PATENT CLAIM ANALYSIS

Application Number: 15885671
Application Type: Utility
Filing Date: 2018-01
Publication Date: 2018-08
Patent Classification: ["514", "220000"]

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 18):
The bifunctional compound of  claim 2 , wherein the PTM a chemical structure that includes at least one of (A), (B), (C), (D), (E), or a combination thereof:\n (A) an estrogen receptor binding moiety (EBM) comprising PTM-I or PTM-II: wherein:\n X PTM  is O or C\u2550O; \n each of X PTM1  and X PTM2  is independently selected from N or CH; \n R PTM1  is independently selected from OH, O(CO)R PTM , O-lower alkyl, wherein R PTM  is an alkyl or aryl group in the ester; \n R PTM2  and R PTM4  are independently selected from H, OH, halogen, CN, CF 3 , SO 2 -alkyl, O-lower alkyl; \n R PTM3  and R PTM5  are independently selected from H, halogen; \n PTM-I has at least one R PTM2  and at least one R PTM3  on each respective rings; and the \n indicates the site of attachment of at least one of the linker, the CLM, a CLM\u2032, or a combination thereof;\n (B) an estrogen receptor protein targeting moiety represented by the chemical structure: \n wherein:\n each X PTM  is independently CH, N; \n  indicates the site of attachment of at least one of the linker, the CLM, a CLM\u2032, or a combination thereof; \n each R PTM1  is independently OH, halogen, alkoxy, methoxy, ethoxy, O(CO)R PTM , wherein the substitution can be a mono-, di- or tri-substitution and the R PTM  is alkyl or cycloalkyl group with 1 to 6 carbons or aryl groups; \n each R PTM2  is independently H, halogen, CN, CF 3 , liner or branched alkyl, alkoxy, methoxy, ethoxy, wherein the substitution can be mono- or di-substitution; \n each R PTM3  is independently H, halogen, wherein the substitution can be mono- or di-substitution; and \n R PTM4  is a H, alkyl, methyl, ethyl. \n (C) an androgen receptor (AR) binding moiety (ABM) comprises a structure selected from the group consisting of: wherein:\n W 1  is aryl, heteroaryl, bicyclic, or biheterocyclic, each independently substituted by 1 or more H, halo, hydroxyl, nitro, CN, C\u2261CH, C 1-6  alkyl (linear, branched, optionally substituted; for example, optionally substituted by 1 or more halo, C 1-6  alkoxyl), C 1-6  alkoxyl (linear, branched, optionally substituted; for example, optionally substituted by 1 or more halo), C 2-6  alkenyl, C 2-6  alkynyl, or CF 3 ; \n Y 1 , Y 2  are each independently NR Y1 , O, S, SO2, heteroaryl, or aryl; \n Y 3 , Y 4 , Y 5  are each independently a bond, O, NR Y2 , CR Y1 R Y2 , C\u2550O, C\u2550S, SO, SO 2 , heteroaryl, or aryl; \n Q is a 3-6 membered ring with 0-4 heteroatoms, optionally substituted with 0-6 R Q , each R Q , is independently H, C 1-6  alkyl (linear, branched, optionally substituted, for example, optionally substituted by 1 or more halo, C 1-6  alkoxyl), halogen, C 1-6  alkoxy, or 2 R Q  groups taken together with the atom they are attached to, form a 3-8 membered ring system containing 0-2 heteroatoms); \n R 1 , R 2 , R a , R b , R Y1 , R Y2  are each independently H, C 1-6  alkyl (linear, branched, optionally substituted; for example, optionally substituted by 1 or more halo, C 1-6  alkoxyl), halogen, C 1-6  alkoxy, cyclic, heterocyclic or R 1 , R 2  together with the atom they are attached to, form a 3-8 membered ring system containing 0-2 heteroatoms); \n W 2  is a bond, C 1-6  alkyl, C 1-6  heteroalkyl, O, aryl, heteroaryl, alicyclic, heterocyclic, biheterocyclic, biaryl, or biheteroaryl, each optionally substituted by 1-10 R W2 ; \n each R W2  is independently H, halo, C 1-6  alkyl (linear or branched optionally substituted; for example, optionally substituted by 1 or more F), \u2014OR W2A , C 3-6  cycloalkyl, C 4-6  cycloheteroalkyl, C 1-6  alkyl (optionally substituted), heterocyclic (optionally substituted), aryl (optionally substituted), or heteroaryl (optionally substituted), bicyclic heteroaryl or aryl, OC 1-3 alkyl (optionally substituted; for example, optionally substituted by 1 or more \u2014F), OH, NH 2 , NR Y1 R Y2 , CN; \n R W2A  is H, C 1-6  alkyl (linear, branched), or C 1-6  heteroalkyl (linear, branched), each optionally substituted by a cycloalkyl, cycloheteroalkyl, aryl, heterocyclic, heteroaryl, halo, or OC 1-3 alkyl; and \n the dashed line indicates the site of attachment of at least one of the linker, the CLM, a CLM\u2032, or a combination thereof; \n (D) a Tau protein targeting moiety that is represented by at least one of Formula I-XI: wherein:\n A, B, C, D, E, and F are independently selected from an optionally substituted 5- or 6-membered aryl or heteroaryl ring, an optionally substituted 4- to 7-membered cycloalkyl or a heterocycloalkyl, where contact between circles indicates ring fusion; \n L PTM  is selected from a bond, an alkyl, an alkenyl or an alkynyl, optionally interrupted by one or more rings (i.e., cycloalkyl, heterocycloalkyl, aryl or heteroaryl), or one or more functional groups selected from the groups \u2014O\u2014, \u2014S\u2014, \u2014NR 1 PTM \u2014, \u2014N\u2550N\u2014, \u2014S(O)\u2014, \u2014SO 2 \u2014, \u2014C(O)\u2014, \u2014NHC(O)\u2014, \u2014C(O)NH\u2014, \u2014NHSO 2 \u2014, \u2014NHC(O)NH\u2014, \u2014NHC(O)O\u2014, or \u2014OC(O)NH\u2014, wherein the said functional group is optionally located at either end of the linker; and \n R 1 PTM  is selected from H or alkyl. \n (E) a tricyclic diazepine or azepine BET/BRD4 binding ligand comprising a group according to the chemical structure PTM-a: wherein:\n Y 1 , Y 2  and Y 3  are independently selected from the group of carbon, nitrogen or oxygen and together with the atoms to form an aromatic fused ring. \n A and B are independently selected from the group of a 5-membered aromatic ring, a 6-membered aromatic ring, a heteroaromatic ring, a carbocyclic, a thiophene a pyrrole ring, a pyridine, a pyrimidine, a pyrazine, a pyrazole ring each optionally substituted with alkyl, alkoxy, halogen, an aromatic and a heteroaromatic ring; wherein ring A is fused to the central azepine (Y1=C) or diazepine (Y1=N) moiety; and \n Z1 is selected from the group of methyl or analkyl group, and \n wherein the dashed line indicates the site of attachment of at least one of the linker, the CLM, a CLM\u2032, or a combination thereof.

Metadata:
- Claim Count in Document: 19.0
- Percentile: 86.0
- Lexical Diversity: 1.675
- Patent Class: 514.0
- Transitional Phrase Type: open
- Component Type: 1
- Foreign Priority: False
- Related Applications: ['15881318', '15730728', '14822309', '16346483', '15148253']

Analysis Scores:
- 35 USC 101 Eligibility (BERT): 0.7664973967957159
- 35 USC 102 Novelty (BERT): 0.5694948683170286
- Combined Prediction Score: 0.7467971439478472
- Mean Citation Score: 336.657926
- Max Citation Score: 477.86942
- Similarity Product: 327.5880446858668

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