DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined
under the first inventor to file provisions of the AIA .
2. 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.
Election/Restrictions
3. This is an acknowledgment of Applicant’s election of species of Compound 14 on page 118, CNS disease from claim 103 and Parkinson’s disease from claim 104, without traverse, in the reply filed on April 3, 2026.
PNG
media_image1.png
102
151
media_image1.png
Greyscale
4. Applicants’ elected species read on claims 74-76, 78-83, 86, 89-90, 93-95, and 101-104.
5. Claim 87 is withdrawn from further consideration pursuant to 37 CFR1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on April 3, 2026.
6. A prior art search of Applicants’ elected Compound 14 of claim 74 for treating Applicants’ elected “CNS disease” and “Parkinson’s disease” retrieved no prior art. Said search only retrieved the instant application and another reference which filed after the effective filing date of the instant application.
7. A prior art search of the compounds of claim 101 retrieved no prior art.
8. An extended Markush search of claim 74 of the following structure retrieved prior art which maps on genus Formula (Im). Therefore, the Markush search will not be extended unnecessarily to additional species in this Office Action.
PNG
media_image2.png
290
411
media_image2.png
Greyscale
PNG
media_image3.png
337
226
media_image3.png
Greyscale
9. The elected species and extended Markush search read on claims 74-76, 78-83, 86, 89-90, 93-95 and 101-104.
Current Status of 18/574,530
10. This Office Action is responsive to the claims of April 3, 2026.
11. Claims 74-76, 78-83, 86, 89-90, 93-95 and 101-104 have been examined on the merits. Claim 87 is withdrawn.
Priority
12. The instant application is a 371 of PCT/US22/35306, filed 06/28/2022 and claims the benefit of priority to US Provisionals 63320155, filed 03/15/2022 and 63216446, filed 06/29/2021.
13. The effective filing date is 06/29/2021.
14. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
15. The information disclosure statements (IDS) submitted on 9 April 2024, are in
compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure
statement is being considered by the examiner.
Claim Objection
16. Claim 90 is objected to due to the following informality:
Line 2, “R6 is piperdinyl” should read “R6 is piperidinyl”.
Appropriate corrections are required.
Claim Rejections - 35 USC § 112
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.
17. Claims 103-104 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.
Per definition in the Specification (para[0087]), the terms of "treatment" or "treating" or "palliating" or "ameliorating" refer to an approach for obtaining beneficial or desired results including but not limited to therapeutic benefit and/or a prophylact--ic benefit. By "therapeutic benefit" is meant eradication or amelioration of the underlying disorder being treated. Also, a therapeutic benefit is achieved with the eradication or amelioration of one or more of the physiological symptoms associated with the underlying disorder such that an improvement is observed in the patient, notwithstanding that the patient is still afflicted with the underlying disorder. For prophylactic benefit, the compositions are administered to a patient at risk of developing a particular disease, or to a patient reporting one or more of the physiological symptoms of a disease, even though a diagnosis of this disease has not been made.
In short, according to the Specification, “treating” a disease means eradication or amelioration of one or more of the physiological symptoms associated with it ("therapeutic benefit" ) and/or preventing someone from developing a particular disease (“prophylactic benefit”).
It is worth noting that the terms of "treatment" or "treating" or "palliating" or "ameliorating" in the Specification are defined much broader than their conventional meanings. For the purpose of clarity, “alleviate” or “alleviating” are used in the Office Action to substitute “treat” or “treating’ to avoid confusion.
The specification and/or prior art, while being enabling for alleviating a metabolic disease, liver disease, lung disease, central nervous system disease, cardiovascular disease, inflammatory disease or autoimmune disease (from instant claim 103) with compound of Formula (Im), does not reasonably provide enablement for alleviating and/or preventing or eradication of diseases of instant claim 103 and the dependent claim 104, with any compound of Formula (Im). 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.
18. The Wands Factors used in an (scope of) enablement rejection include (per MPEP 2164.01(a)):
1. The breadth of the claims:
The broadest reasonable interpretation (BRI) of instant claim 103 is drawn to a method to alleviate and/or prevent or eradicate metabolic disease, liver disease, lung disease, central nervous system disease, cardiovascular disease, inflammatory disease or autoimmune disease with any compound of Formula (Im).
2. The Nature of the Invention:
The invention belongs to medicinals, more specifically, the administration of compounds of Formula (Im) to patients. The BRI of instant claim 103 defines the scope of diseases of metabolic disease, liver disease, lung disease, central nervous system disease, cardiovascular disease, inflammatory disease or autoimmune disease to be delt with any compound of Formula (Im).
3. The state of the prior art:
Recent status and prior art of small molecules as NLRP3 inhibitors:
Focus on the Role of NLRP3 Inflammasome in Diseases Int. J. Mol. Sci. 2020, 21(12), 4223.
This review provides a focus on the available knowledge about the NLRP3 inflammasome role in related pathologies and describe the balance between the activation of the harmful and beneficial inflammasome so that new therapies can be created for patients with these diseases.
The NLRP3 inflammasome in health and disease: the good, the bad and the ugly Clin Exp Immunol. 2011 Oct; 166(1):1–15.
The paper proposes the possibility that anti-IL-1 therapeutics may have broader applications than anticipated previously, and may be utilized across diverse disease states that are linked insidiously through unwanted or heightened inflammasome activity.
However, nothing in the prior art or recent status supports preventing or eradicating any diseases of the claim 103 by administration of compound of Formula (Im).
4. The Level of one of ordinary skill:
The level of one of ordinary skill includes the knowledge/skill to engage in a reasonable amount of experimentation to make and use the pharmaceutical compositions underlying the instant method claims. The level of one of ordinary skill also includes knowledge in using small compounds to alleviate metabolic disease, liver disease, lung disease, central nervous system disease, cardiovascular disease, inflammatory disease or autoimmune disease. However, no one has skill to engage in the undue burdensome level of experimentation required to provide guidance/ enablement for treating or preventing the diseases of the instant method claims 103 and 104.
5. The level of predictability in the art:
The art is predictable to make the instantly claimed pharmaceutical compositions. However, the art does not provide predictability as to which diseases and disorders can be prevented. To generate this level of guidance, one has to engage in undue burdensome experimentation (since no predictability in the art) to test the pharmaceutical composition against every disease known to humanity to determine if the pharmaceutical composition can treat and/or prevent said disease(s). This level of experimentation would be required to match the scope of instant claims 103 and 104.
6-7. The amount of direction provided by the inventor and the existence of working examples
While the Specification teaches IC50 data of Human Monocyte IL-1b Assay of 23 compounds (para [00287]-[00288]), it does not teach how to prevent the assay-related disease, or provide direction for alleviating or preventing or eradicating the diseases/disorders per the BRI of instant claim 103.
8. The quantity of experimentation needed to make or use the invention based on the content of the disclosure:
The scope of diseases per the BRI of instant claim 103 would require an undue amount of experimentation to use the invention as claimed to treat or prevent any disease with compound of Formula (Im). Moreover, the amount of experimentation required to prevent any of the claim 103 diseases would be undue as well, absent evidence in the Specification or prior art.
Therefore, claims 103 and 104 are rejected under 35 USC 112(a) for lacking enablement for the scope of alleviating and/or preventing or eradicating the metabolic disease, liver disease, lung disease, central nervous system disease, cardiovascular disease, inflammatory disease or autoimmune disease of claims 103 and 104 with compound of Formula (Im).
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
19. Claim(s) 74-76, 78, 80-82, 86, 94-95 and 102-104 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by YAMAGUCHI (WO2018221433A1, referenced in IDS of 02/14/2024 and provided by Applicants).
YAMAGUCHI teaches preparation of heteroaryl amine derivatives, pharmaceuti-cally acceptable salts thereof as useful therapeutic medicines for diseases such as diabetes (See Abstract), and discloses the following compound (para [0303], p.95):
PNG
media_image4.png
313
348
media_image4.png
Greyscale
The compound maps on Formula (Im) of instant claim 74, wherein R1 = R2 = R3 = R4 = H; R5 = OR10 wherein R10 = Me; R6 = C6-10aryl substituted with 1-5 R15 groups (F and CH2C(O)N(R10)(R11) wherein R10 = R11 = H); L = N(R9c) wherein R9c = H; W = C(R7a) wherein R7a = H; X = C(R7c) wherein R7c = H; and Z = C(R7g) wherein R7c = H, thus anticipating claim 74.
The compound also reads on:
claims 75 (wherein W = C(R7a), X = C(R7c), Z = C(R7g));
claim 76 (wherein W = CH, X = CH, Z = CH);
claim 78 (wherein R1 = H);
claim 80 (wherein R2 = H);
claim 81 (wherein R2 = R4 = H);
claim 82 (wherein R3 = H);
claim 86 (wherein R5 = OR10 = OMe wherein R10 = Me);
claim 94 (wherein L = N(R9c)), and
claim 95 (wherein L = NH).
Regarding claim 102 of a pharmaceutical composition and a pharmaceutically acceptable excipient, YAMAGUCHI teaches a solution of the test compound (para [0515], p.178). A solution of the test compound at least contains a pharmaceutical acceptable excipient/carrier. So, instant claim 102 is anticipated by YAMAGUCHI.
Regarding claims 103-104, YAMAGUCHI teaches a method comprising administering to a mammal a pharmacologically effective amount of the compound of Formula I or a pharmaceutically acceptable salt thereof for treating diabetes (claim 12), including, … glucose intolerance, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, …, obesity, …, insulinoma or hyperinsulinemia. Thus, claims 103 and 104 are anticipated by YAMAGUCHI.
Art of Record
20. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Recent Progress and Prospects of Small Molecules for NLRP3 Inflammasome Inhibition J. Med. Chem. 2023, 66, 21, 14447–14473
The article provides comprehensive insights and commentary on drugs currently under clinical investigation, as well as other NLRP3 inflammasome inhibitors from a chemical structure point of view, with an aim to provide new insights for the further development of clinical drugs for NLRP3 inflammasome-mediated diseases.
Conclusion
21. Claim 101 is free of the prior art.
22. Claims 74-76, 78-83, 86, 89-90, 93-95 and 102-104 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BIN TAO whose telephone number is (571)272-0398. The examiner can normally be reached Monday-Friday 8-5PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Andrew Kosar can be reached at 571-272-0913. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/B.T./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
Prosecution Insights