Novel FIZZ proteins

• US 20040018980A1
• Filed: 06/13/2003
• Published: 01/29/2004
• Est. Priority Date: 04/24/1998
• Status: Abandoned Application

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: Henzel, William J., Hebert, Caroline, Kabakoff, Rhona, Gurney, Austin L., Tumas, Daniel B., Shelton, David L.
• Application Number:
  US10/461,060
• Publication Number:
  US 20040018980A1
• Time in Patent Office: Days
• US Class Current: 514/12
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/4703 Inhibitors; Suppressors
• CPC Class Codes: C12N 2799/026 where the vector is derived from a baculovirus

Abstract

The present invention is directed to novel polypeptides, designated FIZZ, which are secreted low molecular weight molecules showing no significant sequence homology to any known protein, and nucleic acid sequences encoding such proteins. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptide of the present invention fused to heterologous polypeptide sequences, and antibodies which bind to the polypeptides of the present invention. Methods of using FIZZ polypeptides to treat various neurotrophin-related conditions are further provided.

Claims

1. A method of treating a pathologic condition associated with neurotrophin action on responsive neurons, comprising

administering to a mammal an effective amount of a FIZZ protein or an agonist of a FIZZ protein.

2. The method of claim 1 wherein said FIZZ protein comprises amino acid residues 24-117 of FIG. 5 (SEQ ID NO:

10).

3. The method of claim 1 wherein said FIZZ protein comprises amino acid residues 21-105 of FIG. 10 (SEQ ID NO:

14).

4. The method of claim 1 wherein said FIZZ protein comprises amino acid residues 21-114 of FIG. 12 (SEQ ID NO:

16).

5. The method of claim 1 wherein said FIZZ protein comprises amino acid residues 21-111 of FIG. 14 (SEQ ID NO:

18).

6. The method of claim 1 wherein said FIZZ protein comprises amino acid residues 19-108 of FIG. 26 (SEQ ID NO:

24).

7. A method of treating a pathologic condition associated with the neurotrophin-inhibitory activity of a FIZZ polypeptide, comprising administering to a mammal an antagonist of a FIZZ protein.

8. The method of claim 7 wherein said antagonist is an anti-FIZZ antibody.

9. A method of screening for an antagonist of a FIZZ polypeptide, comprising contacting neurotrophin-responsive neurons, in the presence of a neurotrophin and a FIZZ polypeptide, with a candidate molecule, and monitoring neurotrophin action on the neurons.

10. A method of screening for an agonist of a FIZZ polypeptide, comprising contacting neurotrophin-responsive neurons, in the presence of a neurotrophin, with a candidate molecule, and monitoring neurotrophin action on the neurons.

11. A method of enhancing the immune response in a patient comprising administering to said patient an effective amount of a FIZZ protein or an agonist of a FIZZ protein.

12. The method of claim 11 wherein said FIZZ protein comprises

amino acid residues 24-117 of FIG. 5 (SEQ ID NO:

10).

13. The method of claim 11 wherein said FIZZ protein comprises

amino acid residues 21-105 of FIG. 10 (SEQ ID NO:

14).

14. The method of claim 11 wherein said FIZZ protein comprises

amino acid residues 21-114 of FIG. 12 (SEQ ID NO:

16).

15. The method of claim 11 wherein said FIZZ protein comprises

amino acid residues 21-111 of FIG. 14 (SEQ ID NO:

18).

16. The method of claim 11 wherein said FIZZ protein comprises

amino acid residues 19-108 of FIG. 26 (SEQ ID NO:

24).

17. A method of suppressing the immune response in a mammal comprising administering to said mammal an effective amount of an antagonist of a FIZZ protein.

18. The method of claim 17 wherein said antagonist is an anti-FIZZ antibody.

19. A composition comprising a FIZZ polypeptide, or an agonist or antagonist of a FIZZ polypeptide, in combination with a pharmaceutically acceptable carrier.