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
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 2, 2026, that includes a response to the Final Office Action mailed September 3, 2025, has been entered. Claims 1 and 7-10 have been amended; claims 3, 4, 6, 11, and 15 have been canceled. Claims 5, 7-10, 13, 14, 16, and 18 have been withdrawn. Claims 1, 2, 12, and 17 are under examination.
Withdrawal of Prior Claim Rejections - 35 USC § 112(d)
Claim 15 has been canceled. Therefore, the 35 USC 112(d) rejection presented in the Final Office Action mailed September 3, 2025 is hereby withdrawn.
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 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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, 2, 12, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Falo, JR et al. (U.S. Patent Application Pub. No. 2011/0098651), in view of Shiozuka et al. (Pharmaceutics. 2013; 5: 385-391), Cobleigh et al. (Cancer. 1985; 56(11): abstract), and Salem et al. (J Immunother. 2005; 28(3): 220-228).
Applicant Claims
Applicant claims a method of treating skin cancer at a target skin area of a subject having skin cancer comprising inserting into the target skin area a microneedle array comprising a base portion and a plurality of microneedles; wherein the microneedle array matrix comprises carboxymethylcellulose; wherein the chemotherapeutic agents doxorubicin and Poly(I:C) (i.e. as an immunostimulant) are located in the plurality of microneedles so that the base portion is “substantially free” of doxorubicin and Poly(I:C), wherein the microneedle array matrix comprises at least two layers containing chemotherapeutic agents with a layer of CMC between them; the doxorubicin is present in the microneedle array in the amount of about 50 micrograms or about 200 micrograms, the Poly(I:C) is present in the microneedle array in the amount of about 250 micrograms, and wherein the act of inserting the microneedle array comprises penetrating the stratum corneum to deliver the chemotherapeutic agents to the epidermis and/or dermis.
Determination of the Scope and Content of the Prior Art (MPEP §2141.01)
Falo, JR et al. disclose a method for treating skin cancer at a localized target area comprising inserting into the target skin area a microneedle array comprising a base portion and a plurality of microneedles; wherein the microneedle array matrix comprises carboxymethylcellulose and a therapeutically effective amount of one or more bioactive agents, such as a small molecule chemotherapeutic agent (e.g. CYTOXAN) with potential for localized treatment of skin cancers, wherein substantially all of the one or more bioactive components are located in the plurality of microneedles so that the base portion is “substantially free” of bioactive components contained therein, wherein the bioactive agents are included in one or more “active layers” while additional layers may be free of the bioactive agents (i.e. layers of CMC without the bioactive agents) and wherein the act of inserting the microneedle array comprises penetrating the stratum corneum to deliver the small molecule chemotherapeutic agent to the epidermis and/or dermis.
Shiozuka et al. disclose that adriamycin (i.e. doxorubicin) is a small molecule chemotherapeutic agent with potential for localized treatment of cancers when transdermally delivered to skin in the amount of e.g. 50-300 micrograms; wherein the transdermal delivery can be accomplished via a depilatory agent to increase the drug permeability of the skin.
Cobleigh et al. disclose the treatment of squamous cell carcinoma (i.e. a type of skin cancer) with Adriamycin (i.e. doxorubicin).
Salem et al. disclose that Poly(I:C) can suppress tumor growth, and, specifically, when administered in the amount of 200 micrograms, can enhance antitumor immunity by stimulating an increase in CD8 T-cell function.
Ascertainment of the Difference Between the Scope of the Prior Art and the Claims (MPEP §2141.02)
Falo, JR et al. do not explicitly disclose that the chemotherapeutic agent is doxorubicin, that the doxorubicin is able to treat skin cancer, and that the method further comprises administering Poly(I:C). These deficiencies are cured by the teachings of Shiozuka et al., Cobleigh et al., and Salem et al.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been prima facie obvious for one of ordinary skill in the art at the time the present application was filed to combine the respective teachings of Falo, JR et al., Shiozuka et al., Cobleigh et al., and Salem et al., outlined supra, to devise Applicant's presently claimed method.
Falo, JR et al. disclose a method for treating skin cancer at a localized target area comprising inserting into the target skin area a microneedle array comprising a base portion and a plurality of microneedles; wherein the microneedle array matrix comprises carboxymethylcellulose (CMC) and a therapeutically effective amount of one or more bioactive agents, such as a small molecule chemotherapeutic agent (e.g. CYTOXAN) with potential for localized treatment of skin cancers; wherein the one or more bioactive components are located in the plurality of microneedles so that the base portion is free of bioactive components contained therein; wherein the microneedle is layered and the bioactive agents are included in one or more “active layers” while additional layers may be free of the bioactive agents (i.e. layers of CMC without the bioactive agents); and wherein the act of inserting the microneedle array comprises penetrating the stratum corneum to deliver the small molecule chemotherapeutic agent to the epidermis and/or dermis, whereby the chemotherapeutic agent is effectively and specifically delivered to the skin cancer site for optimal therapeutic effect with minimal side effects. Since Shiozuka et al. disclose that adriamycin (i.e. doxorubicin) is a potent chemotherapeutic agent with potential for localized treatment of cancers when transdermally delivered to skin in the amount of e.g. 50-300 micrograms, since Cobleigh et al. disclose the treatment of squamous cell carcinoma (i.e. a type of skin cancer) with Adriamycin (i.e. doxorubicin), since Salem et al. disclose that Poly(I:C) can suppress tumor growth, and, specifically, when administered in the amount of 200 micrograms, can enhance antitumor immunity by stimulating an increase in CD8 T-cell function, and since Shiozuka et al.’s method of choice for the transdermal delivery of doxorubicin, i.e. a depilatory agent, is notorious for causing or potentially causing severe irritation, pain, and even burning and bleeding, and since Falo, JR. et al. disclose that their microneedle array method for transdermal delivery is efficient, precise, reproducible, and has minimal risk for pain and/or bleeding; one of ordinary skill in the art would be motivated to treat skin cancer by transdermal delivery of doxorubicin and Poly(I:C) via the Falo, JR et al. microneedle array, with the reasonable expectation that the doxorubicin and Poly(I:C) will be successfully delivered to the skin with minimal irritation, pain and/or bleeding, and that the resulting method will successfully treat the skin cancer with minimal side effects.
In light of the foregoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed March 2, 2026 have been fully considered but they are not persuasive.
i) Applicant contends that “claim 1 has been amended to now expressly recite that the microneedle array is fabricated by a spin-drying process comprising one or more centrifugation steps under controlled temperature and purging gas flow conditions”, that “this process is not disclosed, taught, or suggested by any of the cited references”; that “Falo, JR. involves…some tip-loading, but nowhere discloses or suggests a controlled spin-drying process involving specific centrifugation and gas flow parameters for localizing active cargo exclusively within the microneedle tips”.
The Examiner, however, would like to point out the following:
1. Claim 1 says nothing at all about any of method described, i.e. claim 1 says nothing at all about “a spin-drying” process, about centrifugation, and about controlled temperature and purging gas flow conditions.
2. Claim 1 does not appear to require that the active cargo is “localized within the microneedle tip”. While claim 1 stipulates that “the base portion is free of the at least two chemotherapeutic agents”, there is no limitation that the chemotherapeutic agents must be localized to the tip of the microneedle.
3. Further, while claim 1 requires that there are two layers that contain chemotherapeutic agents, these requisite two layers can be located anywhere in the body of the microneedle, either the stem portion or the tip.
For the foregoing reasons, the 35 USC 103 rejections are hereby maintained.
Conclusion
No claims are allowed.
Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID BROWE whose telephone number is (571)270-1320. The examiner can normally be reached Monday - Friday, 9:30 AM to 6 PM EST.
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/DAVID BROWE/Primary Examiner, Art Unit 1617