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 .
Priority
This Application is a 371 of PCT/JP2022/032606, filed Aug. 30, 2022, and claims foreign priority to JP2021141253 and JP2022068967, filed Aug. 31, 2021 and Apr. 19, 2022 in Japan, respectively.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on Jan. 9, 2026; Dec. 1, 2025; May 18, 2025; and Jan 1, 2023 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Status
Claims 1-13, 18-21, and 30-45 are currently pending and subject to examination.
Claim Rejections – 35 USC § 112(d)
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.”
Claims 20-21, 40-41, and 44-45 are 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.
Claims 20-21, 40-41 and 44-45 fail to further limit the subject matter of the claims upon which they depend. The independent claims 19, 39 and 43 do not require that the compound is administered to a subject in need of treatment. They read on administering a dose of the compound to a mammal (the specification uses therapeutically effective amount as synonymous with dose (p. 71)). The mammal does not need to be afflicted with any particular condition, and the preamble just lists effects which may or may not be desired or appreciated (MPEP § 2111.02(II)). Claims 20-21, 40-41 and 44-45 attempt to further limit the preamble, but the preamble is not limiting to the method and therefore claims 20-21, 40-41 and 44-45 are not further limiting to the independent claims 19, 39 and 43.
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 § 112(a) – Enablement
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 18-21 and 38-45 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 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.
In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a), the Federal Circuit developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors to assess whether any necessary experimentation required by the specification is “reasonable” or is “undue.” Consistent with Amgen Inc. et al. v. Sanofi et al., 598 U.S. 594, 2023 USPQ2d 602 (2023), the Wands factors continue to provide a framework for assessing enablement in a utility application or patent, regardless of technology area. See Guidelines for Assessing Enablement in Utility Applications and Patents in View of the Supreme Court Decision in Amgen Inc. et al. v. Sanofi et al., 89 FR 1563 (January 10, 2024). These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The Breadth of the Claims
The claims at issue are directed towards methods of inhibiting NLRP3 inflammasome, or treating or preventing a disease selected from the group consisting of multiple sclerosis, inflammatory bowel disease, arteriosclerosis, Cryopyrin-associated periodic syndrome, nonalcoholic steatohepatitis, gout, ischemic heart disease, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and traumatic brain injury, comprising administering a therapeutically effective amount of the compound of claim 1 or a compound according to claims 30-35, to a mammal.
The term at issue is “therapeutically effective amount.” One of ordinary skill in the art would not know, based on the Applicant’s disclosure, what is a therapeutically effective amount of the compound to achieve the desired result without extensive experimentation. Claim 1 encompasses potentially thousands of compounds. Mammals encompass thousands of species. NLRP3 mediated diseases encompass many diverse conditions. The therapeutically effective amount would have to be determined for each compound, each species, each route of administration and each condition. This issue is particularly acute for claims 18, 38, and 42, which do not require that any particular condition is treated.
The Nature of the Invention and the Level of One of Ordinary Skill in the Art
Applicant’s claimed invention is directed towards pharmaceutical compounds for inhibiting NLRP3 and associated conditions. Those of ordinary skill in the art would understand and practice science related to drug development, immunology, and cellular signaling, to name a few.
The Amount of Guidance and the Existence of Working Examples
In the Background of the Invention (p. 1-11), Applicant discusses NLPR3 and its mechanism of action in mediating inflammation by stimulating the production of pro-inflammatory cytokines. Applicant discusses that hyperactive NLPR3 is implicated in diverse conditions such as multiple sclerosis (MS), chronic kidney disease (CKD), inflammatory bowel disease (IBD), myocardial infarction, cryopyrin-associated periodic syndrome (CAPS), nonalcoholic steatohepatitis (NASH), gout, rheumatoid arthritis, contact dermatitis, dry eye, systemic lupus erythematosus, systemic juvenile idiopathic arthritis, adult-onset Still’s disease, Schnitzler syndrome, Behcet’s disease, lung cancer, psoriasis, Alzheimer’s disease, depressive disorder, autism spectrum disorder (ASD), Parkinson’s disease, and sepsis to name a few.
In the Summary of the Invention (p. 18-48) Applicant presents the compound of formula I, enumerates uses of the compounds of formula I, and describes pharmaceutical composition comprising the compound of formula I. In the Description of Embodiments (p. 48-121), Applicant provides certain general definitions, provides a list of embodiments of the compounds, provides methods of synthesis of the compounds and provides literal support for certain of the claims. Notably, Applicant defines therapeutically effective amount in the following way as synonymous with just administering a dose:
While a dose (herein sometimes referred to as “a therapeutically effective amount”) may vary depending on subjects, diseases, symptoms, dosage forms, routes of administration and the like, for example when it is administered orally to an adult patient the dose of a compound of Formula [I] or a pharmaceutically acceptable salt thereof, or a compound of Formula [IA] or a pharmaceutically acceptable salt thereof as the active ingredient ranges generally from about 0.01 mg to 1 g per day, which may be administered once to several times in a divided amount.
p. 71.
In the Examples (p. 121-210), the Applicant provides Exemplary compounds of formula I, and describes an assay for the inhibition of NLPR3 inflammatory activity and the results of the assay for each exemplary compound. The IC50 for each compounds ranges from potent, e.g. 7.1 nM for compound 240, to inactive, e.g., compound 29 only exhibits 2% inhibition at 24 µM, with most compounds having moderate potency – double digit nanomolar to single digit micromolar (Table 3). Applicant describes two hypothetical formulation examples comprising 30 mg or 10 mg of a compound of Example 1.
The State of the Prior Art and the Level of Predictability in the Art
As with many biotechnology inventions, the relevant art is multidisciplinary. Applicants’ claimed invention related to a number of core technologies and scientific concepts including immunology, oncology, neurology and neuroscience, cellular signaling, molecular biology, pharmacology as well as others. Accordingly, those of skill in the art have a firm understanding of the inter-relationship between each of the disciplines and the functional and physical limitations of the invention.
Taken as a whole, the relevant art suggests that Applicant had not reasonably enabled the claimed invention at the time the application was filed. A recent review (Zhang et al. (International Journal Of Molecular Medicine, 51: 35, 2023) on NLRP3 inflammasome mediated therapies identifies this pathway as a promising therapeutic target for the treatment of a variety of conditions. They note “However, their practical application in treating these diseases is limited because of insufficient clinical research.” (p. 11). They describe that certain structurally unrelated NLRP3 inhibitors have been administered to patients with various conditions in clinical trials at doses of 300 to 800 mg/day, with varying results for efficacy.
The Quantity of Experimentation
The Applicant does not administer the compounds to any animals, or provide a means for one of ordinary skill in the art to determine the therapeutically effective amount of the compound for the treatment of the claimed conditions. The Applicant provides only a very broad range for the therapeutically effective amount of the compound, which would vary based on the species of mammal, the symptoms to be treated, and the condition the subject is suffering from. The Applicant also claims a broad range of species, which differ greatly in their potency. The prior art does not demonstrate that NLRP3 inhibitors are effective in treating any condition – there are no FDA approved NLRP3 inhibitors. Based on the art cited above, the unresolved issues in the relevant art, the amount of non-routine experimentation required would be high. Accordingly, in order to enable the invention as claimed, one of ordinary skill in the art would have to resort to undue experimentation.
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.
Claim(s) 1-7, 13 and 18-21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Cohen et al. (European Journal of Medicinal Chemistry, Volume 95, 5 May 2015, Pages 16-28) in view of Chen et al. (WO2017205766A1) (of record, IDS 12/01/2023, ID no. 6).
Claim 1 is directed towards a compound of formula [IA]:
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156
270
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.
Cohen teaches compounds similar to formula [IA]:
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340
400
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Cohen, Fig. 4, p. 22.
These compounds differ from formula [1A] in that they have a thienopyrimadin-4-one core instead of pyrazolopyrimidine-4-one core. One of ordinary skill in the art, however, would have a reasonable expectation of success to replace the thienopyrimadin-4-one for pyrazolopyrimidine-4-one because these heterocycles are commonly known in the art to have similar properties.
For example, Chen teaches that these compounds have similar properties and both function as kinase inhibitors:
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185
587
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171
593
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Chen, Specification, p. 118;
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512
678
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Chen, Specification, p. 2.
Therefore, claim 1 was prima facie obvious at the time of filing.
Claims 2-7 read on the compounds of Cohen wherein the thienopyrimadin-4-one is replaced with pyrazolopyrimidine-4-one and as such these claims were prima facie obvious for the reasons given in the rejection of claim 1.
Claim 13 is directed towards a pharmaceutical composition comprising the compound, or a pharmaceutically acceptable salt thereof, according to any one of claims 1-12. One of ordinary skill in the art would have a reasonable expectation of success to formulate a pharmaceutical composition comprising the compound according to any one of claims 1-12 because Chen suggests pharmaceutical compositions comprising salts of similar compounds. Chen teaches that compounds 1a, 8a and 20a were administered intraperitoneally to lab mice at a dose of 2.5mg/day BID, with normal saline serving as a vehicle control (Chen, p. 26, col. 2, 4.2.7).
Therefore, claim 13 was prima facie obvious at the time of filing.
Claims 18-21 read on administering a therapeutically effective amount of the compound to a mammal. One of ordinary skill in the art would have a reasonable expectation of success to administer a therapeutically effective amount of the compound to a mammal because Chen teaches to administer a therapeutically effective amount of similar compounds to a mammal. Chen teaches that compounds 1a, 8a and 20a were administered intraperitoneally to lab mice at a dose of 2.5mg/day BID, with normal saline serving as a vehicle control (Chen, p. 26, col. 2, 4.2.7). This is a dose of 0.1 mg/day (20 g = 0.02 kg* 5mg/kg/day = 0.1 mg/day) which falls within the general range given in the specification of 0.01 mg to 1 g per day administered in a divided amount (Specification, p. 71).
Therefore, claims 18-21 were prima facie obvious at the time of filing.
Claim Objections
Claims 8-12 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Allowable Subject Matter
Claims 30-37 are allowable subject matter.
Conclusion
Claims 1-7, 13, 18-21 and 38-45 are rejected. Claims 8-12 are objected to as being dependent upon a rejected base claim. Claims 30-37 are allowable subject matter.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HEATHER DAHLIN whose telephone number is (571)270-0436. The examiner can normally be reached 9-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Lundgren can be reached on (571) 272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/HEATHER DAHLIN/Examiner, Art Unit 1629
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