BAFF receptor polypeptides
View Patent ↗Disclosed are nucleic acids encoding BAFF-R polypeptides, as well as antibodies to BAFF-R polypeptides and pharmaceutical compositions including the same. Methods of treating tumorigenic and autoimmune conditions using the nucleic acids, polypeptides, antibodies and pharmaceutical compositions of this invention are also provided.
1. An isolated polypeptide that binds to BAFF and comprises:
(a) an amino acid sequence that binds to BAFF and is at least 80% identical to SEQ ID NO:13, or
(b) a fragment of (a) that binds to BAFF.
2. The polypeptide of claim 1 , wherein the amino acid sequence of (a) is at least 90% identical to SEQ ID NO:13.
3. The polypeptide of claim 1 , wherein the amino acid sequence of (a) is at least 95% identical to SEQ ID NO:13.
4. The polypeptide of claim 1 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO:13 modified by one or more conservative amino acid substitutions, additions or deletions.
5. The polypeptide of claim 1 , wherein the polypeptide comprises amino acids 19-35 of SEQ ID NO:10.
6. The polypeptide of claim 5 , wherein the polypeptide comprises amino acids 2-71 of SEQ ID NO:10.
7. The polypeptide of claim 1 , wherein the amino acid sequence of (a) is SEQ ID NO:10.
8. The polypeptide of claim 1 , wherein the polypeptide comprises a fragment of SEQ ID NO:13 that binds to BAFF.
9. The polypeptide of claim 1 , wherein the polypeptide comprises a fragment of SEQ ID NO:5 that binds to BAFF.
10. The polypeptide of claim 1 , wherein the polypeptide consists of an amino acid sequence as set out in SEQ ID NO:13.
11. The polypeptide of claim 1 , wherein the amino acid sequence of (a) comprises an amino acid sequence selected from SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, and SEQ ID NO:32.
12. The polypeptide of claim 11 , wherein the amino acid sequence of (a) comprises an amino acid sequence selected from SEQ ID NO:19, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, and SEQ ID NO:27.
13. The polypeptide of claim 1 , comprising the amino acid sequence of amino acids 2-71 of SEQ ID NO:10, except that at least one amino acid residue in the region from C19 to L27 is altered to diminish protein aggregation.
14. The polypeptide of claim 13 , wherein the altered residue(s) comprise(s) one or more residues selected from V20, P21, A22, and L27.
15. The polypeptide of claim 14 , wherein the altered residue(s) include one or more residues selected from V20N, P21Q, A22T, and L27P.
16. The polypeptide of claim 14 , wherein the altered residue(s) is/are selected from:
(a) V20N, P21Q, A22T, and L27P;
(b) L27P and V20N;
(c) P21Q and L27P;
(d) L27P;
(e) V20N and L27A; and
(f) V20N and L27S.
17. An isolated polypeptide comprising an antigenic fragment of SEQ ID NO:5 of at least 15 consecutive amino acid residues.
18. The polypeptide of claim 17 , comprising at least 30 consecutive amino acid residues from SEQ ID NO:5.
19. A pharmaceutical composition comprising the polypeptide of any one of claims 1 , 11 , and 13 and a pharmaceutically acceptable carrier.
20. A method of reducing BAFF activity in a mammal, the method comprising administering an effect amount of the composition of claim 19 to the mammal, thereby reducing BAFF activity in the mammal.
21. A method of treating a mammal for a B-cell mediated disease or condition selected from the group consisting of an autoimmune condition, a tumorigenic condition, a B-cell carcinoma, leukemia, lymphoma, organ transplantation, and Burkitt's lymphoma, comprising administering the composition of claim 19 .
22. The method of claim 21 , wherein the mammal has B cell carcinoma, leukemia, or lymphoma.
23. The method of claim 21 , wherein the autoimmune condition is systemic lupus erythematosus.
24. The method of claim 21 , wherein the autoimmune condition is rheumatoid arthritis.