DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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.
Receipt and consideration of Applicant’s amended claim set and Applicant’s arguments/remarks submitted on May 2, 2025 are acknowledged.
All rejections/objections not explicitly maintained in the instant office action have been withdrawn per Applicant’s claim amendments and/or persuasive arguments. Applicant’s claim amendments have necessitated new grounds of rejections set forth below.
Status of the Claims
Claims 56, 57, 59-66, 68-73, and 75-78 are pending and under consideration in this action. Claims 1-55, 58, 67, and 74 are cancelled.
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.
Claims 56, 57, 59-66, 68-73, and 75-78 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 written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 56, 70, and 72 recite the limitation, “wherein the emulsion composition is formulated so that the large agent can penetrate the site without use of a penetration enhancing agent.” The Specification appears to attribute the ability for the large agent to penetrate the site to the microneedle technology. Applicant discloses that microneedling technologies can enhance transdermal delivery when no other penetration enhancing agent is utilized (e.g., P.G. Pub., para.0086). However, Applicant does not appear to describe how the emulsion composition is formulated so that the large agents can penetrate the site without use of a penetration enhancing agent (e.g., what components should or should not be incorporated, or what is it specifically about the emulsion to arrive at an emulsion composition having the claimed property?). It is noted that Applicant specifically defines “penetration enhancing agent” to exclude mechanical devices such as needles (P.G. Pub., para.0054).
Applicant fails to describe a representative number of emulsion formulations that allow large agents to penetrate the site without use of a penetration enhancing agent. In particular, Applicant fails to describe structural features common to emulsion compositions that possess the claimed property of allowing large agents to penetrate the site without use of a penetration enhancing agent. Accordingly, Applicant fails to provide an adequate written description to support the breadth of the claims.
Claims 57, 59-66, 68, 69, 71, 73, and 75-78 are subsequently rejected as they incorporate the limitation at issue and do not remedy the issue discussed above.
Claim Rejections - 35 USC § 103
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 56, 57, 59-65, 68-73, and 75-78 are rejected under 35 U.S.C. 103 as being unpatentable over Edelson et al. (Edelson) (US 2011/0212157 A1; published Sept. 1, 2011) and David et al. (David) (US 2010/0196445 A1; of record).
Edelson discloses methods of treating conditions or disorders associated with dermal structure by applying to a skin surface a composition containing a nanoparticle composition (e.g., a nanoemulsion) that includes a therapeutic agent useful in the treatment of the condition or disorder (para.0003-0004; Edelson claim 1). The nanoemulsion comprises an aqueous dispersion medium; an oil; and at least one therapeutic agent (reading on an oil-in-water nanoemulsion). In addition to the two immiscible media, a premix may include, for example, one or more surfactants or emulsifying agents (Edelson claim 1; para.0089, 0116).
The formulations suitable for topical administration include liniments, lotions, creams, ointments, solutions, and suspensions (para.0295).
Furthermore, Edelson discloses that the administration step does not include the use of skin permeation enhancers or abrasives (Edelson claim 161). The nanoemulsion penetrates the top layer of the skin, wherein the top layer of the skin is the surface of the stratum corneum (Edelson claims 162-163).
In an embodiment, the therapeutic agent is an antibody (Edelson claim 156).
In an embodiment, the therapeutic agent is botulinum toxin (Edelson claim 130). The molecular weight of a botulinum toxin protein molecule for all seven of the known botulinum toxin serotypes is about 150 kD (para.0140-0141).
Edelson discloses the use of transdermal patches, which often have the added advantage of providing controlled delivery of a compound to the body (par.0289). Edelson discloses that the compositions may be incorporated into a device such as a patch to achieve transdermal administration of the therapeutic agent (e.g., botulinum toxin). The transdermal patch may further comprise a plurality of needles extending from one side of the patch that is applied to the skin, wherein needles extend from the patch to project through the stratum corneum of the skin. In some embodiments, needles do not rupture a blood vessel (para.0290). In some embodiments, the transdermal patch includes an adhesive (par.0291).
The therapeutic agent (e.g., botulinum toxin) can be provided in a depot in the patch so that pressure applied to the patch causes the therapeutic agent to be directed out of the patch and through the stratum corneum (para.0293).
In many embodiments, it may be desirable to limit delivery of a therapeutic agent to only an intended delivery area. A transdermal patch may be utilized to this end (par.0297).
With regards to the limitation in the instant claims 56, 70, and 72 “wherein the emulsion composition is formulated so that the large agent can penetrate the site without use of a penetration enhancing agent,” while the instant specification discloses that in some embodiments, a surfactant may be a “penetration enhancing agent” (P.G. Pub., para.0054), the instant Specification defines the term “penetration enhancing agent” to refer to an agent whose presence or level correlates with increased penetration of an agent of interest across skin as compared with that observed in its absence (P.G. Pub., para.0054). In the present case, the surfactant appears to be present to aid in the formation of the nanoemulsion, not to increase penetration of the therapeutic agent. Furthermore, the claims as currently written do not appear to explicitly preclude the inclusion of penetration enhancing agents. As discussed above, it appears that the ability for the active agent from the nanoemulsion to penetrate the skin is due to the needles’ puncturing of the stratum corneum, not the inclusion of a surfactant.
Edelson does not appear to explicitly disclose wherein the needles on the patch are microneedles. David is relied upon for this disclosure. The teachings of David are set forth herein below.
David discloses devices and formulations for delivery of biologically active agents across tissue membranes such as skin. Biologically active agents include neurotoxins, such as botulinum toxin (para.0019). David discloses the use of microneedle technology for delivery of the neurotoxin or neurotoxin formulation. Microneedle delivery technologies can facilitate drug delivery to various skin depths using arrays of short needles. Such microneedles pierce the stratum corneum and underlying layers of the skin to present drug into the epidermis, dermis, or subcutaneous space. Due to the small size of microneedles, application is virtually pain-free, with minimal (if any) bleeding or application site reaction. David defines “microneedle” to refer to an elongated structure that is sufficiently long to penetrate through the stratum corneum skin layer and into the epidermal/dermal layer, but sufficiently short to not result in substantial pain due to activation of nerve endings (para.0021).
Microneedles can be used as arrays of more than one microneedle. Various sizes of arrays are suitable for use with the invention (para.0025). In an embodiment, the microneedle has a length from 20 micron to approximately 1000 micron, such as from 600 micron to approximately 800 micron. In an embodiment, the microneedle is approximately 700 micron in length (para.0026).
A microneedle can be manufactured from a variety of materials, including but not limited to silicon (reading on biocompatible material), a metal (e.g., nickel, titanium, and allows such as stainless steel), a polymer, and glass (para.0027-0028). In some embodiments, the microneedles are dissolvable (para.0011).
As discussed above, Edelson discloses transdermal patches having a plurality of needles, which are to project through the stratum corneum. One of ordinary skill in the art would have found it prima facie obvious before the effective filing date of the instant invention to combine the teachings of Edelson and David and have Edelson’s patch have microneedles as disclosed by David (i.e., microneedle size and material). One of ordinary skill in the art would have been motivated to do so as such microneedles are known to be suitable for use with patches used for transdermal delivery of active ingredients such as botulinum toxin, and are suitable for piercing the stratum corneum to present the drug into the epidermis, dermis, or subcutaneous space, but are small enough that the application is virtually pain-free and may be done with minimal (if any) bleeding or application site reaction. One of ordinary skill in the art would have had a reasonable expectation of success in doing so as Edelson discloses a patch comprising a plurality of needles to deliver a composition comprising botulinum toxin and wherein the needles are to project through the stratum corneum, and David discloses microneedles for use on transdermal patches, which are known to project through the stratum corneum to allow for delivery of active agents such as botulinum toxin across the skin.
Therefore, the claimed invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention, because the combined teachings of the prior art references is fairly suggestive of the claimed invention.
Claim 66 is rejected under 35 U.S.C. 103 as being unpatentable over Edelson et al. (Edelson) (US 2011/0212157 A1; published Sept. 1, 2011) and David et al. (David) (US 2010/0196445 A1; of record) as applied to claims 56, 57, 59-65, 68-73, and 75-78 set forth above, further in view of Sullivan et al. (Sullivan) (Nature Medicine; of record).
The teachings of Edelson and David, and the motivation for their combination as they apply to claims 56, 57, 59-65, 68-73, and 75-78 are set forth above and incorporated herein.
The combined teachings of Edelson and David do not appear to explicitly disclose wherein the microneedles are composed of a dissolving polymer. Sullivan is relied upon for this disclosure. The teachings of Sullivan are set forth herein below.
Sullivan discloses microneedle patches used for transdermal delivery of an active (abstract; pg.915, col.2, para.1-2). Sullivan discloses the use of polymer microneedles that dissolve within minutes and completely resorb in the skin, resulting in no biohazardous sharps. Sullivan discloses dissolving microneedles also offer additional benefits, both to the individuals an in regard to logistics, including small storage and disposal size, inexpensive fabrication, and ease of use to enable self-administration at home (pg.915, col.2, para.3).
As discussed above, David discloses that the microneedles can be manufactured from a variety of materials including polymer, and discloses that the microneedles are dissolvable in an embodiment. One of ordinary skill in the art would have found it prima facie obvious before the effective filing date of the instant invention to further combine the teachings of Edelson and David with the teachings of Sullivan and use dissolvable polymer microneedles as the microneedles in the microneedle patch of the combined teachings of Edelson and David discussed above. One of ordinary skill in the art would have been motivated to do so in order to obtain the benefits disclosed by Sullivan, e.g., no biohazardous sharps, small storage and disposal size, inexpensive fabrication, and ease of use to enable self-administration at home. One of ordinary skill in the art would have had a reasonable expectation of success in doing so as David discloses that the microneedles may be made of polymer and may be dissolvable, and Sullivan discloses their dissolvable polymer microneedles being suitable for use in patches and for transdermal delivery of actives.
Therefore, the claimed invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention, because the combined teachings of the prior art references is fairly suggestive of the claimed invention.
Response to Arguments
Applicant's arguments filed May 2, 2025 have been fully considered. In light of Applicant’s claim amendments, new rejections citing a new combination of references are set forth above to address the claim amendments.
Conclusion
Claims 56, 57, 59-66, 68-73, and 75-78 are rejected. No claims are 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MONICA A. SHIN whose telephone number is (571)272-7138. The examiner can normally be reached Monday-Friday (9:00AM-5:00PM EST).
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/MONICA A SHIN/Primary Examiner, Art Unit 1616