التفاصيل البيبلوغرافية
| العنوان: |
Peptide Inhibitors of iASPP |
| Document Number: |
20080260756 |
| تاريخ النشر: |
October 23, 2008 |
| Appl. No: |
12/043058 |
| Application Filed: |
March 05, 2008 |
| مستخلص: |
The invention relates to a polypeptide or part thereof which inhibits the apoptotic activity of the tumor suppressor protein p53, and includes screening methods to identify agents which interfere with the activity of the polypeptide. |
| Inventors: |
Lu, Xin (London, GB); Kuwabara, Patricia (Bristol, GB); Selwood, David (London, GB) |
| Assignees: |
LUDWIG INSTITUTE FOR CANCER RESEARCH (New York, NY, US), GENOME RESEARCH LIMITED (Cambridge, GB), UCL CRUCIFORM LIMITED (LONG, GB) |
| Claim: |
1-9. (canceled) |
| Claim: |
10. A polypeptide consisting of an amino acid sequence selected from the group consisting of: i) amino acid residues from about residue 128-224 of the amino acid sequence presented in FIG. 1a or 1b; ii) amino acid residues from about residue 128-224 of the amino acid sequence presented in FIG. 1a or 1b, wherein said sequence has been modified by addition, deletion or substitution of at least one amino acid residue; and iii) a polypeptide as defined in (i) and (ii) wherein said polypeptide substantially retains the biological activity of the polypeptide represented in FIG. 1a or 1b. |
| Claim: |
11-15. (canceled) |
| Claim: |
16. A composition comprising a polypeptide according to claim 10 and a diluent, carrier or excipient. |
| Claim: |
17-18. (canceled) |
| Claim: |
19. A screening method to identify agents which inhibit the binding of a polypeptide, or fragment thereof, to p53 comprising: i) forming a preparation comprising a) a polypeptide according to claim 10; and b) a p53 polypeptide, or a fragment thereof consisting of the binding site(s) for the polypeptide in (a); ii) providing at least one agent to be tested; and iii) determining the activity of the agent with respect to the binding of the polypeptide in (a) to the polypeptide in (b). |
| Claim: |
20. A method according to claim 19 wherein said agent is a polypeptide, a peptide, an antibody, or an antigen binding part of an antibody. |
| Claim: |
21-30. (canceled) |
| Claim: |
31. An isolated polypeptide comprising the amino acid sequence in FIG. 2b or a variant polypeptide which polypeptide is modified by addition, deletion or substitution of at least one amino acid residue and is an inhibitor of p53. |
| Claim: |
32. A method of treatment of an animal comprising administering to the animal an effective amount of a polypeptide according to claim 10 wherein said effective amount induces the apoptotic activity of p53. |
| Claim: |
33. (canceled) |
| Claim: |
34. A method according to claim 32 wherein said treatment is of cancer. |
| Claim: |
35. A peptide comprising an amino acid sequence selected from the group consisting of: DGPEETD; GPEETD; TTLSDG; AEFGDE; or PRNYFG. |
| Claim: |
36. A peptide according to claim 35 wherein the length of said peptide is at least 7 amino acid residues. |
| Claim: |
37. A peptide according to claim 35 wherein the length of said peptide is selected from the group consisting of: is 7 to 20 amino acid residues. |
| Claim: |
38. A peptide according to claim 35 wherein the length of said peptide is 20 to 100 amino acid residues. |
| Claim: |
39. A peptide according to claim 35 having an amino acid sequence consisting of an amino acid sequence selected from the group consisting of: DGPEETD; GPEETD; TTLSDG; AEFGDE; or PRNYFG. |
| Claim: |
40. A peptide according to any of claims 35-39 wherein said peptide further comprises a plurality of arginine residues. |
| Claim: |
41. A peptide according to claim 40 wherein said plurality of arginine residues is 2, 3, 4, 5, 6, 7, 8, 9, or 10 arginine residues in length. |
| Claim: |
42. (canceled) |
| Claim: |
43. A composition comprising a peptide according to claim 35 and a carrier, diluent, or excipient. |
| Claim: |
44. A composition comprising a peptide according to claim 39 and a carrier, diluent or excipient. |
| Claim: |
45. A composition comprising at least one peptide according any of claims 35-41 and at least one anti-cancer agent. |
| Claim: |
46. A composition according to claim 45 wherein said anticancer agent is selected from the group consisting of: cisplatin; carboplatin; cyclosphosphamide; melphalan; carmusline; methotrexate; 5-fluorouracil; cytarabine; mercaptopurine; daunorubicin; doxorubicin; epirubicin; vinblastine; vincristine; dactinomycin; mitomycin C; taxol; L-asparaginase; G-CSF; etoposide; colchicine; derferoxamine mesylate; and camptothecin. |
| Claim: |
47. A composition according to claim 46 wherein said anticancer agent is cisplatin. |
| Claim: |
48. A composition according to claim 46 wherein said anticancer agent is doxorubicin. |
| Claim: |
49. A complex comprising a peptide according to any of claims 35-41 and an antibody, or antigen-binding part thereof. |
| Claim: |
50. A complex according to claim 49 wherein said antibody or antigen binding part is a cell specific antibody. |
| Claim: |
51. A complex according to claim 49 wherein said antibody is a cancer cell specific antibody. |
| Claim: |
52. A method of treatment of an animal, wherein said animal would benefit from the induction of apoptosis comprising administering an effective amount of a peptide according to any of claims 35-41. |
| Claim: |
53. A method of treatment of an animal, wherein said animal would benefit from the induction of apoptosis comprising administering an effective amount of a composition according to any of claims 43-48 or a complex according to any of claims 49-51. |
| Claim: |
54. A method according to claim 52 or 53 wherein said treatment is cancer treatment. |
| Current U.S. Class: |
4241/781 |
| Current International Class: |
61; 07; 01; 07; 07; 61; 61; 61; 61 |
| رقم الانضمام: |
edspap.20080260756 |
| قاعدة البيانات: |
USPTO Patent Applications |