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 .
Claims 19-22, 24-27, and 29-50 have been cancelled previously. 1-18, 23, and 28 are pending.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-12, 23, and 28 in the reply filed on 10/10/2025 is acknowledged.
Claims 13-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/10/2025.
Claims 1-12, 23, and 28 are under current examination.
Claim Objections
Claims 10 and 12 are objected to because of the following informalities:
Claim 10 recites “middle layer further comprise an absorption enhancer”. This is ungrammatical because the noun and verb in the sentence do not agree in number. Amending the claim to recites “comprises an absorption enhancer” would be remedial.
Claim 12 is missing the word “wherein” between the transitional phrase and the body of the claim.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-12 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites the limitation "the active agent" in line 4. There is insufficient antecedent basis for this limitation in the claim because the claim recites “an active agent” describing the active agent that must be delivered to a subject and must therefore be present in the patch in line 1 and also in line 3 describing an active agent in the top layer. As it is unclear whether the phrase “an active agent” recited in line 1 and the phrase “an active agent” recited in line 3 refer to the same or different active agents, it is unclear whether “the active agent” recited in line 4 refers back to, and identifies the substance for the active agent delivered to the patient, the active agent that is present in the adhesive, or necessarily limits both. As histamine can be used as a vasodilator to improve transdermal delivery of other active agents, the interpretation that the claim can read on a patch for delivering one active agent to a subject that contains histamine in one or both of the layers in order to increase systemic levels of the other active agent. This ambiguity could be addressed by amending the claim to recite “an active agent” only in line 1, and identifying the active agent as “a histamine or salt thereof” directly after the recitation of “an active agent”, if this is the meaning intended by Applicant.
Claim 2 recites a limitation on the amount of histamine or salt thereof in the patch in terms of mg/mL without identifying what the volume refers to. The volume could be of the top or middle layer or the entire patch. As such, one having ordinary skill cannot unambiguously ascertain the amount of drug that must be present in the claimed invention.
Claim 4 recites the transitional phrase “comprising” followed by a list of substances, implying that each of these substances must be present in the patch; however, the phrase “and mixtures thereof” is recited at the end of the claim, implying that the claim reads on patches containing only one of the listed substances. The rejection could be overcome by reciting traditional Markush language to indicate that the claim reads on patches containing only one of the listed substances. See MPEP 2173.05(h). In the interest of compact prosecution, the examiner has interpreted the claim to read on patches containing only one of the listed substances.
Claim 7 recites the limitation "the release liner and top liner" in line 1. There is insufficient antecedent basis for this limitation “the … top liner” in the claim.
Claims depending from rejected claims have also been rejected because they incorporate all of the limitations of the claims from which they depend, but fail to resolve the indefiniteness concerns outlined above.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 12 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Specifically, claim 12 fails to include all the limitations of the claim upon which it depends. Claim 1 requires three layers including a drug-in-adhesive layer. Claim 12 recites the limitation that the patch can be a single-layer drug-in-adhesive patch or a reservoir patch, which both embrace patches that do not include some of the layers required by claim 1. Therefore, claim 12 embraces scope outside of the scope of claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claim 23 is rejected under 35 U.S.C. 103 as being unpatentable over Tavares et al. US 20030035828; publication date: 02/20/2003) in view of Prausnitz et al. (US 20080045879; publication date: 02/21/2008).
Tavares discloses a device for transdermal delivery (title) comprising a reservoir and active drug/adhesive matrix formulation containing loratadine (i.e. an antihistamine that acts by modulating the histamine receptor; see page 5 of the instant specification which states “the histamine receptor modulator is selected from the group consisting of diphenhydramine, loratadine,…”). The formulation is formed by dissolving the loratadine with ethanol and water as well as the gelling agent, Kucel HF, dispersing additional loratadine in an adhesive matrix, coating a polyethylene membrane with the drug/adhesive matrix and then drying the gel containing the loratadine onto the loratadine/adhesive matrix coating (Example 15: 0220 – 0224). Tavares discloses further that in reservoir devices, an exemplary construction includes a backing layer, an active drug and optional permeation enhancing solvent gel, a membrane, a skin contact adhesive layer, and a protective release coated liner film (0115). The polyethylene film is considered to be the backing in the above example, and for storage prior to application to protect the formulation, it would have been prima facie obvious to cover the hydrogel reservoir-side of the device with a release liner as described in para 01150, because such was contemplated by Tavares.
Thus, in example 15A in view of the broader disclosure, Tavares discloses a transdermal drug delivery system for delivering at least one drug into a tissue membrane of a subject, the system comprising a patch, wherein the patch comprises a top layer comprising an adhesive, a middle layer comprising at least one drug, and a bottom layer, wherein the bottom layer comprises a release liner, wherein the at least one drug is a histamine receptor modulator.
Tavares does not disclose an applicator configured to supply a drug delivery patch.
Prausnitz discloses that microneedles can increase transport of molecules, including antihistamines, across skin or other membranes (0050).
It would have been prima facie obvious to supply Tavares’s patch with a microneedle device (i.e. an applicator, see page 5 of the instant specification). The artisan of ordinary skill would have been motivated to do so in order to increase drug delivery to the body and had reasonable expectation of success because the microneedle device was known to accomplish this as of the instant effective filing date.
Claims 1-10, 12, 23, and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Hellstrand et al. (US 6221893; issue date: 04/24/2001) in view of Cantor et al. (US 9144671; issue date: 09/29/2001).
With regard to claims 1 and 23, Hellstrand discloses administering a therapeutically effective amount of histamine, histamine dihydrochloride, histamine phosphate, or other salts (col 7, lines 1-4) to a patient through use of a transdermal patch (claim 13). Dosing may be optimized by controlled release products (paragraph bridging col 16-17). Hellstrand describes transdermal patches as having “steady state reservoirs sandwiched between an impervious backing and a membrane face” that can be used with or without penetration enhancers such as DMSO, sucrose fatty acid esters with a sulfoxide or phosphoric oxide, eugenol, or azone (col 18).
Thus, Hellstrand discloses a patch for delivering an active agent to a subject in need thereof, comprising a reservoir sandwiched within other layers (i.e. that patches can have multiple layers), wherein the active agent is a histamine or salt thereof.
Hellstrand does not disclose the particular arrange of layers required by instant claims 1 or 23.
Cantor discloses a transdermal adhesive patch with a microneedle array (i.e. a patch and an applicator; title, abstract) for enhancing drug delivery from a transdermal patch into the skin (col 1, lines 25-53). The patch can contain a backing and a matrix coupled to the backing (col 2, lines 11-20), which may be a hydrogel capable of swelling and retaining an aqueous liquid configured to achieve a desired delivery rate of the active ingredient (i.e. the hydrogel matrix layer comprises active agent; col 5, lines 9-14). The active ingredient may be present in the matrix and also in the skin contact adhesive layer (col 13, lines 13-16). The type of active agent that can be delivered is highly varied (col 13, line 16-col 14, line 10). The patch also may contain a release liner (also referred to in the disclosure as a release layer; col 4, lines 25-30) configured to cover the drug releasing components of the patch during storage and shipment that is easily removed during application (col 7, lines 14-20).
It would have been prima facie obvious to combine a drug-in-adhesive layer containing histamine and a hydrogel matrix reservoir containing histamine in the arrangement required by the instant claims because this arrangement was a known means of achieving transdermal drug delivery as of the instant filing date. This would merely have been combining prior art elements according to known techniques to yield predictable results (see MPEP 2143(I)(A)). One having ordinary skill would have expected the histamine, or salt thereof, to have been released from the patch at a rate that combines the release through the adhesive matrix and the hydrogel reservoir that reflects the combined individual release rates of these components. Additionally, it would have been obvious to cover the side of the patch that adheres to the skin with a release liner, as described by Cantor, in a patch to deliver histamine transdermally as described by Hellstrand in order to protect the adhesive layer during storage and shipping, leaving it ready for application and adhesion on removal of the release liner. The skilled artisan would have had reasonable expectation of success because this was routine practice as of the instant effective filing date.
With regard to claim 2, Hellstrand discloses that preferably, the histamine is injected, infused, or released into the patient at a rate of from 0.025 – 0.2 mg/min(col 18, line 39), or 0.4 – 10 mg/day (col 10, line 20), reaching circulating blood histamine concentration of at least 0.2 mmol/L (col 10, lines 24-26). Hellstrand states that the dose can be optimized (col 16, line 65), that the histamine or salt thereof can be delivered via transdermal patch, and Cantor describes various known arrangements of transdermal patches for achieving transdermal delivery, as described above. It would have been a matter of routine to optimize the amount of drug that must be present in the patch, as well as the release rates from the reservoir and adhesive to achieve desired delivery after disrupting the stratum corneum with the microneedle device disclosed by Cantor (see MPEP 2144.05).
With regard to claims 3-6, as described above, the patch rendered obvious by Hellstrand/Cantor comprises a hydrogel matrix carrier, and this would contain water.
With regard to claim 7, the release liner may be polyester or polyethylene (col 15, lines 59-61 and col 16, line 1) and the backing (i.e. the top liner as recited in the instant claims) may be polyethylene or polyester (col 11, lines 12-18).
With regard to claim 8, Cantor provides guidance on the thickness of the various layers (e.g. col 14, lines 54-60). This would provide one of ordinary skill a starting point to optimize the amount of reservoir and adhesive required to hold the desired dose of histamine or salt thereof, and also the comfort or other physical requirements of the patch, such as strength. See MPEP 2144.05(II).
With regard to claims 9 and 10, as noted above, Hellstrand discloses the patches may contain penetration enhancers such as DMSO, sucrose fatty acid esters with a sulfoxide or phosphoric oxide, eugenol, or azone, which the examiner considers to fall within the scope of the terms “permeation enhancing agent” and “absorption enhancer” recited in the instant claims.
With regard to claim 12, The patch of Hellstrand/Cantor is at least a reservoir patch, a drug-in-adhesive multilayer patch, and a microneedle patch, as described above.
With regard to claim 28, as detailed above the patch it would have been obvious to formulate the patch for delivery of histamine or a salt thereof.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Hellstrand et al. (US 6221893; issue date: 04/24/2001) and Cantor et al. (US 9,144,671; issue date: 09/29/2001) as applied to claims 1-10, 12, 23, and 28 above, and further in view of Deasy et al. (US 20130085015; publication date: 04/04/2013) and Rigby et al. (US 2002/0077337; publication date: 06/20/2002).
The relevant disclosures of Hellstrand and Cantor are set forth above. Neither reference discusses the pH of the composition.
Deasy, in the analogous art of transdermal administration of bioactive agents (title), discloses that pH of an aqueous vehicle [such as the hydrogel of the Hellstrand/Cantor patch] can affect the permeation of a weakly acidic or basic drug (0132).
Rigby discloses that histamine is a basic amine (0007).
It would have been prima facie obvious to adjust the pH of the Hellstrand/Cantor patch as a means to optimize the release rate of histamine from the patch to achieve the target plasma concentrations described by Hellstrand because this was a recognized result-effective variable as of the instant effective filing date. See MPEP 2144.05(II).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KATHERINE PEEBLES whose telephone number is (571)272-6247. The examiner can normally be reached Monday through Friday: 9 am to 3 pm.
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/KATHERINE PEEBLES/Primary Examiner, Art Unit 1617