Human anti-folate receptor alpha antibodies and antibody fragments for the radioimmunotherapy of ovarian carcinoma
Antibody or fragment thereof, which specifically binds to folate receptor-alpha (FRα), wherein said antibody or fragment thereof comprises a light chain whose variable region comprises at least one of the following amino acid sequences: —RASESVSFLGINLIH (SEQ ID NO: 3), —QASNKDT (SEQ ID NO: 4), —LQSKNFPPYT (SEQ ID NO: 5), and wherein the constant region of said light chain is a kappa constant region.
1. An isolated or purified antibody or fragment thereof, which specifically binds to folate receptor-alpha (FRa),
wherein said antibody or fragment thereof is a Fab fragment comprising a light chain and a heavy chain, the light chain having a variable region (V L ) and a constant region (C L ), the heavy chain having a variable region (V H ) and a first constant region (C H1 ), and
wherein
the variable region (V L ) comprises the following amino acid sequences:
RASESVSFLGINLIH,
(SEQ ID NO: 3)
QASNKDT,
(SEQ ID NO: 4)
LQSKNFPPYT,
(SEQ ID NO: 5)
the constant region (C L ) is a kappa constant region,
the variable region (V H ) has the amino acid sequence of SEQ ID NO: 2; and
the first constant region (C H1 ) is an IgG heavy chain.
2. The antibody or fragment thereof according to claim 1 , which comprises a light chain having the amino acid sequence of FIG. 1 (SEQ ID NO: 1).
3. The antibody or fragment thereof according to claim 1 which is fully human.
4. The antibody or fragment thereof according to claim 1 which is monoclonal.
5. The antibody fragment according to claim 1 , which is a Fab' fragment, wherein the heavy chain further comprises a hinge region suitable for covalent bonding to a second antibody fragment.
6. The antibody or fragment thereof according to claim 1 which is conjugated to an effector moiety selected from a cytotoxic agent or a marker.
7. The antibody or fragment thereof according to claim 6 wherein the cytotoxic agent is a radionuclide.
8. The antibody or fragment thereof according to claim 7 wherein the radionuclide is selected from the group consisting of 131 I, 90 Y, 177 Lu, 188 Re and 99 Tc.
9. A dimer formed by the two covalently bound Fab' fragments of claim 5 .
10. A pharmaceutical composition comprising the antibody, or fragment thereof, according to claim 1 , in association with a pharmaceutically acceptable carrier.
11. The pharmaceutical composition according to claim 10 wherein the antibody or fragment thereof is conjugated to an effector moiety selected from a cytotoxic agent or a marker.
12. The pharmaceutical composition according to claim 11 wherein the cytotoxic agent is a radionuclide.
13. The pharmaceutical composition according to claim 12 wherein the radionuclide is selected from 131 I, 90 Y, 177 Lu, 188 Re and 99 Tc.
14. The pharmaceutical composition according to claim 11 further comprising a therapeutic agent selected from the group consisting of a chemotherapeutic agent and a radiotherapeutic agent.
15. A method for treating a disorder involving overexpression of folate receptor-alpha (FRa) which comprises administering to a subject in the need thereof an antibody or fragment thereof as defined in claim 1 , wherein the disorder is ovarian carcinoma in humans.