Binding polypeptides and methods based thereon

• US 20070293434A9
• Filed: 09/20/2005
• Published: 12/20/2007
• Est. Priority Date: 08/18/2000
• Status: Abandoned Application

• Current Assignee: Human Genome Sciences Incorporated (GSK plc), Dyax Corporation (Shire plc)
• Original Assignee: Human Genome Sciences Incorporated (GSK plc), Dyax Corporation (Shire plc)
• Inventors: Potter, Marilou, Beltzer, James, ROSEN, CRAIG, Fleming, Tony, Potter, M.
• Application Number:
  US11/232,439
• Publication Number:
  US 20060084608A1
• Time in Patent Office: Days
• US Class Current: 514/1.1
• 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 BLyS protein or BLyS-like polypeptides can be used in methods of the invention for detecting, diagnosing, or prognosing a disease or disorder associated with aberrant BLyS or BLyS receptor expression or inappropriate function of BLyS or BLyS receptor, comprising BLyS binding polypeptides or fragments or variants thereof, that specifically bind to BLyS. The present invention further relates to methods and compositions for preventing, treating or ameliorating a disease or disorder associated with aberrant BLyS or BLyS receptor expression or inappropriate BLyS function or BLyS receptor function, comprising administering to an animal, preferably a human, an effective amount of one or more BLyS binding polypeptides or fragments or variants thereof, that specifically bind to BLyS.

Claims

1. A method of treating, preventing or ameliorating a disease or disorder associated with aberrant B Lymphocyte Stimulator (BLyS) or BLyS receptor expression or activity, comprising administering to an animal in which such treatment, prevention or amelioration is desired, a BLyS binding polypeptide in an amount effective to treat, prevent or ameliorate the disease or disorder.

2. The method of claim 1, wherein the disease or disorder is an immune system disease or disorder.

3. The method of claim 2, wherein the immune system disease or disorder is an autoimmune disease or disorder.

4. The method of claim 2, wherein the immune system disease or disorder is an immunodeficiency.

5. The method of claim 3, wherein the autoimmune disease or disorder is lupus.

6. The method of claim 1, wherein the disease or disorder is glomerular nephritis.

7. The method of claim 2, wherein the immune system disease or disorder is rheumatoid arthritis, multiple sclerosis, hypogammaglobulinemia or hypergammaglobulinemia.

8. The method of claim 2 wherein the immune system disease or disorder is graft vs. host disease.

9. The method of claim 2, wherein the immune system disease or disorder is a proliferative disease or disorder.

10. The method of claim 9, wherein the proliferative disorder is cancer.

11. The method of claim 1, wherein the disease or disorder is an infectious disease or disorder.

69. The method according to claim 1, wherein the BLyS binding polypeptide comprises an amino acid sequence selected from the group consisting of:

70. The method according to claim 69, wherein the BLyS binding polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:

20-168 and 186-435, as depicted in Tables 1-8 and 13.

71. The method according to claim 69, wherein the BLyS binding polypeptide comprises an amino acid sequence selected from the group consisting of:

Ala-Gly-Lys-Glu-Pro-Cys-Tyr-Phe-Tyr-Trp-Glu-Cys-Ala-Val-Ser-Gly (SEQ ID NO;

     450);

Ala-Gly-Val-Pro-Phe-Cys-Asp-Leu-Leu-Thr-Lys-His-Cys-Phe-Glu-Ala-Gly (SEQ ID NO;

     451);

Gly-Ser-Ser-Arg-Leu-Cys-His-Met-Asp-Glu-Leu-Thr-His-Val-Cys-Val-His-Phe-Ala-Pro (SEQ ID NO;

     452);

Gly-Asp-Gly-Gly-Asn-Cys-Tyr-Thr-Asp-Ser-Leu-Thr-Lys-Leu-His-Phe-Cys-Met-Gly-Asp-Glu (SEQ ID NO;

     453);

Gly-Tyr-Asp-Val-Leu-Thr-Lys-Leu-Tyr-Phe-Val-Pro-Gly-Gly (SEQ ID NO;

     454);

Trp-Thr-Asp-Ser-Leu-Thr-Gly-Leu-Trp-Phe-Pro-Asp-Gly-Gly (SEQ ID NO;

     455);

Ala-Asn-Trp-Tyr-Asp-Pro-Leu-Thr-Lys-Leu-Trp-Leu-Pro-Asp (SEQ ID NO;

186);

Trp-Tyr-Asp-Pro-Leu-Thr-Lys-Leu-Trp-Leu-Pro-Asp (SEQ ID NO;

     456);

Trp-Tyr-Asp-Pro-Leu-Thr-Lys-Leu-Trp-Leu (SEQ ID NO;

     457);

Ala-Asn-Trp-Tyr-Asp-Pro-Leu-Thr-Lys-Leu-Trp-Leu-Pro-Val (SEQ ID NO;

189);

Ala-Asn-Trp-Phe-Asp-Pro-Leu-Thr-Lys-Leu-Trp-Leu-Pro-Asp (SEQ ID NO;

     309);

Ala-Asn-Trp-Tyr-Asp-Pro-Leu-Thr-Lys-Leu-Ser-Leu-Pro-Asp (SEQ ID NO;

     458);

Ala-Asn-Trp-Tyr-Asp-Pro-Leu-Thr-Lys-Leu-Trp-Phe-Pro-Asp (SEQ ID NO;

     353);

Ala-Asn-Trp-Tyr-Asp-Ser-Leu-Thr-Lys-Leu-Trp-Leu-Pro-Asp (SEQ ID NO;

     327).

12-68. -68. (canceled)