USC 102(a)(1).
Regarding claims 31 and 38: Nagosa et al disclose the role in which miR-184 has on epidermal differentiation (Title). As such, Nagosa et al disclose the transfection of foreskin keratinocytes with pre-miR-184 mimic and subsequent calcium-induced stratification, or differentiation (Pages 1994-1995, miR-184 Modulates…; Figure 4).
Although Nagosa et al disclose the calcium-induced differentiation of the keratinocytes, Nagosa et al do not disclose the addition of a store-operated calcium entry modulator to the composition comprising the pre-miR-184 mimic, as required by instant claim 31.
Numaga-Tomita et al, however, disclose the physiological significance of Orai1 – a store-operated calcium channel – in keratinocytes (Abstract).
As such, Numaga-Tomita et al disclose that calcium signaling plays a major role in the development and maintenance of the epidermis, wherein an outward gradient of calcium in the extracellular matrix orchestrates the differentiation of keratinocytes from an undifferentiated to a fully differentiated state (Pages 605, 609-610). Accordingly, siRNA-mediated knockdown of Orai1 in keratinocytes reduced store-operated calcium entry and diminished expression of KRT1 (a keratinocyte-associated gene that is expressed in differentiated keratinocytes), thereby indicating that keratinocyte differentiation is under the positive control of the Orai1 channel (Pages 606-609, 611; Figure 7).
Therefore, it would have been prima facie obvious to modify the composition of Nagosa et al such that an Orai1 siRNA is included within the active composition comprising pre-miR-184 mimic that is administered to the primary keratinocytes. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to combine two products that are known to enhance the differentiation potential of primary keratinocytes, and would have had a reasonable expectation of success based on the combined disclosures of Nagosa et al (Pages 1994-1995, 2001) and Numaga-Tomita et al (Page 611). See MPEP § 2143(I)(A) and MPEP § 2143(I)(G).
Consequently, Nagosa et al as modified by Numaga-Tomita et al render obvious an active composition comprising a pre-miR-184 mimic and Orai1 siRNA that is utilized in the transfection of primary keratinocytes, thereby allowing for the subsequent calcium-induced (claim 38) differentiation of the keratinocytes. This therefore renders obvious the composition of instant claim 31.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 ALYSSA G WESTON whose telephone number is (571)272-0337. The examiner can normally be reached Monday-Thursday 8AM - 4PM (CT); Friday 8AM - 11AM (CT).
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/ALYSSA G WESTON/Examiner, Art Unit 1633 /CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633