PATENT CLAIM ANALYSIS

Application Number: 15881318
Application Type: Utility
Filing Date: 2018-01
Publication Date: 2018-08
Patent Classification: ["514", "443000"]

Abstract:
The present disclosure relates to bifunctional compounds, which find utility as modulators of estrogen receptor (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a cereblon, Von Hippel-Lindau ligase-binding moiety, Inhibitors of Apotosis Proteins, or mouse double-minute homolog 2 ligand, which binds to the respective E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

Claim (Index 6):
The bifunctional compound of  claim 1 , wherein the VLM comprises a group of the chemical structure: wherein:\n R 1\u2032  of ULM-g is an optionally substituted C 1 -C 6  alkyl group, an optionally substituted \u2014(CH 2 ) n OH, an optionally substituted \u2014(CH 2 ) n SH, an optionally substituted (CH 2 ) n \u2014O\u2014(C 1 -C 6 )alkyl group, an optionally substituted (CH 2 ) n \u2014WCOCW\u2014(C 0 -C 6 )alkyl group containing an epoxide moiety WCOCW where each W is independently H or a C 1 -C 3  alkyl group, an optionally substituted \u2014(CH 2 ) n COOH, an optionally substituted \u2014(CH 2 ) n C(O)\u2014(C 1 -C 6  alkyl), an optionally substituted \u2014(CH 2 ) n NHC(O)\u2014R 1 , an optionally substituted \u2014(CH 2 ) n C(O)\u2014NR 1 R 2 , an optionally substituted \u2014(CH 2 ) n OC(O)\u2014NR 1 R 2 , \u2014(CH 2 O) n H, an optionally substituted \u2014(CH 2 ) n OC(O)\u2014(C 1 -C 6  alkyl), an optionally substituted \u2014(CH 2 ) n C(O)\u2014O\u2014(C 1 -C 6  alkyl), an optionally substituted \u2014(CH 2 O) n COOH, an optionally substituted \u2014(OCH 2 ) n O\u2014(C 1 -C 6  alkyl), an optionally substituted \u2014(CH 2 O) n C(O)\u2014(C 1 -C 6  alkyl), an optionally substituted \u2014(OCH 2 ) n NHC(O)\u2014R 1 , an optionally substituted \u2014(CH 2 O) n C(O)\u2014NR 1 R 2 , \u2014(CH 2 CH 2 O) n H, an optionally substituted \u2014(CH 2 CH 2 O) n COOH, an optionally substituted \u2014(OCH 2 CH 2 ) n O\u2014(C 1 -C 6  alkyl), an optionally substituted \u2014(CH 2 CH 2 O) n C(O)\u2014(C 1 -C 6  alkyl), an optionally substituted \u2014(OCH 2 CH 2 ) n NHC(O)\u2014R 1 , an optionally substituted -(CH 2 CH 2 O) n C(O)\u2014NR 1 R 2 , an optionally substituted \u2014SO 2 R S , an optionally substituted S(O)R S , NO 2 , CN or halogen (F, Cl, Br, I, preferably F or Cl); \n R 1  and R 2  of ULM-g are each independently H or a C 1 -C 6  alkyl group which may be optionally substituted with one or two hydroxyl groups or up to three halogen groups (preferably fluorine); \n R S  of ULM-g is a C 1 -C 6  alkyl group, an optionally substituted aryl, heteroaryl or heterocycle group or a \u2014(CH 2 ) m NR 1 R 2  group; \n X and X\u2032 of ULM-g are each independently C\u2550O, C\u2550S, \u2014S(O), S(O) 2 , (preferably X and X\u2032 are both C\u2550O); \n R 2\u2032  of ULM-g is an optionally substituted \u2014(CH 2 ) n \u2014(C\u2550O) u (NR 1 ) v (SO 2 ) w alkyl group, an optionally substituted \u2014(CH 2 ) n \u2014(C\u2550O) u (NR 1 ) v (SO 2 ) w NR 1N R 2N  group, an optionally substituted \u2014(CH 2 ) n \u2014(C\u2550O) u (NR 1 ) v (SO 2 ) w -Aryl, an optionally substituted \u2014(CH 2 ) n \u2014(C\u2550O) u (NR 1 ) v (SO 2 ) w -Heteroaryl, an optionally substituted \u2014(CH 2 ) n \u2014(C\u2550O)NR 1 (SO 2 ) w -Heterocycle, an optionally substituted \u2014NR 1 \u2014(CH 2 ) n \u2014C(O) u (NR 1 ) v (SO 2 ) w -alkyl, an optionally substituted \u2014NR 1 \u2014(CH 2 ) n \u2014C(O) u (NR 1 ) v (SO 2 ) w \u2014 NR 1N R 2N , an optionally substituted \u2014NR 1 \u2014(CH 2 ) n \u2014C(O) u (NR 1 ) v (SO 2 ) w \u2014NR 1 C(O)R 1N , an optionally substituted \u2014NR 1 \u2014(CH 2 ) n \u2014(C\u2550O) u (NR 1 ) v (SO 2 ) w -Aryl, an optionally substituted \u2014NR 1 \u2014(CH 2 ) n \u2014(C\u2550O) u (NR 1 ) v (SO 2 ) w -Heteroaryl or an optionally substituted \u2014NR 1 \u2014(CH 2 ) n \u2014(C\u2550O) v NR 1 (SO 2 ) w -Heterocycle, an optionally substituted \u2014X R2\u2032 -alkyl group; an optionally substituted \u2014X R2\u2032 \u2014 Aryl group; an optionally substituted \u2014X R2\u2032 \u2014 Heteroaryl group; an optionally substituted \u2014X R2\u2032 \u2014 Heterocycle group; an optionally substituted; \n R 3\u2032  of ULM-g is an optionally substituted alkyl, an optionally substituted \u2014(CH 2 ) n \u2014(O) u (NR 1 ) v (SO 2 ) w -alkyl, an optionally substituted \u2014(CH 2 ) n \u2014C(O) u (NR 1 ) v (SO 2 ) w \u2014NR 1N R 2N , an optionally substituted \u2014(CH 2 ) n \u2014C(O) u (NR 1 ) v (SO 2 ) w \u2014NR 1 C(O)R N , an optionally substituted \u2014(CH 2 ) n \u2014C(O) u (NR 1 ) v (SO 2 ) w \u2014C(O)NR 1 R 2 , an optionally substituted \u2014(CH 2 ) n \u2014C(O) u (NR 1 ) v (SO 2 )-Aryl, an optionally substituted \u2014(CH 2 ) n \u2014C(O) u (NR 1 ) v (SO 2 ) w -Heteroaryl, an optionally substituted \u2014(CH 2 ) n \u2014C(O) u (NR 1 ) v (SO 2 ) w -Heterocycle, an optionally substituted \u2014NR 1 \u2014(CH 2 ) n \u2014C(O) u (NR 1 ) v (SO 2 ) w -alkyl, an optionally substituted \u2014NR 1 \u2014(CH 2 ) n \u2014C(O) u (NR 1 ) v (SO 2 ) w \u2014NR 1N R 2N , an optionally substituted \u2014NR 1 \u2014(CH 2 ) n \u2014C(O) u (NR 1 ) v (SO 2 ) w \u2014NR 1 C(O)R 1N , an optionally substituted \u2014NR 1 \u2014(CH 2 ) n \u2014C(O) u (NR 1 ) v (SO 2 )-Aryl, an optionally substituted \u2014NR 1 \u2014(CH 2 ) n \u2014C(O) u (NR 1 ) v (SO 2 ) w -Heteroaryl, an optionally substituted \u2014NR 1 \u2014(CH 2 ) n \u2014C(O) u (NR 1 ) v (SO 2 ) w -Heterocycle, an optionally substituted \u2014O\u2014(CH 2 ) n \u2014(C\u2550O) u (NR 1 ) v (SO 2 ) w -alkyl, an optionally substituted \u2014O\u2014(CH 2 ) n \u2014(C\u2550O) u (NR 1 ) v (SO 2 ) w \u2014NR 1N R 2N , an optionally substituted \u2014O\u2014(CH 2 )n-(C\u2550O) u (NR 1 ) v (SO 2 ) w \u2014NR 1 C(O)R N , an optionally substituted \u2014O\u2014(CH 2 )n-(C\u2550O) u (NR 1 ) v (SO 2 )-Aryl, an optionally substituted \u2014O\u2014(CH 2 ) n \u2014(C\u2550O) u (NR 1 ) v (SO 2 ) w -Heteroaryl or an optionally substituted \u2014O\u2014(CH 2 ) n \u2014(C\u2550O) u (NR 1 ) v (SO 2 ) w -Heterocycle; \u2014(CH 2 ) n \u2014(V) n\u2032 \u2014(CH 2 ) n \u2014(V) n\u2032 -alkyl group, an optionally substituted \u2014(CH 2 ) n \u2014(V) n\u2032 \u2014(CH 2 ) n \u2014(V) n\u2032 -Aryl group, an optionally substituted \u2014(CH 2 ) n \u2014(V) n\u2032 \u2014(CH 2 ) n \u2014(V) n\u2032 -Heteroaryl group, an optionally substituted \u2014(CH 2 ) n \u2014(V) n\u2032 \u2014(CH 2 )\u2014(V) n\u2032 -Heterocycle group, an optionally substituted \u2014(CH 2 ) n \u2014N(R 1\u2032 )(C\u2550O) m\u2032 \u2014(V) n\u2032 -alkyl group, an optionally substituted \u2014(CH 2 ) n \u2014N(R 1\u2032 )(C\u2550O) m\u2032 \u2014(V) n\u2032 -Aryl group, an optionally substituted \u2014(CH 2 )\u2014N(R 1\u2032 )(C\u2550O) m\u2032 \u2014(V) n\u2032 -Heteroaryl group, an optionally substituted \u2014(CH 2 ) n \u2014N(R 1\u2032 )(C\u2550O) m\u2032 \u2014(V) n\u2032 -Heterocycle group, an optionally substituted \u2014X R3\u2032 \u2014 alkyl group; an optionally substituted \u2014X R3\u2032 \u2014 Aryl group; an optionally substituted \u2014X R3\u2032 \u2014 Heteroaryl group; an optionally substituted \u2014X R3\u2032 -Heterocycle group; an optionally substituted; \n R 1N  and R 2N  of ULM-g are each independently H, C 1 -C 6  alkyl which is optionally substituted with one or two hydroxyl groups and up to three halogen groups or an optionally substituted \u2014(CH 2 ) n -Aryl, \u2014(CH 2 ) n -Heteroaryl or \u2014(CH 2 ) n -Heterocycle group; \n V of ULM-g is O, S or NR 1 ; \n R 1  of ULM-g is the same as above; \n R 1  and R 1\u2032  of ULM-g are each independently H or a C 1 -C 3  alkyl group; \n X R2\u2032  and X R3\u2032  of ULM-g are each independently an optionally substituted \u2014CH 2 ) n \u2014, \u2014CH 2 ) n \u2014CH(X v )\u2550CH(X v )\u2014 (cis or trans), \u2014CH 2 ) n \u2014CH\u2261CH\u2014, \u2014(CH 2 CH 2 O) n \u2014 or a C 3 -C 6  cycloalkyl group, where X v  is H, a halo or a C 1 -C 3  alkyl group which is optionally substituted; \n each m of ULM-g is independently 0, 1, 2, 3, 4, 5, 6; \n each m\u2032 of ULM-g is independently 0 or 1; \n each n of ULM-g is independently 0, 1, 2, 3, 4, 5, 6; \n each n\u2032 of ULM-g is independently 0 or 1; \n each u of ULM-g is independently 0 or 1; \n each v of ULM-g is independently 0 or 1; \n each w of ULM-g is independently 0 or 1; and \n any one or more of R 1\u2032 , R 2\u2032 , R 3\u2032 , X and X\u2032 of ULM-g is optionally modified to be covalently bonded to the PTM group through a linker group when PTM is not ULM\u2032, or when PTM is ULM\u2032, any one or more of R 1\u2032 , R 2\u2032 , R 3\u2032 , X and X\u2032 of each of ULM and ULM\u2032 are optionally modified to be covalently bonded to each other directly or through a linker group, or a pharmaceutically acceptable salt, stereoisomer, solvate or polymorph thereof.

Metadata:
- Claim Count in Document: 24.0
- Percentile: 86.0
- Lexical Diversity: 1.88462
- Patent Class: 514.0
- Transitional Phrase Type: none
- Component Type: 0
- Foreign Priority: False
- Related Applications: ['14822309', '15730728', '16094102', '16346483', '14707930']

Analysis Scores:
- 35 USC 101 Eligibility (BERT): 0.7951423575248043
- 35 USC 102 Novelty (BERT): 0.5525844171878659
- Combined Prediction Score: 0.7708865634911105
- Mean Citation Score: 301.119948
- Max Citation Score: 412.60214
- Similarity Product: 311.95281187762265

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

Dataset: test