US 11,732,038 B2
Conjugates comprising cell-binding agents and cytotoxic agents
Nathan Elliott Fishkin, Weymouth, MA (US); Daniel J. Tavares, Natick, MA (US); Lingyun Rui, Weston, MA (US); Luke B. Harris, Boston, MA (US); Manami Shizuka, Belmont, MA (US); Michael Louis Miller, Framingham, MA (US); and Ravi V. J. Chari, Newton, MA (US)
Assigned to IMMUNOGEN, INC., Waltham, MA (US)
Filed by IMMUNOGEN, INC., Waltham, MA (US)
Filed on Feb. 12, 2021, as Appl. No. 17/174,911.
Application 17/174,911 is a division of application No. 14/843,429, filed on Sep. 2, 2015, granted, now 10,988,531.
Claims priority of provisional application 62/186,235, filed on Jun. 29, 2015.
Claims priority of provisional application 62/149,379, filed on Apr. 17, 2015.
Claims priority of provisional application 62/086,986, filed on Dec. 3, 2014.
Claims priority of provisional application 62/045,264, filed on Sep. 3, 2014.
Prior Publication US 2021/0299271 A1, Sep. 30, 2021
Int. Cl. A61K 47/68 (2017.01); C07K 16/28 (2006.01); A61K 31/5517 (2006.01); A61K 39/00 (2006.01)
CPC C07K 16/28 (2013.01) [A61K 31/5517 (2013.01); A61K 47/6803 (2017.08); A61K 47/6849 (2017.08); A61K 47/6851 (2017.08); C07K 16/2866 (2013.01); A61K 2039/505 (2013.01); C07K 2317/21 (2013.01); C07K 2317/24 (2013.01); C07K 2317/515 (2013.01); C07K 2317/56 (2013.01); C07K 2317/73 (2013.01)] 6 Claims
OG exemplary drawing
 
1. A cytotoxic compound represented by the following structural formula:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
LD″ and LD′″ are both —H;
LD′ is represented by the following formula:
—NR5—P—C(═O)—(CRaRb)f—Zd1—(CRaRb)r′-JCB  (A′)
Zd1 is absent, —C(═O)—NR9— or —NR9—C(═O)—;
P is a peptide containing between 2 to 5 amino acid residues;
Ra and Rb, for each occurrence, are independently —H, (C1-C3)alkyl or a charged substituent or an ionizable group Q;
r and r′ are independently an integer from 1 to 6;
the double line custom character between N and C represents a single bond or a double bond, provided that when it is a double bond X is absent and Y is —H, and when it is a single bond, X is —H, and Y is —OH or —SO3M, wherein M is H+, Na+or K+;
X′ is —H
Y′ is —H
R1, R2, R3, R4, R1′, R2′, R3′ and R4′ are each —H;
R6 is —OMe;
A and A′ are each —O;
R5 and R9 are each independently —H or Me;
JCB is

OG Complex Work Unit Chemistry