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 .
Restriction Response
Applicant’s election with traverse of Group I (claims 1-6 and 10-14) in the reply filed on 12/09/25 is acknowledged. The Declaration under 37 CFR 1.130 by Jun Lou (“the 130 Declaration”) to demonstrate that the subject matter disclosed in Lou et al. (WO 2020/135771 A1 – “Lou”) was obtained directly from the inventor of the current application is also acknowledged. Applicant argues that (i) Lou is not prior art, (ii) the “white solid” of compound 172 disclosed in Lou is amorphous and not the same as the crystalline forms of in the pharmaceutical composition of claim 1. Applicant argues that Lou does not expressly or inherently disclose the specific crystalline forms in the pharmaceutical composition of claim 1.
Based on the Applicant’s arguments and the 130 Declaration, the lack of unity of 10/10/25 is withdrawn.
Status of Claims
Claims 1-7 and 9-21 are pending and included in the prosecution.
Priority
This Application is a 371 of PCT/CN2022/098223 filed on 06/10/22. This Application also claims foreign priority to CN 2021 106511369 filed on 06/10/21. Receipt is acknowledged of certified copies of papers submitted under 35 U.S.C. 119 (a)-(d), which papers have been placed of record in the file. Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) an English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e). Failure to provide a translation may result in no benefit being accorded for the non-English application.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 07/19/24 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97 and 1.98. Accordingly, the examiner is considering the information disclosure statement. Please see the attached copy of PTO-1449.
Claim Objections
Claims 1, 2, 6, 9, 11-12, 15-16, and 19 are objected to because of the following informalities:
In claim 1, the term “and” should be added at the end of line 12.
In claim 2, the term “and” should be added at the penultimate line.
In claim 9, lines 3 and 4, one iteration of “further” should be deleted.
Claims 6, 11-12, 15-16, and 19 are objected to because they do not correct the defects of claim 1.
Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 10 is rejected under 35 U.S.C. 101 because the claimed recitation of a use, without setting forth any steps involved in the process, results in an improper definition of a process, i.e., results in a claim which is not a proper process claim under 35 U.S.C. 101. See for example Ex parte Dunki, 153 USPQ 678 (Bd.App. 1967) and Clinical Products, Ltd. v. Brenner, 255 F. Supp. 131, 149 USPQ 475 (D.D.C. 1966).
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.
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 20-21 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.
Instant claim 20 is directed to a method for preventing, curing, treating, or alleviating a disease in animals that is at least partially mediated by P2X3 or related to P2X3 activity or a method for the treatment of pain, pruritus, endometriosis, urinary tract disease, or respiratory disease in a subject in need thereof, comprising: administering the pharmaceutical composition according to claim 1 to the subject. Thus, the method includes “… preventing, curing, … or alleviating …” (emphasis added) which are not described in the instant specification.
The Guidelines for Examination of Patent Applications Under the 35 U.S.C. 112, Paragraph 1, “Written Description” Requirement, published at Federal Register, Vol. 66, No. 4, pp. 1099-1111 outline the method of analysis of claims to determine whether adequate written description is present. The first step is to determine what the claim as a whole covers, i.e., discussion of the full scope of the claim. Second, the application should be fully reviewed to understand how applicant provides support for the claimed invention including each element and/or step, i.e., compare the scope of the claim with the scope of the description. Third, determine whether the applicant was in possession of the claimed invention as a whole at the time of filing. This should include the following considerations: (1) actual reduction to practice, (2) disclosure of drawings or structural chemical formulas, (3) sufficient relevant identifying characteristics such as complete structure, partial structure, physical and/or chemical properties and functional characteristics when coupled with a known or disclosed correlation between function and structure, (4) method of making the claimed invention, (5) level of skill and knowledge in the art and (6) predictability of the art. For each claim drawn to a single embodiment or species, each of these factors is to be considered with regard to that embodiment or species. For each claim drawn to a genus, each of these factors is to be considered to determine whether there is disclosure of a representative number of species that would lead one skilled in the art to conclude that applicant was in possession of the claimed invention. Where skill and knowledge in the art is high adequate written description would require fewer species to be disclosed than in an art where little is known; further, more species would need to be disclosed to provide adequate written description for a highly variable genus.
First, what do the claims as a whole cover? Claim 20 is directed to a method for preventing, curing, treating, or alleviating a disease in animals that is at least partially mediated by P2X3 or related to P2X3 activity or a method for the treatment of pain, pruritus, endometriosis, urinary tract disease, or respiratory disease in a subject in need thereof, comprising: administering the pharmaceutical composition according to claim 1 to the subject. Thus, the method includes “… preventing, curing, … or alleviating …” (emphasis added) which are not described in the instant specification. Claim 21 is directed to the method of claim 20 and recites 3 conditions which are (1) pain, (2) urinary tract disease, and (3) respiratory disease.
Second, how does the scope of the claims compare to the scope of the disclosure? The disclosure mentions “… preventing, curing, … or alleviating …” (emphasis added) ([0092], [0111]-[0112], [0129]), and “… administering a prophylactically … effective amount of the pharmaceutical preparation to a patient” (emphasis added) ([0129], [0138]-[0139]). However, the specification does not present any evidence or embodiment demonstrating prevention, curing or alleviating specific diseases in a specific patient population.
Third, the factors need to be considered.
(1) What was actually reduced to practice?
Clearly, the method of preparing the compound of formula A was reduced to practice (Example 1 – [0219]-[0235]). Example 16 describes the pharmacokinetic analysis of different crystals in animals ([0328]-[0366]). Example 17 describes the preparation of 25 mg and 100 mg coated tablets ([0367]-[0422]). Example 18 describes the investigation of preparation process on stability of crystal form III ([0423]-[0425]). Example 19 describes the dissolution of coated tablets and investigation of crystal changes in API ([0426]-[0427]). Example 20 describes the investigation of tablet stability ([0429]-[0440]). Therefore, the preparation of the compound of formula A and tablets containing the compound of formula A were actually reduced to practice.
(2) Is there disclosure of drawings or structural chemical formulas?
There are structural chemical formulae for the compound of formula A and the preparation thereof. There are drawings showing the amorphous, and crystal forms of the compound of formula A, as well as various test results for the compound. However, there is no disclosure of administering the active compound to any specific patient population, dosing regimen, clinical efficacy studies to show that a particular condition or disease was prevented, cured, or alleviated.
(3) Are there sufficient relevant identifying characteristics disclosed?
There are no identifying characteristics with respect to specific conditions, patient populations, dosages or dosage ranges, or dosage regimens that prevent, cure, or alleviate specific conditions or diseases.
(4) Is there at least one method of making the claimed invention disclosed?
Given the method of preparing the compound of formula A and tablet formulations, one of ordinary skill in the art could easily synthesize the compound and tablet formulations, since only basic organic chemical synthesis and tabletting skills would be needed.
(5) What is the level of skill in the art and what knowledge is present in the art?
The level of skill in the art of treating a disease in animals that is at least partially mediated by P2X3 or related to P2X3 activity or a method for the treatment of pain, pruritus, endometriosis, urinary tract diseases or respiratory diseases is very high, about that of an MD/PhD clinician with several years’ experience in internal medicine.
The following references show the state of the art:
Muccino et al. (Pulmonary Pharmacology & Therapeutics 56 (2019) 75-78 – “Muccino”) teach that gefapixant, a P2X3 receptor antagonist demonstrated efficacy and was generally well tolerated in phase 2 clinical trials in patients with refractory chronic cough (RCC) (Abstract).
Chauret et al. (Journal of Investigative Dermatology, (2019), Volume 139, Issue 9, S232 – “Chauret”) teach that BLU-5937 is a potent P2X3 receptor antagonist that is currently in Phase 2 clinical trial for the treatment of chronic cough, and present evidence that the ATP-induced hypersensitization mediated by P2X3 receptors in cutaneous C-fibers plays a role in chronic itch and that BLU-5937 may represent a novel treatment modality for chronic pruritus (Page S232 - # 106).
White (Medical Principles and Practice 2020;29:501-513) teaches that: “The principles of etiology and natural history of disease are essential to recognizing opportunities for prevention across the illness spectrum Opportunities for prevention arise at every stage in the process, and three main levels are described: primary, secondary, and tertiary. Prevention strategies include health promotion focused on determinants, clinical prevention to reduce modifiable risk factors, case finding, screening, and addressing functional outcomes relevant to quality of life; the importance of preventing errors is also recognized” (Abstract).
(6) What is the level of predictability of the art?
The level of predictability in this art is very low since the prevention, curing, or alleviation of a particular condition or disease is dependent on numerous factors such as the etiology, patient populations, co-morbidities, dosage of active pharmaceutical ingredient, dosage regimens, administration forms (oral, parenteral etc.), duration of administration, etc.
Thus, having analyzed the claims with regard to the Written Description guidelines, it is clear that the instant specification does not disclose how to prevent, cure, or alleviate the claimed conditions or diseases which would lead one skilled in the art to conclude that applicant was in possession of the claimed invention.
Claim Rejections - 35 USC § 112 (b)
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 3-5, 7, 10, 13-14, 17-18, and 21 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 pre-AIA the applicant regards as the invention.
In claim 3, line 10; claim 4, line 12; claim 5, line 18; claim 7, line 3; claim 13, line 2; claim 14, line 10; claim 17, lines 5, 6, and 7; claim 18, line 7; and claim 21, penultimate line, the term “preferably” renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 10 provides for the use of a pharmaceutical composition, but, since the claim does not set forth any steps involved in the method/process, it is unclear what method/process applicant is intending to encompass. A claim is indefinite where it merely recites a use without any active, positive steps delimiting how this use is actually practiced.
In claim 18, lines 2-4, the parenthetical phrases render the claim indefinite because it is unclear whether the limitation(s) in the parentheses are part of the claimed invention. See MPEP § 2173.05(d). It is recommended that the parentheses be removed.
Regarding claim 18, lines 2-4, the recitations of "e.g." render the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Pertinent Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Chauret et al. (WO 2021/161105 A1 – “Chauret”) is cited as art of interest for teaching P2X3 modulators and the compound of Formula (I), or a pharmaceutically acceptable salt or solvent thereof (Abstract, claims 1-58) and a pharmaceutical composition comprising the compounds. However, none of the compounds taught by Chauret are the same as a compound of formula A as recited in instant claim 1.
Taranto-Montemurro et al. (WO 2025/255215 A1 – “Taranto-Montemurro”) is cited as art of interest for teaching pharmaceutical compositions comprising a P2X3 receptor antagonist (Abstract) which is relicpixant ([0014], [0025], [0084], and claims 3 and 32). Relicpixant is the claimed compound. However, due to the publication date of 11 December 2025 and the priority date of 05 June 2024, Taranto-Montemurro is not available as prior art.
Conclusion
No claims are allowed.
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/ARADHANA SASAN/Primary Examiner, Art Unit 1615