Anti-EGFR antibodies and antibody drug conjugates

Patent metadata

Field	Value
Publication number	US-9493568-B2
Application number	US-201514664453-A
Country	US
Kind code	B2
Filing date	Mar 20, 2015
Priority date	Mar 21, 2014
Publication date	Nov 15, 2016
Grant date	Nov 15, 2016

Abstract

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.

First claim

The invention claimed is:

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.

Assignees

• Abbvie Inc

Inventors

• Reilly Edward B
• Phillips Andrew C
• Benatuil Lorenzo
• Hsieh Chung-Ming
• Perez Jennifer

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07K16/3053

  Skin, nerves, brain · CPC title

• C07K2317/73

  Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation · CPC title

• C07K2317/34

  Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues · CPC title