DETAILED ACTION
This Office Action is in response to Applicant’s Amendment and Remarks filed on 24 July 2025 in which claim 1 was amended to change the scope and breadth of the claims, and claim 5 was newly added.
Claims 1-5 are pending in the current application and are examined on the merits herein.
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 .
Modified Rejections
The following are new ground(s) or modified rejections necessitated by Applicant's amendment, filed on 24 July 2025, where the limitations in pending claim 1 as amended now have been changed and claim 5 has been newly added. Therefore, rejections from the previous Office Action, dated 21 April 2025, have been modified and are listed below.
Response to Arguments
Applicant's arguments filed 24 July 2025 have been fully considered but they are not persuasive.
Applicant contends the claims as amended require a two-step process, and that neither Park nor Levy disclose or suggest using ultrafine bubbles in a separate step to promote skin permeation in a further step.
The above arguments are not found persuasive. Levy et al. was expressly cited for teaching the application of microbubbles to selectively increase tissue permeation at the desired area. A permeability map is prepared. Levy et al. teach “Once the mapped region is verified to substantially (e.g., ±5% or ±10% by volume) match the defined target region, the therapeutic agent may be administered to the target region for treatment.” (para [0010]). Thus, Levy et al. very clearly teach first applying microbubbles, and then administering a therapeutic agent. Furthermore, Levy et al. do not teach applying the therapeutic agent in the form of a bubble.
While Park teaches administering adenosine as part of a bubble system, Park still teaches the use of adenosine with permeability enhancers. The ordinary artisan would have been motivated to apply adenosine separately, after permeation has been enhanced because the goal of both Levy and Park is to increase the permeation of an active agent across the skin barrier.
The rejection is hereby maintained.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 4 and 5 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Levy et al. (WO 2019/002940, cited in previous Office Action).
Levy et al. teach a method for improving the targeted delivery of drugs, including in combination with nanobubble technology (para [0003]-[0006]). In one embodiment, microbubbles are generated, which when coupled with ultrasound, increases tissue permeability (para [0008]). A tissue permeability map can be created based on the use of microbubbles. After permeability has been induced, the therapeutic agent may be administered for treatment (para [0010]). Levy et al. teach “Once the mapped region is verified to substantially (e.g., ±5% or ±10% by volume) match the defined target region, the therapeutic agent may be administered to the target region for treatment.” (para [0010]; also see claim 23). Thus, Levy et al. very clearly teach first applying microbubbles, and then administering a therapeutic agent. Levy et al. teach the method accommodates a patient’s anatomy and movement during delivery, thereby improving the release and/or activation of drugs for treatment.
The therapeutic agents, cytarabine (cytosine arabinoside), 5-fluorouracil, and others (claim 11). Levy et al. do not teach applying the therapeutic agent in the form of a bubble.
Thus, Levy et al. disclose a two step method of applying a liquid that contains ultrafine bubbles onto a portion of a human body, followed by applying an external skin agent that is an external pharmaceutical preparation, and the external skin agent does not contain ultrafine bubbles. Additionally, Levy et al. disclose the express purpose is to promote permeation of the therapeutic agent into the skin.
Thus, the disclosure of Levy et al. anticipates claims 1, 4 and 5 of the present application.
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.
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.
Claim(s) 1-5 are rejected under 35 U.S.C. 103 as being unpatentable over Levy et al. (WO 2019/002940, cited in previous Office Action) in view of Park et al. (US 2021/0259953, cited in previous Office Action).
Levy et al. teach as discussed above.
Levy et al. do not expressly disclose wherein the specific component is adenosine (present claim 2). Levy et al. do not expressly disclose water as a principle component of the liquid containing ultrafine bubbles (present claim 3).
Park teaches a drug delivery system having both nanobubbles and a drug encapsulated therein (claim 9). The drug is an active ingredient in cosmetics (claim 13). The nanobubbles have a diameter of 50 nm to 200 nm (claim 2). Park teaches a method of delivering a drug, comprising the steps of administering to an object, the drug delivery system (claims 16 and 17). The active cosmetic ingredient may include adenosine (para [0020]). Park teaches mixing the nanobubble solution with an aqueous solution containing a surfactant (see e.g. para [0035], [0055], [0067], [0070]). The composition may have effects such as skin whitening, skin elasticity improvement, and wrinkle improvement (para [0041]). Park teaches the drug delivery system having the nanobubbles enhances the permeability of the active agent (fig.6, para [0065]; ex.1).
The recitation “a principal component of the liquid is water” is broadly and reasonably interpreted to include a composition comprising water.
The recitation “ultrafine bubbles” is broadly and reasonably interpreted to include bubbles having a diameter of 1000 nm or less (see present Specification, para [0006]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to apply nanobubbles to the skin, followed by applying adenosine onto the skin.
In accordance with the method taught by Levy et al., the ordinary artisan would have been motivated to apply nanobubbles/microbubbles to the skin and wait until permeability has been induced to apply a drug because it improves the permeation of the drug. ]). Levy et al. teach “Once the mapped region is verified to substantially (e.g., ±5% or ±10% by volume) match the defined target region, the therapeutic agent may be administered to the target region for treatment.” (para [0010]). The step-wise method of Levy et al. ensures optimal drug release.
The skilled artisan would have been motivated to subsequently administer adenosine to the skin because Park teaches the composition may have effects such as skin whitening, skin elasticity improvement, and wrinkle improvement, and cosmetic skin active agents including adenosine are suitable for use with the nanobubble delivery system.
While Park teaches administering adenosine as part of a bubble system, Park still teaches the use of adenosine with permeability enhancers. The ordinary artisan would have been motivated to apply adenosine separately, after permeation has been enhanced because the goal of both Levy and Park is to increase the permeation of an active agent across the skin barrier.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
Conclusion
In view of the rejections to the pending claims set forth above, no claim is allowed.
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.
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/BAHAR CRAIGO/
Primary Examiner
Art Unit 1699