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 .
DETAILED ACTION
This Office Action is responsive to the Response to Election/Restriction filed 02/02/2026.
The preliminary amendment filed 10/10/2024, amended claims 1, 3-4, 6, and 15-18, cancelled claims 20-24, and added claims 31-37.
Claims 1-19 and 25-37 are pending.
Priority
This application claims the following priority:
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Information Disclosure Statement
The information disclosure statement filed 12/16/2024 fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. It has been placed in the application file, but the information referred to therein has not been considered.
None of the NPL references were provided.
Election/Restrictions
Applicant’s election without traverse of Group I, and the following as a species of the compound,
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, in the reply filed on 02/02/2026, is acknowledged.
In the course of the search, the entire genus of instant formula (I) was searched, and found to be allowable. As such, the election of species requirement is hereby withdrawn.
Claims 1-19, 25, and 31-37 are directed to an allowable product. Pursuant to the procedures set forth in MPEP § 821.04(B), claims 26-30, directed to the process of using an allowable product, previously withdrawn from consideration as a result of a restriction requirement, are hereby rejoined and fully examined for patentability under 37 CFR 1.104.
Because all claims previously withdrawn from consideration under 37 CFR 1.142 have been rejoined, the restriction requirement as set forth in the Office action mailed on 12/09/2025, is hereby withdrawn. In view of the withdrawal of the restriction requirement as to the rejoined inventions, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Claims 1-19 and 25-37 are examined on the merits herein.
Claim Rejections - 35 USC § 112(a)-Scope of 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 26-30 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of inhibiting NLRP3 inflammasome activation by administering to a patient in need thereof, a therapeutically effective amount of a compound of formula (I) wherein R2 is aryl, and one of T, U, V, or W is N, or V and U are both N, does not reasonably provide enablement for a method of treating or preventing a disorder, condition, or diseases that is responsive to the inhibition of NLRP3 in a patient in need thereof comprising administering of a therapeutically effect amount of a compound of formula (I) . The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The criteria for enablement set out in the In re Wands, MPEP 2164.01(a), considers the following factors:
Breadth of the Claims
Independent claim 26 is directed toward a method of treating or preventing any disorder, condition, or diseases that is responsive to the inhibition of NLRP3 by administering any compound of formula (I):
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.
As such, the breadth of the claim is great.
Level of Skill in Art
The level of skill in the art is a clinician or a scientist with PhD.
State of the Prior Art
WO 2009/035568 (IDS of 12/16/2024) teaches structurally similar compounds,
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, such as
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(pg. 79) for the treatment of tumors (pgs. 83-85, 91, claims 1-5, 33-35).
GB2528298 (IDS of 12/16/2024) teaches structurally similar compounds,
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, such as
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(pgs. 12-13), for the treatment of cancer (pgs. 44-45, claims 1-3, abstract).
WO2018/080216 (IDS of 05/06/2025) teaches structurally similar compounds,
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, such as
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(pg. 56), for the treatment of cardiovascular diseases (pgs. 63, 72 claims 1, 14).
As such, while the prior art teaches structurally similar compounds, it does not teach compounds of formula (I), and does not teach these compounds for the treatment of any disorder, condition or disease that is responsive to the inhibition of NLRP3.
The prior art teaches these structurally similar compounds for the treatment of cancer and cardiovascular disease, two specific classes of disease.
Predictability in the Art
Zhang (Inhibitors of the NLRP3 inflammasome pathway as promising therapeutic candidates for inflammatory diseases, published 2023, PTO-892) teaches the aberrant activation of the NLRP3 inflammasome has been linked to various inflammatory diseases, such as atherosclerosis, ischemic stroke, Alzheimer’s disease, diabetes mellitus, and inflammatory bowel disease. Therefore, the NLRP3 inflammasome has emerged as a promising therapeutic target for inflammatory diseases (abstract, introduction).
Zang teaches that inhibitors of the NLRP3 inflammasome pathways can target different parts of the pathway (pgs. 6-9).
Zang teaches that the treatment efficacy of NLRP3 inhibitors in inflammatory diseases has been largely documented in animal and cellular experiments, but that their practical application in treating these diseases is limited because of insufficient clinical research. Zang teaches that only a handful of NLRP3 inhibitors, i.e., Tranilast, OLT1177, NAC, DMF, and disulfiram, have been tested and found useful for the treatment of a few diseases, such as diabetic nephropathy, coronary artery diseases, and ulcerative colitis.
The instant specification provides the EC50 value for the inhibition of NLRP3 inflammasome activation for species of instant formula (I). Though examples 1-13, 16-19 and 22-57 share the same core structure, the EC50values vary from 5 to 3966. As such, it is impossible to determine a predictable structure-function relationship between the inhibition of the NLRP3 inflammasome and compounds of formula (I), in view of the great variation of EC50 values in compounds with the same core structure.
As such, the treatment of disorders, conditions, and diseases that are responsive to the inhibition of NLRP3 by administering NLRP3 inhibitors, such as the compounds of instant formula (I), is unpredictable.
Working Examples
The instant specification provides EC50 values for the inhibition of NLRP3 inflammasome activation in a biological assay, of exemplified compounds 1-57. The EC50 values vary from 5-1851nm. It is noted that compound numbers 14-15 and 20-21 fall outside of the scope of instant formula (I). Out of the 54 remaining compounds within the scope of instant Formula (I), they all depict an aryl group at R2 substituted with two Rb groups, and 51 of the compounds depict a single nitrogen in the T-U-V-W ring, and two of the 54 compounds contain two adjacent nitrogen atoms in the T-U-V-W ring. Thus, the scope of the tested compounds is limited in view of the genus of Formula (I).
As such, the working example is not commensurate in scope with the instant method claims. Moreover, while the working example provides EC50 values of inhibition of NLRP3 inflammasome activation, it does not provide data for the treatment of any diseases.
Direction and Guidance
In view of the lack of working examples showing the treatment of any diseases, the state of the prior art which does not teach the instant compounds in methods of treating or preventing conditions or diseases responsive to the inhibition of NLRP3, and the unpredictability of the art, as taught by Zhang, the instant specification does not provide sufficient direction or guidance to use the invention as instantly claimed.
Quantity of Experimentation
The amount of experimentation required to determine which compounds of Formula (I) treat or prevent which disorders, conditions, or diseases that are responsive to the inhibition of NLRP3, would be astronomical, amounting to invention, and not development; this is an undue amount of experimentation.
Thus, while being enabling for a method of inhibiting NLRP3 inflammasome activation by administering to a patient in need thereof, a therapeutically effective amount of a compound of formula (I) wherein R2 is aryl, and one of T, U, V, or W is N, or V and U are both N, the specification does not reasonably provide enablement for a method of treating or preventing a disorder, condition, or diseases that is responsive to the inhibition of NLRP3 in a patient in need thereof comprising administration of a therapeutically effect amount of a compound of Formula (I) .
Allowable Subject Matter
Claims 1-19, 25 and 31-37 are allowed.
The closest prior art is GB2528298 (published 2016, IDS of 12/16/2024), which teaches compounds of formula:
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, such as
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(pgs. 12-13), for the treatment of cancer (pgs. 44-45, claims 1-3, abstract).
The reference does not teach the piperidine ring as unsubstituted or as substituted with one to six substituents selected from Ra:
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, which is a distinct feature of the instantly claimed compound.
Galeta (Single-Step Formation of Pyrimido[4,5-d]pyridazines by a Pyrimidine-Tetrazine Tandem Reaction, published 2016, PTO-892), is also the closest prior art.
Galeta teaches the following compounds:
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,
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(pgs. S14 and S16).
However, the compounds of instant Formula (I) only teach the following R6 groups at “U,” when U is “CR6:”
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. R6 cannot be a “SEt” group as depicted by Galeta, and there is no motivation in Galeta or the prior art to substitute the “SEt” group of Galeta with any of the groups defined as instant R6.
Therefore, the prior art neither anticipates nor reasonably makes obvious the claimed invention and therefore, the claimed invention is deemed novel and unobvious over the
prior art.
Conclusion
Claims 1-19, 25 and 31-37 are allowed.
Claims 26-30 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAUREN WELLS whose telephone number is (571)272-7316. The examiner can normally be reached M-F 7:00-4:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James (Jim) Alstrum-Acevedo can be reached on 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LAUREN WELLS/Examiner, Art Unit 1622
Prosecution Insights