Back to results
US 2021/0260211 A1Published application
Antibody Drug Conjugates Having Derivatives of Amatoxin As The Drug
AssigneeSorrento Therapeutics, Inc.
InventorsTong Zhu, Hong Zhang, Alisher B. Khasanov, Gang Chen
Life of this patent
Estimating the term…
Abstract
There is disclosed derivatives of amanitin conjugated to a targeting antibody to form an ADC (antibody drug conjugate).
Claims30
1-3. (canceled)
A compound having a structure of the following formula:
- L1-L2-X-D
- or a pharmaceutically acceptable salt thereof,
- wherein:
- L1-L2 is a linker selected from
- L2-X has a structure of
- wherein R4 is hydrogen or C1-6 alkyl;
- and the wavy line indicates the point of attachment to D;
- L2 is a linker comprising (a) —R6OC(O)NR5—, and (b) —(CH2)p—, —(CH2CH2O)m—, —C(O)NH—, —NHC(O)—, or a combination of two or more thereof, wherein:
- R5 is hydrogen, C1-6 alkyl, —(CH2)p—, —(CH2CH2O)m—, or a combination of two or more thereof;
- R6 is Val-Cit-PAB or Ala-Ala-Asn-PAB;
- wherein —R6OC(O)NR5— is connected to L1 through R5 or R6;
- D is a drug moiety active agent derived from amatoxin having a structure of Formula (II):
- wherein R1 is NH2 or OR2;
- R2 is H or C1-10 alkyl;
- R3 is H or OH;
- and the wavy line indicates the point of attachment to X;
- m is an integer from 1-24;
- and
- p is an integer from 1-6.
16 more elements
An antibody drug conjugate (ADC) having the structure of Formula (I):
- AbL1-L2-X-D)n (I)
- or a pharmaceutically acceptable salt thereof,
- wherein:
- Ab is a monoclonal antibody;
- L1-L2 is a linker selected from
- wherein the wavy line indicates the point of attachment to Ab;
- L2-X has a structure of
- wherein R4 is hydrogen or C1-6 alkyl;
- and the wavy line indicates the point of attachment to D;
- L2 is a linker comprising —R8—S—S—R7—, wherein:
- R7 is C2-6 alkylene or —(CH2CH2O)m—;
- R8 is selected from C1-6 alkyl, C1-6 alkylene, substituted C1-6 alkylene, —C(O)NH—, —C(O)—NH—CHR9—CR10R11—, —NHC(O)—CHR9—CR10R11—, —(CH2CH2O)m—, and combinations thereof;
- R9 is selected from hydrogen, C1-6 alkyl, C1-6 alkylene, —(CH2CH2O)m—, —C(O)NH—, —NHC(O)—, —C(O)NH—(CH2)p—SO3H, C(O)NH—(CH2)p—CO2H, —NHC(O)—(CH2)p—SO3H, —NHC(O)—(CH2)p—CO2H, and combinations thereof;
- R10 and R11 are each independently selected from hydrogen, C1-6 alkyl, and combinations thereof;
- wherein —R8—S—S—R7— is connected to L1 through R8;
- D is a drug moiety active agent derived from amatoxin having a structure of Formula (II):
- wherein R1 is NH2 or OR2;
- R2 is H or C1-10 alkyl;
- R3 is H or OH;
- and the wavy line indicates the point of attachment to X;
- n is an integer from 1-10;
- m is an integer from 1-24;
- and
- p is an integer from 1-6.
21 more elements
A compound having the structure of the following formula:
- L1-L2-X-D
- or a pharmaceutically acceptable salt thereof,
- wherein:
- L1-L2 is a linker selected from
- L2-X has a structure of
- wherein R4 is hydrogen or C1-6 alkyl;
- and the wavy line indicates the point of attachment to D;
- L2 is a linker comprising —R8—S—S—R7—, wherein:
- R7 is C2-6 alkylene or —(CH2CH2O)m—;
- R8 is selected from C1-6 alkyl, C1-6 alkylene, substituted C1-6 alkylene, —C(O)NH—, —C(O)—NH—CHR9—CR10R11—, —NHC(O)—CHR9—CR10R11—, —(CH2CH2O)m—, and combinations thereof;
- R9 is selected from hydrogen, C1-6 alkyl, C1-6 alkylene, —(CH2CH2O)m—, —C(O)NH—, —NHC(O)—, —C(O)NH—(CH2)p—SO3H, C(O)NH—(CH2)p—CO2H, —NHC(O)—(CH2)p—SO3H, —NHC(O)—(CH2)p—CO2H, and combinations thereof;
- R10 and R11 are each independently selected from hydrogen, C1-6 alkyl, and combinations thereof;
- wherein —R8—S—S—R7— is connected to L1 through R8;
- D is a drug moiety active agent derived from amatoxin having a structure of Formula (II):
- wherein R1 is NH2 or OR2;
- R2 is H or C1-10 alkyl;
- R3 is H or OH;
- and the wavy line indicates the point of attachment to X;
- m is an integer from 1-24;
- and
- p is an integer from 1-6.
18 more elements
A method of treating a cancer in an individual in need thereof, comprising administering an effective amount of an antibody drug conjugate (ADC) to the individual, wherein the ADC has the structure of Formula (I):
- AbL1-L2-X-D)n (I)
- or a pharmaceutically acceptable salt thereof,
- wherein:
- Ab is a monoclonal antibody;
- L1-L2 is a linker selected from
- wherein the wavy line indicates the point of attachment to Ab;
- L2-X has a structure of
- wherein R4 is hydrogen or C1-6 alkyl, and the wavy line indicates the point of attachment to D;
- L2 is a linker comprising (a) —R6OC(O)NR5—, and (b) —(CH2)p—, —(CH2CH2O)m—, —C(O)NH—, —NHC(O)—, or a combination of two or more thereof, wherein:
- R5 is hydrogen, C1-6 alkyl, —(CH2)p—, —(CH2CH2O)m—, or a combination of two or more thereof;
- R6 is Val-Cit-PAB or Ala-Ala-Asn-PAB;
- wherein —R6OC(O)NR5— is connected to L1 through R5 or R6;
- D is a drug moiety active agent derived from amatoxin having a structure of Formula (II):
- wherein R1 is NH2 or OR2, R2 is H or C1-10 alkyl, and R3 is H or OH;
- and
- the wavy line indicates the point of attachment to X;
- n is an integer from 1-10;
- m is an integer from 1-24;
- and
- p is an integer from 1-6.
17 more elements
Dependencies are inferred from the claim text.