Recombinant tumor specific antibody and use thereof

• US 7,803,618 B2
• Filed: 08/29/2008
• Issued: 09/28/2010
• 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: Qian, Susan Xiuqi, Gillies, Stephen D., Lo, Kin-Ming
• Primary Examiner(s): Rawlings; Stephen L
• Application Number:
  US12/201,935
• Publication Number:
  US 20100174056A1
• Time in Patent Office: 760 Days
• Field of Search: 536/23.5, 435/69.1, 435/320.1, 435/325, 435/328, 530/387.3, 530/387.7, 530/388.22
• US Class Current: 435/328
• 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 nucleic acid encoding an anti-EpCAM protein comprising an antibody that binds human EpCAM and that comprises:

(a) 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

(b) 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 nucleic acid of claim 1, wherein the antibody comprises amino acids 1-106 of SEQ ID NO:

9.

3. The nucleic acid of claim 1, wherein the antibody has a Kd for EpCAM of at least 10⁻

8 M.

4. The nucleic acid of claim 1, wherein the protein comprises a cytokine.

5. The nucleic acid of claim 4, wherein the cytokine is IL-2.

6. A cell comprising the nucleic acid of claim 1.

7. A nucleic acid encoding an anti-EpCAM protein, wherein the protein comprises an antibody that binds human EpCAM and that comprises:

(a) 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

(b) 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.

8. The nucleic acid of claim 7, wherein the antibody comprises amino acids 1-116 of SEQ ID NO:

18.

9. The nucleic acid of claim 7, wherein the antibody has a Kd for EpCAM of at least 10⁻

8 M.

10. The nucleic acid of claim 7, wherein the protein comprises a cytokine.

11. The nucleic acid of claim 10, wherein the cytokine is IL-2.

12. A cell comprising the nucleic acid of claim 7.

13. A nucleic acid encoding an anti-EpCAM protein, wherein the protein comprises an antibody that binds human EpCAM and that comprises an antibody light chain variable region comprising an amino acid sequence defined by residues 1-106 of SEQ ID NO:

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

18.

14. The nucleic acid of claim 13, wherein the protein comprises a cytokine.

15. The nucleic acid of claim 14, wherein the cytokine is IL-2.

16. A cell comprising the nucleic acid of claim 13.

17. A nucleic acid encoding 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 and that comprises:

(a) 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

(b) 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.

18. A nucleic acid encoding 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 and that comprises:

(a) 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

(b) 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.

19. A nucleic acid encoding 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 and that comprises an antibody light chain variable region comprising an amino acid sequence defined by residues 1-106 of SEQ ID NO:

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

18.