PATENT CLAIM ANALYSIS

Application Number: 15975423
Application Type: Utility
Filing Date: 2018-05
Publication Date: 2018-12
Patent Classification: ["424", "179100"]

Abstract:
The present disclosure relates to compounds of formula (I): RCG1-L-P  (I) wherein RCG1 represents a reactive chemical group being reactive towards a chemical group present on a polypeptide such as an antibody; P represents H, OH or an activated O; and L represents a specific linker. The disclosure also relates to cryptophycin payloads, as well as to cryptophycin conjugates, to compositions containing them and to their therapeutic use, especially as anticancer agents. The disclosure also relates to the process for preparing these conjugates.

Claim (Index 1):
A Compound of formula (I):\n RCG1-L-P\u2003\u2003 (I) \n wherein\n RCG1 represents a reactive chemical group that is reactive towards a chemical group present on a polypeptide such as an antibody; \n P represents a hydrogen atom, \u2014OH or an activated O; \n L represents a linker of formula (II): \n wherein:\n L1 is of formula (III): \n wherein:\n when P represents a hydrogen atom, then x=0 or 1 and y=1 and z=0; \n when P represents \u2014OH, then x=y=z=0; \n when P represents an activated O, then x=1 and y=z=0, or x=y=z=1; \n J 1 , J 2 , J 3  and J 4  are chosen, independently of each other, from CA 1  and N; \n ALK represents a (C 1 -C 12 )alkylene group; \n A 1 , A 2 , A 3 , A 4 , A 5 , and A 6  represent, independently of each other, a hydrogen atom or a (C 1 -C 6 )alkyl group; \n (AA)w represents a sequence of w substituted amino acids (AA s ) or non-substituted amino acids (AA ns ) connected together via peptide bonds; \n w represents an integer ranging from 1 to 12; \n wherein:\n if (AA)w contains at least one substituted amino acid (AA s ), then L2 represents a single bond, a (C 1 -C 6 )alkyl group, a (C 1 -C 6 )alkyl-(OCH 2 CH 2 ) i  group, a (C 1 -C 6 )alkyl-(OCH 2 CH 2 ) i \u2014O(C 1 -C 6 )alkyl group, a (CH 2 CH 2 O) i (C 1 -C 6 )alkyl group, a CH(SO 3 H)\u2014(C 1 -C 6 )alkyl group, a (C 1 -C 6 )alkyl-CH(SO 3 H) group, a (C 1 -C 6 )alkyl-cyclohexyl group, a C(\u2550O)\u2014(C 1 -C 6 )alkyl group, a C(\u2550O)\u2014(C 1 -C 6 )alkyl-(OCH 2 CH 2 ) i  group, a C(\u2550O)\u2014(C 1 -C 6 )alkyl-(OCH 2 CH 2 ) i \u2014O(C 1 -C 6 )alkyl group, a C(\u2550O)\u2014(CH 2 CH 2 O) i (C 1 -C 6 )alkyl group, a C(\u2550O)\u2014CH(SO 3 H)\u2014(C 1 -C 6 )alkyl group, a C(\u2550O)\u2014(C 1 -C 6 )alkyl-CH(SO 3 H) group, a C(\u2550O)\u2014(C 1 -C 6 )alkyl-cyclohexyl group, a NA 8 -(C 1 -C 6 )alkyl group, a NA 8 -(C 1 -C 6 )alkyl-(OCH 2 CH 2 ) i  group, a NA 8 -(C 1 -C 6 )alkyl-(OCH 2 CH 2 ) i \u2014O(C 1 -C 6 )alkyl group, a NA 8 -(CH 2 CH 2 O) i (C 1 -C 6 )alkyl group, a NA 8 -(C 1 -C 6 )alkyl-CH(SO 3 H) group, a C(\u2550O)\u2014NA 8 -(C 1 -C 6 )alkyl group, a C(\u2550O)\u2014NA 8 -(C 1 -C 6 )alkyl-(OCH 2 CH 2 ) i  group, a C(\u2550O)\u2014NA 8 -(C 1 -C 6 )alkyl-(OCH 2 CH 2 ) i \u2014O(C 1 -C 6 )alkyl group, a C(\u2550O)\u2014NA 8 -(CH 2 CH 2 O) i (C 1 -C 6 )alkyl group, a C(\u2550O)\u2014NA 8 -(C 1 -C 6 )alkyl-CH(SO 3 H) group, a NA 7 -(C 1 -C 6 )alkyl group, a (C 1 -C 6 )alkyl-NA 7  group, a NA 7 -(CH 2 CH 2 O) i (C 1 -C 6 )alkyl group, a NA 7 -aryl group, a NA 7 -heteroaryl group, a (C 1 -C 6 )alkyl-NA 7 C(\u2550O)\u2014(C 1 -C 6 )alkyl group, a (C 1 -C 6 )alkyl-NA 7 C(\u2550O)\u2014(C 1 -C 6 )alkyl-(OCH 2 CH 2 ) i  group, a (C 1 -C 6 )alkyl-C(\u2550O)NA 7 -(C 1 -C 6 )alkyl group, a (C 1 -C 6 )alkyl-C(\u2550O)NA 7 -(C 1 -C 6 )alkyl-(OCH 2 CH 2 ) i  group, a (C 1 -C 6 )alkyl-NA 7 -(C 1 -C 6 )alkyl group, a (C 1 -C 6 )alkyl-NA 7 -(C 1 -C 6 )alkyl-(OCH 2 CH 2 ) i  group, a (C 1 -C 6 )alkyl-(OCH 2 CH 2 ) i \u2014NA 7 -(C 1 -C 6 )alkyl group, a C(\u2550O)\u2014NA 7 -(C 1 -C 6 )alkyl group, a C(\u2550O)\u2014(C 1 -C 6 )alkyl-NA 7  group, a C(\u2550O)\u2014NA 7 -(CH 2 CH 2 O) i (C 1 -C 6 )alkyl group, a C(\u2550O)\u2014NA 7 -aryl group, a C(\u2550O)\u2014NA 7 -heteroaryl group, a C(\u2550O)\u2014(C 1 -C 6 )alkyl-NA 7 C(\u2550O)\u2014(C 1 -C 6 )alkyl group, a C(\u2550O)\u2014(C 1 -C 6 )alkyl-NA 7 C(\u2550O)\u2014(C 1 -C 6 )alkyl-(OCH 2 CH 2 ) i  group, a C(\u2550O)\u2014(C 1 -C 6 )alkyl-C(\u2550O)NA 7 -(C 1 -C 6 )alkyl group, a C(\u2550O)\u2014(C 1 -C 6 )alkyl-C(\u2550O)NA 7 -(C 1 -C 6 )alkyl-(OCH 2 CH 2 ) i  group, a C(\u2550O)\u2014(C 1 -C 6 )alkyl-NA 7 -(C 1 -C 6 )alkyl group, a C(\u2550O)\u2014(C 1 -C 6 )alkyl-NA 7 -(C 1 -C 6 )alkyl-(OCH 2 CH 2 ) i  group, a C(\u2550O)\u2014(C 1 -C 6 )alkyl-(OCH 2 CH 2 ) i \u2014NA 7 -(C 1 -C 6 )alkyl group, a NA 8 -(C 1 -C 6 )alkyl-NA 7  group, a NA 8 -(C 1 -C 6 )alkyl-NA 7 C(\u2550O)\u2014(C 1 -C 6 )alkyl group, a NA 8 -(C 1 -C 6 )alkyl-NA 7 C(\u2550O)\u2014(C 1 -C 6 )alkyl-(OCH 2 CH 2 ) i  group, a NA 8 -(C 1 -C 6 )alkyl-C(\u2550O)NA 7 -(C 1 -C 6 )alkyl group, a NA 8 -(C 1 -C 6 )alkyl-C(\u2550O)NA 7 -(C 1 -C 6 )alkyl-(OCH 2 CH 2 ) i  group, a NA 8 -(C 1 -C 6 )alkyl-NA 7 -(C 1 -C 6 )alkyl group, a NA 8 -(C 1 -C 6 )alkyl-NA 7 -(C 1 -C 6 )alkyl-(OCH 2 CH 2 ) i  group, a NA 8 -(C 1 -C 6 )alkyl-(OCH 2 CH 2 ) i \u2014NA 7 -(C 1 -C 6 )alkyl group, a C(\u2550O)\u2014NA 8 -(C 1 -C 6 )alkyl-NA 7  group, a C(\u2550O)\u2014NA 8 -(C 1 -C 6 )alkyl-NA 7 C(\u2550O)\u2014(C 1 -C 6 )alkyl group, a C(\u2550O)\u2014NA 8 -(C 1 -C 6 )alkyl-NA 7 C(\u2550O)\u2014(C 1 -C 6 )alkyl-(OCH 2 CH 2 ) i  group, a C(\u2550O)\u2014NA 8 -(C 1 -C 6 )alkyl-C(\u2550O)NA 7 -(C 1 -C 6 )alkyl group, a C(\u2550O)\u2014NA 8 -(C 1 -C 6 )alkyl-C(\u2550O)NA 7 -(C 1 -C 6 )alkyl-(OCH 2 CH 2 ) i  group, a C(\u2550O)\u2014NA 8 -(C 1 -C 6 )alkyl-NA 7 -(C 1 -C 6 )alkyl group, a C(\u2550O)\u2014NA 8 -(C 1 -C 6 )alkyl-NA 7 -(C 1 -C 6 )alkyl-(OCH 2 CH 2 ) i  group or a C(\u2550O)\u2014NA 8 -(C 1 -C 6 )alkyl-(OCH 2 CH 2 ) i \u2014NA 7 -(C 1 -C 6 )alkyl group; \n wherein:\n if (AA)w represents a sequence of w non-substituted amino acids (AA ns ), then L2 represents a NA 7 -(C 1 -C 6 )alkyl group, a (C 1 -C 6 )alkyl-NA 7  group, a NA 7 -(CH 2 CH 2 O) i (C 1 -C 6 )alkyl group, a NA 7 -aryl group, a NA 7 -heteroaryl group, a (C 1 -C 6 )alkyl-NA 7 C(\u2550O)\u2014(C 1 -C 6 )alkyl group, a (C 1 -C 6 )alkyl-NA 7 C(\u2550O)\u2014(C 1 -C 6 )alkyl-(OCH 2 CH 2 ) i  group, a (C 1 -C 6 )alkyl-C(\u2550O)NA 7 -(C 1 -C 6 )alkyl group, a (C 1 -C 6 )alkyl-C(\u2550O)NA 7 -(C 1 -C 6 )alkyl-(OCH 2 CH 2 ) i  group, a (C 1 -C 6 )alkyl-NA 7 -(C 1 -C 6 )alkyl group, a (C 1 -C 6 )alkyl-NA 7 -(C 1 -C 6 )alkyl-(OCH 2 CH 2 ) i  group, a (C 1 -C 6 )alkyl-(OCH 2 CH 2 ) i \u2014NA 7 -(C 1 -C 6 )alkyl group, a C(\u2550O)\u2014NA 7 -(C 1 -C 6 )alkyl group, a C(\u2550O)\u2014(C 1 -C 6 )alkyl-NA 7  group, a C(\u2550O)\u2014NA 7 -(CH 2 CH 2 O) i (C 1 -C 6 )alkyl group, a C(\u2550O)\u2014NA 7 -aryl group, a C(\u2550O)\u2014NA 7 -heteroaryl group, a C(\u2550O)\u2014(C 1 -C 6 )alkyl-NA 7 C(\u2550O)\u2014(C 1 -C 6 )alkyl group, a C(\u2550O)\u2014(C 1 -C 6 )alkyl-NA 7 C(\u2550O)\u2014(C 1 -C 6 )alkyl-(OCH 2 CH 2 ) i  group, a C(\u2550O)\u2014(C 1 -C 6 )alkyl-C(\u2550O)NA 7 -(C 1 -C 6 )alkyl group, a C(\u2550O)\u2014(C 1 -C 6 )alkyl-C(\u2550O)NA 7 -(C 1 -C 6 )alkyl-(OCH 2 CH 2 ) i  group, a C(\u2550O)\u2014(C 1 -C 6 )alkyl-NA 7 -(C 1 -C 6 )alkyl group, a C(\u2550O)\u2014(C 1 -C 6 )alkyl-NA 7 -(C 1 -C 6 )alkyl-(OCH 2 CH 2 ) i  group, a C(\u2550O)\u2014(C 1 -C 6 )alkyl-(OCH 2 CH 2 ) i \u2014NA 7 -(C 1 -C 6 )alkyl group, a NA 8 -(C 1 -C 6 )alkyl-NA 7  group, a NA 8 -(C 1 -C 6 )alkyl-NA 7 C(\u2550O)\u2014(C 1 -C 6 )alkyl group, a NA 8 -(C 1 -C 6 )alkyl-NA 7 C(\u2550O)\u2014(C 1 -C 6 )alkyl-(OCH 2 CH 2 ) i  group, a NA 8 -(C 1 -C 6 )alkyl-C(\u2550O)NA 7 -(C 1 -C 6 )alkyl group, a NA 8 -(C 1 -C 6 )alkyl-C(\u2550O)NA 7 -(C 1 -C 6 )alkyl-(OCH 2 CH 2 ) i  group, a NA 8 -(C 1 -C 6 )alkyl-NA 7 -(C 1 -C 6 )alkyl group, a NA 8 -(C 1 -C 6 )alkyl-NA 7 -(C 1 -C 6 )alkyl-(OCH 2 CH 2 ) i  group, a NA 8 -(C 1 -C 6 )alkyl-(OCH 2 CH 2 ) i \u2014NA 7 -(C 1 -C 6 )alkyl group, a C(\u2550O)\u2014NA 8 -(C 1 -C 6 )alkyl-NA 7  group, a C(\u2550O)\u2014NA 8 -(C 1 -C 6 )alkyl-NA 7 C(\u2550O)\u2014(C 1 -C 6 )alkyl group, a C(\u2550O)\u2014NA 8 -(C 1 -C 6 )alkyl-NA 7 C(\u2550O)\u2014(C 1 -C 6 )alkyl-(OCH 2 CH 2 ) i  group, a C(\u2550O)\u2014NA 8 -(C 1 -C 6 )alkyl-C(\u2550O)NA 7 -(C 1 -C 6 )alkyl group, a C(\u2550O)\u2014NA 8 -(C 1 -C 6 )alkyl-C(\u2550O)NA 7 -(C 1 -C 6 )alkyl-(OCH 2 CH 2 ) i  group, a C(\u2550O)\u2014NA 8 -(C 1 -C 6 )alkyl-NA 7 -(C 1 -C 6 )alkyl group, a C(\u2550O)\u2014NA 8 -(C 1 -C 6 )alkyl-NA 7 -(C 1 -C 6 )alkyl-(OCH 2 CH 2 ) i  group or a C(\u2550O)\u2014NA 8 -(C 1 -C 6 )alkyl-(OCH 2 CH 2 ) i \u2014NA 7 -(C 1 -C 6 )alkyl group; \n A 7  represents a straight or branched, saturated or unsaturated, optionally substituted C 1 -C 160  hydrocarbon chain wherein optionally at least one methylene unit is independently replaced by \u2014NHC(\u2550O)\u2014, \u2014N(alkyl)C(\u2550O)\u2014, \u2014C(\u2550O)NH\u2014, \u2014C(\u2550O)N(alkyl)-, \u2014OC(\u2550O)\u2014, \u2014C(\u2550O)O\u2014, \u2014OC(\u2550O)O\u2014, \u2014CH(OH)\u2014, \u2014CH(SO 3 H)\u2014, \u2014O\u2014, \u2014C(\u2550O)\u2014, \u2014S(\u2550O)\u2014, \u2014S(\u2550O) 2 \u2014, \u2014NHS(\u2550O) 2 \u2014, \u2014N(alkyl)S(\u2550O) 2 \u2014, \u2014S(\u2550O) 2 NH\u2014, \u2014S(\u2550O) 2 N(alkyl)-, \u2014P(\u2550O)(OH)\u2014, \u2014P(\u2550O)(OH)O\u2014, \u2014O\u2014P(\u2550O)(OH)\u2014, \u2014O\u2014P(\u2550O)(OH)\u2014O\u2014 or a heterocycloalkyl group optionally substituted with at least one substituent, identical or different, chosen from \u2014OH, \u2014Oalkyl, -alkyl, a halogen atom, \u2014NH 2 , \u2014NHalkyl, and \u2014N(alkyl) 2 , wherein \u2014CH(SO 3 H)\u2014 is optionally the alkali metal salt; \n A 8  represents a hydrogen atom or a (C 1 -C 6 )alkyl group; and \n i represents an integer ranging from 1 to 50.

Metadata:
- Claim Count in Document: 55.0
- Percentile: 93.0
- Lexical Diversity: 1.61667
- Patent Class: 424.0
- Transitional Phrase Type: none
- Component Type: 0
- Foreign Priority: True
- Related Applications: ['14069057', '15581749', '15280563', '14843520', '14818455']

Analysis Scores:
- 35 USC 101 Eligibility (BERT): 0.7689765257209897
- 35 USC 102 Novelty (BERT): 0.5201640666652542
- Combined Prediction Score: 0.7440952798154162
- Mean Citation Score: 309.744996
- Max Citation Score: 313.26495
- Similarity Product: 214.99173091263768

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