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: 20; and
a light chain CDR3 domain comprising the amino acid sequence set forth in SEQ ID NO: 28, a light chain CDR2 domain comprising the amino acid sequence set forth in SEQ ID NO: 27, and a light chain CDR1 domain comprising the amino acid sequence set forth in SEQ ID NO: 26,
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: 76, and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 77.
3. The antibody of claim 1 , which is conjugated to at least one drug.
4. The antibody of claim 3 , wherein the at least one drug is selected from the group consisting of a dolastatin, a maytansinoid, and a plant alkaloid.
5. The antibody of claim 3 , wherein the at least one drug is an auristatin.
6. An isolated nucleic acid encoding the antibody of claim 1 .
7. 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: 20; and
a light chain variable region comprising a CDR3 domain comprising the amino acid sequence set forth in SEQ ID NO: 28, a CDR2 domain comprising the amino acid sequence set forth in SEQ ID NO: 27, and a CDR1 domain comprising the amino acid sequence set forth in SEQ ID NO: 26.
8. The ADC of claim 7 , wherein the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 76, and wherein the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 77.
9. The ADC of claim 8 , wherein the antibody is an IgG1 isotype.
10. The ADC of claim 9 , wherein the auristatin is monomethylauristatin E (MMAE).
11. The ADC of claim 10 , wherein the antibody is conjugated to MMAE via a maleimidocaproyl, valine-citrulline linker.
12. A pharmaceutical composition comprising an ADC mixture comprising a plurality of the ADC of claim 11 , and a pharmaceutically acceptable carrier.
13. The pharmaceutical composition of claim 12 , wherein the ADC mixture has an average drug to antibody ratio (DAR) of 1 to 4.