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 .
Election/Restrictions
Applicant’s election without traverse of compound I-17 in the reply filed on 2026 February 17 is acknowledged. A search of the entire scope of formula (I) of claim 1 has been conducted for purposes of compact prosecution and the restriction of 2026 February 17 is withdrawn. Claims 1, 2, 5-8, 16, 17, 22,24, 27, 29, 44, 45, 53, 54, 56, 57, 60, and 61 are pending and examined on the merits.
Because all claims previously withdrawn from consideration under 37 CFR 1.142 have been rejoined, the restriction requirement as set forth in the Office action mailed on 2026 February 17 is hereby withdrawn.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 Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable.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.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 2024 March 13, 2025 August 28, and 2026 February 17 were submitted in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are considered by the examiner.
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.
Claims 57, 60, and 61 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification is enabling for the alleviation of Alzheimer’s disease, allergy, asthma, gastric cancer, prostate cancer, breast cancer, melanoma, hepatocellular carcinoma, head and neck squamous cell carcinoma, and adenocarcinoma of the lung, glioblastoma with a compound of formula (I) and non-enabling for the alleviation or prevention of the scope of diseases claimed with 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 make and/or use the invention commensurate in scope with these claims.
The factors to be considered in determining whether a disclosure meets the enablement requirements of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 858 F.2d 731, 8 USPQ2d 1400 (Fed. Cir., 1988). The court in Wands states, “Enablement is not precluded by the necessity for some experimentation, such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is ‘undue’, not ‘experimentation’” (Wands, 8 USPQ2sd 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. “Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations” (Wands, 8 USPQ2d 1404). Among these factors are: (1) the nature of the invention; (2) the breadth of the claims; (3) the state of the prior art; (4) the predictability or unpredictability of the art; (5) the relative skill of those in the art; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
Consideration of the relevant factors sufficient to establish a prima facie case for lack of enablement is set forth herein below:
The nature of the invention and (2) the breadth of the claims:
The claims are drawn to a method of treating an NLRP3-mediated disorder with a compound of claim 1, formula (I). The definition of treatment includes prevention (specification, page 8, line 25 to page 9, line 8). Thus, the claims taken together with the specification imply a compound of formula (I) can ameliorate or prevent a disorder.
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The state of the prior art and (4) the predictability or unpredictability of the art:
SWANSON (Nature Reviews: Immunology, 2019, 19, 477-489) describes the following ideas: MCC950, an NLRP3 inflammasome inhibitor, has demonstrated therapeutic efficacy against Alzheimer’s disease; tranilast treats allergy and asthma; and more research is needed to understand the targeting of NLRP3 (page 485, column 2, last paragraph to page 486; column 1, paragraph 3; page 487, column 1, paragraph 2 to column 2, paragraph 1).
SONNESSA (Frontiers in Oncology, 2020, 10, article 1587, 1-11) describes the following ideas: nod-like receptor protein 3 (NLRP3) is linked to gastric cancer, hepatocellular carcinoma, melanoma, non-small cell lung cancer, adenocarcinoma of the lung, prostate cancer, glioblastoma, head and neck squamous cell carcinoma, and breast cancer (page 2, column 2, last paragraph; page 4, column 2, paragraph 5 to page 6, paragraph 6); and more research is needed to understand NLRP3 as a therapeutic target (page 8, paragraph 5).
PULLEY (US 7067507, published 2006 June 27) describes there is no way to prevent Alzheimer’s disease (column 2, lines 40-45).
Prostate cancer cannot be prevented through medicinal means (“Prevention - Prostate Cancer Foundation (PCF)”, http://www.pcf.org/site/c.leJRIROrEpH/b.5802029/k.31EA/Prevention.htm, accessed 2016 April 8)
The relative skill of those in the art:
While the artisan generally would have an advanced degree in [area of claims], their high level of skill and knowledge is insufficient to overcome the lack of understanding as to how [disease] functions in the body or to overcome the art recognition that this disease is poorly understood and treatments have generally failed.
The amount of direction or guidance presented and the presence or absence of working examples:
The specification has provided guidance for the alleviation of Alzheimer’s disease, allergy, asthma, gastric cancer, prostate cancer, breast cancer, melanoma, hepatocellular carcinoma, head and neck squamous cell carcinoma, and adenocarcinoma of the lung, glioblastoma with a compound of formula (I).
The specification does not provide guidance for the alleviation or prevention of the scope of diseases claimed with a compound of formula (I).
The quantity of experimentation necessary:
Considering the state of the art as discussed by the references above, particularly with regards to alleviation or prevention of a disorder recited in claims 56 and 57 with a compound of formula (I) and the high unpredictability in the art as evidenced therein, and the lack of guidance provided in the specification, one of ordinary skill in the art would be burdened with undue experimentation to practice the invention commensurate in the scope of the claims.
Claim Rejections - 35 USC § 102
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.
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 –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1, 2, 6, 8, 22, 24, 27, 29, 44, 45, 54, and 56 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by AXTEN (ACS Medicinal Chemistry Letters, 2013, 4, 964-968, cited in IDS). Axten describes compounds 6, 8, and 12 (page 965, table 1). In these compounds, the following examined definitions apply: R2 is H; Y is N; R1 is Me; X is CH; R3 is F; and A is 6-[methyl or CF3]-pyridine or 3,5-dimethyl-imidazole. Pharmaceutical compositions (page 965, table 1; page 966, column 1, paragraph 3; page 967, column 2, paragraph 3). Because the specified compounds meet the limitations of claim 1, they are expected to work as an inhibitor of NEK7 or a modulator of the NLRP3 inflammasome.
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Claim(s) 1, 2, 6, 8, 22, 24, 27, 29, 44, 45, 54, and 56 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by AXTEN (US 20120077858, published 2012 March 29). Axten describes examples 113 and 114 (page 81, paragraph [0818] to page 82, paragraph [0821]; examples 135-139 and 141 (page 95, paragraph [0885] to page 99, paragraph [0900]); and examples 149-150 (page 103, paragraph [0922] to page 104, paragraph [00931]). In these compounds, the following examined definitions apply: R2 is H; Y is N; R1 is Me; X is CH; R3 is F; and A is selected from 1-methyl-pyrrolidine, 2,5-difluorophenyl, m-CF3-phenyl, 6-[methyl or CF3]—pyridine, 3,5-dimethyl-imidazole; 3-trifluoromethyl-4-F-phenyl. Pharmaceutical compositions (page 104, paragraph [0932] to page 105, paragraph [0931]). PERK testing is described (page 106, paragraphs [0947] to [0952]). Because the specified compounds meet the limitations of claim 1, they are expected to work as an inhibitor of NEK7 or a modulator of the NLRP3 inflammasome.
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Claim(s) 1, 2, 6, 8, 22, 24, 27, 29, 44, 45, 54, and 56 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by MULVIHILL (WO 2021041976, published 2021 March 4). Mulvihill describes compound 21 and 22 (page 83). In these compounds, the following examined definitions apply: R2 is Me; Y is N; R1 is Me; X is CH; R3 is F; and A is 6-[methyl or CF3]—pyridine. Pharmaceutical compositions (page 29, paragraph [0107] to page 34, paragraph [0134]) are described. Because the specified compounds meet the limitations of claim 1, they are expected to work as an inhibitor of NEK7 or a modulator of the NLRP3 inflammasome.
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Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) 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.
Claims 1, 2, 6, 8, 22, 24, 27, 29, 44, 45, 54, and 56 are rejected under 35 U.S.C. 103(a) as being unpatentable over AXTEN (ACS Medicinal Chemistry Letters, 2013, 4, 964-968, cited in IDS).
Determining the scope and contents of the prior art
Axten describes compounds 5, 7, and 11 (page 965, table 1). In these compounds, the following examined definitions apply: R2 is H; Y is N; R1 is Me; X is CH; R3 is H; and A is 6-[methyl or CF3]-pyridine or 3,5-dimethyl-imidazole. Pharmaceutical compositions (page 965, table 1; page 966, column 1, paragraph 3; page 967, column 2, paragraph 3). Because the specified compounds obviate the limitations of claim 1, they are expected to work as an inhibitor of NEK7 or a modulator of the NLRP3 inflammasome.
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Ascertaining the differences between the prior art and the claims at issue
In the prior art, examined variable R3, attached to the 4-position of 2,3‐dihydro‐1H‐indole is H.
Resolving the level of ordinary skill in the pertinent art
Those of relative skill in the art are those with level of skill of the authors of the references cited to support the examiner’s position (MD’s, PhD’s, or those with advanced degrees and the requisite experience in preparation of compounds of the elected group).
Considering objective evidence present in the application indicating obviousness or nonobviousness
Axten describes that H and F are alternative substituents attached to the 4-postion of 2,3‐dihydro‐1H‐indole. Compounds of Axten are used as protein kinase R (PKR)-like ER-kinase (PERK) inhibitors and studied in vivo in rats. Table 1 shows that these substituents can be varied and still be tested in vitro and in vivo.
A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). In light of the foregoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
The Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper “functional approach” to the determination of obviousness as laid down in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit.
Exemplary rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) “Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel.
Claims 1, 2, 6, 8, 22, 24, 27, 29, 44, 45, and 56 are rejected under 35 U.S.C. 103(a) as being unpatentable over ROJAS-RIVERA (Cell Death and Differentiation, 2017, 24, 1100-1110).
Determining the scope and contents of the prior art
Rojas-Rivera describes compounds GSK’414 and GSK’157 (page 1105, figure 3c). In these compounds, the following examined definitions apply: R2 is H; Y is N; R1 is Me; X is CH; R3 is F; and A is 6-methyl-pyridine or m-CF3-phenyl. Pharmaceutical compositions (page 965, table 1; page 966, column 1, paragraph 3; page 967, column 2, paragraph 3). GSK’414 is the same compound as compound 6 of Axten and is used as a reference in this rejection. Because the specified compounds obviate the limitations of claim 1, they are expected to work as an inhibitor of NEK7 or a modulator of the NLRP3 inflammasome.
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Ascertaining the differences between the prior art and the claims at issue
In the prior art, examined variable R3, attached to the 4-position of 2,3‐dihydro‐1H‐indole is H.
Resolving the level of ordinary skill in the pertinent art
Those of relative skill in the art are those with level of skill of the authors of the references cited to support the examiner’s position (MD’s, PhD’s, or those with advanced degrees and the requisite experience in preparation of compounds of the elected group).
Considering objective evidence present in the application indicating obviousness or nonobviousness
Rojas-Rivera shows that H and F are alternative substituents attached to compounds having GST-[hRIPK1 or hPERK] activity (page 1105, figures 3a and 3b).
A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). In light of the foregoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
The Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper “functional approach” to the determination of obviousness as laid down in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit.
Claims 1, 2, 6, 8, 22, 24, 27, 29, 44, 45, and 56 are rejected under 35 U.S.C. 103(a) as being unpatentable over AXTEN (US 20120077858, published 2012 March 29).
Determining the scope and contents of the prior art
Axten describes examples 112 (page 80, paragraph [0810] to page 81, paragraph [0817]). Compound 114 is used as a reference fort this rejection (page 81, paragraph [0821] to page 82, paragraph [0822]). In these compounds, the following examined definitions apply: R2 is H; Y is N; R1 is Me; X is CH; R3 is F; and A is unsubstituted phenyl. Pharmaceutical compositions (page 104, paragraph [0932] to page 105, paragraph [0931]). PERK testing is described (page 106, paragraphs [0947] to [0952]). Because the specified compounds obviate the limitations of claim 1, they are expected to work as an inhibitor of NEK7 or a modulator of the NLRP3 inflammasome.
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Ascertaining the differences between the prior art and the claims at issue
In the prior art examined variable R7 is H.
Resolving the level of ordinary skill in the pertinent art
Those of relative skill in the art are those with level of skill of the authors of the references cited to support the examiner’s position (MD’s, PhD’s, or those with advanced degrees and the requisite experience in preparation of compounds of the elected group).
Considering objective evidence present in the application indicating obviousness or nonobviousness
When one compares examples 112 and 114, the difference is the ring present for examined variable A. Axten shows that an unsubstituted phenyl ring is alternative embodiment to an substituted phenyl ring. Even though all of the compounds are not tested there is a reasonable expectation of success that each will inhibit PERK.
A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). In light of the foregoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
The Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper “functional approach” to the determination of obviousness as laid down in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit.
Allowable Subject Matter
Claims 1, 2, 6, 8, 22, 24, 27, 29, 44, 45, 54, 56, 57, 60, and 61 are not allowed. Claims 53 is allowed.
Claims 5, 7, 16, and 17 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.
The following is a statement of reasons for the indication of allowable subject matter: AXTEN (ACS Medicinal Chemistry Letters, 2013, 4, 964-968, cited in IDS) describes compounds 6, 8, and 12 (page 965, table 1). In these compounds, the following examined definitions apply: R2 is H; Y is N; R1 is Me; X is CH; R3 is F; and A is 6-[methyl or CF3]-pyridine or 3,5-dimethyl-imidazole. None of these compounds anticipate a compound of the objected claims because X is CH, Y is N, and none of the compounds are anticipatory or obvious against a compound of claim 53.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to NOBLE E JARRELL whose telephone number is (571)272-9077. The examiner can normally be reached 9:00 AM to 5:00 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Fereydoun Sajjadi can be reached at 571-272-3311. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/NOBLE E JARRELL/Primary Examiner, Art Unit 1699