Recombinant tumor specific antibody and use thereof

• US 6,969,517 B2
• Filed: 05/03/2002
• Issued: 11/29/2005
• Est. Priority Date: 05/03/2001
• Status: Expired due to Fees

• Current Assignee: Merck Patent GmbH (Merck & Co., Inc.)
• Original Assignee: EMD Lexigen Research Center Corp.
• Inventors: Gillies, Stephen D., Lo, Kin-Ming, Qian, Susan X.
• Primary Examiner(s): Helms, Larry R.
• Assistant Examiner(s): Rawlings, Stephen L.
• Application Number:
  US10/138,727
• Publication Number:
  US 20030157054A1
• Time in Patent Office: 1,306 Days
• Field of Search: 424/133.1, 424/181.1, 424/182.1, 424/138.1, 530/387.3, 530/387.7, 530/391.7
• US Class Current: 424/133.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/30 from tumour cells
• CPC Class Codes: C07K 16/46 Hybrid immunoglobulins hybrids of an immunoglobulin with a peptide not being an immunoglobulin C07K19/00
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto

Abstract

The invention provides a family of antibodies that specifically bind the human epithelial cell adhesion molecule. The antibodies comprise modified variable regions, more specially, modified framework regions, which reduce their immunogenicity when administered to a human. The antibodies, when coupled to the appropriate moiety, may be used in the diagnosis, prognosis and treatment of cancer.

Claims

1. A method of treating a human patient having a cancer associated with EpCAM over-expression, said method comprising the step of administering an anti-EpCAM protein, wherein the protein comprises an antibody that binds human EpCAM, said antibody comprising a light chain comprising (i) amino acid residues 24-31 of SEQ ID NO:

1;

(ii) amino acid residues 49-55 of SEQ ID NO;

1; and

(iii) amino acid residues 88-96 of SEQ ID NO;

1; and

further comprising an amino acid sequence defining an immunoglobulin light chain framework region selected from the group consisting of;

(i) amino acid residues 1-23 of SEQ ID NO;

8; and

(ii) amino acid residues 1-23 of SEQ ID NO;

9.

2. The method of claim 1, wherein said light chain comprises amino acids 1-106 of SEQ ID NO:

9.

3. A method of treating a human patient having a cancer associated with EpCAM over-expression, said method comprising the step of administering an anti-EpCAM protein, wherein the protein comprises an antibody that binds human EpCAM, said antibody comprising a heavy chain comprising (i) amino acid residues 26-35 of SEQ ID NO:

2, (ii) amino acid residues 50-62 of SEQ ID NO;

2, and (iii) amino acid residues 101-105 of SEQ ID NO;

2; and

further comprising an amino acid sequence defining an immunoglobulin heavy chain framework region selected from the group consisting of;

(i) amino acid residues 1-25 of SEQ ID NO;

18; and

(ii) amino acid residues 67-98 of SEQ ID NO;

18.

4. The method of claim 3, wherein said heavy chain comprises amino acids 1-116 of SEQ ID NO:

18.

5. A method of treating a human patient having a cancer associated with EpCAM over-expression, said method comprising the step of administering an anti-EpCAM protein comprising an antibody that binds human EpCAM and that comprises an antibody light chain comprising an amino acid sequence defined by residues 1-106 of SEQ ID NO:

9 and an antibody heavy chain comprising an amino acid sequence defined by residues 1-116 of SEQ ID NO;

18.