Antibody drug conjugates (ADC) that bind to 158P1D7 proteins
View Patent ↗Antibody drug conjugates (ADC's) that bind to 158P1D7 protein and variants thereof are described herein. 158P1D7 exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in glioblastoma, lung cancer, bladder cancer, and breast cancer. Consequently, the ADC's of the invention provide a therapeutic composition for the treatment of cancer.
1. An antibody drug conjugate comprising:
an antibody or antigen binding fragment thereof which binds to a 158P1D7 protein, wherein the antibody or antigen binding fragment thereof is conjugated to 2 to 8 units of monomethyl auristatin E (MMAE), each unit of MMAE being conjugated via a linker, and wherein the antibody or antigen binding fragment thereof comprises:
a heavy chain variable region comprising complementarity determining regions (CDRs) consisting of the amino acid sequences of the CDRs according to Kabat numbering in the heavy chain variable region sequence set forth in SEQ ID NO: 7, and
a light chain variable region comprising CDRs consisting of the amino acid sequences of the CDRs according to Kabat numbering in the light chain variable region sequence set forth in SEQ ID NO: 8.
2. The antibody drug conjugate of claim 1 , wherein the antibody comprises a heavy chain variable region consisting of the amino acid sequence ranging from position 1 to position 120 of SEQ ID NO: 7 and a light chain variable region consisting of the amino acid sequence ranging from position 1 to position 113 of SEQ ID NO: 8.
3. The antibody drug conjugate of claim 1 , wherein the antibody comprises a heavy chain consisting of the amino acid sequence ranging from position 1 to position 446 of SEQ ID NO: 7 and a light chain consisting of the amino acid sequence ranging from position 1 to position 219 of SEQ ID NO: 8.
4. The antibody drug conjugate of claim 1 , wherein the antigen binding fragment is an Fab, F(ab′) 2 , Fd, dAb Fv or scFv fragment.
5. The antibody drug conjugate of claim 1 , wherein the antibody or antigen binding fragment thereof is a fully human antibody or antigen binding fragment thereof.
6. The antibody drug conjugate of claim 1 , wherein the antibody or antigen binding fragment thereof is recombinantly produced.
7. The antibody drug conjugate of claim 1 , wherein the linker comprises valine citrulline.
8. The antibody drug conjugate of claim 1 , wherein the antibody drug conjugate has the following structure:
wherein L-represents the antibody or antigen binding fragment thereof and p ranges from 2 to 8.
9. The antibody drug conjugate of claim 8 , wherein the antibody or antigen binding fragment thereof comprises the heavy chain variable region consisting of the amino acid sequence ranging from residue 1 to residue 120 of SEQ ID NO: 7 and the light chain variable region consisting of the amino acid sequence ranging from residue 1 to residue 113 of SEQ ID NO: 8.
10. The antibody drug conjugate of claim 8 , wherein the antibody comprises the heavy chain consisting of the amino acid sequence ranging from residue 1 to residue 446 of SEQ ID NO: 7 and the light chain consisting of the amino acid sequence ranging from residue 1 to residue 219 of SEQ ID NO: 8.
11. An isolated polynucleotide encoding an antibody or antigen binding fragment thereof that binds to a 158P1D7 protein, wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region comprising complementarity determining regions(CDRs) having the amino acid sequences of the CDRs in the heavy chain variable region set forth in SEQ ID NO: 7 and/or a light chain variable region comprising CDRs having the amino acid sequences of the CDRs in the light chain variable region set forth in SEQ ID NO: 8.
12. The isolated polynucleotide of claim 11 , wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region comprises:
a heavy chain variable region comprising CDRs consisting of the amino acid sequences of the CDRs according to Kabat numbering in the heavy chain variable region sequence set forth in SEQ ID NO: 7, and
a light chain variable region comprising CDRs consisting of the amino acid sequences of the CDRs according to Kabat numbering in the light chain variable region sequence set forth in SEQ ID NO: 8.
13. The isolated polynucleotide of claim 11 , wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region consisting of the amino acid sequences ranging from position 1 to position 120 of SEQ ID NO: 7, and a light chain variable region consisting of the amino acid sequences ranging from position 1 to 113 of SEQ ID NO: 8.
14. The isolated polynucleotide of claim 11 , wherein the antibody comprises a heavy chain consisting of the amino acid sequences ranging from position 1 to position 446 of SEQ ID NO: 7, and a light chain consisting of the amino acid sequences ranging from position 1 to position 219 of SEQ ID NO: 8.
15. The isolated polynucleotide of claim 11 , wherein the antigen binding fragment is a Fab, Fab′, Fv, scFv, or F(ab′) 2 fragment.
16. An isolated vector comprising the polynucleotide of claim 11 .
17. An isolated host cell comprising the vector of claim 16 .
18. The host cell of claim 17 , wherein the host cell is a CHO cell.
19. A method of making an anti-158P1D7 antibody drug conjugate, wherein the method comprises:
a) culturing the host cell of claim 17 under conditions suitable for expression of the polynucleotide encoding the antibody or antigen binding fragment thereof;
b) isolating the antibody or antigen binding fragment thereof; and
c) conjugating at least one unit of monomethyl auristatin E (MMAE) to the antibody or antigen binding fragment thereof, wherein each unit of MIMAE is conjugated via a linker.
20. The method of claim 19 , wherein the host cell is a CHO cell.
21. The method of claim 19 , wherein the antigen binding fragment is a Fab, Fab′, Fv, scFv, or F(ab′)2 fragment.
22. The method of claim 19 , wherein the linker comprises valine citrulline.
23. The method of claim 19 , wherein the antibody drug conjugate has the following structure:
wherein L-represents the antibody or antigen binding fragment thereof and p ranges from 1 to about 10.
24. An anti-158P1D7 antibody drug conjugate produced by the method of claim 19 , wherein the antibody or antigen binding fragment thereof is conjugated to 2-8 units of MMAE.