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 .
Request for Continued Examination (RCE)
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 2/18/26 has been entered.
Status of the Claims
Claims 7-9, 12 are pending.
Any claim rejection not reiterated in this action is withdrawn.
Priority
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Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
A certified translation of the priority document was made of record 7/11/2025.
New Claim Rejections - 35 USC § 112(a)
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.
Claims 7-9, 12 are rejected under 35 U.S.C. 112(a) as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Claim 7 is to a “method for treating and/or preventing itch, comprising administering to a subject in need thereof an effective amount of a compound [of] formula (I)” with R1 to a genus of substituents including alkenyloxy, haloalkoxy, or substituted phenyl, and R2 of the same scope as R1 with the addition of alkyl. Claim 9 is also for treating itch with a compound of formula (II) with R as substituted phenyl, pyrazolyl, aralkyl groups. The instant disclosure does not contain sufficient information regarding the subject matter of the claims as to enable one skilled in the pertinent art to make and use the claimed invention upon consideration of the factors set forth in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1998), as follows. See also MPEP § 2164.01(a) and § 2164.04.
The breadth of the claims – claims 7 and 9 are to a method of “treating and/or preventing itch” by administering a large genus of compounds each claim in excess of millions of compounds.
The nature of the invention – the nature of the claimed invention is to affect treating and preventing by antagonism of PAC1 receptor in a patient.
The state of the prior art – the therapeutic approach of PAC1 antagonist treating or preventing itch is unknown and Applicant cites no known successful demonstrations of the approach.
The level of one of ordinary skill – the level of skill in the art is high as evidenced by Bergenby et al. (WO 2017/029202).
The level of predictability in the art – the art is highly unpredictable due to the complex nature of the disease and the mode of action of the compounds used. The particular art is also unpredictable because there is no known or articulated rationale for how the compounds are alleged to induce antipruritic effect. Furthermore, as evidenced by Takasaki et al. (J Pharmacol Exp Ther 365:1–8, April 2018, 11 pages) after screening more than 4 million compounds only two showed notable levels of pharmacologic activity.
The amount of direction provided by the inventor – the primary guidance provided by the inventor is given in the Examples evaluating mouse models of itch through administering compounds PA-8, compound 2j and 2o relating to claim 7 and compounds PA-9 and 3d relating to claim 9. It is noted that none of these compounds are within the scope of the claims, and PA-8 and PA-9 are taught in the prior art. There is no apparent correlation between the structure of the compounds within the claims and those tested. This lack of supporting data and explanation would cause one of skill in the art to question whether the examples support enablement of the claims. Regarding dosing and effective amounts, all of the guidance provided regarding dosing and effective amounts is completely generic without any specificity related to response curves or any experimental data of compounds within the claims.
The existence of working examples – there are no working examples of the claimed compounds treating disease and as indicated above, there are no known use of PAC1 antagonists for treating or preventing itch.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure – given the high level of unpredictability in the art, the lack of working examples, and the limited guidance provided in the examples, there would be a tremendous amount of experimentation required before one of skill in the art could treat itch in a subject.
In view of the specification and evidence of record, one of skill in the art would be required to perform an undue amount of experimentation to test each of the compounds of the claims using an appropriate model select candidates for further development in vivo, perform testing to determine dosing, and finally efficacy testing. Thus, one of skill in the art would be required to start ab initio and develop any compound within the scope of the claims. Such a level of experimentation is undue. Weighing the above factors by a preponderance of the evidence results in the conclusion that the claims are not enabled for treating itch in a subject with the full scope of Formula (I).
Claim Rejections - 35 USC § 103
Claims 7-9, 12 are rejected under 35 U.S.C. 103 as being unpatentable over Kurihara et al. US 11,365,194 B2 in view of :
Seeliger et al. Am. J. Path. 2010, 177, 2563, Atopic dermatitis (eczema) (October 7, 2017),
Mayo Clinic. Retrieved on March 8, 2025 from Internet Archive website: https://web.archive.org/web/20171007012512/https://www.mayoclinic.org/diseases-conditions/atopic-dermatitis-eczema/symptoms-causes/syc-20353273,
Reich A, Szepietowski JC. Clinical Aspects of Itch: Psoriasis. In: Carstens E, Akiyama T, editors. Itch: Mechanisms and Treatment. Boca Raton (FL): CRC Press/Taylor & Francis; 2014. Chapter 4. Available from: https://www.ncbi.nlm.nih.gov/books/NBK200930/ and
Patani et al. (Chem. Rev. 1996, 96, 3147-3176).
Kurihara et al. teach PACAP (Pituitary Adenylate Cyclase - Activating Poly
peptide) mediates pain by acting on PACAP receptors (PAC1, VPAC1 and/or VPAC2). Kurihara 1:61 to 2:9. With the goal of treating pain, Kurihara studied PAC-1 antagonists of formula (I),
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, compounds 2a-u, and formula (II),
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, compounds 3a-r. See, e.g. col. 3-4, 11 and 17.
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Kurihara does not teach treating itching or related skin conditions, such as dermatitis, dry skin or psoriasis and differs from claim 7’s formula (I) by the particular substitutions at R1/R2 (i.e. 2h R2 OMe vs. alkyl or haloalkoxy).
Seeliger teaches “inhibition of this potent neuropeptide [PACAP] and its receptors may be a novel strategy for the treatment of inflammatory skin diseases that have a neurogenic component” (p. 2573 right col.). Psoriasis and atopic dermatitis are examples of such skin diseases. See, e.g., p. 2563 (right col.) and p. 2573 (left col.).
Mayo Clinic teaches that atopic dermatitis is characterized by dry skin and itching (p.1), and Reich teaches that psoriasis is often characterized by itching, which is exacerbated by dry skin (4.2).
Patani teaches bioisosteric replacement of groups in pharmaceuticals which are well-known equivalents in the art. Patani specifically teaches the successful substitution of halogens with a trifluoromethyl group (p. 3172). One of ordinary skill in the art following the teaching of Kurihara would have considered bioisosteres as taught by Patani and had a reasonable expectation of equivalent activity. Thus, one of ordinary skill in the art had a reasonable expectation of success in modifying Kurihara’s compound to a trifluoromethyl at R1/R2.
Since Seelinger teaches treating psoriasis and atopic dermatitis by inhibiting PACAP and its receptors, which include PAC1, and since Kurihara teaches PAC1 inhibitors, a PHOSITA would have found it obvious to use Kurihara’s PAC1 inhibitors for treating psoriasis and atopic dermatitis. A PHOSITA would have had a reasonable expectation that treating these skin conditions would have resulted in a reduction or prevention of some degree of itching and skin dryness associated with such skin conditions, since Mayo and Reich teach that these symptoms are prevalent in psoriasis and atopic dermatitis. Therefore, a PHOSITA would have found it obvious to practice the method of claims 7-14 pertaining to treating/preventing itch associated with psoriasis or atopic dermatitis, comprising administering a compound of formula (I),
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Regarding claims 9 and 12 to formula (II),
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, Kurihara teaches 3n where R is pyrazolyl which is within the scope of the instant claim, and analogously to claim 7 in view of the secondary references one of ordinary skill in the art would have arrived at the claimed invention with a reasonable expectation of success.
Response to Remarks - 35 USC § 103
Applicant argues that the mechanism of pain and itch are completely different. This argument is not persuasive because Kurihara and Seelinger are in the same field of endeavor including relating to the same PACAP pathway. In addition, Seelinger teaches “[a]ntagonists to PACAP function may be beneficial for the treatment of inflammatory skin diseases” (Abstract) and generally for the treatment of skin conditions such as atopic dermatitis, urticara, and rosacea (p. 2573) which clearly suggests the combination of Seelinger with Kurihara’s antagonists of the same receptor.
Applicant cites Liu and Davidson but does not provide the Exhibit or any IDS. Regardless, the points made are to support the assertion that pain and itch have differing mechanism. Even accepting the assertion as true, the particular cited art teaches the PACAP pathway as the mechanism of action in treating inflammatory skin diseases such as atopic dermatitis, urticara, and rosacea such that one of ordinary skill in the art would have had an expectation that the compounds would be effective via the same mechanism in treating the conditions within the scope of the instant claims.
Conclusion
No claim allowed.
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/ROBERT H HAVLIN/Primary Patent Examiner, Art Unit 1626