Anti-EGFR antibodies and antibody drug conjugates
The invention relates to anti-epidermal growth factor (EGFR) antibodies and antibody drug conjugates (ADCs), including compositions and methods of using said antibodies and ADCs.
1. An anti-human epidermal growth factor receptor (anti-hEGFR) antibody comprising
a heavy chain CDR3 domain comprising the amino acid sequence set forth in SEQ ID NO: 12, a heavy chain CDR2 domain comprising the amino acid sequence set forth in SEQ ID NO: 11, and a heavy chain CDR1 domain comprising the amino acid sequence set forth in SEQ ID NO: 10; and
a light chain CDR3 domain comprising the amino acid sequence set forth in SEQ ID NO: 8, a light chain CDR2 domain comprising the amino acid sequence set forth in SEQ ID NO: 7, and a light chain CDR1 domain comprising the amino acid sequence set forth in SEQ ID NO: 6,
wherein the antibody is an IgG isotype.
2. The antibody of claim 1 , wherein the antibody comprises a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 9, and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 5.
3. The antibody of claim 1 , comprising a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 15, and a light chain comprising the amino acid sequence set forth in SEQ ID NO: 13.
4. The antibody of claim 1 , which is conjugated to at least one drug.
5. The antibody of claim 4 , wherein the at least one drug is selected from the group consisting of a dolastatin, a maytansinoid, and a plant alkaloid.
6. An isolated nucleic acid encoding an antibody of claim 1 .
7. The antibody of claim 4 , wherein the at least one drug is an auristatin.
8. The antibody of claim 7 , wherein the auristatin is monomethyauristatin E (MMAE).
9. The antibody of claim 7 , wherein the auristatin is monomethylaurisatin F (MMAF).
10. An antibody drug conjugate (ADC) comprising an anti-human epidermal growth factor receptor (anti-hEGFR) antibody conjugated to at least one auristatin, wherein the anti-hEGFR antibody is an IgG isotype and comprises
a heavy chain variable region comprising a CDR3 domain comprising the amino acid sequence set forth in SEQ ID NO: 12, a CDR2 domain comprising the amino acid sequence set forth in SEQ ID NO: 11, and a CDR1 domain comprising the amino acid sequence set forth in SEQ ID NO: 10; and
a light chain variable region comprising a CDR3 domain comprising the amino acid sequence set forth in SEQ ID NO: 8, a CDR2 domain comprising the amino acid sequence set forth in SEQ ID NO: 7, and a CDR1 domain comprising the amino acid sequence set forth in SEQ ID NO: 6.
11. The ADC of claim 10 , wherein the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 9, and wherein the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 5.
12. The ADC of claim 10 , wherein the antibody comprises a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 15, and comprises a light chain comprising the amino acid sequence set forth in SEQ ID NO: 13.
13. The ADC of claim 11 , wherein the antibody is an IgG1 isotype.
14. The ADC of claim 13 , wherein the auristatin is monomethylauristatin E (MMAE).
15. The ADC of claim 14 , wherein the antibody is conjugated to MMAE via a maleimidocaproyl, valine-citrulline linker.
16. A pharmaceutical composition comprising an ADC mixture comprising a plurality of the ADC of claim 15 , and a pharmaceutically acceptable carrier.
17. The pharmaceutical composition of claim 16 , wherein the ADC mixture has an average drug to antibody ratio (DAR) of 1 to 4.
18. An antibody drug conjugate (ADC) comprising an anti-EGFR IgG1 antibody covalently linked to maleimidocaproyl, valine-citrulline, p-aminobenzyloxycarbamyl-monomethylauristatin E (mc-vc-PABA-MMAE),
wherein the antibody comprises a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 9, and comprises a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 5, and
wherein 1 to 4 molecules of MMAE are linked to the antibody.
19. The ADC of claim 18 , wherein the antibody comprises a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 15, and comprises a light chain comprising the amino acid sequence set forth in SEQ ID NO: 13.
20. The ADC of claim 18 , wherein 2 to 4 molecules of MMAE are linked to the antibody.
21. A pharmaceutical composition comprising an ADC mixture comprising a plurality of the ADC of claim 18 , and a pharmaceutically acceptable carrier.
22. The pharmaceutical composition of claim 21 , wherein the ADC mixture has an average drug to antibody ratio (DAR) of 2 to 4.