Internalizing ErbB2 Antibodies

Patent metadata

Field	Value
Publication number	US-2016279262-A1
Application number	US-201615177999-A
Country	US
Kind code	A1
Filing date	Jun 9, 2016
Priority date	Apr 24, 1998
Publication date	Sep 29, 2016
Grant date	—

Abstract

This invention provides novel erbB2-binding internalizing antibodies. The antibodies, designated F5 and C1, specifically bind to c-erbB2 antigen and, upon binding, are readily internalizing into the cell bearing the c-erbB2 marker. Chimeric molecules comprising the F5 and/or C1 antibodies attached to one or more effector molecules are also provided.

First claim

What is claimed is:

1 . An internalizing antibody that specifically binds to an ErbB2 epitope bound by a C1 antibody comprising the amino acid sequence set forth in SEQ ID NO: 2, which internalizing antibody binds to ErbB2 with an affinity of 10 −5 M to 10 −12 M and shares at least 70% sequence identity with the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2.

2 . The internalizing antibody of claim 1 , wherein the antibody binds to ErbB2 with an affinity of about 100 nM or better.

3 . The internalizing antibody of claim 1 , wherein the internalizing antibody comprises an amino acid sequence that differs from the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2 by no more than 30 residues.

4 . The internalizing antibody of claim 2 , wherein the antibody comprises a C-terminal cysteine residue.

5 . The internalizing antibody of claim 4 , wherein the internalizing antibody is coupled to a liposome.

6 . The liposome-coupled antibody of claim 5 , wherein the liposome bears an external hydrophilic polymer.

7 . The liposome-coupled antibody of claim 6 , wherein the external hydrophilic polymer is a polyethylene glycol (PEG).

8 . The liposome-coupled antibody of claim 7 , wherein the antibody is coupled to the liposome through the external hydrophilic polymer.

9 . The liposome-coupled antibody of claim 8 , wherein the antibody is coupled to the liposome through the polyethylene glycol.

10 . The liposome-coupled antibody of claim 9 , wherein the liposome is a doxorubicin containing liposome.

11 . The liposome-coupled antibody of claim 10 , wherein the liposome is taken up by SKBR3 cells in vitro.

12 . A pharmaceutical composition comprising the liposome-coupled antibody of claim 9 in a pharmaceutically acceptable carrier.

13 . A method of treating a HER2 positive carcinoma, the method comprising administering the composition of claim 12 to a patient suffering from a HER2 positive carcinoma in therapeutically effective dose.

14 . The method of claim 13 , wherein the composition is administered by single or multiple administrations.

15 . The method of claim 14 , wherein the composition is administered intravenously.

16 . An internalizing antibody comprising the six CDRs of a C1 antibody comprising the amino acid sequence set forth in SEQ ID NO: 2.

17 . The internalizing antibody of claim 16 , wherein the antibody is a human antibody.

Assignees

• Univ California

Inventors

• Marks James D
• Poul Marie Alix

Classifications

• C07K16/32

  against translation products of oncogenes · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• A61K47/6855

  the tumour determinant being from breast cancer cell · CPC title

• C07K2319/02

  containing a signal sequence · CPC title

• C12N2795/10043

  viral genome or elements thereof as genetic vector · CPC title