Self-stabilizing linker conjugates
View Patent ↗The present invention provides Ligand-Drug Conjugates, Drug-Linkers, Linkers, and Ligand-Linker Conjugates comprising a self-stabilizing linker assembly component.
1. A Ligand-Functional Agent Conjugate having the formula:
or a salt thereof, wherein
L is a Ligand unit directly attached to the succinimide ring of the Functional Agent Conjugate via a thioether linkage;
D′ is a Drug unit;
the subscript p ranges from 1 to 20;
—W— is an optional Cleavable unit,
the subscript w′ is 0 or 1;
—Y— is an optional Spacer unit,
the subscript y′ is 0 or 1;
A′ is an optional Stretcher unit; and
the subscript a′ is 0 or 1.
2. A Ligand-Functional Agent Conjugate of claim 1 , or a pharmaceutically acceptable salt thereof; wherein
L is an antibody.
3. A Ligand-Functional Agent Conjugate of claim 1 wherein p is 1 to 12.
4. A Ligand-Functional Agent Conjugate of claim 1 wherein p is 1 to 8.
5. A Ligand-Functional Agent Conjugate of claim 1 wherein a′ is 0, and W w′ is a dipeptide.
6. A Ligand-Functional Agent Conjugate of claim 1 wherein D′ is a cytotoxic agent.
7. A Ligand-Functional Agent Conjugate of claim 1 wherein D′ is an auristatin selected from the group consisting of AE, AFP, AEB, AEVB, MMAF and MMAE.
8. A Ligand-Functional Agent Conjugate of claim 1 wherein W w′ is selected from the group consisting of Val-Cit, Phe-Lys and Val-Ala.
9. A Ligand-Functional Agent Conjugate of claim 1 wherein Y y′ is a PAB unit.
10. A Ligand-Functional Agent Conjugate of claim 2 wherein the antibody is a monoclonal antibody.
11. A Ligand-Functional Agent Conjugate of claim 1 wherein the subscript a′ is 0; W w′ is Val-Cit; and Y y′ is PAB.
12. A Ligand-Functional Agent Conjugate of claim 1 wherein the subscript a′ is 0; W w′ is Val-Cit; Y y′ is PAB; and D′ is a cytotoxic agent.
13. A Ligand-Functional Agent Conjugate of claim 1 wherein the subscript a′ is 0; W w′ is Val-Cit; Y y′ is PAB; D′ is a cytotoxic agent; and p is 1 to 8.
14. A Ligand-Functional Agent Conjugate of claim 1 , wherein D′ is MMAE.
15. A Ligand-Functional Agent Conjugate of claim 1 , wherein the subscript a′ is 0; W w′ is Val-Cit; Y y′ is PAB; and D′ is MMAE.