PATENT CLAIM ANALYSIS

Application Number: 15898258
Application Type: Utility
Filing Date: 2018-02
Publication Date: 2019-02
Patent Classification: ["514", "263400"]

Abstract:
This disclosure features chemical entities (e.g., a compound or a pharmaceutically acceptable salt, and/or hydrate, and/or cocrystal, and/or drug combination of the compound) that modulate (e.g., agonizes or partially agonizes) NLRP3 that are useful, e.g., for treating a condition, disease or disorder in which an increase in NLRP3 signaling may correct a deficiency in innate immune activity (e.g., a condition, disease or disorder associated with an insufficient immune response) that contributes to the pathology and/or symptoms and/or progression of the condition, disease or disorder (e.g., cancer) in a subject (e.g., a human). This disclosure also features compositions as well as other methods of using and making the same.

Claim (Index 1):
A compound having formula (I), or a pharmaceutically acceptable salt thereof: wherein R 1  and R 2 , are defined according to (1) or (2) below: (1): R 1  is independently selected from the group consisting of: H, unsubstituted C 1-6  alkyl, CHO, C(\u2550O)R a , \u2014C(\u2550O)OR a , \u2014S(O) 1-2 (R b ), \u2014S(O) 1-2 NR c R d ; and \u2014C(\u2550O)NR c R d ; R 2  is independently selected from the group consisting of: H and unsubstituted C 1-6  alkyl; OR (2): R 1  and R 2 , together with the nitrogen atom to which each is attached forms a saturated or unsaturated ring including from 3-10 ring atoms, wherein the ring includes: (a) from 1-9 ring carbon atoms, each of which is optionally substituted with from 1-2 independently selected R f , and (b) from 0-3 ring heteroatoms (in addition to the nitrogen atom attached to R 1  and R 2 ), each of which is independently selected from the group consisting of N, N(R e ), O, and S; and provided that at least one of the 3-10 ring atoms is \u2014C(O)\u2014; R 3  is: (i) H; (ii) unsubstituted C 1-2  alkyl; (iii) X\u2014R 8 , wherein X is an unbranched C 1-6  alkylene, and R 8  is \u2014OH, C 1-4  alkoxy, \u2014C 1-4  haloalkoxy, CO 2 R a ; \u2014CONR c R d , cyano, or \u2014NR c\u2032 R d\u2032 ; (iv) (C 1-3  alkylene)-(C 6 -C 10  aryl), wherein the aryl is optionally substituted with from 1-3 substituents independently selected from the group consisting of: C 1-6  alkyl, C 1-4  haloalkyl, C 1-4  alkoxy, and C 1-4  haloalkoxy; or (v) (C 1-3  alkylene)heteroaryl including from 5-6 ring atoms, wherein from 1-4 ring atoms are each independently selected from the group consisting of N, N(R e ), O, and S, and wherein the heteroaryl is optionally substituted with from 1-3 substituents independently selected from the group consisting of: C 1-6  alkyl, C 1-4  haloalkyl, C 1-4  alkoxy, and C 1-4  haloalkoxy; R 4  and R 5  are each independently selected from the group consisting of: (i) hydrogen; (ii) halo; (iii) cyano; (iv) \u2014C(\u2550O)OH; (iv) \u2014C(\u2550O)OR a ; (v) \u2014C(\u2550O)NR c R d ; (vi) \u2014(C 0-3  alkylene)-C 3-10  cycloalkyl, wherein the cycloalkyl is optionally substituted with from 1-4 independently selected R f ; (vii) \u2014(C 0-3  alkylene)-heterocyclyl including from 3-10 ring atoms, wherein from 1-3 ring atoms are each independently selected from the group consisting of N(R e ), O, and S, wherein the heterocyclyl is optionally substituted with from 1-4 independently selected R f ; (viii) \u2014(C 0-3  alkylene)-(C 6 -C 10  aryl) optionally substituted with from 1-4 R g ; (ix) \u2014(C 0-3  alkylene)-heteroaryl including from 5-10 ring atoms, wherein from 1-4 ring atoms are each independently selected from the group consisting of N, N(R e ), O, and S, wherein the heteroaryl is optionally substituted with from 1-3 R g ; (x) \u2014Y\u2014 C 6 -C 10  aryl optionally substituted with from 1-4 R g , wherein Y is O, N(R e ), or S; (xi) \u2014Y-heteroaryl including from 5-10 ring atoms, wherein from 1-4 ring atoms are each independently selected from the group consisting of N, N(R e ), O, and S, wherein the heteroaryl is optionally substituted with from 1-3 R g , wherein Y is O, N(R e ), or S; (xii) \u2014NR c\u2032 R d\u2032 ; (xiii) C 1-6  alkyl optionally substituted with from 1-2 independently selected R h ; (xiv) C 1-4  haloalkyl; (xv) C 1-6  alkoxy; (xvi) C 1-4  haloalkoxy; (xvii) \u2014S(O) 1-2 (R b ); (xviii) \u2014S(O) 1-2 NR c R d ; (xviv) \u2014(C 0-3  alkylene)-heterocycloalkenyl including from 3-10 ring atoms, wherein from 1-3 ring atoms are each independently selected from the group consisting of N(R e ), O, and S, wherein the heterocyclyl is optionally substituted with from 1-4 independently selected R f ; each of R 6  and R 7  is independently selected from the group consisting of: H and unsubstituted C 1-2  alkyl; or R 6  and R 7  together with the carbon atom to which each is attached, forms a C 3 -C 5  cycloalkyl, optionally substituted with from 1-4 independently selected R f ; provided that when R 1  and R 2 , are defined according to (1), then each of R 6  and R 7  is H; provided that when R 1  and R 2 , are defined according to (2), then each of R 6  and R 7  is independently selected from the group consisting of: H and unsubstituted C 1-2  alkyl; or R 6  and R 7  together with the carbon atom to which each is attached, forms a C 3 -C 5  cycloalkyl, optionally substituted with from 1-4 independently selected R f ; R a  is: (i) C 1-6  alkyl optionally substituted with from 1-2 independently selected R h ; (ii) \u2014(C 0-3  alkylene)-C 3-10  cycloalkyl, wherein the cycloalkyl is optionally substituted with from 1-4 independently selected R f ; (iii) \u2014(C 1-3  alkylene)-heterocyclyl including from 3-10 ring atoms, wherein from 1-3 ring atoms are each independently selected from the group consisting of N(R e ), O, and S, wherein the heterocyclyl is optionally substituted with from 1-4 independently selected R f ; (iv) \u2014(C 0-3  alkylene)-phenyl optionally substituted with from 1-5 independently selected R g ; or (v) \u2014(C 0-3  alkylene)-heteroaryl including from 5-10 ring atoms, wherein from 1-4 ring atoms are each independently selected from the group consisting of N, N(R e ), O, and S, wherein the heteroaryl is optionally substituted with from 1-3 independently selected R g ; R b  is: C 1-6  alkyl, C 1-4  haloalkyl, C 1-4  alkoxy, C 1-4  haloalkoxy, phenyl optionally substituted with from 1-3 R g , or heteroaryl including from 5-6 ring atoms, wherein from 1-4 ring atoms are each independently selected from the group consisting of N, N(R e ), O, and S, wherein the heteroaryl is optionally substituted with from 1-3 R g ; each occurrence of R c  and R d  is independently selected from the group consisting of: H and C 1-4  alkyl; or R c  and R d  together with the nitrogen atom to which each is attached forms a ring including from 3-8 ring atoms, wherein the ring includes: (a) from 1-7 ring carbon atoms, each of which is optionally substituted with from 1-2 independently selected R f ; and (b) from 0-3 ring heteroatoms (in addition to the nitrogen atom attached to R c  and R d ), which are each independently selected from the group consisting of N(R e ), O, and S; each occurrence of R c\u2032  and R d\u2032  is independently selected from the group consisting of: H, R a , \u2014C(\u2550O)R a , \u2014C(\u2550O)OR a , \u2014S(O) 1-2 (R b ), and \u2014C(\u2550O)NR c R d ; or R c\u2032  and R d\u2032  together with the nitrogen atom to which each is attached forms a ring including from 3-8 ring atoms, wherein the ring includes: (a) from 1-7 ring carbon atoms, each of which is optionally substituted with from 1-2 independently selected R f ; and (b) from 0-3 ring heteroatoms (in addition to the nitrogen atom attached to R c\u2032  and R d\u2032 ), which are each independently selected from the group consisting of N(R e ), O, and S; each occurrence of R e  is independently selected from the group consisting of: H; C 1-4  alkyl; C 3-6  cycloalkyl; phenyl; \u2014C(\u2550O)(C 1-4  alkyl); \u2014C(\u2550O)O(C 1-4  alkyl); and \u2014S(O) 1-2 (C 1-4  alkyl); wherein each C 1-4  alkyl is optionally substituted with from 1-2 independently selected R h ; each C 3-6  cycloalkyl is optionally substituted with from 1-2 independently selected R f ; and each phenyl is optionally substituted with from 1-2 independently selected R g ; each occurrence of R f  is independently selected from the group consisting of: C 1-6  alkyl optionally substituted with from 1-2 independently selected R h ; C 1-4  haloalkyl; \u2014OH; oxo; \u2014F; \u2014Cl; \u2014N(R\u2032)(R\u2033); \u2014N(R\u2032)(C(\u2550O)C 1-4  alkyl); C 1-4  alkoxy; C 1-4  haloalkoxy; \u2014C(\u2550O)(C 1-4  alkyl); \u2014C(\u2550O)O(C 1-4  alkyl); \u2014C(\u2550O)OH, \u2014C(\u2550O)N(R\u2032)(R\u2033), \u2014S(O) 1-2 (C 1-4  alkyl); cyano; heteroaryl including from 5-10 ring atoms, wherein from 1-4 ring atoms are each independently selected from the group consisting of N, N(R e ), O, and S, wherein the heteroaryl is optionally substituted with from 1-3 R g ; and phenyl optionally substituted with from 1-4 R g ; and wherein each occurrence of R\u2032 and R\u2033 is independently selected from the group consisting of: H and C 1-4  alkyl; each occurrence of R g  is independently selected from the group consisting of: (i) halo; (ii) cyano; (iii) C 1-6  alkyl optionally substituted with from 1-2 independently selected R h ; (iv) C 2-6  alkenyl; (v) C 2-6  alkynyl; (vi) C 1-4  haloalkyl; (vii) C 1-4  alkoxy; (viii) C 1-4  haloalkoxy; (ix) \u2014(C 0-3  alkylene)-C 3-6  cycloalkyl optionally substituted with from 1-4 independently selected C 1-4  alkyl; (x) \u2014(C 0-3  alkylene)-heterocyclyl including from 3-6 ring atoms, wherein from 1-3 ring atoms are each independently selected from the group consisting of nitrogen, oxygen and sulfur, wherein the heterocyclyl is optionally substituted with from 1-4 independently selected C 1-4  alkyl; (xi) \u2014S(O) 1-2 (C 1-6  alkyl); (xii) \u2014NO 2 ; (xiii) \u2014OH; (xiv) \u2014N(R\u2032)(R\u2033), (xv) \u2014N(R\u2032)(C(\u2550O)C 1-3  alkyl); (xvi) \u2014C(\u2550O)(C 1-4  alkyl); (xvii) \u2014C(\u2550O)O(C 1-4  alkyl); (xviii) \u2014C(\u2550O)OH, and (xix) \u2014C(\u2550O)N(R\u2032)(R\u2033); wherein each occurrence of R\u2032 and R\u2033 is independently selected from the group consisting of: H and C 1-4  alkyl; and each occurrence of R h  is independently selected from the group consisting of: \u2014OH, \u2014OBn, \u2014F, \u2014N(R\u2032)(R\u2033), \u2014N(R\u2032)(C(\u2550O)C 1-4  alkyl), \u2014N(R\u2032)(C(\u2550O)OC 1-4  alkyl), C 1-4  alkoxy, C 1-4  haloalkoxy, \u2014C(\u2550O)O(C 1-4  alkyl); \u2014C(\u2550O)OH, \u2014C(\u2550O)N(R\u2032)(R\u2033), \u2014S(O) 1-2 (C 1-4  alkyl); and cyano; wherein each occurrence of R\u2032 and R\u2033 is independently selected from the group consisting of: H and C 1-4  alkyl; and with the proviso that when R 8  is NR c\u2032 R d\u2032 , then R 1  is not \u2014S(O) 1-2 (R b ); with the proviso that when R 8  is NR c\u2032 R d\u2032  and R 1  and R 2 , together with the nitrogen atom to which each is attached, forms heterocyclyl including from 3-10 ring atoms, then none of the ring atoms of the heterocyclyl formed from R 1  and R 2  are S; with the proviso that when R 8  is NR c\u2032 R d\u2032  and R 1  and R 2 , together with the nitrogen atom to which each is attached, forms heterocyclyl, then the heterocyclyl formed from R 1  and R 2  does not include 5 ring atoms; with the proviso that when R 8  is NR c\u2032 R d\u2032 , then R 1  and R 2 , together with the nitrogen atom to which each is attached does not form with the proviso that when R 8  is NR c\u2032 R d\u2032 , then R 1  is not \u2014C(\u2550O)NR c R d ; with the proviso that when R 8  is NR c\u2032 R d\u2032 , R 1  is \u2014C(\u2550O)NR c R d , and one of R c  and R d  is H; then the other of R c  and R d  is not selected from H or C 1-4  alkyl; with the proviso that when R 8  is NR c\u2032 R d\u2032 , R 1  is \u2014C(\u2550O)NR c R d , and one of R c  and R d  is H; then the other of R c  and R d  is not selected from H, Me, or Et; with the proviso that the compound of Formula I is not selected from:

Metadata:
- Claim Count in Document: 1.0
- Percentile: 88.0
- Lexical Diversity: 1.95588
- Patent Class: 514.0
- Transitional Phrase Type: closed
- Component Type: 1
- Foreign Priority: False
- Related Applications: ['16093990', '16094000', '12813148', '15016841', '14982131']

Analysis Scores:
- 35 USC 101 Eligibility (BERT): 0.8054229396058681
- 35 USC 102 Novelty (BERT): 0.5083431896686984
- Combined Prediction Score: 0.7757149646121512
- Mean Citation Score: 263.79211200000003
- Max Citation Score: 286.65015
- Similarity Product: 212.2357415632814

Labels:
- Claim Label 101: 1
- Claim Label 102: 0
- Claim Label 103: 1
- Claim Label 112: 0
- Combined Label: 0
- Label 101 Adjusted: 1

Dataset: test