Self-stabilizing linker conjugates

Patent metadata

Field	Value
Publication number	US-9504756-B2
Application number	US-201313799244-A
Country	US
Kind code	B2
Filing date	Mar 13, 2013
Priority date	May 15, 2012
Publication date	Nov 29, 2016
Grant date	Nov 29, 2016

Abstract

The present invention provides Ligand-Drug Conjugates, Drug-Linkers, Linkers, and Ligand-Linker Conjugates comprising a self-stabilizing linker assembly component.

First claim

What is claimed is:

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.

Assignees

• Seattle Genetics Inc

Inventors

• Lyon Robert
• Doronina Svetlana O
• Bovee Timothy

Classifications

• C07D207/36 Primary

  Oxygen or sulfur atoms · CPC title

• C07D207/40 Primary

  2,5-Pyrrolidine-diones · CPC title

• A61K47/65

  Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers · CPC title

• C07K7/02

  Linear peptides containing at least one abnormal peptide link · CPC title

• C07K5/06052

  Val-amino acid · CPC title