Truncated EGF receptor

• US 7,449,559 B2
• Filed: 08/22/2005
• Issued: 11/11/2008
• Est. Priority Date: 06/28/2000
• Status: Expired due to Fees

• Current Assignee: Commonwealth Scientific & Industrial Research Organisation (Commonwealth Of Australia As Represented By Department Of Industry, Innovation, Climate Change, Science, Research And Tertiary Education), Ludwig Institute for Cancer Research, Ltd.
• Original Assignee: Commonwealth Scientific & Industrial Research Organisation (Commonwealth Of Australia As Represented By Department Of Industry, Innovation, Climate Change, Science, Research And Tertiary Education), Ludwig Institute for Cancer Research, Ltd.
• Inventors: Nice, Edouard Collins, McKern, Neil Moreton, Adams, Timothy Edward, Domagala, Teresa Anne, Garrett, Thomas Peter John, Lovrecz, George Oscar, Elleman, Thomas Charles, Jorissen, Robert Nicholas, Ward, Colin Wesley, Burgess, Antony Wilkes
• Primary Examiner(s): Spector; Lorraine
• Assistant Examiner(s): KAUFMAN, CLAIRE M
• Application Number:
  US11/209,187
• Publication Number:
  US 20060234343A1
• Time in Patent Office: 1,177 Days
• Field of Search: None
• US Class Current: 530/402
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/71 for growth factors; for growth regulators

Abstract

The present invention relates to truncated EGF receptor molecules that exhibit increased binding affinities for EGFR ligands such as EGF and TGF1. The present invention also relates to methods of screening for EGF receptor ligands and methods of treatment which involve the use of these molecules.

Claims

1. An isolated or purified truncated ErbB4 epidermal growth factor receptor (EGFR) ectodomain comprising at least residues 1 to 488 of ErbB4 (SEQ ID NO:

4), the truncated EGFR ectodomain lacking at least the third to seventh modules of the CR2 domain such that a homodimer of the truncated EGFR ectodomain has an increased binding affinity for at least one EGFR ligand when compared to a homodimer of the full length EGFR ectodomain.

2. The truncated EGFR ectodomain as claimed in claim 1 wherein the truncated EGFR ectodomain lacks at least the second to seventh modules of the CR2 domain.

3. The truncated EGFR ectodomain as claimed in claim 1 wherein the truncated EGFR ectodomain further lacks a portion of the first module of the CR2 domain.

4. The truncated EGFR ectodomain as claimed in claim 1 wherein the truncated EGFR ectodomain lacks residues 510-626 of ErbB4 (SEQ ID NO:

4).

5. The truncated EGFR ectodomain as claimed in claim 4 wherein the truncated EGFR ectodomain lacks residues 498-626 of ErbB4 (SEQ ID NO:

4).

6. The truncated EGFR ectodomain as claimed in claim 1 wherein the truncated EGFR ectodomain comprises residues 1-497 or residues 1-509 of ErbB4 (SEQ ID NO:

4).

7. The truncated EGFR ectodomain as claimed in claim 1 wherein the truncated EGFR ectodomain consists of residues 1-497 or residues 1-509 of ErbB4 (SEQ ID NO:

4).

8. A chimeric or fusion construct comprising a truncated EGFR ectodomain as claimed in claim 1.

9. The chimeric or fusion construct as claimed in claim 8 wherein the truncated EGFR ectodomain is conjugated to an immunoglobulin constant domain.

10. The chimeric or fusion construct as claimed in claim 9 wherein the construct comprises residues 1-497 of ErbB4 (SEQ ID NO:

4) fused to an immunoglobulin constant domain.

11. A homodimer of the chimeric or fusion protein of claim 9.

12. A pharmaceutical composition comprising the truncated EGFR ectodomain as claimed in claim 1 and a pharmaceutically acceptable carrier or diluent.

13. A pharmaceutical composition comprising the chimeric or fusion construct as claimed in claim 9 and a pharmaceutically acceptable carrier or diluent.