Claims
- 1. A method of treating a mammal for a condition associated with undesired cell proliferation, said method comprising administering to said mammal a therapeutically effective amount of a composition comprising an APRIL-R antagonist, wherein the APRIL-R antagonist comprises a polypeptide that antagonizes the interaction between APRIL and its cognate receptor or receptors, with a pharmaceutically acceptable recipient.
- 2. The method of claim 1 wherein the APRIL-R antagonist is selected from the group consisting of:
a) a soluble APRIL-R polypeptide; b) a soluble chimeric molecule comprising a soluble APRIL-R polypeptide fused to a heterologous amino acid sequence; and c) an anti-APRIL-R antibody homolog.
- 3. The method of claim 2 wherein the soluble APRIL-R polypeptide is selected from the group consisting of:
a) an isolated APRIL-R polypeptide variant having at least 80% amino acid sequence identity with native sequence APRIL-R polypeptide comprising amino acid residues 1 to 184 of SEQ ID NO:8 (FIG. 3A) or a fragment thereof; b) a isolated APRIL-R polypeptide variant having at least 80% amino acid sequence identity with amino acid residues 1-52 of SEQ ID NO:8 (FIG. 3A) or a fragment thereof; and c) a isolated APRIL-R polypeptide comprising amino acid residues 8-41 of SEQ ID NO:8 (FIG. 3A) or a fragment thereof.
- 4. The method of claim 2 wherein the soluble chimeric molecule comprises:
a) a soluble APRIL-R polypeptide selected from the group consisting of:
i. an isolated APRIL-R polypeptide variant having at least 80% amino acid sequence identity with native sequence APRIL-R polypeptide comprising amino acid residues 1 to 184 of SEQ ID NO:8 (FIG. 3A) or a fragment thereof; ii. a isolated APRIL-R polypeptide variant having at least 80% amino acid sequence identity with amino acid residues 1-52 of SEQ ID NO:8 (FIG. 3A) or a fragment thereof; and iii. a isolated APRIL-R polypeptide comprising amino acid residues 8-41 of SEQ ID NO:8 (FIG. 3A) or a fragment thereof, b) fused to a heterologous amino acid sequence.
- 5. The method of claim 4 wherein the heterologous amino acid sequence is from an IgG Fc domain of an immunoglobulin.
- 6. The method of claim 4 wherein the heterologous amino acid sequence is from a signal sequence of a secreted protein.
- 7. The method of claim 2 wherein the anti-APRIL-R antibody homolog comprises an antibody which binds to an APRIL-R polypeptide selected from the group consisting of:
a) an isolated APRIL-R polypeptide variant having at least 80% amino acid sequence identity with native sequence APRIL-R polypeptide comprising amino acid residues 1 to 184 of SEQ ID NO:8 (FIG. 3A) or a fragment thereof; b) a isolated APRIL-R polypeptide variant having at least 80% amino acid sequence identity with amino acid residues 1-52 of SEQ ID NO:8 (FIG. 3A) or a fragment thereof; and c) a isolated APRIL-R polypeptide comprising amino acid residues 8-41 of SEQ ID NO:8 (FIG. 3A) or a fragment thereof.
- 8. A method of treating a mammal for a condition associated with undesired cell proliferation, said method comprising administering to said mammal a therapeutically effective amount of two or more antagonists, wherein at least two of the antagonists include a first APRIL-R antagonist that antagonizes the interaction between APRIL and BCMA, and a second APRIL-R antagonist that antagonizes an interaction between APRIL and another cognate APRIL receptor or receptors that are not BCMA.
- 9. The method of claims 1 to 8, wherein the undesired cell proliferation is a carcinoma.
- 10. The method of claims 1 to 8, wherein the condition associated with undesired cell proliferation is cancer.
- 11. The methods of claims 1 to 8, wherein the mammal is a human.
- 12. A method of treating a patient having a carcinoma whose proliferation is modulated by APRIL comprising administering to said patient a therapeutically effective amount of a composition comprising an APRIL-R antagonist, wherein the APRIL-R antagonist comprises a polypeptide that antagonizes the interaction between APRIL and APRIL-R.
- 13. The method of claim 9, wherein the carcinoma is selected from the group consisting of human lung carcinoma, colon carcinoma, breast carcinoma, prostate carcinoma, and other carcinomas whose proliferation is modulated by APRIL.
RELATED APPLICATIONS
[0001] This is a continuation of PCT/US00/27579, filed on Oct. 5, 2000, which claims priority from U.S. provisional application Serial No. 60/157,933 filed on Oct. 6, 1999, U.S. provisional application Serial No. 60/181,807 filed Feb. 11, 2000 and U.S. provisional application Serial No. 60/215,688 filed Jun. 30, 2000.
Provisional Applications (3)
|
Number |
Date |
Country |
|
60157933 |
Oct 1999 |
US |
|
60181807 |
Feb 2000 |
US |
|
60215688 |
Jun 2000 |
US |
Continuations (1)
|
Number |
Date |
Country |
Parent |
PCT/US00/27579 |
Oct 2000 |
US |
Child |
10115192 |
Apr 2002 |
US |