Antibodies against human CSF-1R and uses thereof

1. An isolated nucleic acid encoding an antibody binding to human CSF-1R, wherein the antibody comprises a heavy chain variable domain and a light chain variable domain, and wherein:

a) the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:7 and the light chain variable domain comprises the amino acid sequence of SEQ ID NO:8;

b) the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:15 and the light chain variable domain comprises the amino acid sequence of SEQ ID NO:16;

c) the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:75 and the light chain variable domain comprises the amino acid sequence of SEQ ID NO:76;

d) the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:83 and the light chain variable domain comprises the amino acid sequence of SEQ ID NO84;

or a humanized version thereof.

2. An isolated nucleic acid encoding an antibody binding to human CSF-1R, wherein the antibody comprises a heavy chain variable domain and a light chain variable domain, and wherein:

a) the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:23 and the light chain variable domain comprises the amino acid sequence of SEQ ID NO:24,

b) the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:31 and the light chain variable domain comprises the amino acid sequence of SEQ ID NO:32,

c) the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:39 and the light chain variable domain comprises the amino acid sequence of SEQ ID NO:40,

d) the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:47 and the light chain variable domain comprises the amino acid sequence of SEQ ID NO:48, or

e) the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:55 and the light chain variable domain comprises the amino acid sequence of SEQ ID NO:56.

3. An isolated nucleic acid encoding an antibody binding to human CSF-1R, wherein the antibody comprises a heavy chain variable domain and a light chain variable domain, and wherein:

a) the heavy chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO: 1, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 2, and a CDR1 region comprising the amino acid sequence of SEQ ID NO:3, and the light chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO: 4, a CDR2 region comprising the amino acid sequence of SEQ ID NO:5, and a CDR1 region comprising the amino acid sequence of SEQ ID NO:6;

b) the heavy chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO: 9, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 10, and a CDR1 region comprising the amino acid sequence of SEQ ID NO: 11, and the light chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO:12, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 13, and a CDR1 region comprising the amino acid sequence of SEQ ID NO: 14;

c) the heavy chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO: 17, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 18, and a CDR1 region comprising the amino acid sequence of SEQ ID NO:19, and the light chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO: 20, a CDR2 region comprising the amino acid sequence of SEQ ID NO:21, and a CDR1 region comprising the amino acid sequence of SEQ ID NO:22;

d) the heavy chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO: 25, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 26, and a CDR1 region comprising the amino acid sequence of SEQ ID NO: 27, and the light chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO:28, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 29, and a CDR1 region comprising the amino acid sequence of SEQ ID NO: 30;

e) the heavy chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO: 33, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 34, and a CDR1 region comprising the amino acid sequence of SEQ ID NO: 35, and the light chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO:36, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 37, and a CDR1 region comprising the amino acid sequence of SEQ ID NO: 38;

f) the heavy chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO:41, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 42, and a CDR1 region comprising the amino acid sequence of SEQ ID NO:43, and the light chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO: 44, a CDR2 region comprising the amino acid sequence of SEQ ID NO:45, and a CDR1 region comprising the amino acid sequence of SEQ ID NO:46;

g) the heavy chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO: 49, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 50, and a CDR1 region comprising the amino acid sequence of SEQ ID NO: 51, and the light chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO:52, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 53, and a CDR1 region comprising the amino acid sequence of SEQ ID NO: 54;

h) the heavy chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO:69, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 70, and a CDR1 region comprising the amino acid sequence of SEQ ID NO:71, and the light chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO: 72, a CDR2 region comprising the amino acid sequence of SEQ ID NO:73, and a CDR1 region comprising the amino acid sequence of SEQ ID NO:74; or

i) the heavy chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO: 77, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 78, and a CDR1 region comprising the amino acid sequence of SEQ ID NO: 79, and the light chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO:80, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 81, and a CDR1 region comprising the amino acid sequence of SEQ ID NO: 82.

4. The isolated nucleic acid of claim 3 , wherein the antibody is of human IgGlsubclass or is of human IgG4 subclass.

5. The isolated nucleic acid of claim 3 , wherein the antibody is a chimeric, single chain, multispecific, or humanized antibody.

6. The isolated nucleic acid of claim 3 , wherein the antibody is an antigen binding fragment.

7. An expression vector comprising the nucleic acid of claim 3 for the expression of the antibody in a prokaryotic or eukaryotic host cell.

8. A prokaryotic or eukaryotic host cell comprising the vector of claim 7 .

9. A method for the production of a recombinant antibody, the method comprising expressing the nucleic acid of claim 3 in a prokaryotic or eukaryotic host cell and recovering the antibody from said cell or cell culture supernatant.

10. The isolated nucleic acid of claim 1 , wherein the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:7 and the light chain variable domain comprises the amino acid sequence of SEQ ID NO:8.

11. The isolated nucleic acid of claim 1 , wherein the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:15 and the light chain variable domain comprises the amino acid sequence of SEQ ID NO:16.

12. The isolated nucleic acid of claim 1 , wherein the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:75 and the light chain variable domain comprises the amino acid sequence of SEQ ID NO:76.

13. The isolated nucleic acid of claim 1 , wherein the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:83 and the light chain variable domain comprises the amino acid sequence of SEQ ID NO:84.

14. The isolated nucleic acid of claim 2 , wherein the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:23 and the light chain variable domain comprises the amino acid sequence of SEQ ID NO:24.

15. The isolated nucleic acid of claim 2 , wherein the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:31 and the light chain variable domain comprises the amino acid sequence of SEQ ID NO:32.

16. The isolated nucleic acid of claim 2 , wherein the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:47 and the light chain variable domain comprises the amino acid sequence of SEQ ID NO:48.

17. The isolated nucleic acid of claim 2 , wherein the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:55 and the light chain variable domain comprises the amino acid sequence of SEQ ID NO:56.

18. The isolated nucleic acid of claim 3 , wherein the heavy chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO: 1, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 2, and a CDR1 region comprising the amino acid sequence of SEQ ID NO:3, and the light chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO: 4, a CDR2 region comprising the amino acid sequence of SEQ ID NO:5, and a CDR1 region comprising the amino acid sequence of SEQ ID NO:6.

19. The isolated nucleic acid of claim 3 , wherein the heavy chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO: 9, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 10, and a CDR1region comprising the amino acid sequence of SEQ ID NO: 11, and the light chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO:12, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 13, and a CDR1 region comprising the amino acid sequence of SEQ ID NO: 14.

20. The isolated nucleic acid of claim 3 , wherein the heavy chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO: 17, a CDR2region comprising the amino acid sequence of SEQ ID NO: 18, and a CDR1 region comprising the amino acid sequence of SEQ ID NO:19, and the light chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO: 20, a CDR2 region comprising the amino acid sequence of SEQ ID NO:21, and a CDR1 region comprising the amino acid sequence of SEQ ID NO:22.

21. The isolated nucleic acid of claim 3 , wherein the heavy chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO: 25, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 26, and a CDR1 region comprising the amino acid sequence of SEQ ID NO: 27, and the light chain variable domain comprises a CDR3region comprising the amino acid sequence of SEQ ID NO:28, a CDR2region comprising the amino acid sequence of SEQ ID NO: 29, and a CDR1 region comprising the amino acid sequence of SEQ ID NO: 30.

22. The isolated nucleic acid of claim 3 , wherein the heavy chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO:41, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 42, and a CDR1 region comprising the amino acid sequence of SEQ ID NO:43, and the light chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO: 44, a CDR2 region comprising the amino acid sequence of SEQ ID NO:45, and a CDR1 region comprising the amino acid sequence of SEQ ID NO:46.

23. The isolated nucleic acid of claim 3 , wherein the heavy chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO: 49, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 50, and a CDR1 region comprising the amino acid sequence of SEQ ID NO: 51, and the light chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO:52, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 53, and a CDR1 region comprising the amino acid sequence of SEQ ID NO: 54.

24. The isolated nucleic acid of claim 3 , wherein the heavy chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO:69, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 70, and a CDR1 region comprising the amino acid sequence of SEQ ID NO:71, and the light chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO: 72, a CDR2 region comprising the amino acid sequence of SEQ ID NO:73, and a CDR1 region comprising the amino acid sequence of SEQ ID NO:74.

25. The isolated nucleic acid of claim 3 , wherein the heavy chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO: 77, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 78, and a CDR1 region comprising the amino acid sequence of SEQ ID NO: 79, and the light chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO:80, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 81, and a CDR1 region comprising the amino acid sequence of SEQ ID NO: 82.

26. An isolated nucleic acid encoding an antibody binding to human CSF-1R, wherein the antibody comprises a heavy chain variable domain and a light chain variable domain, and wherein the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:39 and the light chain variable domain comprises the amino acid sequence of SEQ ID NO:40.

27. An isolated nucleic acid encoding an antibody binding to human CSF-1R, wherein the antibody comprises a heavy chain variable domain and a light chain variable domain, and wherein the heavy chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO: 33, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 34, and a CDR1 region comprising the amino acid sequence of SEQ ID NO: 35, and the light chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO:36, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 37, and a CDR1 region comprising the amino acid sequence of SEQ ID NO: 38.

28. The isolated nucleic acid of claim 27 , wherein the antibody is of human IgG1subclass or is of human IgG4 subclass.

29. The isolated nucleic acid of claim 27 , wherein the antibody is a chimeric, single chain, multispecific, or humanized antibody.

30. The isolated nucleic acid of claim 27 , wherein the antibody is an antigen binding fragment.

31. An expression vector comprising the nucleic acid of claim 27 for the expression of the antibody in a prokaryotic or eukaryotic host cell.

32. A prokaryotic or eukaryotic host cell comprising the vector of claim 27 .

33. A method for the production of a recombinant antibody, the method comprising expressing the nucleic acid of claim 27 in a prokaryotic or eukaryotic host cell and recovering the antibody from said cell or cell culture supernatant.