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
Pursuant to the amendment dated 04/02/2026, claim 3 has been cancelled. Claims 19-22, 24-27, and 29-50 have been cancelled previously. 1, 2, 4-18, 23, and 28 are pending.
Claims 13-18 stand withdrawn without traverse.
Claims 1, 2, 4-12, 23, and 28 are under current examination.
All rejections not reiterated have been withdrawn.
Information Disclosure Statement
The information disclosure statement filed 04/02/2026 fails to comply with the provisions of 37 CFR 1.98(a)(4) because it lacks the appropriate size fee assertion. It has been placed in the application file, but the information referred to therein has not been considered as to the merits.
Claim Objections
Claim 23 is objected to because of the following informalities: Claim 23 repeats the exact phrase “wherein the at least one drug is a histamine receptor modulator” in lines 8 and 9. Amending the claim to delete one instance would improve the readability.
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, 2, and 4-12 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 "an active agent" in line 1 and again 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. Although histamine is clearly the active agent of line 4, 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. That is to say, the claim does not clearly identify whether the active agent in line 1 must also be histamine or whether it may be a different active substance. 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 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.
Response to Arguments
Applicant's arguments filed 04/02/2026 have been fully considered but they are not persuasive. On pages 5-6, Applicants argue that the amendment to the claims have addressed the indefiniteness rejections; however, claims 4 and 7 have not been amended and the amendment to claim 1 introduces language that is similarly indefinite to the previous claim language, as detailed in the rejection 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 28 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 28 fails to further limit the claim upon which it depends. Claim 28 recites wherein the histamine receptor modulator is histamine, a histamine salt, or a combination thereof; however, the amendment to the claims filed 04/02/2026 has introduced this limitation into claim 23, from which claim 28 depends. Thus, claim 28 does not further limit claim 23.
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.
Claims 1, 2, 4-10, 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). The examiner points out that the substance histamine activates each of H1, H2, H3, and H4.
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 arrangement 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 (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 an 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 reflects release from the hydrogel reservoir. 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).
Response to Arguments
Applicant’s arguments, filed 04/02/2026, traversing the rejection over Tavares and Prausnitz are moot as this rejection has been withdrawn in view of the amendment to the claims requiring histamine to be present in the patch of claim 23.
Applicant's arguments filed 04/02/2026 traversing the rejection over Hellstrand in view of Cantor and the rejection over Hellstrand in view of Cantor, Deasy, and Rigby have been fully considered but they are not persuasive:
On page 8, Applicant argues that Hellstrand and Cantor fundamentally teach away from the proposed combination. Hellstrand is directed to systemic administration of histamine to maintain stable, high blood levels for treating malignancies or viral infection and Cantor teaches a microneedle patch. Applicant argues that avoiding skin irritation is a well known challenge in transdermal delivery, that histamine can cause irritation, and that delivering histamine into the microwounds created by Cantor’s microneedles would lead to profound localized dermatitis, exacerbating the inflammatory response. Applicant concludes that this constitutes a teaching away.
This argument is unpersuasive on several levels: Firstly, Hellstrand claims a patch for delivery of histamine, therefore transdermal delivery via patch is incontrovertibly part of Hellstrand’s invention. When the reference relied on expressly anticipates or makes obvious all of the elements of the claimed invention, the reference is presumed to be operable. Once such a reference is found, the burden is on applicant to rebut the presumption of operability. In re Sasse, 629 F.2d 675, 207 USPQ 107 (CCPA 1980). See MPEP 2121(I). Cantor is merely cited to provide more detailed information on well-known patch designs as of the instant effective filing date. With regard to the argument that Hellstrand’s purpose is systemic delivery for treatment of malignancy, Applicant is reminded that the claims are directed to a composition of matter, the patch, and not the method for using that patch. The instant claims are rejected under 35 USC 103 because they read on obvious variants of the patch disclosed by Hellstrand. In response to applicant's argument that Hellstrand uses the patch for treating malignancies or viral infection, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). Regarding the allegation that the prior art teaches away from the claimed combination, this assertion is merely speculation on behalf of Applicant. MPEP 2145(X)(D)(1) states that it is improper to combine references where the references teach away from their combination. In re Grasselli, 713 F.2d 731, 743, 218 USPQ 769, 779 (Fed. Cir. 1983); however, in this case, Applicant has not pointed out anywhere that the cited prior art discloses that histamine is incompatible with transdermal delivery and, indeed, the primary reference lists a transdermal histamine patch as part of the claimed invention. Therefore the argument that the references teach away from the claimed invention, a transdermal patch containing histamine, is not persuasive. Applicant has also not provided any other evidence to support the position that one of ordinary skill would under no circumstances have had reason to deliver histamine transdermally. In contrast, examples abound in the prior art of transdermal delivery of histamine, e.g. in allergy testing, a setting where one would seek to induce an allergic response on the skin, or multiple sclerosis treatment (see Gilson et al. Altern Med Rev 1999 Dec;4(6):424-8; abstract only). No additional evidence has been made of record to support Applicant’s assertion that one having ordinary skill would under no circumstances be motivated to formulate histamine in a transdermal patch.
On pages 9-15 Applicant presents an argument that the instant invention possesses unexpected properties sufficient to overcome the obviousness rejection. Applicant describes their discovery of histamine dysregulation during migraine (pages 9-10); describes a method disclosed in the instant specification for selective activation of histamine receptors through multi-segment, time-phased regimen that varies one or more of concentration, volume, and or timing to adjust cellular distribution [not clear what the distribution is of, histamine in the skin?] and receptor contact; describes successive dosing to achieve selective receptor activation including altering sequence of activation; describes observations on histamine levels in migraine patients (pages 10-11); describes an interaction between nerve and mast cells via histamine signaling (page 12); Applicant presents data regarding affinity for histamine of each of H1 - H4 and describes the various different EC50 values etc. of histamine for the different receptors (page 12); reports an observation that a precise receptor modulation profile is achievable at the claimed low concentrations, whereas conventional OTC histamine creams require higher concentrations to achieve a similar profile; presents data regarding a patch “at 0.5 ng” activation of T- and B-lymphocytes/NK cells in “Figure 4” [no specifics of the formulation are discussed other than “0.5 ng”] (page 14); asserts that Hellstrand “requires higher dosages that are significantly higher, potentially by a factor of one million or more” and that this is a difference in kind from the “ultra-low doses” of the instant invention.
On page 10, Applicant cites Gazerani et al. This reference has not been considered on the record by the examiner because it has not been properly cited in an IDS. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office.
The data presented on pages 9-14 does not appear to have been presented in the specification of the as-filed application and therefore cannot constitute evidence on the record. As such, Applicant cannot rely on these data to overcome an obviousness rejection with secondary considerations unless properly filed in a declaration or affidavit. See MPEP 716.01(c)(II): Arguments presented by the applicant cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965) and In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984). Examples of statements which are not evidence and which must be supported by an appropriate affidavit or declaration include statements regarding unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the inventor or at least one joint inventor.
In the interest of compact prosecution, the examiner responds here to the data and arguments on pages 9-14:
Please refer to MPEP 716.02(b) which details the burden on Applicant to establish that results in a side-by-side comparison to the closest prior art are unexpected and significant. Specifically, Applicant must establish that differences in results are in fact unexpected and unobvious and are of both practical and statistical significance. Additionally, evidence of unexpected properties must be commensurate in scope with the claims.
Applicant’s arguments on pages 9-14 regarding the dysregulation of histamine in migraine patients, histamine values in migraine patients, an interaction between nerve and mast cells via histamine signaling, affinity of histamine for its receptors, data regarding activation of T- and B-lymphocytes/NK cells, may provide an argument in support of the practical significance of the patch; however, nothing on the record establishes how the limitations in the claim are linked to any of these features. To be of probative value, any secondary consideration must be related to the claimed invention (see MPEP 716.01(b)). In this case, although the patch may be able to mediate some of the phenomena listed by Applicant, no evidence exists on the record that it does any of these things in a surprisingly different way than known prior art transdermal delivery systems, including other histamine patches. If the evidence is to be given substantial weight in the determination of obviousness or nonobviousness, evidence of secondary considerations must be relevant to the subject matter as claimed, and therefore the examiner must determine whether there is a nexus between the merits of the claimed invention and the evidence of secondary considerations. Ashland Oil, Inc. v. Delta Resins & Refractories, Inc., 776 F.2d 281, 305 n.42, 227 USPQ 657, 673-674 n. 42 (Fed. Cir. 1985), cert. denied, 475 U.S. 1017 (1986). The term "nexus" designates a factually and legally sufficient connection between the objective evidence of nonobviousness and the claimed invention so that the evidence is of probative value in the determination of nonobviousness. Demaco Corp. v. F. Von Langsdorff Licensing Ltd., 851 F.2d 1387, 7 USPQ2d 1222 (Fed. Cir.), cert. denied, 488 U.S. 956 (1988). See also Yita LLC v. MacNeil IP LLC, 69 F.4th 1356, 1363, 2023 USPQ2d 667 (Fed. Cir. 2023). In this case, no side by side comparison has been made to the closest prior art and any alleged benefit of the instant invention has not been clearly linked to the claim language. See also MPEP 716.02(e): An affidavit or declaration under 37 CFR 1.132 must compare the claimed subject matter with the closest prior art to be effective to rebut a prima facie case of obviousness. In re Burckel, 592 F.2d 1175, 201 USPQ 67 (CCPA 1979). "A comparison of the claimed invention with the disclosure of each cited reference to determine the number of claim limitations in common with each reference, bearing in mind the relative importance of particular limitations, will usually yield the closest single prior art reference." In re Merchant, 575 F.2d 865, 868, 197 USPQ 785, 787 (CCPA 1978) (emphasis in original). Where the comparison is not identical with the reference disclosure, deviations therefrom should be explained, In re Finley, 174 F.2d 130, 81 USPQ 383 (CCPA 1949), and if not explained should be noted and evaluated, and if significant, explanation should be required. In re Armstrong, 280 F.2d 132, 126 USPQ 281 (CCPA 1960) (deviations from example were inconsequential).
Applicants descriptions of a method disclosed in the instant specification for selective activation of histamine receptors through multi-segment, time-phased regimen that varies one or more of concentration, volume, and or timing to adjust cellular distribution and receptor contact as well as the successive dosing to achieve selective receptor activation including altering sequence of activation and precise receptor modulation do not relate to the claimed invention and no explanations of how the structural limitations recited in the claim achieve these methods or why other prior art patches could not also accomplish the above outcomes have been presented. As discussed elsewhere, there is no nexus between these alleged benefits (noting the claims are directed to a composition of matter) and the language of the claims. See MPEP 716.01(b).
The arguments that the instant invention allows precise receptor modulation profile that is achievable at the claimed low concentrations, whereas conventional OTC histamine creams require higher concentrations to achieve a similar profile as well as the assertion that Hellstrand “requires higher dosages that are significantly higher, potentially by a factor of one million or more” and that this is a difference in kind from the “ultra-low doses” of the instant invention is not the type of conclusive evidence required to establish superior performance over the closest prior art. No actual test has been performed to evaluate the performance of the claimed invention relative to any closest prior art product. Applicant makes mention generically of prior art histamine OTC creams; however, as histamine patches had been proposed in the prior art, a cream is not the correct comparison because it is not the closest prior art. Also, as discussed elsewhere, a general assertion that the claimed patch is superior over OTC histamine creams is not the type of evidence required to overcome an obviousness rejection with a persuasive showing of unexpected results. The examiner also points out that the claims, other than claim 2 and its dependent claim 4 place no limitation whatsoever on amount of histamine and claim 2 allows for as much as 100 mg/mL histamine but also does not specify a dose, therefore there is no nexus between any allegedly superior “ultra-low” dose and the claimed invention. See MPEP 716.02(b), noted above, and 716.01(c). See also MPEP 716.02(e): An affidavit or declaration under 37 CFR 1.132 must compare the claimed subject matter with the closest prior art to be effective to rebut a prima facie case of obviousness. In re Burckel, 592 F.2d 1175, 201 USPQ 67 (CCPA 1979). "A comparison of the claimed invention with the disclosure of each cited reference to determine the number of claim limitations in common with each reference, bearing in mind the relative importance of particular limitations, will usually yield the closest single prior art reference." In re Merchant, 575 F.2d 865, 868, 197 USPQ 785, 787 (CCPA 1978) (emphasis in original). Where the comparison is not identical with the reference disclosure, deviations therefrom should be explained, In re Finley, 174 F.2d 130, 81 USPQ 383 (CCPA 1949), and if not explained should be noted and evaluated, and if significant, explanation should be required. In re Armstrong, 280 F.2d 132, 126 USPQ 281 (CCPA 1960) (deviations from example were inconsequential).
On page 14, Applicant argues that the claims are directed to specific patch structures and concentrations that support the receptor-specific approach described in the preceding pages.
This argument amounts to a general allegation that the claims define a patentable invention without specifically pointing out how the language of the claims achieves this “receptor-specific approach”. To be of probative value, any secondary evidence must be related to the claimed invention; the weight attached to evidence of secondary considerations by the examiner will depend upon its relevance to the issue of obviousness and the amount and nature of the evidence. (MPEP 716.01(b)).
On page 14, Applicant points to fig 6A/B and fig 16 of the instant specification as presenting data to tune receptor engagement across epidermis/dermis/hypodermis rather than target systemic serum levels and asserts that this is not “routine optimization”.
Please see above regarding the burden on Applicant to overcome an obviousness rejection with a persuasive showing of unexpected results. Figures 6A and 6B describe histamine in the skin delivered by patchs containing 2.7 mg/mL and 30 mg/mL histamine, respectively. It is unclear what the unexpected improvement over the prior art is and there is no apparent nexus between any difference between the closest prior art and the instant invention, as claimed. Indeed there does not appear to be any comparison to the closest prior art here. Figure 16 shows a histamine gradient in the various layers of the skin, and there is no link between these data and the limitations recited in the claim. These figures do not appear to be germane to the issues underlying the patentability of the instant claims.
On page 15, Applicant argues that Hellstrand is directed away from Applicant’s migraine focused strategy of normalizing histamine imbalance etc. and Cantor does not teach or suggest Applicant’s specific receptor-selective dosing logic or timed-phase concentration strategy.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., a time-phased dosing strategy) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). In response to applicant's argument that histamine might affect migraine, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
On page 15, Applicant argues that the specification links histamine differences and predicted skin-layer concentration gradients to the claimed approach of administering histamine via transdermal devices at controlled concentrations and through successive dosing to achieve selective receptor modulation and histamine balance restoration.
It is wholly unclear how these arguments support the patentability the claimed histamine patch having a much broader range in amount of histamine only required by claim 2 (and dependent claim 4), or any of claims 1, 5-12, 23, or 28, which do not limit the amount of histamine present and claim standard transdermal patch structures. Additionally, no data links the features of the claimed patch to any of these outcomes (e.g. selective modulation of histamine, histamine balance restoration). Finally, Applicant is reminded that the claims are directed to a product and not an approach of administering (i.e. not a method).
On page 15, Applicant asserts there is a nexus between the claimed concentration ranges [this would only possibly be relevant to claim 2 and dependent claim 4; however even claim 2 does not limit the amount of total histamine in the patch], patch configurations, and time-phased dosing strategy.
The examiner finds no such nexus on the record. The arguments to support Applicant’s assertion of unexpected results consist of mechanistic discussions of how histamine may interact with its receptors, be distributed within the body, and interact with certain cells, but nothing links these putative phenomena to the limitations set forth in the claims. Instead, the claim language describes standard structures used for formulating transdermal patches, and the concentration recited in claim 2 is much broader than any allegedly “ultra-low” dose, allowing up to 100mg/mL concentration and not placing any limitation on the total dose of histamine. To be of probative value, any secondary evidence must be related to the claimed invention. [A]ppellants have the burden of explaining the data in any declaration they proffer as evidence of non-obviousness." Ex parte Ishizaka, 24 USPQ2d 1621, 1624 (Bd. Pat. App. & Inter. 1992). See MPEP 716.02(b) and 716.01(b).
Conclusion
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 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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ali Soroush can be reached at (571)272-9925. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KATHERINE PEEBLES/ Primary Examiner, Art Unit 1617
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