Monoclonal antibodies for detection of folate receptor 1
The invention generally relates to antibodies that bind to human folate receptor and diagnostic assays for folate receptor 1-based therapies. Methods of using the antibodies to monitor therapy are further provided.
1. A monoclonal antibody or antigen-binding fragment thereof that specifically binds to the same folate receptor 1 (FOLR1) epitope as an antibody comprising a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO:27 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO:28,
wherein the monoclonal antibody or antigen-binding fragment thereof binds to an epitope of FOLR1 comprising an N-glycosylated amino acid.
2. The monoclonal antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or fragment thereof comprises the VH CDR1-3 and VL CDR1-3 polypeptide sequences selected from the group consisting of:
(a) SEQ ID NOs:3-8, respectively;
(b) SEQ ID NOs:9-14, respectively;
(c) SEQ ID NOs:15-20, respectively;
(d) SEQ ID NOs: 3-5 and SEQ ID NOs: 59, 7, and 8, respectively;
(e) SEQ ID NOs: 3, 60, and 5 and SEQ ID NOs: 6-8, respectively;
(e) SEQ ID NOs: 3, 61, and 5 and SEQ ID NOs: 6-8, respectively;
(g) SEQ NOs: 3, 60, and 5 and SEQ ID NOs: 59, 7, and 8, respectively; and
(h) SEQ ID NOs: 3, 61, and 5 and SEQ ID NOs: 59, 7, and 8, respectively.
3. A polypeptide that specifically binds FOLR1, wherein said polypeptide comprises VH CDR1-3 and VL CDR1-3 polypeptide sequences selected from the group consisting of:
(a) SEQ ID NOs:3-8, respectively;
(b) SEQ ID NOs:9-14, respectively;
(c) SEQ ID NOs: 15-20, respectively;
(d) SEQ ID NOs: 3-5 and SEQ ID NOs: 59, 7, and 8, respectively;
(e) SEQ ID NOs: 3, 60, and 5 and SEQ ID NOs: 6-8, respectively;
(f) SEQ ID NOs: 3, 61, and 5 and SEQ NOs: 6-8, respectively;
(f) SEQ ID NOs: 3, 60, and 5 and SEQ ID NO 59, 7, and 8, respectively; and
(h) SEQ ID NOs: 3, 61, and 5 and SEQ ID NOs: 59, 7, and 8, respectively.
4. A composition comprising the monoclonal antibody or antigen-binding fragment thereof of claim 1 and a buffer selected from the group consisting of: a FACS buffer, an IHC buffer, and an ELISA buffer.
5. A monoclonal antibody or antigen-binding fragment thereof that specifically binds to FOLR1, wherein said antibody or fragment thereof competitively inhibits binding to FOLR1 of an antibody comprising a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO:27 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO:28, wherein the monoclonal antibody or antigen-binding fragment thereof binds to an epitope of FOLR1 comprising an N-glycosylated amino acid.
6. The monoclonal antibody or antigen-binding fragment thereof that specifically binds to FOLR1 of claim 5 , comprising a heavy chain variable region (VH) and a light chain variable region (VL) selected from the group consisting of:
a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO:27 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO:28;
a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO:29 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO:30;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:31 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO:32;
a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO:62 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO:63 or SEQ ID NO:64; and
a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO:65 and a light chain variable region (VL) comprising the amino acid sequence of SEQ NO:66 or SEQ ID NO:67.
7. The monoclonal antibody or antigen-binding fragment thereof of claim 5 , wherein said antibody or antigen-binding fragment thereof is chimeric or humanized.
8. The monoclonal antibody or antigen-binding fragment thereof of claim 5 , which is a full-length antibody.
9. The monoclonal antibody or antigen-binding fragment thereof of claim 5 , which is an antigen-binding fragment.
10. The monoclonal antibody or antigen-binding fragment thereof of claim 5 , which binds to a human folate receptor 1 with a Kd of about 0.5 to about 10 nM.
11. The monoclonal antibody or antigen-binding fragment thereof of claim 5 , which binds to a human folate receptor 1 with a Kd of about 1.0 nM or less.
12. The monoclonal antibody or antigen-binding fragment thereof of claim 5 , wherein the antibody or antigen-binding fragment thereof is detectably labeled.
13. The monoclonal antibody or antigen-binding fragment thereof of claim 12 , wherein said detectable label is selected from the group consisting of immunofluorescent label, chemiluminescent label, phosphorescent label, enzyme label, radiolabel, avidin/biotin, colloidal gold particles, colored particles and magnetic particles.
14. An antibody or antigen-binding fragment thereof that specifically binds to FOLR1, wherein said antibody or fragment thereof comprises the VH CDR1-3 and VL CDR1-3 polypeptide sequences of SEQ ID NOs: 3-8, respectively.
15. The antibody or antigen-binding fragment thereof of claim 14 , wherein the antibody or fragment thereof comprises a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO:27 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO:28.
16. An antibody or antigen-binding fragment thereof that specifically binds to FOLR1, wherein said antibody or fragment thereof comprises the VH CDR1-3 and VL CDR1-3 polypeptide sequences of SEQ ID NOs: 9-14, respectively.
17. The antibody or antigen-binding fragment thereof of claim 16 , wherein the antibody or fragment thereof comprises a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO:29 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO:30.
18. An antibody or antigen-binding fragment thereof that specifically binds to FOLR1, wherein said antibody or fragment thereof comprises the VH CDR1-3 and VL CDR1-3 polypeptide sequences of SEQ ID NOs: 15-20, respectively.
19. The antibody or antigen-binding fragment thereof of claim 18 , wherein the antibody or fragment thereof comprises a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO:31 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO:32.
20. The antibody or antigen-binding fragment thereof of claim 14 , wherein the antibody or antigen-binding fragment thereof is detectably labeled.
21. The antibody or antigen-binding fragment thereof of claim 20 , wherein said detectable label is selected from the group consisting of: immunofluorescent label, chemiluminescent label, phosphorescent label, enzyme label, radiolabel, avidin/biotin, colloidal gold particles, colored particles and magnetic particles.
22. A composition comprising the antibody or antigen-binding fragment thereof of claim 14 and a buffer selected from the group consisting of: a FACS buffer, an IHC buffer, and an ELISA buffer.
23. The antibody or antigen-binding fragment thereof of claim 16 , wherein the antibody or antigen-binding fragment thereof is detectably labeled.
24. The antibody or antigen-binding fragment thereof of claim 23 , wherein said detectable label is selected from the group consisting of: immunofluorescent label, chemiluminescent label, phosphorescent label, enzyme label, radiolabel, avidin/biotin, colloidal gold particles, colored particles and magnetic particles.
25. A composition comprising the antibody or antigen-binding fragment thereof of claim 16 and a buffer selected from the group consisting of: a FACS buffer, an IHC buffer, and an ELISA buffer.
26. The antibody or antigen-binding fragment thereof of claim 18 , wherein the antibody or antigen-binding fragment thereof is detectably labeled.
27. The antibody or antigen-binding fragment thereof of claim 26 , wherein said detectable label is selected from the group consisting of: immunofluorescent label, chemiluminescent label, phosphorescent label, enzyme label, radiolabel, avidin/biotin, colloidal gold particles, colored particles and magnetic particles.
28. A composition comprising the antibody or antigen-binding fragment thereof of claim 18 and a buffer selected from the group consisting of: a FACS buffer, an IHC buffer, and an ELISA buffer.
29. The antibody or antigen-binding fragment thereof of claim 15 , wherein the antibody or antigen-binding fragment thereof is detectably labeled.
30. The antibody or antigen-binding fragment thereof of claim 29 , wherein said detectable label is selected from the group consisting of: immunofluorescent label, chemiluminescent label, phosphorescent label, enzyme label, radiolabel, avidin/biotin, colloidal gold particles, colored particles and magnetic particles.
31. A composition comprising the antibody or antigen-binding fragment thereof of claim 15 and a buffer selected from the group consisting of: a FACS buffer, an IHC buffer, and an ELISA buffer.
32. The antibody or antigen-binding fragment thereof of claim 15 , wherein the antibody or fragment thereof comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:33 and a light chain comprising the amino acid sequence of SEQ ID NO:34.
33. The antibody or antigen-binding fragment thereof of claim 17 , wherein the antibody or fragment thereof comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:35 and a light chain comprising the amino acid sequence of SEQ ID NO:36.
34. The antibody or antigen-binding fragment thereof of claim 19 , wherein the antibody or fragment thereof comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:37 and a light chain comprising the amino acid sequence of SEQ ID NO:38.
35. A hybridoma producing the monoclonal antibody or antigen-binding fragment thereof of claim 1 .
36. A method of making the monoclonal antibody or antigen-binding fragment thereof of claim 1 , comprising (a) culturing the hybridoma of claim 35 ; and (b) isolating said antibody or antigen-binding fragment thereof from said cultured hybridoma.