Folate receptor 1 antibodies and immunoconjugates and uses thereof

1. An antibody or antigen binding fragment thereof that specifically binds a human folate receptor 1, wherein the antibody or antigen binding fragment thereof comprises:

(a) a heavy chain CDR1 comprising the amino acid sequence SSFGMH (SEQ ID NO:72); a heavy chain CDR2 comprising the amino acid sequence YISSGSSTIS (SEQ ID NO:73); and a heavy chain CDR3 comprising the amino acid sequence EAYGSSMEY (SEQ ID NO:74) and (b) a light chain CDR1 comprising the amino acid sequence RASQNINNNLH (SEQ ID NO:69); a light chain CDR2 comprising the amino acid sequence YVSQSVS (SEQ ID NO:70); and a light chain CDR3 comprising the amino acid sequence QQSNSWPHYT (SEQ ID NO:71).

2. The antibody or antigen binding fragment thereof of claim 1 which is a full length antibody.

3. The antibody or antigen binding fragment thereof of claim 1 which is an antigen binding fragment, wherein the antigen binding fragment comprises a Fab, a Fab′, a F(ab′)2, a single chain Fv (scFv), a disulfide linked Fv, an IgG-CH2, a F(ab′)3, a tetrabody, a triabody, a diabody, a (scFv)2, or a scFv-Fc.

4. A method of making the antibody or antigen binding fragment thereof of claim 1 comprising (a) culturing a cell expressing said antibody or antigen binding fragment thereof; and (b) isolating the antibody or antigen binding fragment thereof from said cultured cell, wherein the cell is a eukaryotic cell.

5. An immunoconjugate having the formula (A)-(L)-(C), wherein:

(A) is the antibody or antigen binding fragment of claim 1 ;

(L) is a linker; and

(C) is a cytotoxic agent;

wherein said linker (L) links (A) to (C).

6. The immunoconjugate of claim 5 , wherein said linker is selected from the group consisting of a cleavable linker, a non-cleavable linker, a hydrophilic linker, and a dicarboxylic acid based linker.

7. The immunoconjugate of claim 6 , wherein said linker is selected from the group consisting: N-succinimidyl 4-(2-pyridyldithio)pentanoate (SPP) or N-succinimidyl 4-(2-pyridyldithio)-2-sulfopentanoate (sulfo-SPP); N-succinimidyl 4-(2-pyridyldithio)butanoate (SPDB) or N-succinimidyl 4-(2-pyridyldithio)-2-sulfobutanoate (sulfo-SPDB); N-succinimidyl 4-(maleimidomethyl) cyclohexanecarboxylate (SMCC); N-sulfosuccinimidyl 4-(maleimidomethyl) cyclohexanecarboxylate (sulfoSMCC); N-succinimidyl-4-(iodoacetyl)-aminobenzoate (SIAB); and N-succinimidyl-[(N-maleimidopropionamido)-tetraethyleneglycol] ester (NHS-PEG4-maleimide).

8. The immunoconjugate of claim 5 , wherein said cytotoxic agent is selected from the group consisting of a maytansinoid, benzodiazepine, taxoid, CC-1065, duocarmycin, calicheamicin, dolastatin, auristatin, tomaymycin, and leptomycin or a prodrug of the agent.

9. The immunoconjugate of claim 8 , wherein said maytansinoid is N(2′)-deacetyl-N(2′)-(3-mercapto-1-oxopropyl)-maytansine or N(2′)-deacetyl-N2-(4-mercapto-4-methyl-1-oxopentyl)-maytansine.

10. The immunoconjugate of claim 5 comprising 2-6 (C) or 3-4 (C).

11. A pharmaceutical composition comprising the antibody or antigen binding fragment thereof of claim 1 and a pharmaceutically acceptable carrier.

12. A pharmaceutical composition comprising the immunoconjugate of claim 5 and a pharmaceutically acceptable carrier.

13. The pharmaceutical composition of claim 12 , wherein the immunoconjugates have an average of about 3 to about 4 (C) per (A) or an average of about 3.5±0.5 (C) per (A).

14. A diagnostic reagent comprising the antibody or antigen binding fragment thereof of claim 1 and a label selected from the group consisting of: a radiolabel, a fluorophore, a chromophore, an imaging agent and a metal ion.

15. A kit comprising the antibody or antigen binding fragment thereof of claim 1 .

16. The antibody or antigen binding fragment thereof of claim 1 , wherein the heavy chain CDR2 comprises the amino acid sequence YISSGSSTISYADSVKG (SEQ ID NO:85).

17. The antibody or antigen binding fragment thereof of claim 16 , wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:101 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO:100.

18. The antibody or antigen binding fragment thereof of claim 1 , wherein the heavy chain CDR2 comprises the amino acid sequence YISSGSSTISYADTVKG (SEQ ID NO:84).

19. The antibody or antigen binding fragment thereof of claim 18 , wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:93 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO:92.

20. A diagnostic reagent comprising the immunoconjugate of claim 5 and a label selected from the group consisting of: a radiolabel, a fluorophore, a chromophore, an imaging agent and a metal ion.

21. A kit comprising the immunoconjugate of claim 5 .

22. The antibody or antigen binding fragment thereof of claim 1 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:117 and a light chain comprising the amino acid sequence of SEQ ID NO:116.

23. A pharmaceutical composition comprising the antibody or antigen binding fragment thereof of claim 17 and a pharmaceutically acceptable carrier.

24. An immunoconjugate having the formula (A)-(L)-(C), wherein:

(A) is the antibody or antigen binding fragment of claim 17 ;

(L) is a linker; and

(C) is a cytotoxic agent;

wherein said linker (L) links (A) to (C).

25. The immunoconjugate of claim 24 , wherein said cytotoxic agent is N(2′)-deacetyl-N(2′)-(3-mercapto-1-oxopropyl)-maytansine or N(2′)-deacetyl-N2-(4-mercapto-4-methyl-1-oxopentyl)-maytansine.

26. A pharmaceutical composition comprising the immunoconjugate of claim 9 and a pharmaceutically acceptable carrier.

27. A pharmaceutical composition comprising the immunoconjugate of claim 24 and a pharmaceutically acceptable carrier.

28. A pharmaceutical composition comprising the immunoconjugate of claim 25 and a pharmaceutically acceptable carrier.