B-lymphocyte stimulator binding polypeptides and methods based thereon

• US 8,062,906 B2
• Filed: 02/05/2010
• Issued: 11/22/2011
• Est. Priority Date: 08/18/2000
• Status: Expired due to Fees

• Current Assignee: Human Genome Sciences Incorporated (GSK plc)
• Original Assignee: Human Genome Sciences Incorporated (GSK plc)
• Inventors: Beltzer, James P., Potter, M. Daniel, Fleming, Tony J.
• Primary Examiner(s): DUFFY, PATRICIA ANN
• Application Number:
  US12/701,301
• Publication Number:
  US 20100144058A1
• Time in Patent Office: 655 Days
• Field of Search: None
• US Class Current: 436/501
• 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 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: C07K 14/70578 NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 NGF-receptor C07K14/71, TNF-receptor C07K14/7151
• CPC Class Codes: C07K 14/7151 for tumor necrosis factor [TNF], for lymphotoxin [LT]
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C07K 7/08 having 12 to 20 amino acids gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68

Abstract

Binding polypeptides that specifically bind B lymphocyte stimulator protein or B lymphocyte stimulator-like polypeptides can be used in methods of the invention for detecting, diagnosing, or prognosing a disease or disorder associated with aberrant B lymphocyte stimulator or B lymphocyte stimulator receptor expression or inappropriate function of B lymphocyte stimulator or B lymphocyte stimulator receptor, comprising B lymphocyte stimulator binding polypeptides or fragments or variants thereof, that specifically bind to B lymphocyte stimulator. The present invention further relates to methods and compositions for preventing, treating or ameliorating a disease or disorder associated with aberrant B lymphocyte stimulator or B lymphocyte stimulator receptor expression or inappropriate B lymphocyte stimulator function or B lymphocyte stimulator receptor function, comprising administering to an animal, preferably a human, an effective amount of one or more B lymphocyte stimulator binding polypeptides or fragments or variants thereof, that specifically bind to B lymphocyte stimulator.

Claims

1. An isolated B lymphocyte stimulator binding polypeptide comprising an amino acid sequence at least 90% identical to X₁-X₂-X₃-Cys-X₅-X₆-X₇-X₈-X₉-X₁₀-X₁₁-X₁₂-X₁₃-X₁₄-Cys-X₁₆-X₁₇-X₁₈ (SEQ ID NO:

5), wherein

X₁ is Arg, Asp, Gly, His, Leu, Phe, Pro, Ser, Trp, Tyr, or is absent;

X₂ is Ala, Arg, Asn, Asp, Gly, Pro, Ser, or is absent;

X₃ is Arg, Asn, Gln, Glu, Gly, Lys, Met, Pro, Trp or Val;

X₅ is Arg, Asn, Gln, Glu, His, Leu, Phe, Pro, Trp, Tyr, or Val;

X₆ is Arg, Asp, Gln, Gly, Ile, Lys, Phe, Thr, Trp or Tyr;

X₇ is Ala, Arg, Asp, Glu, Gly, Leu, Ser, or Tyr;

X₈ is Asp, Gln, Glu, Leu, Met, Phe, Pro, Ser, or Tyr;

X₉ is Asp, Leu, Pro, Thr, or Val;

X₁₀ is Arg, Gln, His, Ile, Leu, Lys, Met, Phe, Thr, Trp or Tyr;

X₁₁ is Ala, Arg, Asn, Gln, Glu, His, Leu, Lys, Met, or Thr;

X₁₂ is Ala, Asn, Gln, Gly, Leu, Lys, Phe, Pro, Thr, Trp, or Tyr;

X₁₃ is Ala, Arg, Gln, His, Lys, Met, Phe, Pro, Thr, Trp, or Tyr;

X₁₄ is Arg, Gln, Glu, Gly, His, Leu, Met, Phe, Pro, Ser, Thr, Tyr, or Val;

X₁₆ is Arg, Asp, Gly, His, Lys, Met, Phe, Pro, Ser, or Trp;

X₁₇ is Arg, Asn, Asp, Gly, His, Phe, Pro, Ser, Trp or Tyr; and

X₁₈ is Ala, Arg, Asn, Asp, His, Leu, Phe, or Trp, and

wherein the B lymphocyte stimulator binding polypeptide binds a B lymphocyte stimulator protein selected from the group consisting of;

(a) a protein whose amino acid sequence consists of amino acid residues 1-285 of SEQ ID NO;

173;

(b) a protein whose amino acid sequence consists of amino acid residues 134-285 of SEQ ID NO;

173; and

(c) a trimer of the protein of (b).

2. The B lymphocyte stimulator binding polypeptide of claim 1, wherein X₈ and X₉ are Leu (SEQ ID NO:

460).

3. The B lymphocyte stimulator binding polypeptide of claim 1, wherein X₂ and X₁₇ are Pro (SEQ ID NO:

461).

4. The B lymphocyte stimulator binding polypeptide of claim 1, wherein X₃ is Gly.

5. The B lymphocyte stimulator binding polypeptide of claim 1, wherein X₆ and X₁₃ are Trp (SEQ ID NO:

462).

6. The B lymphocyte stimulator binding polypeptide of claim 1, wherein X₇ and X₁₆ are Asp (SEQ ID NO:

463).

7. The B lymphocyte stimulator binding polypeptide of claim 1, wherein X₁₀ is Ile.

8. The B lymphocyte stimulator binding polypeptide of claim 1, wherein X₁₁ is Lys.

9. The B lymphocyte stimulator binding polypeptide of claim 1, wherein X₁₂ is Gln.

10. The B lymphocyte stimulator binding polypeptide of claim 1, wherein X₁₄ is Val.

11. A fusion protein comprising the B lymphocyte stimulator binding polypeptide of claim 1 fused to a heterologous polypeptide.

12. The fusion protein of claim 11, wherein the heterologous polypeptide comprises an Fc region of an immunoglobulin.

13. A method of isolating a B lymphocyte stimulator or B lymphocyte stimulator-like polypeptide comprising

(a) contacting a solid support that comprises the B lymphocyte stimulator binding polypeptide of claim 1 immobilized thereon with a solution containing a B lymphocyte stimulator or B lymphocyte stimulator-like polypeptide, and

(b) separating the solution from the support.

14. A method for detecting a B lymphocyte stimulator or B lymphocyte stimulator-like polypeptide in a solution comprising

(a) contacting the solution with the B lymphocyte stimulator binding polypeptide of claim 1, and

(b) detecting binding of B lymphocyte stimulator or B lymphocyte stimulator-like polypeptide to the B lymphocyte stimulator binding polypeptide, thereby detecting the presence of a B lymphocyte stimulator or B lymphocyte stimulator-like polypeptide in the solution.

15. The B lymphocyte stimulator binding polypeptide of claim 1, wherein X₁ is Leu.

16. The B lymphocyte stimulator binding polypeptide of claim 1, wherein X₅ is Arg.

17. The B lymphocyte stimulator binding polypeptide of claim 1, wherein X₁₈ is Leu.

18. The B lymphocyte stimulator binding polypeptide of claim 1, wherein X₆ is Trp, X₇ is Asp, X₉ is Leu, X₁₂ is Gln, and X₁₃ is Trp (SEQ ID NO:

464).

19. A fusion protein comprising the B lymphocyte stimulator binding polypeptide of claim 18 fused to a heterologous polypeptide.

20. The fusion protein of claim 19, wherein the heterologous polypeptide comprises an Fc region of an immunoglobulin.

21. A method of isolating a B lymphocyte stimulator or B lymphocyte stimulator-like polypeptide comprising

(a) contacting a solid support that comprises the B lymphocyte stimulator binding polypeptide of claim 8 immobilized thereon with a solution containing a B lymphocyte stimulator or B lymphocyte stimulator-like polypeptide, and

(b) separating the solution from the support.

22. A method for detecting a B lymphocyte stimulator or B lymphocyte stimulator-like polypeptide in a solution comprising

(a) contacting the solution with the B lymphocyte stimulator binding polypeptide of claim 8, and

(b) detecting binding of B lymphocyte stimulator or B lymphocyte stimulator-like polypeptide to the B lymphocyte stimulator binding polypeptide, thereby detecting the presence of a B lymphocyte stimulator or B lymphocyte stimulator-like polypeptide in the solution.

23. The B lymphocyte stimulator binding polypeptide of claim 1, wherein X₆ is Trp, X₇ is Asp, X₉ is Leu, X₁₄ is Val, and X₁₆ is Asp (SEQ ID NO:

465).

24. A fusion protein comprising the B lymphocyte stimulator binding polypeptide of claim 23 fused to a heterologous polypeptide.

25. The fusion protein of claim 24, wherein the heterologous polypeptide comprises an Fc region of an immunoglobulin.

26. A method of isolating a B lymphocyte stimulator or B lymphocyte stimulator-like polypeptide comprising

(a) contacting a solid support that comprises the B lymphocyte stimulator binding polypeptide of claim 23 immobilized thereon with a solution containing a B lymphocyte stimulator or B lymphocyte stimulator-like polypeptide, and

(b) separating the solution from the support.

27. A method for detecting a B lymphocyte stimulator or B lymphocyte stimulator-like polypeptide in a solution comprising

(a) contacting the solution with the B lymphocyte stimulator binding polypeptide of claim 23, and

(b) detecting binding of B lymphocyte stimulator or B lymphocyte stimulator-like polypeptide to the B lymphocyte stimulator binding polypeptide, thereby detecting the presence of a B lymphocyte stimulator or B lymphocyte stimulator-like polypeptide in the solution.