Bispecific EGFR/c-Met antibodies

Patent metadata

Field	Value
Publication number	US-9695242-B2
Application number	US-201615386195-A
Country	US
Kind code	B2
Filing date	Dec 21, 2016
Priority date	Nov 21, 2012
Publication date	Jul 4, 2017
Grant date	Jul 4, 2017

Abstract

Bispecific EGFR/c-Met antibodies and methods of making and using the molecules.

First claim

What is claimed:

1. An isolated synthetic polynucleotide encoding a heavy chain 1 (HC1), a light chain 1 (LC1), a heavy chain 2 (HC2) and/or the light chain 2 (LC2) of an isolated bispecific epidermal growth factor receptor (EGFR)/hepatocyte growth factor receptor (c-Met) antibody wherein the HC1, the LC1, the HC2 and the LC2 comprise the amino acid sequences of SEQ ID NOs: 199, 200, 201 and 202, respectively.

2. The isolated polynucleotide of claim 1 , comprising the polynucleotide sequence of SEQ ID NOs: 205, 206, 207 or 208.

3. A vector comprising the polynucleotide of claim 1 or 2 .

4. An isolated host cell comprising the vector of claim 3 .

5. A method of producing an isolated bispecific EGFR/c-Met antibody, comprising:
a) combining an isolated monospecific bivalent anti-EGFR antibody comprising two heavy chains of SEQ ID NO: 199 and two light chains of SEQ ID NO: 200 and an isolated monospecific bivalent anti-c-Met antibody comprising two heavy chains of SEQ ID NO: 201 and two light chains of SEQ ID NO: 202 in a mixture of about 1:1 molar ratio;
b) introducing a reducing agent into the mixture;
c) incubating the mixture about ninety minutes to about six hours;
d) removing the reducing agent; and
e) purifying the bispecific EGFR/c-Met antibody that comprises a first heavy chain of SEQ ID NO: 199 and a second heavy chain of SEQ ID NO: 201, a first light chain of SEQ ID NO: 200 and a second light chain of SEQ ID NO: 202, wherein the first heavy chain of SEQ ID NO: 199 pairs with the first light chain of SEQ ID NO: 200 to form the first binding domain that specifically binds EGFR, and the second heavy chain of SEQ ID NO: 201 pairs with the second light chain of SEQ ID NO: 202 to form the second binding domain that specifically binds c-Met.

6. The method of claim 5 , wherein the reducing agent is 2-mercaptoethanolamine (2-MEA).

7. The method of claim 6 , wherein the 2-MEA is present at a concentration of about 25 mM to about 75 mM.

8. The method of claim 7 , wherein the incubating step is performed at a temperature of about 25° C. to about 37° C.

Assignees

• Janssen Biotech Inc

Inventors

• Chiu Mark
• Moores Sheri
• Neijssen Joost
• Parren Paul
• Schuurman Janine

Classifications

• A61P35/04

  specific for metastasis · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• C07K2318/20

  Antigen-binding scaffold molecules wherein the scaffold is not an immunoglobulin variable region or antibody mimetics · CPC title

• C07K2317/73

  Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation · CPC title