Peptides and compounds that bind to the IL-5 receptor

• US 7,482,433 B2
• Filed: 05/02/2006
• Issued: 01/27/2009
• Est. Priority Date: 12/16/1999
• Status: Expired due to Fees

• Current Assignee: Affymax Incorporated
• Original Assignee: Affymax Incorporated
• Inventors: England, Bruce, Balu, Palani, Yin, Qun
• Primary Examiner(s): Weber; Jon
• Assistant Examiner(s): Mohamed; Abdel A
• Application Number:
  US11/381,172
• Publication Number:
  US 20070173444A1
• Time in Patent Office: 1,001 Days
• Field of Search: 530/351, 530/324, 530/326, 530/327, 530/388.2, 530/402, 424/85.2, 514/12, 514/13, 514/14
• US Class Current: 530/351
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 38/10 Peptides having 12 to 20 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: C07K 14/5409 IL-5
• CPC Class Codes: C07K 7/08 having 12 to 20 amino acids gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68

Abstract

Interleukin-5 receptor (IL-5R) ligands comprising amino sequences of formula TGGGDGYVX₃VEX₄ARCPTCK, EGYVX₃VEX₄ARCPTCK, EGYVX₃VEX₄ARCPTCR, GYVX₃VEX₄ARCPTCG, EGYVX₃VEX₄ARCPTCG, GYVX₃VEX₄ARCPTCR, and EGYVX₃VEX₄AACPTCR, and methods of using the same, are described and claimed.

Claims

1. A method for treating a patient having a condition mediated by IL-5 comprising administering to the patient a therapeutically effective amount of a compound that effects homodimerization of the alpha chain of the IL-5 receptor, wherein said compound comprises a member selected from the group of peptides consisting of:

2. The method of claim 1, wherein the sequence is fourteen to fifty amino acid residues in length.

3. The method of claim 1, wherein the sequence is fourteen to twenty amino acid residues in length.

4. A method of claim 1, wherein the N-terminus of said peptide is selected from the group consisting of

—

NRR₁, —

NRC(O)R, —

NRC (O)OR, —

NRS (O)₂R, —

NHC(O)NHR, succinimide, benzyloxycarbonyl-NH—

, and benzyloxycarbonyl-NH-having from 1 to 3 substituents on the phenyl ring of said benzyloxycarbonyl-NH—

, said benzyloxycarbonyl-NH-substituents selected from the group consisting of lower alkyl, lower alkoxy, chioro, and brorno, where R and R, are independently selected from the group consisting of hydrogen and lower alkyl,

wherein the C-terminus of said peptide has the formula-C(O)R₂ where R₂ is selected from the group consisting of hydroxy, lower alkoxy, and-NR₃R₄ wherein R₃ and R₄ are independently selected from the group consisting of hydrogen and lower alkyl and wherein the nitrogen atom of the-NR₃R₄ group can optionally be the amine group of the N-terminus of the peptide so as to form a cyclic peptide, and physiologically acceptable salts thereof.

5. The method of claim 1, wherein the compound binds to the interleukin 5 receptor (IL-5R) with an IC₅₀ of no more than about 2 mM as determined by a binding affinity assay.

6. The method claim 1, wherein the compound binds to the IL-5R with an IC50 of no more than about 100 uM as determined by a binding affinity assay.

7. The method of claim 1, wherein the compound comprises a sequence of amino acids selected from the groups consisting of

8. The method of claim 1, wherein the compound further comprises an intramolecular disulfide linkage between two Cys residues.

9. The method of claim 1, wherein the compound further comprises a dimer with intermolecular disulfide, amide, carbamate, or urea linkages.

10. The method of claim 1 further comprising administering to said patient at least one other compound selected from the group consisting of β

-adrenergic agonists, anticholinergics and anti-inflammatory corticosteroids.

11. The method of claim 1, wherein the compound is coupled to a polyethylene glycol molecule.

12. The method of claim 11, wherein the polyethylene glycol has an average molecular weight of between about 500 to about 100,000 daltons.

13. The method of claim 11, wherein the polycthylene glycol has an average molecular weight of between about 2,000 to about 40,000 daltons.

14. A method of claim 11, wherein the polyethylene glycol has an average molecular weight of between about 5,000 to about 20,000 daltons.