Immunoconjugates with an intracellularly-cleavable linkage

Patent metadata

Field	Value
Publication number	US-9388237-B2
Application number	US-201313921747-A
Country	US
Kind code	B2
Filing date	Jun 19, 2013
Priority date	Dec 13, 2002
Publication date	Jul 12, 2016
Grant date	Jul 12, 2016

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 comprising:
a) an anti-EGP-1 antibody or an antigen-binding fragment thereof; and
b) six or more molecules of SN-38 covalently attached to the antibody or antibody fragment, wherein the attachment between SN-38 and antibody or antibody fragment involves a covalent bond with the C-20 hydroxyl group of the SN-38.

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

3. The immunoconjugate of claim 1 , further comprising a linker between the antibody or antibody fragment and the SN-38.

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

5. The immunoconjugate of claim 1 , wherein the antibody is hRS7.

6. 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.

7. The immunoconjugate according to claim 1 , wherein said antibody or antibody fragment comprises light chain variable region complementarity determining region (CDR) sequences CDR1 (KASQDVSIAVA, SEQ ID NO:7), CDR2 (SASYRYT, SEQ ID NO:8) and CDR3 (QQHYITPLT, SEQ ID NO:9) and heavy chain variable region CDR sequences CDR1 (NYGMN, SEQ ID NO:10), CDR2 (WINTYTGEPTYTDDFKG, SEQ ID NO:11) and CDR3 (GGFGSSYWYFDV, SEQ ID NO:12).

8. An immunoconjugate comprising:
a) an anti-EGP-1 antibody or antigen-binding fragment thereof; and
b) at least one molecule of SN-38 covalently attached to the antibody or antibody fragment, wherein the attachment between SN-38 and antibody or antibody fragment involves a covalent bond with the C-20 hydroxyl group of the SN-38.

9. The immunoconjugate of claim 8 wherein the antibody is RS7.

10. The immunoconjugate of claim 8 , wherein the antibody or antibody fragment comprises light chain variable region CDR sequences CDR1 (KASQDVSIAVA, SEQ ID NO:7), CDR2 (SASYRYT, SEQ ID NO:8) and CDR3 (QQHYITPLT, SEQ ID NO:9) and heavy chain variable region CDR sequences CDR1 (NYGMN, SEQ ID NO:10), CDR2 (WINTYTGEPTYTDDFKG, SEQ ID NO:11) and CDR3 (GGFGSSYWYFDV, SEQ ID NO:12).

11. The immunoconjugate of claim 8 , wherein the antibody is a humanized antibody.

Assignees

• Immunomedics Inc

Inventors

• Govindan Serengulam V

Classifications

• A61P7/06

  Antianaemics · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P37/06

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

• A61P31/12

  Antivirals · CPC title

• A61P31/10

  Antimycotics · CPC title