Nogo-receptor antagonists for the treatment of conditions involving amyloid plaques
(19)AUSTRALIAN PATENT OFFICE (54) Title Nogo-receptor antagonists for the treatment of conditions involving amyloid plaques (51)G International Patent Classification(s) AG IK 038/02 A61K 038/16 A61 P 025/28 (21) Application No: 2004231742 (22) Application Date: 2004.04.16 (87) WIPONo: WO04/093893 (30) Priority Data (31) Number (32) Date 60/463,424 2003.04.16 (33) Country US 7 (43) Publication Date : 2004.11.04 (71) Applicant(s) Biogen Idee MA Inc.; Stephen Strittmatter (72) Inventor(s) Strittmatter, Stephen M.; Li, Weiwei; Lee, Daniel H. S. (74) Agent/Attorney Cullen & Co, 239 George Street Brisb ane, OLD, 4000 fM) Application NoAU2004231742 A1(19)AUSTRALIAN PATENT OFFICE (54) Title Nogo-receptor antagonists for the treatment of conditions involving amyloid plaques (51)G International Patent Classification(s) AG IK 038/02 A61K 038/16 A61 P 025/28 (21) Application No: 2004231742 (22) Application Date: 2004.04.16 (87) WIPONo: WO04/093893 (30) Priority Data (31) Number (32) Date 60/463,424 2003.04.16 (33) Country US 7 (43) Publication Date : 2004.11.04 (71) Applicant(s) Biogen Idee MA Inc.; Stephen Strittmatter (72) Inventor(s) Strittmatter, Stephen M.; Li, Weiwei; Lee, Daniel H. S. (74) Agent/Attorney Cullen & Co, 239 George Street Brisb ane, OLD, 4000 The invention provides methods for treating diseases involving aberrant amyloid-beta (Abeta) peptide deposition, including Alzheimer's Disease, by the administration of Nogo receptor antagonists. The invention also provides method for reducing levels of Abeta peptide in a mammal by the administration of soluble Nogo receptor polypeptides 1. A method of reducing the levels of A[3 peptide in a mammal, said method comprising administering to said mammal a therapeutically effective amount of a soluble Nogo receptor polypeptide. 2. The method of claim 1, wherein the levels oral3 peptide in said mammal are elevated in association with a disease, disorder or condition. 3. A method of preventing or treating a disease, disorder or condition associated with plaques of A[3 peptide in a mammal, said method comprising administering to said mammal a therapeutically effective amount of a soluble Nogo receptor polypeptide. 4. The method of claim 2 or claim 3, wherein the disease, disorder or condition is Alzheimer's disease. 5. The method of any one of claims 1-4, wherein said soluble Nogo receptor polypeptide is administered by bolus injection or chronic infusion. 6. The method ofctaim 5, wherein said soluble Nogo receptor polypeptide is administered intravenously. 7. The method of claim 5, wherein said soluble Nogo receptor polypeptide is administered directly into the central nervous system. 8. The method of claim 7, wherein said soluble Nogo receptor polypeptide is administered directly into a lateral ventricle. 9. The method of any one of claims 1-8, wherein said soluble Nogo receptor polypeptide is a soluble form of a mammalian NgRI. 10. The method of claim 9, wherein said soluble form of a mammalian NgRI comprises a peptide selected from the group consisting of:
(a) amino acids 26 to 310 of human NgR1 (SEQ ID NO:3) with up to ten conservative amino acid substitutions; (b) amino acids 26 to 344 of human NgR1 (SEQ ID NO:4) with up to ten conservative amino acid substitutions; (c) amino acids 27 to 310 of rat NgR1 (SEQ ID NO:5) with up to ten conservative amino acid substitutions; and (d) amino acids 27 to 344 of rat NgRI (SEQ ID NO:6) with up to ten conservative amino acid substitutions. 11. The method of claim 10, wherein said soluble form of a mammalian NgR1 comprises a peptide selected from the group consisting of:
(a) amino acids 26 to 310 of human NgR1 (SEQ ID NO:3); (b) amino acids 26 to 344 of human NgR1 (SEQ ID NO:4); (c) amino acids 27 to 310 of rat NgR1 (SEQ ID NO:5); and (d) amino acids 27 to 344 of rat NgR1 (SEQ ID NO:6). 12. The method of any one of claims 9-11, wherein said soluble form of a mammalian NgRI further comprises a fusion moiety. 13. The method of claim 12, wherein said fusion moiety is an immunoglobulin moiety. 14. The method of claim 13, wherein said immunoglobulin moiety is an Fc moiety. 15. The method of any one of claims 1-14, wherein said soluble Nogo receptor polypeptide is administered to said mammal at a dose of 0.001 mg/kg to 10mg/kg. 16. The method of claim 15, wherein said dose is from 0.01 mg/kg to 1.0mg/kg. 17. The method of claim 16, wherein said dose is from 0.05 mg/kg to 0.5 mg/kg. 18. A method of reducing the levels of A[3 peptide in a mammal, said method comprising administering to said mammal a therapeutically effective amount of an antibody or antigenbinding fragment thereof that binds mammalian NgRI. 19. The method of claim 18, wherein the levels of A[3 peptide in said mammal are elevated in association with a disease, disorder or condition. 20. A method of preventing or treating a disease, disorder or condition associated with plaques of A[3 peptide in a mammal, said method comprising administering to said mammal a therapeutically effective amount of an antibody or antigen-binding fragment thereof that binds mammalian NgRI. 21. The method of claim 19 or claim 20, wherein the disease, disorder or condition is Alzheimer's disease. 22. The method of any one of claims 18-21, wherein said antibody or antigen-binding fragment thereof is administered by bolus injection or chronic infusion. 23. The method of claim 22, wherein said antibody or antigen-binding fragment thereof is administered intravenously. 24. The method of claim 22, wherein said antibody or antigen-binding fragment thereof is administered directly into the central nervous system. 25. The method of claim 24, wherein said antibody or antigen-binding fragment thereof is administered directly into a lateral ventricle. 26. The method of any one of claims 18-25, wherein said antibody or antigen-binding fragment thereof is selected from the group consisting of a polyclonal antibody, a monoclonal antibody, a Fab fragment, a Fab' fragment, a F(ab') 2 fragment, an Fv fragment, an Fd fragment, a diabody, and a single-chain antibody. 27. The method of claim 26, wherein the antibody or antigen-binding fragment thereof binds to a polypeptide bound by a monoctonal antibody produced by a hybridoma selected from the group consisting of:
HB 7El1 (ATCC® accession No. PTA-4587); HB 1 H2 (ATCC® accession No. PTA-4584); HB 3G5 (ATCC® accession No.PTA-4586); HB 5B 10 (ATCC® accession No. PTA-4588); and HB 2F7 (ATCC® accession No. PTA-4585). 28. The method of claim 27, wherein the polypeptide comprises an amino acid sequence selected from the group consisting of:
AAAFGLTLLEQLDLSDNAQLR (SEQ NO:7); LDLSDNAQLR (SEQ ID NO:8); LDLSDDAELR (SEQ ID NO:9); LDLASDNAQLR (SEQ ID NO: I0); LDLASDDAELR (SEQ ID NO:I 1); LDALSDNAQLR (SEQ ID NO:I 2); LDALSDDAELR (SEQ ID NO: 13); LDLSSDNAQLR (SEQ ID NO: 14); LDLSSDEAELR (SEQ ID NO:I 5); DNAQLRVVDPTT (SEQ ID NO: 16); DNAQLR (SEQ ID NO:I 7); ADLSDNAQLRVVDPTT (SEQ ID NO:18); LALSDNAQLRVVDPTT (SEQ ID NO: 19); LDLSDNAALRVVDPTT (SEQ ID NO:20); LDLSDNAQLHVVDPTT (SEQ ID NO :2 t); and LDLSDNAQLAVVDPTT (SEQ ID NO:22). 29. The method of any one of claims 18-28, wherein said antibody or antigen-binding fragment thereof is administered to said mammal at a dose of 0.001 mg/kg to t 0 mg/kg. 30. The method of claim 29, wherein said dose is from 0.01 mg/kg to 1.0mg/kg. 31. The method of claim 30, wherein said dose is from 0.05 mg/kg to 0.5 mg/kg.
Yale University Biogen Idec MA Inc.
By their patent attorneys CULLEN & CO.
Date: 27 February 2006