Immunoconjugates with an intracellularly-cleavable linkage

Patent metadata

Field	Value
Publication number	US-10280220-B2
Application number	US-201615174304-A
Country	US
Kind code	B2
Filing date	Jun 6, 2016
Priority date	Dec 13, 2002
Publication date	May 7, 2019
Grant date	May 7, 2019

Abstract

The invention relates to therapeutic conjugates with improved ability to target various cancer cells containing a targeting moiety and a therapeutic moiety. The targeting and therapeutic moieties are linked via an acid cleavable linkage that increases therapeutic efficacy of the immunoconjugate.

First claim

What is claimed is:

1. An immunoconjugate consisting essentially of:
a) an antibody or an antigen-binding fragment thereof, wherein said antibody or fragment thereof binds to a tumor-associated antigen CEACAM5; and
b) six or more molecules of SN-38 covalently attached to the antibody or antibody fragment; and
c) a linker attaching the SN-38 to the antibody or fragment thereof.

2. The immunoconjugate of claim 1 , wherein the linker moiety comprises a maleimide moiety that binds to a reduced sulfhydryl on the antibody or antibody fragment.

3. The immunoconjugate of claim 1 , wherein the linker is an intracellularly cleavable linker.

4. The immunoconjugate of claim 3 , wherein the linker comprises a peptide moiety that is cleavable by a lysosomal enzyme.

5. The immunoconjugate of claim 1 , wherein 7 to 12 SN-38 are attached to the antibody or antibody fragment.

6. The immunoconjugate of claim 1 , wherein the antibody is a chimeric, humanized or human antibody.

7. The immunoconjugate of claim 1 , wherein the antibody is hMN-14.

8. The immunoconjugate of claim 1 , wherein the antibody fragment is selected from the group consisting of a Fab, Fab′, F(ab) 2 , F(ab) 2 and scFv antibody fragment.

9. The immunoconjugate according to claim 1 , wherein said antibody comprises the heavy chain variable region CDR sequences CDR1 (TYWMS, SEQ ID NO:36), CDR2 (EIHPDSSTINYAPSLKD, SEQ ID NO:37) and CDR3 (LYFGFPWFAY, SEQ ID NO:38) and light chain variable region CDR sequences CDR1 (KASQDVGTSVA, SEQ ID NO:39), CDR2 (WTSTRHT, SEQ ID NO:40) and CDR3 (QQYSLYRS, SEQ ID NO:41).

10. The immunoconjugate of claim 1 , wherein the antibody is a humanized antibody.

Assignees

• Immunomedics Inc
• Ibc Pharmaceuticals Inc

Inventors

• Govindan Serengulam V

Classifications

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P7/06

  Antianaemics · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P33/02

  Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis · CPC title