PATENT CLAIM ANALYSIS

Application Number: 15953108
Application Type: Utility
Filing Date: 2018-04
Publication Date: 2018-08
Patent Classification: ["514", "279000"]

Abstract:
The description relates to cereblon E3 ligase binding compounds, including bifunctional compounds comprising the same, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present disclosure. In particular, the description provides compounds, which contain on one end a ligand which binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. Compounds can be synthesized that exhibit a broad range of pharmacological activities consistent with the degradation/inhibition of targeted polypeptides of nearly any type.

Claim (Index 21):
The bifunctional compound according to any of  claims 2 - 16 , wherein the PTM is a BRaf targeting moiety that is represented by at least one of chemical structures PTM-Ia, PTM-Ib, PTM-IIa, PTM-IIb, PTM-IIIa, PTM-IIIb, PTM-IVa, PTM-IVb: wherein:\n double dotted bonds are aromaric bonds; \n V PTM , W PTM , X PTM , Y PTM , Z PTM  is one of the following combinations: C, CH, N, N, C; C, N, N, CH, C; C, O, C, CH, C; C, S, C, CH, C; C, CH, C, O, C; C, CH, C, S, C; C, CH, N, CH, C; N, CH, C, CH, C; C, CH, C, CH, N; N, N, C, CH, C; N, CH, C, N, C; C, CH, C, N, N; C, N, C, CH, N; C, N, C, N, C; and C, N, N, N, C; \n R PTM1  is covalently joined to a ULM, a chemical linker group (L), a CLM, an ILM, a VLM, MLM, a ULM\u2032, a CLM\u2032, a ILM\u2032, a VLM\u2032, a MLM\u2032, or combination thereof; \n R PTM2  is hydrogen, halogen, aryl, methyl, ethyl, OCH 3 , NHCH 3  or M1-CH 2 \u2014CH 2 -M2, wherein M1 is CH 2 , O and NH, and M2 is hydrogen, alkyl, cyclic alkyl, aryl or heterocycle; \n R PTM3  is absent, hydrogen, aryl, methyl, ethyl, other alkyl, cyclic alkyl, OCH 3 , NHCH 3  or M1-CH 2 \u2014CH 2 -M2, wherein M1 is CH 2 , O and NH, and M2 is hydrogen, alkyl, cyclic alkyl, aryl or heterocycle; \n R PTM4  is hydrogen, halogen, aryl, methyl, ethyl, OCH 3 , NHCH 3  or M1-CH 2 \u2014CH 2 -M2, wherein M1 is CH 2 , O and NH, and M2 is hydrogen, alkyl, cyclic alkyl, aryl or heterocycle; \n each of R PTM5  and R PTM22  is independently selected from the group consisting of \n X PTM1 , X PTM2 , X PTM3 , X PTM4 , X PTM5 , X PTM6 , X PTM7 , X PTM8 , X PTM9 , X PTM10 , X PTM11 , X PTM12 , X PTM13 , X PTM14 , X PTM15 , X PTM16 , X PTM17 , X PTM18 , X PTM19 , X PTM20 , X PTM21 , X PTM22 , X PTM23 , X PTM24 , X PTM25 , X PTM26 , X PTM27 , X PTM28 , X PTM29 , X PTM30 , X PTM31 , X PTM32 , X PTM33 , X PTM34 , X PTM35 , X PTM36 , X PTM37 , X PTM38  are independently selected from CH or N; R PTM5a  is selected from the group consisting of: H, optionally substituted amide (e.g., optionally substituted with an alkyl, methyl, ethyl, propyl, or butyl group), optionally substituted amine, \u2003\u2014NHC(O)R PTM5 ; R PTM6a  and R PTM6b  are each independently selected from hydrogen, halogen, or C 1 -C 6  alkyl (linear, branched, optionally substituted); R PTM6  is either of the following groups: absent, hydrogen, halogen, aryl, methyl, ethyl, OCH 3 , NHCH 3  or M1-CH 2 \u2014CH 2 -M2, wherein M1 is CH 2 , O and NH, and M2 is hydrogen, alkyl, cyclic alkyl, aryl or heterocycle. R PTM7  is absent, hydrogen, halogen, aryl, methyl, ethyl, OCH 3 , NHCH 3  or M1-CH 2 \u2014CH 2 -M2, wherein M1 is CH 2 , O and NH, and M2 is hydrogen, alkyl, cyclic alkyl, aryl or heterocycle. R PTM8 , R PTM9  or R PTM10  are independently selected from the group consisting of absent, hydrogen, halogen, aryl, heteroaryl, alkyl, cycloalkyl, heterocycle, methyl, ethyl, OCH 3 , NHCH 3  or M1-CH 2 \u2014CH 2 -M2, wherein M1 is CH 2 , O and NH, and M2 is hydrogen, alkyl, cyclic alkyl, aryl or heterocycle; R PTM11  is absent, hydrogen, halogen, methyl, ethyl, OCH 3 , NHCH 3  or M1-CH 2 \u2014CH 2 -M2 in which Ml, wherein CH 2 , O and NH, and M2 is hydrogen, alkyl, cyclic alkyl, aryl or heterocycle; R PTM12 , R PTM13 , R PTM14 , R PTM15 , R PTM16 , R PTM17 , R PTM18 , R PTM19  are independently Selected from the group consisting of absent, hydrogen, halogen, aryl, heteroaryl, cycloalkyl, heterocycle, methyl, ethyl, other alkyl, OCH 3 , NHCH 3  or M1-CH 2 \u2014CH 2 -M2, wherein M1 is CH 2 , O and NH, and M2 is hydrogen, alkyl, cyclic alkyl, aryl or heterocycle; R PTM20  is a small group containing less than four non-hydrogen atoms; R PTM21  is selected from the group consisting of trifluoromethyl, chloro, bromo, fluoro, methyl, ethyl, propyl, isopropyl, tert-butyl, butyl, iso-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, OCH 3 , NHCH 3 , dimethylamino or M1-CH 2 \u2014CH 2 -M2, wherein M1 is CH 2 , O or NH, and M2 is hydrogen, alkyl, cyclic alkyl, aryl or heterocycle; R PTM25a  and R PTM25b  are each independently selected from hydrogen, halogen, or C 1 -C 6  alkyl (linear, branched, optionally substituted); R PTM23 , R PTM24 , R PTM28 , R PTM29 , R PTM30 , R PTM31 , R PTM32  are independently selected from the group consisting of absent, bond, hydrogen, halogen, aryl (optionally substituted), heteroaryl (optionally substituted), cycloalkyl (optionally substituted), heterocycle (optionally substituted), methyl, ethyl (optionally substituted), other alkyl (linear, branched, optionally substituted), OCH 3 , NHCH 3  or M1-CH 2 \u2014CH 2 -M2, wherein M1 is CH 2 , O and NH, and M2 is hydrogen, alkyl (linear, branched, optionally substituted), cyclic alkyl (optionally substituted), aryl (optionally substituted) or heterocycle (optionally substituted); R PTM25  is selected from absent, hydrogen, halogen, C 1 -C 6  alkyl (linear, branched, optionally substituted), OCH 3 , NHCH 3  or SCH 3 ; R PTM26  is selected from absent, hydrogen, halogen, C 1 -C 6  alkyl (linear, branched, optionally substituted), OCH3, NHCH 3  or SCH 3 ; R PTM27  is selected from the group consisting of absent, hydrogen, halogen, C 1 -C 6  alkyl (linear, branched, optionally substituted), OCH 3 , NHCH 3  or SCH 3 ; and at least one of R PTM8 , R PTM9  or R PTM10 , R PTM12 , R PTM13 , R PTM16 , R PTM24 , R PTM29 , and R PTM32  is modified to be covalently joined to a ULM, a chemical linker group (L), a CLM, an ILM, a VLM, MLM, a ULM\u2032, a CLM\u2032, a ILM\u2032, a VLM\u2032, a MLM\u2032, or combination thereof.

Metadata:
- Claim Count in Document: 1.0
- Percentile: 91.0
- Lexical Diversity: 1.675
- Patent Class: 514.0
- Transitional Phrase Type: closed
- Component Type: 1
- Foreign Priority: False
- Related Applications: ['15881318', '14822309', '15730728', '16346483', '15148253']

Analysis Scores:
- 35 USC 101 Eligibility (BERT): 0.8142035449856837
- 35 USC 102 Novelty (BERT): 0.5720961908878349
- Combined Prediction Score: 0.7899928095758989
- Mean Citation Score: 365.22769200000016
- Max Citation Score: 518.0048
- Similarity Product: 360.5568027068138

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

Dataset: test