Recombinant tumor specific antibody and use thereof

• US 7,459,538 B2
• Filed: 07/01/2005
• Issued: 12/02/2008
• Est. Priority Date: 05/03/2001
• Status: Expired due to Fees

• Current Assignee: Merck Patent GmbH (Merck & Co., Inc.)
• Original Assignee: Merck Patent GmbH (Merck & Co., Inc.)
• Inventors: Gillies, Stephen D., Lo, Kin-Ming, Qian, Susan Xiuqi
• Primary Examiner(s): Rawlings; Stephen L
• Application Number:
  US11/174,186
• Publication Number:
  US 20050244418A1
• Time in Patent Office: 1,250 Days
• Field of Search: 530/387.3, 530/387.7, 530/391.7, 530/350
• US Class Current: 530/387.3
• 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. An anti-EpCAM protein comprising an antibody that binds human EpCAM, said antibody comprising an immunoglobulin light chain variable region 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 anti-EpCAM protein of claim 1, wherein the antibody comprises amino acids 1-106 of SEQ ID NO:

9.

3. The anti-EpCAM protein of claim 1, wherein the antibody has a Kd for EpCAM of at least 10⁻

8 M.

4. The anti-EpCAM protein of claim 1, wherein the protein comprises a cytokine.

5. The anti-EpCAM protein of claim 4, wherein the cytokine is IL-2.

6. An anti-EpCAM protein, wherein the protein comprises an antibody that binds human EpCAM, said antibody comprising an immunoglobulin heavy chain variable region 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.

7. The anti-EpCAM protein of claim 6, wherein the antibody comprises amino acids 1-116 of SEQ ID NO:

18.

8. The anti-EpCAM protein of claim 6, wherein the antibody has a Kd for EpCAM of at least 10⁻

8 M.

9. The anti-EpCAM protein of claim 6, wherein the protein comprises a cytokine.

10. The anti-EpCAM protein of claim 9, wherein the cytokine is IL-2.

11. An anti-EpCAM protein, wherein the protein comprises an antibody that binds human EpCAM, said antibody comprising an antibody light chain comprising the amino acid sequence defined by residues 1-106 of SEQ ID NO:

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

18.

12. The anti-EpCAM protein of claim 11, wherein the protein comprises a cytokine.

13. The anti-EpCAM protein of claim 12, wherein the cytokine is IL-2.

14. A humanized or deimmunized anti-EpCAM protein suitable for administering into a human patient for treating a disease associated with EpCAM over-expression, wherein the protein comprises an antibody that binds human EpCAM, said antibody comprising an immunoglobulin light chain variable region 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.

15. A humanized or deimmunized anti-EpCAM protein suitable for administering into a human patient for treating a disease associated with EpCAM over-expression, wherein the protein comprises an antibody that binds human EpCAM, said antibody comprising an immunoglobulin heavy chain variable region 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.

16. A humanized or deimmunized anti-EpCAM protein suitable for administering into a human patient for treating a disease associated with EpCAM over-expression, wherein the protein comprises an antibody that binds human EpCAM, said antibody comprising an antibody light chain comprising the amino acid sequence defined by residues 1-106 of SEQ ID NO:

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

18.