Nucleic acid molecules encoding antibody drug conjugates (ADC) that bind to 191P4D12 proteins
View Patent ↗Antibody drug conjugates (ADC's) that bind to 191P4D12 protein and variants thereof are described herein. 191P4D12 exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in the cancers listed in Table I. Consequently, the ADC's of the invention provide a therapeutic composition for the treatment of cancer.
1. An isolated polynucleotide comprising a sequence encoding a heavy chain variable region comprising complementarity determining regions (CDRs) having the amino acid sequences of the CDRs in the heavy chain variable region sequence set forth in SEQ ID NO:7 and a light chain variable region comprising CDRs having the amino acid sequences of the CDRs in the light chain variable region sequence set forth in SEQ ID NO:8 of an antibody or antigen binding fragment thereof that binds to a 191P4D12 protein.
2. The polynucleotide of claim 1 , wherein the heavy chain variable region consists of the amino acid sequence ranging from position 20 to position 136 of SEQ ID NO: 7, and the light chain variable region consists of the amino acid sequence ranging from position 23 to position 130 of SEQ ID NO: 8.
3. The polynucleotide of claim 2 , wherein the heavy chain consists of the amino acid sequence ranging from position 20 to position 466 of SEQ ID NO: 7, and the light chain consists of the amino acid sequence ranging from position 23 to position 236 of SEQ ID NO: 8.
4. The polynucleotide of claim 1 , wherein the antibody binding fragment is a Fab, Fv, scFv, or F(ab') 2 fragment.
5. An isolated vector comprising the polynucleotide of claim 1 .
6. An isolated host cell comprising the vector of claim 5 .
7. The host cell of claim 6 , wherein the host cell is a CHO cell.
8. A method of making an anti-191P4D12 antibody or antigen binding fragment thereof, wherein the method comprises:
a) culturing the host cell of claim 6 under conditions suitable for expression of the polynucleotide encoding the antibody or antigen binding fragment thereof; and
b) isolating the antibody or antigen binding fragment thereof.
9. The method of claim 8 , wherein the host cell is a CHO cell.
10. The method of claim 8 , wherein the antigen binding fragment is a Fab, Fv, scFv, or F(ab') 2 fragment.
11. An anti-191P4D12 antibody or antigen binding fragment thereof produced by the method of claim 8 .
12. The antigen binding fragment of claim 11 , wherein the antigen binding fragment is a Fab, Fv, scFv, or F(ab') 2 fragment.
13. A method of making an anti-191P4D12 antibody drug conjugate, wherein the method comprises:
a) culturing the host cell of claim 6 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 a drug to the antibody or antigen binding fragment thereof.
14. The method of claim 13 , wherein the host cell is a CHO cell.
15. The method of claim 13 , wherein the drug is a cytotoxin, a cytostatic agent, or an immunomodulatory agent.
16. The method of claim 15 , wherein the cytotoxin is an antitubulin agent.
17. The method of claim 16 , wherein the antitubulin agent is selected from the group consisting of auristatin phenylalanine phenylenediamine (AFP), monomethyl auristatin phenylalanine (MMAF), and monomethyl auristatin E (MMAE).
18. The method of claim 17 , wherein the antitubulin agent is monomethyl auristatin E (MMAE).
19. The method of claim 13 , wherein the antibody drug conjugate has the following structure:
wherein mAb represents an anti-191P4D12 antibody or antigen binding fragment thereof and p ranges from 1 to about 10.
20. An anti-191P4D12 antibody drug conjugate produced by the method of claim 13 .
21. The anti-191P4D12 antibody drug conjugate of claim 20 , wherein the antigen binding fragment is a Fab, Fv, scFv, or F(ab') 2 fragment.
22. A host cell which is selected from the group consisting of the following:
(a) a host cell transformed with an expression vector comprising a polynucleotide comprising a sequence encoding a heavy chain variable region of an antibody or antigen binding fragment thereof and a polynucleotide comprising a sequence encoding a light chain variable region of an antibody or antigen binding fragment thereof; and
(b) a host cell transformed with an expression vector comprising a polynucleotide comprising a sequence encoding a heavy chain variable region of an antibody or antigen binding fragment thereof and an expression vector comprising a polynucleotide comprising a sequence encoding a light chain variable region of an antibody or antigen binding fragment thereof,
wherein the antibody or fragment comprises a heavy chain variable region comprising CDRs having the amino acid sequences of the CDRs in the heavy chain variable region sequence set forth in SEQ ID NO:7 and a light chain variable region comprising CDRs having the amino acid sequences of the CDRs in the light chain variable region sequence set forth in SEQ ID NO:8.
23. The host cell of claim 22 , wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region consisting of the amino acid sequence ranging from position 20 to position 136 of SEQ ID NO: 7 and a light chain variable region consisting of the amino acid sequence ranging from position 23 to position 130 of SEQ ID NO: 8.
24. The host cell of claim 23 , wherein the antibody or antigen binding fragment thereof comprises a heavy chain consisting of the amino acid sequence ranging from position 20 to position 466 of SEQ ID NO: 7 and a light chain consisting of the amino acid sequence ranging from position 23 to position 236 of SEQ ID NO: 8.
25. A method of producing an anti-191P4D12 antibody or antigen binding fragment thereof, comprising culturing the host cell of claim 24 under conditions suitable for expression of an anti-191P4D12 antibody or antigen binding fragment.
26. An anti-191P4D12 antibody or antigen binding fragment thereof produced by the method of claim 25 .
27. A method of producing an anti-191P4D12 antibody or antigen binding fragment thereof, comprising culturing the host cell of claim 23 under conditions suitable for expression of an anti-191P4D12 antibody or antigen binding fragment.
28. An anti-191P4D12 antibody or antigen binding fragment thereof produced by the method of claim 27 .
29. A method of producing an anti-191P4D12 antibody or antigen binding fragment thereof, comprising culturing the host cell of claim 22 under conditions suitable for expression of an anti-191P4D12 antibody or antigen binding fragment.
30. An anti-191P4D12 antibody or antigen binding fragment thereof produced by the method of claim 29 .
31. The anti-191P4D12 antibody or antibody binding fragment thereof of anyone of claim 30 , 28 , or 26 , further comprising a cytotoxin, a cytostatic agent, or an immunomodulatory agent conjugated thereto.
32. The anti-191P4D12 antibody or antibody binding fragment thereof of claim 31 , wherein the cytotoxin is monomethyl auristatin E (MMAE).
33. The anti-191P4D12 antibody or antibody binding fragment thereof of claim 32 , wherein the antibody drug conjugate has the following structure:
wherein mAb represents an anti-191P4D12 antibody or antigen binding fragment thereof and p ranges from 1 to about 10.