Antibodies that immunospecifically bind to B lymphocyte stimulator protein

• US 7,605,236 B2
• Filed: 11/04/2005
• Issued: 10/20/2009
• Est. Priority Date: 06/16/2000
• Status: Expired due to Term

• Current Assignee: Human Genome Sciences Incorporated (GlaxoSmithKline PLC)
• Original Assignee: Human Genome Sciences Incorporated (GlaxoSmithKline PLC)
• Inventors: Vaughan, Tristan, Choi, Gil H., Hilbert, David, Ruben, Steven M., Barash, Steven C.
• Primary Examiner(s): DUFFY, PATRICIA ANN
• Application Number:
  US11/266,444
• Publication Number:
  US 20060062789A1
• Time in Patent Office: 1,446 Days
• Field of Search: None
• US Class Current: 530/387.9
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 47/6849 the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
• CPC Class Codes: A61K 49/0004 Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: C07K 14/52 Cytokines; Lymphokines; Interferons
• CPC Class Codes: C07K 14/70575 NGF/TNF-superfamily, e.g. CD70, CD95L, CD153, CD154 NGF C07K14/48, TNF C07K14/525
• CPC Class Codes: C07K 16/2875 against the NGF/TNF superfamily, e.g. CD70, CD95L, CD153, CD154 against NGF C07K16/22, against TNF C07K16/241
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• CPC Class Codes: G01N 33/564 for pre-existing immune complex or autoimmune disease , i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9

Abstract

The present invention relates to antibodies and related molecules that immunospecifically bind to B Lymphocyte Stimulator. The present invention also relates to methods and compositions for detecting or diagnosing a disease or disorder associated with aberrant B Lymphocyte Stimulator expression or inappropriate function of B Lymphocyte Stimulator comprising antibodies or fragments or variants thereof or related molecules that immunospecifically 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 expression or inappropriate B Lymphocyte Stimulator function comprising administering to an animal an effective amount of one or more antibodies or fragments or variants thereof or related molecules that immunospecifically bind to B Lymphocyte Stimulator.

Claims

1. An isolated or purified antibody that immunospecifically binds to B Lymphocyte Stimulator protein comprising:

(a) an amino acid sequence that is at least 85% identical to residues 1-126 of SEQ ID NO;

1321; and

(b) an amino acid sequence that is at least 85% identical to residues 143-251 of SEQ ID NO;

1049;

wherein the B Lymphocyte Stimulator protein is selected from the group consisting of;

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

3228;

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

3228; and

(3) a trimer of the protein of (2).

2. The antibody of claim 1, wherein the antibody comprises:

(a) an amino acid sequence that is at least 95% identical to residues 1-126 of SEQ ID NO;

1321; and

(b) an amino acid sequence that is at least 95% identical to residues 143-251 of SEQ ID NO;

1049.

3. The antibody of claim 1, wherein the antibody comprises:

(a) an amino acid sequence comprising residues 1-126 of SEQ ID NO;

1321; and

(b) an amino acid sequence comprising residues 143-251 of SEQ ID NO;

1049.

4. The antibody of claim 1, wherein the antibody is selected from the group consisting of a whole immunoglobulin molecule, a scFv a Fab fragment, a Fab′

fragment, a F(ab′

)2, a Fv and a disulfide linked Fv.

5. The antibody of claim 1, wherein the antibody is monoclonal.

6. The antibody of claim 1, wherein the antibody has a dissociation constant (K_D) of less than or equal to 10−

9M.

7. The antibody of claim 1, wherein the antibody is labeled.

8. The antibody of claim 7, wherein the antibody is labeled with a radiolabel, an enzyme, a fluorescent label, a luminescent label, a bioluminescent label, or biotin.

9. The antibody of claim 1, wherein the antibody diminishes or abolishes the ability of B Lymphocyte Stimulator protein or a fragment thereof to bind to a B Lymphocyte Stimulator protein receptor.

10. The antibody of claim 1, wherein the antibody diminishes or abolishes the ability of B Lymphocyte Stimulator protein or a fragment thereof to stimulate B cell proliferation, differentiation, or survival.

14. The antibody of claim 1, wherein the antibody further comprises a heavy chain immunoglobulin constant domain selected from the group consisting of:

(a) a human IgM constant domain;

(b) a human IgG1 constant domain;

(c) a human IgG2 constant domain;

(d) a human IgG3 constant domain;

(e) a human IgG4 constant domain; and

(f) a human IgA constant domain.

15. The antibody of claim 14, wherein the heavy chain immunoglobulin constant domain is a human IgG1 constant domain.

16. The antibody of claim 14, wherein the heavy chain immunoglobulin constant domain is a human IgG4 constant domain.

17. The antibody of claim 1, wherein the antibody further comprises a light chain immunoglobulin constant domain selected from the group consisting of:

(a) a human kappa constant domain; and

(b) a human lamba constant domain.

18. The antibody of claim 17, wherein the light chain immunoglobulin constant domain is a human kappa constant domain.

24. The antibody of claim 1, wherein the antibody further comprises a human IgG1 or IgG4 heavy chain immunoglobulin constant domain and a human kappa light chain immunoglobulin constant domain.

11. An isolated or purified antibody that immunospecifically binds to B Lymphocyte Stimulator protein comprising:

(a) an amino acid sequence that is at least 90% identical to residues 1-126 of SEQ ID NO;

1321; and

(b) an amino acid sequence that is at least 90% identical to residues 143-251 of SEQ ID NO;

1049;

wherein the B Lymphocyte Stimulator protein is selected from the group consisting of;

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

3228;

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

3228; and

(3) a trimer of the protein of (2).

12. The antibody of claim 11, wherein the antibody is selected from the group consisting of a whole immuno globulin molecule, a scFV a Fab fragment an a Fab′

fragment, a F(ab′

)2, a Fv and a disulfide linked Fv.

13. The antibody of claim 11, wherein the antibody diminishes or abolishes the ability of B Lymphocyte Stimulator protein or a fragment thereof to bind to a B Lymphocyte Stimulator protein receptor, or diminishes or abolishes the ability of B Lymphocyte Stimulator protein or a fragment thereof to stimulate B cell proliferation, differentiation, or survival.

19. The antibody of claim 11, wherein the antibody further comprises a heavy chain immunoglobulin constant domain selected from the group consisting of:

(a) a human IgM constant domain;

(b) a human IgG1 constant domain;

(c) a human IgG2 constant domain;

(d) a human IgG3 constant domain;

(e) a human IgG4 constant domain; and

(f) a human IgA constant domain.

20. The antibody of claim 19 wherein the heavy chain immunoglobulin constant domain is a human IgG1 constant domain.

21. The antibody of claim 19 wherein the heavy chain immunoglobulin constant domain is a human IgG4 constant domain.

22. The antibody of claim 11, wherein the antibody further comprises a light chain immunoglobulin constant domain selected from the group consisting of:

(a) a human kappa constant domain; and

(b) a human lamba constant domain.

23. The antibody of claim 22 wherein the light chain immunoglobulin constant domain is a human kappa constant domain.

25. The antibody of claim 11, wherein the antibody further comprises a human IgG1 or IgG4 heavy chain immunoglobulin constant domain and a human kappa light chain immunoglobulin constant domain.