PATENT CLAIM ANALYSIS

Application Number: 15961531
Application Type: Utility
Filing Date: 2018-04
Publication Date: 2018-08
Patent Classification: ["514", "001100"]

Abstract:
Disclosed herein are novel cytotoxic peptides of formula (I) as described herein: and the use of such peptides in making immunoconjugates (i.e Antibody Drug Conjugates) Also described herein are immunoconjugates (i.e Antibody Drug Conjugates) comprising such novel cytotoxic peptide linked to an antigen binding moiety, such as an antibody; where such immunoconjugates are useful for treating cell proliferative disorders. The invention further provides pharmaceutical compositions comprising these immunoconjugates, compositions comprising the immunoconjugates with a therapeutic co-agent, and methods to use these immunoconjugates and compositions for treating cell proliferation disorders.

Claim (Index 1):
An immunoconjugate of Formula (III): wherein:\n Ab represents an antigen binding moiety; \n L is selected from -L 1 L 2 L 3 L 4 L 5 L 6 -, -L 6 L 5 L 4 L 3 L 2 L 1 -, -L 1 L 2 L 3 L 4 L 5 -, -L 5 L 4 L 3 L 2 L 1 -, -L 1 L 2 L 3 L 4 -, -L 4 L 3 L 2 L 1 -, -L 1 L 2 L 3 -, -L 3 L 2 L 1 -, -L 1 L 2 -, -L 2 L 1 - and -L 1 , \n wherein \n L 1  is selected from \u2014(CH 2 ) m \u2014, \u2014C(\u2550O)(CH 2 ) m \u2014, \u2014C(\u2550O)X 1 X 2 C(\u2550O)(CH 2 ) m \u2014, \u2014C(\u2550O)X 1 X 2 C(\u2550O)(CH 2 ) m NR 12 C(\u2550O)(CH 2 ) m \u2014, \u2014C(\u2550O)X 1 X 2 C(\u2550O)(CH 2 ) m X 3 (CH 2 ) m \u2014, \u2014C(\u2550O)X 1 X 2 C(\u2550O)((CH 2 ) m O) 1 CH 2 ) m \u2014, \u2014C(\u2550O)X 1 X 2 C(\u2550O)((CH 2 ) m O) n (CH 2 ) m NR 12 C(\u2550O)(CH 2 ) m \u2014, \u2014C(\u2550O)X 1 X 2 C(\u2550O)((CH 2 ) m O) n (CH 2 ) m NR 12 C(\u2550O)(CH 2 ) m X 3 (CH 2 ) m \u2014, \u2014C(\u2550O)X 1 X 2 C(\u2550O)((CH 2 ) m O) n (CH 2 ) m X 3 (CH 2 ) m \u2014, \u2014C(\u2550O)X 1 X 2 C(\u2550O)(CH 2 ) m NR 12 C(\u2550O)((CH 2 ) m O) n (CH 2 ) m \u2014, \u2014C(\u2550O)X 1 X 2 C(\u2550O)(CH 2 ) m NR 12 C(\u2550O)((CH 2 ) m O) n (CH 2 ) m X 3 (CH 2 ) m \u2014, \u2014C(\u2550O)X 1 X 2 (CH 2 ) m X 3 (CH 2 ) m \u2014, \u2014C(\u2550O)X 1 X 2 ((CH 2 ) m O) n (CH 2 ) m \u2014, \u2014C(\u2550O)X 1 X 2 ((CH 2 ) m O) n (CH 2 ) m NR 12 C(\u2550O)(CH 2 ) m \u2014, \u2014C(\u2550O)X 1 X 2 ((CH 2 ) m O) n (CH 2 ) m NR 12 C(\u2550O)(CH 2 ) m X 3 (CH 2 ) m \u2014, \u2014C(\u2550O)X 1 X 2 ((CH 2 ) m O) n (CH 2 ) m X 3 (CH 2 ) m \u2014, \u2014C(\u2550O)X 1 X 2 (CH 2 ) m NR 12 ((CH 2 ) m O) n (CH 2 ) m \u2014, \u2014C(\u2550O)X 1 X 2 C(\u2550O)(CH 2 ) m NR 12 ((CH 2 ) m O) n (CH 2 ) m X 3 (CH 2 ) m \u2014, \u2014(CH 2 ) m NR 12 C(\u2550O)(CH 2 ) m \u2014, \u2014C(\u2550O)((CH 2 ) m O) n (CH 2 ) m \u2014, \u2014(CH 2 ) m S(\u2550O) 2 ((CH 2 ) m O) n (CH 2 ) m \u2014, \u2014C(\u2550O)(CH 2 ) m NR 12 (CH 2 ) m \u2014, \u2014C(\u2550O)NR 12 (CH 2 ) m \u2014, \u2014C(\u2550O)NR 12 (CH 2 ) m X 3 (CH 2 ) m \u2014, \u2014C(\u2550O)NH(CH 2 ) m NR 12 C(\u2550O)X 1 X 2 C(\u2550O)(CH 2 ) m \u2014, \u2014C(\u2550O)X 1 C(\u2550O)NR 12 (CH 2 ) m NR 12 C(\u2550O)(CH 2 ) m \u2014, \u2014C(\u2550O)X 1 C(\u2550O)NR 12 (CH 2 ) m X 3 (CH 2 ) m \u2014, \u2014C(\u2550O)NR 12 (CH 2 ) m NR 12 C(\u2550O)(CH 2 ) m \u2014, \u2014C(\u2550O)NR 12 (CH 2 ) m NR 12 C(\u2550O)(CH 2 ) m X 3 (CH 2 ) m \u2014, \n \u2003\u2014(CH 2 ) m C(\u2550O)NR 12 (CH 2 ) m NR 12 C(\u2550O)(CH 2 ) m \u2014, \u2014(CH 2 ) m C(\u2550O)\u2014, \u2014(CH 2 ) m C(\u2550O)X 2 X 1 C(\u2550O)\u2014, \u2014(CH 2 ) m X 3 (CH 2 ) m C(\u2550O)X 2 X 1 C(\u2550O)\u2014, \u2014(CH 2 ) m C(\u2550O)NR 12 (CH 2 ) m \u2014, \u2014(CH 2 ) m X 3 (CH 2 ) m C(\u2550O)NR 12 (CH 2 ) m \u2014, \u2014(CH 2 ) m NR 12 C(\u2550O)(CH 2 ) m X 3 (CH 2 ) m \u2014, \u2014(CH 2 ) m (O(CH 2 ) m ) n C(\u2550O)\u2014, \u2014(CH 2 ) m (O(CH 2 ) m ) n S(\u2550O) 2 (CH 2 ) m \u2014, \u2014(CH 2 ) m NR 12 (CH 2 ) m C(\u2550O)\u2014, \u2014(CH 2 ) m NR 12 C(\u2550O)\u2014, \u2014(CH 2 ) m C(\u2550O)X 2 X 1 C(\u2550O)NR 12 (CH 2 ) m NHC(\u2550O)\u2014, \u2014(CH 2 ) m C(\u2550O)NR 12 (CH 2 ) m NR 12 C(\u2550O)X 1 \u2014, \u2014(CH 2 ) m C(\u2550O)NR 12 (CH 2 ) m NR 12 C(\u2550O)\u2014, \u2003\u2014((CH 2 ) m O) n (CH 2 ) m \u2014, \u2014(CH 2 ) m (O(CH 2 ) m ) n \u2014, \u2014(CH 2 ) m (O(CH 2 ) m ) n X 3 (CH 2 ) m \u2014, \u2014(CH 2 ) m X 3 ((CH 2 ) m O) n (CH 2 ) m \u2014, \u2014(CH 2 ) m X 3 (CH 2 ) m C(\u2550O)\u2014, \u2014C(\u2550O)(CH 2 ) m X 3 (CH 2 ) m \u2014, \u2014(CH 2 ) m X 3 (CH 2 ) m (O(CH 2 ) m ) n C(\u2550O)\u2014, \u2014C(\u2550O)((CH 2 ) m O) n (CH 2 ) m X 3 (CH 2 ) m \u2014, \u2014(CH 2 ) m C(\u2550O)NR 12 (CH 2 ) m C(\u2550O)\u2014, \u2014C(\u2550O)(CH 2 ) m NR 12 C(\u2550O)(CH 2 ) m \u2014, \u2014C(\u2550O)(CH 2 ) m NR 12 C(\u2550O)O(CH 2 ) m \u2014, \u2014(CH 2 ) m OC(\u2550O)NR 12 (CH 2 ) m C(\u2550O)\u2014, \u2014S(\u2550O) 2 (CH 2 ) m NR 12 C(\u2550O)O(CH 2 ) m \u2014, \u2014(CH 2 ) m OC(\u2550O)NR 12 (CH 2 ) m S(\u2550O) 2 \u2014, \u2014(CH 2 ) m C(\u2550O)NR 12 (CH 2 ) m (O(CH 2 ) m ) n C(\u2550O)\u2014, \u2014C(\u2550O)((CH 2 ) m O) n (CH 2 ) m NR 12 C(\u2550O)(CH 2 ) m \u2014, \u2014(CH 2 ) m C(\u2550O)NR 12 (CH 2 ) m C(\u2550O)NR 12 (CH 2 ) m \u2014, \u2014(CH 2 ) m NR 12 C(\u2550O)(CH 2 ) m NR 12 C(\u2550O)(CH 2 ) m \u2014, \u2014C(\u2550O)NR 12 (CH 2 ) m NR 12 C(\u2550O)\u2014, \u2014(CH 2 ) m S(CH 2 ) m \u2014, \u2014NR 12 C(\u2550O)(CH 2 ) m \u2014, \u2014NR 12 C(\u2550O)(CH 2 ) m X 3 (CH 2 ) m \u2014, \u2014(CH 2 ) m X 3 (CH 2 ) m C(\u2550O)NR 12 \u2014, \u2014(CH 2 ) m C(\u2550O)NR 12 \u2014, \u2014(CH 2 ) m NR 12 (CH 2 ) m \u2014, \u2014(CH 2 ) m X 3 (CH 2 ) m \u2014, \u2014((CH 2 ) m O) n (CH 2 ) m X 3 (CH 2 ) m \u2014, \u2014(CH 2 ) m X 3 (CH 2 ) m (O(CH 2 ) m ) n \u2014, \u2014NR 12 (CH 2 ) m \u2014, \u2014NR 12 C(R 12 ) 2 (CH 2 ) m \u2014, \u2014(CH 2 ) m C(R 12 ) 2 NR 12 \u2014, \u2014(CH 2 ) m C(\u2550O)NR 12 (CH 2 ) m NR 12 \u2014, \u2014NR 12 (CH 2 ) m NR 12 C(\u2550O)(CH 2 ) m \u2014, \u2014NR 12 C(R 12 ) 2 (CH 2 ) m NR 12 C(\u2550O)(CH 2 ) m \u2014, \u2014(CH 2 ) m C(\u2550O)NR 12 (CH 2 ) m C(R 12 ) 2 NR 12 \u2014, \u2014NR 12 (CH 2 ) m X 3 (CH 2 ) m \u2014, \u2014NR 12 C(R 12 ) 2 (CH 2 ) m X 3 (CH 2 ) m \u2014, \u2014(CH 2 ) m X 3 (CH 2 ) m C(R 12 ) 2 NR 12 \u2014, \u2014NR 12 C(R 12 ) 2 (CH 2 ) m OC(\u2550O)NR 12 (CH 2 ) m \u2014, \u2014(CH 2 ) m NR 12 C(\u2550O)O(CH 2 ) m C(R 12 ) 2 NR 12 \u2014, \u2014NR 12 C(R 12 ) 2 (CH 2 ) m OC(\u2550O)NR 12 (CH 2 ) m X 3 (CH 2 ) m \u2014, \u2014NR 12 (CH 2 ) m O) n (CH 2 ) m X 3 (CH 2 ) m \u2014, \u2014(CH 2 ) m X 3 (CH 2 ) m (O(CH 2 ) m ) n NR 12 \u2014, \u2014NR 12 (CH 2 ) m O) n (CH 2 ) m \u2014, \u2014(CH 2 ) m (O(CH 2 ) m ) n NR 12 \u2014, \u2014NR 12 (CH 2 ) m O) n (CH 2 ) m \u2014, \u2014(CH 2 ) m X 3 (CH 2 ) m NR 12 C(\u2550O)O(CH 2 ) m C(R 12 ) 2 NR 12 \u2014, \u2014NR 12 C(R 12 ) 2 (CH 2 ) m OC(\u2550O)NR 12 ((CH 2 ) m O) n (CH 2 ) m \u2014, \u2014(CH 2 ) m (O(CH 2 ) m ) n NR 12 C(\u2550O)O(CH 2 ) m C(R 12 ) 2 NR 12 \u2014, \u2014NR 12 C(R 12 ) 2 (CH 2 ) m OC(\u2550O)NR 12 ((CH 2 ) m O) n (CH 2 ) m X 3 (CH 2 ) m \u2014, \u2014(CH 2 ) m X 3 (CH 2 ) m (O(CH 2 ) m ) n NR 12 C(\u2550O)O(CH 2 ) m C(R 12 ) 2 NR 12 \u2014, \u2014(CH 2 ) m X 3 (CH 2 ) m NR 12 \u2014, \u2014NR 12 ((CH 2 ) m O) n (CH 2 ) m X 3 (CH 2 ) m \u2014, \u2014(CH 2 ) m X 3 (CH 2 ) m (O(CH 2 ) m ) n NR 12 \u2014, \u2014(CH 2 ) m NR 12 \u2014, \u2014NR 12 ((CH 2 ) m O) n (CH 2 ) m \u2014, \u2014NR 12 ((CH 2 ) m O) n (CH 2 ) m NR 12 C(\u2550O)(CH 2 ) m \u2014, \u2014(CH 2 ) m C(\u2550O)NR 12 (CH 2 ) m (O(CH 2 ) m ) n NR 12 \u2014, \u2014(CH 2 ) m (O(CH 2 ) m ) n NR 12 \u2014, \u2014(C(R 12 ) 2 ) m \u2014, \u2014(CH 2 CH 2 O) n \u2014, \u2014(OCH 2 CH 2 ) n \u2014, \u2014(CH 2 ) m O(CH 2 ) m \u2014, \u2014S(\u2550O) 2 (CH 2 ) m \u2014, \u2014(CH 2 ) m S(\u2550O) 2 \u2014, \u2014S(\u2550O) 2 (CH 2 ) m NR 12 C(\u2550O)(CH 2 ) m \u2014, \u2014(CH 2 ) m C(\u2550O)NR 12 (CH 2 ) m S(\u2550O) 2 \u2014, \u2014S(\u2550O) 2 (CH 2 ) m X 3 (CH 2 ) m \u2014, \u2014(CH 2 ) m X 3 (CH 2 ) m S(\u2550O) 2 \u2014, \u2014(CH 2 ) m X 2 X 1 C(\u2550O)\u2014, \u2014C(\u2550O)X 1 X 2 (CH 2 ) m \u2014, \u2014(CH 2 ) m (O(CH 2 ) m ) n C(\u2550O)X 2 X 1 C(\u2550O)\u2014, \u2014C(\u2550O)X 1 X 2 C(\u2550O)((CH 2 ) m O) n (CH 2 ) m \u2014, \u2014(CH 2 ) m (O(CH 2 ) m ) n X 2 X 1 C(\u2550O)\u2014, \u2014(CH 2 ) m X 3 (CH 2 ) m X 2 X 1 C(\u2550O)\u2014, \u2014C(\u2550O)X 1 X 2 (CH 2 ) m X 3 (CH 2 ) m \u2014, \u2014(CH 2 ) m X 3 (CH 2 ) m (O(CH 2 ) m ) n X 2 X 1 C(\u2550O)\u2014, \u2014(CH 2 ) m X 3 (CH 2 ) m C(\u2550O)NR 12 (CH 2 ) m NR 12 C(\u2550O)\u2014, \u2014(CH 2 ) m X 3 (CH 2 ) m C(\u2550O)NR 12 (CH 2 ) m C(\u2550O)\u2014, \u2014C(\u2550O)(CH 2 ) m NR 12 C(\u2550O(CH 2 ) m X 3 (CH 2 ) m \u2014, \u2014(CH 2 ) m X 3 (CH 2 ) m C(\u2550O)NR 12 (CH 2 ) m (O(CH 2 ) m ) n C(\u2550O)\u2014, \u2014C(\u2550O)((CH 2 ) m O) n (CH 2 ) m NR 12 C(\u2550O)(CH 2 ) m X 3 (CH 2 ) m \u2014, \u2014(CH 2 ) m NR 12 C(\u2550O)X 1 X 2 C(\u2550O)(CH 2 ) m \u2014, \u2014(CH 2 ) m C(\u2550O)X 2 X 1 C(\u2550O)NR 12 (CH 2 ) m \u2014, \u2014X 4 X 1 X 2 C(\u2550O)(CH 2 ) m \u2014, \u2014(CH 2 ) m C(\u2550O)X 2 X 1 X 4 \u2014, \u2014X 1 C(\u2550O)(CH 2 ) m NHC(\u2550O)(CH 2 ) m \u2014, \u2014(CH 2 ) m C(\u2550O)NH(CH 2 ) m C(\u2550O)X 1 \u2014, \u2014C(\u2550O)CHR aa NR 12 \u2014, \u2014CHR aa C(\u2550O)\u2014, \u2014C(\u2550O)NR 12 \u2014, \u2014C(\u2550O)O\u2014, \u2014S\u2014, \u2014SCH 2 (C\u2550O)NR 12 \u2014, \u2014NR 12 C(\u2550O)CH 2 S\u2014, \u2014S(\u2550O) 2 CH 2 CH 2 S\u2014, \u2014SCH 2 CH 2 S(\u2550O) 2 \u2014, \u2014(CH 2 ) 2 S(\u2550O) 2 CH 2 CH 2 S\u2014, \u2014SCH 2 CH 2 S(\u2550O) 2 CH 2 CH 2 \u2014, \u2014NR 12 C(\u2550S)\u2014, \u2014(CH 2 ) m X 3 (O(CH 2 ) m ) n C(\u2550O)\u2014, \u2014C(\u2550O)((CH 2 ) m O) n X 3 (CH 2 ) m \u2014, \u2014(CH 2 ) m NR 12 C(\u2550O)((CH 2 ) m O) n (CH 2 ) m \u2014, \u2014(CH 2 ) m (O(CH 2 ) m ) n C(\u2550O)NR 12 (CH 2 ) m \u2014, \u2014(CH 2 ) m NR 12 C(\u2550O)NR 12 (CH 2 ) m \u2014, \u2014(CH 2 ) m X 3 (CH 2 ) m NR 12 C(\u2550O)\u2014, \u2014C(\u2550O)NR 12 (CH 2 ) m X 3 (CH 2 ) m \u2014, \u2014NR 12 S(\u2550O) 2 (CH 2 ) m X 3 (CH 2 ) m \u2014, \u2014(CH 2 ) m X 3 (CH 2 ) m S(\u2550O) 2 NR 12 \u2014, R 20  is H or Me, and R 30  is H, \u2014CH 3  or Phenyl: R 21  is each R 25  is independently selected from H or C 1-4  alkyl; R aa  is a side chain of an amino acid selected from glycine, alanine, tryptophan, tyrosine, phenylalanine, leucine, isoleucine, valine, asparagine, glutamic acid, glutamine, aspatic acid, histidine, arginine, lysine, cysteine, methionine, serine, threonine, phenylglycine and t-butylglycine; R 32  is independently selected from H, C 1-4  alkyl, phenyl, pyrimidine and pyridine; R 33  is independently selected from R 34  is independently selected from H, C 1-4  alkyl, and C 1-6  haloalkyl; X 1  is self immolative spacer selected from X 2  is dipeptide selected from X 3  is \u2003, and X 4  is and L 2 , L 3 , L 4 , L 5 , and L 6  are each independently selected from a bond and L 1 ; y is an integer from 1 to 16; R 1  is a 6 membered heterocycloalkyl containing 1-2 N heteroatoms and a C 1 -C 2 alkylene bridge, wherein the 6 membered heterocycloalkyl is unsubstituted or substituted with 1 to 3 substituents independently selected from R 5  and R 6 ; or R 1  is a 5-8 membered fused bicyclic heterocycloalkyl containing 1-2 N heteroatoms, wherein the 5-8 membered fused bicyclic heterocycloalkyl is unsubstituted or substituted with 1 to 3 substituents independently selected from R 5  and R 6 ; R 2  is \u2014C 1 -C 6 alkyl; R 3  is R 5  is C 1 -C 6 alkyl, \u2014C(\u2550O)R 11 , \u2014(CH 2 ) m OH, \u2014C(\u2550O)(CH 2 ) m OH, \u2014C(\u2550O)((CH 2 ) m O) n R 12 , \u2014((CH 2 ) m O) n R 12 , or C 1 -C 6 alkyl which is optionally substituted with \u2014CN, \u2014C(\u2550O)NH 2  or 1 to 5 hydroxyl; R 6  is halo, oxo, OH, C 1 -C 6 alkyl, \u2014N(R 14 ) 2 , \u2014R 16  and \u2014NR 12 C(\u2550O)R 11 ; R 11  is C 1 -C 6 alkyl or C 1 -C 6 alkyl which is optionally substituted with 1 to 5 hydroxyl; each R 12  is independently selected from H and C 1 -C 6 alkyl; each R 14  is independently selected from H and C 1 -C 6 alkyl; R 16  is an N-linked 4-8 membered heterocycloalkyl containing 1-2 heteroatoms independently selected from N and O; R 17  is a bond, \u2014NH\u2014, \u2014NHS(\u2550O) 2 \u2014, R 18  is a bond, R 19  is H or C 1 -C 6 alkyl; each m is independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10, and each n is independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 and 18.

Metadata:
- Claim Count in Document: 23.0
- Percentile: 91.0
- Lexical Diversity: 1.75862
- Patent Class: 514.0
- Transitional Phrase Type: none
- Component Type: 0
- Foreign Priority: False
- Related Applications: ['15104727', '15822930', '15524197', '16098289', '14305643']

Analysis Scores:
- 35 USC 101 Eligibility (BERT): 0.7929630608482588
- 35 USC 102 Novelty (BERT): 0.6952364901520925
- Combined Prediction Score: 0.7831904037786422
- Mean Citation Score: 488.761508
- Max Citation Score: 729.10266
- Similarity Product: 688.4232361055409

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

Dataset: test