Method for inhibiting BAFF-R activity
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. A method for inhibiting the activity of BAFF-R in a cell comprising the step of contacting the cell with:
(a) an isolated soluble polypeptide that binds to BAFF and comprises:
(1) an amino acid sequence that binds to BAFF and is at least 80% identical to SEQ ID NO:13, or
(2) a fragment of (1) that binds to BAFF; or
(b) an isolated antibody, or an antigen binding fragment thereof, that specifically binds to the amino acid sequence of SEQ ID NO:5 or SEQ ID NO:10.
2. The method of claim 1 , wherein the polypeptide of (a)(1) comprises an amino acid sequence that is at least 90% identical to SEQ ID NO:13.
3. The method of claim 1 , wherein the polypeptide of (a)(1) comprises an amino acid sequence that is at least 95% identical to SEQ ID NO:13.
4. The method of claim 1 , wherein the polypeptide of (a)(1) comprises the amino acid sequence of SEQ ID NO:13 modified by one or more conservative amino acid substitutions, additions or deletions.
5. The method of claim 1 , wherein the polypeptide of (a)(2) comprises amino acids 19-35 of SEQ ID NO:10.
6. The method of claim 1 , wherein the polypeptide of (a)(1) consists of the amino acid sequence set forth in SEQ ID NO:13.
7. The method of claim 1 , wherein the polypeptide of (a)(1) 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.
8. The method of claim 1 , wherein the polypeptide of (a)(1) 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.
9. The method of claim 1 , wherein the polypeptide of (a)(1) comprises the amino acid sequence set forth in SEQ ID NO:13, except that at least one amino acid residue in the region from C19 to L27 is altered to diminish protein aggregation.
10. The method of claim 9 , wherein the altered residue(s) comprise(s) one or more residues selected from V20, P21, A22, and L27.
11. The method of claim 9 , wherein the altered residue(s) include one or more residues selected from V20N, P21Q, A22T, and L27P.
12. The method of claim 9 , 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.
13. The method of claim 1 , wherein the antibody or antigen binding fragment of (b) specifically binds to the amino acid sequence of SEQ ID NO:10.
14. The method of claim 1 , wherein the antibody or antigen binding fragment of (b) specifically binds to the amino acid sequence of SEQ ID NO:13.
15. The method of claim 1 , wherein the antibody or antigen binding fragment of (b) is chimeric.
16. The method of claim 1 , wherein the antibody or antigen binding fragment of (b) is humanized.
17. The method of claim 1 , wherein the antibody or antigen binding fragment of (b) is monoclonal.
18. The method of claim 1 , wherein the antibody or antigen binding fragment of (b) is polyclonal.
19. The method of claim 1 , wherein the antibody or antigen binding fragment is a single chain antibody.
20. The method of claim 1 , wherein the antibody or antigen binding fragment of (b) is a Fab fragment.
21. The method of claim 1 , wherein the antibody or antigen binding fragment of (b) is a F(ab′)2 fragment.
22. The method of claim 1 , wherein the antibody or antigen binding fragment of (b) blocks binding of B Cell Activating Factor of the TNF family (BAFF) to its receptor.
23. The method of claim 1 , wherein the antibody or antigen binding fragment of (b) is produced by hybridoma clone #2.1, deposited under ATCC No. PTA-3689 or binds to the same epitope as the antibody produced by hybridoma clone #2.1.
24. The method of claim 1 , wherein the antibody or antigen binding fragment of (b) is produced by hybridoma clone #9.1 deposited under ATCC No. PTA-3688 or binds to the same epitope as the antibody produced by hybridoma clone #9.1.