Chemokine-binding protein and methods of use

• US 7,892,727 B2
• Filed: 05/03/2006
• Issued: 02/22/2011
• Est. Priority Date: 12/18/2001
• Status: Expired due to Fees

• Current Assignee: Centre National De La Recherche Scientifique
• Original Assignee: Centre National De La Recherche Scientifique
• Inventors: Roussigne, Myriam, Amalric, Francois, Girard, Jean-Philippe
• Primary Examiner(s): Yu; Misook
• Assistant Examiner(s): Yao; Lei
• Application Number:
  US11/417,317
• Publication Number:
  US 20060194287A1
• Time in Patent Office: 1,756 Days
• Field of Search: None
• US Class Current: 435/4
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 14/47 from mammals
• CPC Class Codes: C07K 14/4747 Apoptosis related proteins
• CPC Class Codes: G01N 33/6863 Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors

Abstract

Described herein are chemokine-binding domains of THAP-family polypeptides and pharmaceutical compositions which include a polypeptide comprising a chemokine-binding domain of a THAP-family polypeptide. Also disclosed are methods of binding chemokines, inhibiting the activity of chemokines, detecting chemokines, and reducing the symptoms associated with a chemokine mediated or influenced condition by contacting the chemokine with an agent that includes a polypeptide comprising a chemokine binding domain of a THAP-family polypeptide.

Claims

1. A method of identifying a chemokine binding domain having an altered specificity or affinity, said method comprising the steps of:

(a) altering the nucleotide sequence of a nucleic acid comprising a polynucleotide sequence that encodes a chemokine binding domain of the amino acid sequence 143-213 of SEQ ID NO;

3, thereby generating an altered chemokine binding domain;

(b) determining whether the specificity or chemokine binding affinity of said altered chemokine binding domain is changed as compared to the chemokine binding domain prior to the alteration;

(c) optionally, repeating steps (a) and (b); and

(d) selecting the desired chemokine binding domain having an altered specificity or affinity.

2. The method of claim 1, wherein said altered chemokine binding domain comprises one or more additional amino acids as compared to the chemokine binding domain prior to the alteration of claim 1.

3. The method of claim 1, wherein said altered chemokine binding domain comprises at least one amino acid deletion as compared to the chemokine binding domain prior to the alteration of claim 1.

4. The method of claim 1, wherein said altered chemokine binding domain comprises at least one amino acid substitution as compared to the chemokine binding domain prior to the alteration of claim 1.

5. The method of claim 1, wherein the altered chemokine binding domain binds at least one chemokine that does not bind to the chemokine binding domain prior to the alteration of claim 1.

6. The method of claim 1, wherein the altered chemokine binding domain does not bind to at least one chemokine that binds to the chemokine binding domain prior to the alteration of claim 1.

7. The method of claim 1, wherein the altered chemokine binding domain binds at least one chemokine that is bound by the chemokine binding domain prior to the alteration of claim 1 more tightly than the unaltered chemokine binding domain.

8. The method of claim 1, wherein the altered chemokine binding domain binds at least one chemokine that is bound by the chemokine binding domain prior to the alteration of claim 1 less tightly than the unaltered chemokine binding domain.

9. The method of claim 1, wherein the amino acid sequence of the altered chemokine binding domain remains at least 70% identical to the amino acid sequence of an unaltered chemokine binding domain of the amino acid sequence 143-213 of SEQ ID NO:

3.

10. The method of claim 1, wherein the amino acid sequence of the altered chemokine binding domain remains at least 80% identical to the amino acid sequence of an unaltered chemokine binding domain of the amino acid sequence 143-213 of SEQ ID NO:

3.

11. The method of claim 1, wherein the amino acid sequence of the altered chemokine binding domain remains at least 90% identical to the amino acid sequence of an unaltered chemokine binding domain of the amino acid sequence 143-213 of SEQ ID NO:

3.

12. The method of claim 1, wherein the amino acid sequence of the altered chemokine binding domain remains at least 95% identical to the amino acid sequence of an unaltered chemokine binding domain of the amino acid sequence 143-213 of SEQ ID NO:

3.