Patent EA-004635-B1 (EA)
Title: Baff receptor (bcma), an immunoregulatory agent
Inventor: MACKAY FABIENNE
IPC: A61K39/00
Filed: 2000-08-16
Abstract: 1. A method of inhibiting B-cell growth in an animal comprising the step of administering a therapeutically effective amount of a composition selected from the group consisting of: (a) a BAFF-R polypeptide or fragment thereof; (b) a chimeric molecule comprising a BAFF-R polypeptide or fragment thereof fused to a heterologous amino acid sequence; and (c) an anti-BAFF-R antibody homolog. 2. A method of inhibiting immunoglobulin production in an animal comprising the step of administering a therapeutically effective amount of a composition selected from the group consisting of: (a) a BAFF-R polypeptide or fragment thereof; (b) a chimeric molecule comprising a BAFF-R polypeptide or fragment thereof fused to a heterologous amino acid sequence; and (c) an anti-BAFF-R antibody homolog. 3. A method of inhibiting dendritic cell-induced B-cell growth and maturation in an animal comprising the step of administering a therapeutically effective amount of a composition selected from the group consisting of: (a) a BAFF-R polypeptide or fragment thereof; (b) a chimeric molecule comprising aBAFF-R polypeptide or fragment thereof fused to a heterologous amino acid sequence; and (c) an anti-BAFF-R antibody homolog. 4. A method of treatment of an autoimmune disease comprising the step of administering a therapeutically effective amount of a composition selected from the group consisting of: (a) a BAFF-R polypeptide or fragment thereof; (b) a chimeric molecule comprising a BAFF-R polypeptide or fragment thereof fused to a heterologous amino acid sequence; and (c) an anti-BAFF-R antibody homolog. 5. A method of treating hypertension in an animal comprising the step of administering a therapeutically effective amount of a B-cell growth inhibitor selected from the group consisting of: (a) a BAFF-R polypeptide or fragment thereof; (b) a chimeric molecule comprising a BAFF-R polypeptide or fragment thereof fused to a heterologous amino acid sequence; and (c) an anti-BAFF-R antibody homolog. 6. A method of treating renal disorders in an animal comprising the step of administering a therapeutically effective amount of a B-cell growth inhibitor selected from the group consisting of: (a) a BAFF-R polypeptide or fragment thereof; (b) a chimeric molecule comprising a BAFF-R polypeptide or fragment thereof fused to a heterologous amino acid sequence; and (c) an anti-BAFF-R antibody homolog. 7. A method of treating B-cell lympho-proliferate disorders comprising the step of administering a therapeutically effective amount of a B-cell growth inhibitor selected from the group consisting of: (a) a BAFF-R polypeptide or fragment thereof; (b) a chimeric molecule comprising a BAFF-R polypeptide or fragment thereof fused to a heterologous amino acid sequence; and (c) an anti-BAFF-R antibody homolog. 8. A method according to claims 1 to 7, wherein the BAFF-R polypeptide is soluble. 9. The method according to claim 8, wherein the soluble BAFF-R polypeptide comprises a BAFF-R extracellular domain. 10. The method of claim 9 wherein the BAFF-R extracellular domain is fused to an immunoglobulin. 11. A method according to claims 1 to 7, wherein the BAFF-R polypeptide is selected from the group consisting of: a) an isolated native sequence BAFF-R polypeptide comprising amino acid residues 1 to 184 of SEQ ID NO: 1 or a fragment thereof; b) an isolated BAFF-R polypeptide having at least 80% amino acid sequence identity with native sequence BAFF-R polypeptide comprising amino acid residues 1 to 184 of SEQ ID NO: 1 or a fragment thereof; c) an isolated BAFF-R polypeptide having at least 90% amino acid sequence identity with native sequence BAFF-R polypeptide comprising amino acid residues 1 to 184 of SEQ ID NO: 1 or a fragment thereof; d) an isolated BAFF-R polypeptide comprising amino acid residues 1 to 51 of SEQ ID NO: 1 or a fragment thereof; and e) an isolated BAFF-R polypeptide comprising amino acid residues 8 to 41 of SEQ ID NO: 1 or a fragment thereof. 12. A method according to claims 1 to 7, wherein the anti-BAFF-R antibody homolog is a monoclonal antibody. 13. A method according to claims 1 to 7, wherein the anti-BAFF-R antibody homolog comprises BCMA-IgG. 14. A method according to claims 1 to 7, wherein the animal is a mammal. 15. The method according to claim 14, wherein the mammal is human. 16. A method of treating, suppressing or altering an immune response involving a signaling pathway between a BAFF-R and BAFF comprising the step of administering an effective amount of the composition selected from the group consisting of: (a) a BAFF-R polypeptide or fragment thereof; (b) a chimeric molecule comprising a BAFF-R polypeptide or fragment thereof fused to a heterologous amino acid sequence; and (c) an anti-BAFF-R antibody homolog. 17. A method of inhibiting inflammation comprising the step of administering a therapeutically effective amount of an antibody specific for a BAFF-R or an active fragment thereof. 18. A method of inhibiting inflammation comprising the step of administering a therapeutically effective amount of an antibody specific for a BAFF-R or an epitope thereof. 19. A pharmaceutical composition comprising a therapeutically effective amount of an isolated BAFF-R polypeptide or a fragment thereof and a pharmaceutically acceptable carrier. 20. The pharmaceutical composition of claim 19 wherein the isolated BAFF-R polypeptide is selected from the group consisting of: a) an isolated native sequence BAFF-R polypeptide comprising amino acid residues 1 to 184 of SEQ ID NO: 1 or a fragment thereof; b) an isolated BAFF-R polypeptide having at least 80% amino acid sequence identity with native sequence BAFF-R polypeptide comprising amino acid residues 1 to 184 of SEQ ID NO: 1 or a fragment thereof; c) an isolated BAFF-R polypeptide having at least90% amino acid sequence identity with native sequence BAFF-R polypeptide comprising amino acid residues 1 to 184 of SEQ ID NO:1 or a fragment thereof; d) an isolated BAFF-R polypeptide comprising amino acid residues 1 to 51 of SEQ ID NO:1 or a fragment thereof; and e) an isolated BAFF-R polypeptide comprising amino acid residues 8 to 41 of SEQ ID NO: 1 or a fragment thereof. 21. The pharmaceutical composition of claim 19 wherein the BAFF-R polypeptide fragment comprises a BAFF-R extracellular domain fused to an immunoglobulin.