Humanized EGFR antibodies

1. A humanized antibody or a fragment thereof which is capable of binding to an epidermal growth factor receptor (EGFR) and which comprises:

(a) a heavy chain variable region, comprising

(i) the amino acid sequence of SEQ ID NO: 20, or

(ii) an amino acid sequence which shares an identity of at least 90% with the amino acid sequence of SEQ ID NO: 20 and wherein VH CDR1 has the amino acid sequence of SEQ ID NO: 1, VH CDR2 has the amino acid sequence of SEQ ID NO: 2, and VH CDR3 has the amino acid sequence of SEQ ID NO: 3; and

(b) a light chain variable region, comprising

(i) the amino acid sequence of SEQ ID NO: 29, or

(ii) an amino acid sequence which shares an identity of at least 90% with the amino acid sequence of SEQ ID NO: 29 and wherein VL CDR1 has the amino acid sequence of SEQ ID NO: 5, VL CDR2 has the amino acid sequence of SEQ ID NO: 6, and VL CDR3 has the amino acid sequence of SEQ ID NO: 7;

and wherein the antibody or fragment thereof binds to EGFR with an affinity having a dissociation constant which is at most 10-fold higher than that of a reference antibody comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 4 and a light chain variable region with the amino acid sequence of SEQ ID NO: 8.

2. The humanized antibody or fragment thereof according to claim 1 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 20 and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 29.

3. The antibody or fragment thereof according to claim 1 , wherein the antibody comprises:

(a) a heavy chain variable region which:

(i) comprises an amino acid sequences which shares an identity of at least 90% with the amino acid sequence of SEQ ID NO: 20,

(ii) comprises a VH CDR1 amino acid sequence set forth in SEQ ID NO: 1, a VH CDR2 amino acid sequence set forth in SEQ ID NO: 2, and a VH CDR3 amino acid sequence set forth in SEQ ID NO: 3, and

(iii) comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:19, 20, 22, 23; and

(b) a light chain variable region which:

(i) comprises an amino acid sequence which shares an identity of at least 90% with the amino acid sequence of SEQ ID NO: 29

(ii) comprises a VL CDR1 amino acid sequence set forth in SEQ ID NO: 5, a VL CDR2 amino acid sequence set forth in SEQ ID NO: 6, and a VL CDR3 amino acid sequence set forth in SEQ ID NO: 7; and

(iii) comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 27, 28, 29, and 30.

4. The humanized antibody or fragment thereof according to claim 1 , which does not have a glycosylation site in its heavy chain variable region.

5. The humanized antibody or fragment thereof according to claim 4 , having the following characteristics:

(a) it does not have a glycosylation site in its Fab part;

(b) it does not have an asparagine residue at amino acid position 85 of the heavy chain variable region according to the Kabat numbering; and/or

it does not have a serine or threonine at position 87 of the heavy chain variable region according to the Kabat numbering; and

(c) it has a higher circulation half-life in primates than a corresponding antibody having a glycosylation site in the Fab part.

6. The humanized antibody or fragment thereof according to claim 1 , having a glycosylation pattern which has one or more of the following characteristics:

(a) it is a human glycosylation pattern;

(b) it enhances its binding affinity to its specific epitope, its binding affinity to one or more of its downstream receptors, its complement dependent cytotoxicity (CDC), and/or its antibody-dependent cell-mediated cytotoxicity (ADCC);

(c) it is a glycosylation pattern as obtained when expressing the antibody or fragment thereof in a cell line selected from the group consisting of K562, KG1, MUTZ-3, NM-F9, NM-D4, NM-H9D8, NM-H9D8-E6, NM H9D8-E6Q12, and GT-2X.

7. A nucleic acid encoding the antibody or fragment thereof according to claim 1 .

8. An expression cassette or vector comprising the nucleic acid according to claim 7 and a promoter operatively connected with said nucleic acid.

9. An isolated host cell comprising the expression cassette or vector according to claim 8 .

10. A conjugate comprising the antibody or fragment thereof according to claim 1 conjugated to a further agent.

11. A composition comprising the conjugate according to claim 10 and one or more components selected from the group consisting of solvents, diluents, and excipients.

12. A composition comprising the antibody or fragment thereof according to claim 1 and one or more components selected from the group consisting of solvents, diluents, and excipients.

13. A method for treatment of cancer in a patient, comprising administering to the patient a therapeutically effective amount of the antibody or fragment, thereof according to claim 1 , thereby treating cancer.

14. The method according to claim 13 , wherein the cancer is selected from the group consisting of colorectal cancer, head and neck cancer, and lung cancer.

15. The method according to claim 13 , wherein the treatment of cancer further comprises the administration of a cytotoxic agent.

16. The method according to claim 15 , wherein the cytotoxic agent is selected from the group consisting of doxorubicin, taxol and cisplatin.

17. A humanized antibody or a fragment thereof which is capable of binding to an epidermal growth factor receptor (EGFR) and comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:20 and a light chain variable region comprising the amino acid sequence of SEQ IN NO:29.

18. A humanized antibody or a fragment thereof which is capable of binding to an epidermal growth factor receptor (EGFR) comprising heavy and light chain variable regions, wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:20.

19. A humanized antibody or a fragment thereof which is capable of binding to an epidermal growth factor receptor (EGFR) comprising heavy and light chain variable regions, wherein the light chain variable region comprises the amino acid sequence of SEQ ID NO:29.