US 12,268,752 B2
Non-natural amatoxin-type antibody conjugate
Yi Zhu, Sichuan (CN); Jie Li, Sichuan (CN); Yongguo Yu, Sichuan (CN); Weijia Liu, Sichuan (CN); and Shi Zhuo, Sichuan (CN)
Assigned to SYSTIMMUNE, INC., Redmond, WA (US)
Appl. No. 16/975,406
Filed by SICHUAN BAILI PHARMACEUTICAL CO. LTD., Sichuan (CN)
PCT Filed Aug. 18, 2018, PCT No. PCT/CN2018/101213
§ 371(c)(1), (2) Date Aug. 25, 2020,
PCT Pub. No. WO2019/034175, PCT Pub. Date Feb. 21, 2019.
Claims priority of application No. 201710710293.6 (CN), filed on Aug. 18, 2017.
Prior Publication US 2021/0030887 A1, Feb. 4, 2021
Int. Cl. A61K 47/68 (2017.01); C07K 16/32 (2006.01)
CPC A61K 47/6831 (2017.08) [A61K 47/6849 (2017.08); C07K 16/32 (2013.01)] 17 Claims
 
1. A non-natural amatoxin-antibody conjugate, comprising a toxin moiety having a structural formula (I) or a pharmaceutically acceptable salt thereof, and a biomacromolecule moiety A having a binding affinity to a target,

OG Complex Work Unit Chemistry
wherein:
R1 is H, —OH or —O-L-A;
R2 is H or —OH;
R3 is OC1-6 alkyl;
R4 is H or -L-A-NH2 or —OH;
R5 is —NH2, —OH, —NH-L-A or —O-L-A;
wherein O is an oxygen atom, N is a nitrogen atom and H is a hydrogen atom,
wherein A represents a biomacromolecule moiety, and
wherein L is a linker, comprising the following structure:
-L1-[L2]m-[AA]n-L3-,
wherein: L1 is a linker for connecting to A, and wherein L1 is selected from:

OG Complex Work Unit Chemistry
wherein a wavy line connects to A;
L2 is a spacer connecting L1 to AA; m is an integer selected from 1-6; L3 is a structural fragment connecting to the toxin moiety; AA is a structural fragment consisting of 1 to 6 amino acids, and n is 0 or 1.