P
USRE47103EActiveUtilityPatentIndex 84

Antibody drug conjugates (ADC) that bind to 158P1D7 proteins

Assignee: AGENSYS INCPriority: Aug 23, 2012Filed: Mar 2, 2017Granted: Oct 30, 2018
Est. expiryAug 23, 2032(~6.1 yrs left)· nominal 20-yr term from priority
Inventors:MORRISON ROBERT KENDALLAN ZILIMORRISON KAREN JANE MEYRICKSNYDER JOSHJIA XIAO-CHI
A61K 47/6861C07K 2317/21C07K 2317/92A61K 45/06A61K 2039/505C07K 16/3015A61K 47/6811C07K 16/30A61K 47/6855A61K 47/6859A61K 47/6851C07K 16/3023C07K 2317/73A61K 47/6817A61K 47/6849C07K 16/3038A61K 47/6865C07K 16/3053C07K 16/18A61K 47/6857C07K 2317/56A61K 47/6813C07K 2317/76C07K 2317/77A61P 35/00A61K 2300/00A61K 39/395A61K 47/68031
84
PatentIndex Score
7
Cited by
73
References
67
Claims

Abstract

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.

Claims

exact text as granted — not AI-modified
We claim: 
     
       1. An antibody drug conjugate comprising an antibody or antigen binding fragment which binds to a 158P1D7 protein, wherein the antibody or antigen binding fragment is conjugated to monomethyl auristatin E (MMAE), and wherein the antibody or fragment 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. 
     
     
       2. The antibody drug conjugate of  claim 1 , wherein the antibody comprises a the heavy chain consisting of the amino acid sequence ranging from position 1 to position 446 of SEQ ID NO: 7 and a the light chain consisting of the amino acid sequence ranging from position 1 to position 219 of SEQ ID NO: 8. 
     
     
       3. An antibody drug conjugate comprising an antibody or antigen binding fragment which binds to a 158P1D7 protein, wherein the antibody or antigen binding fragment is conjugated to monomethyl auristatin E (MMAE), wherein the antibody or fragment comprises a heavy chain variable region consisting of the amino acid sequence of the heavy chain variable region of an antibody produced by a Chinese Hamster Ovary (CHO) cell deposited under American Type Culture Collection (ATCC) Accession No. PTA-13102, and a light chain variable region consisting of the amino acid sequence of the light chain variable region of an antibody produced by a Chinese Hamster Ovary (CHO) cell deposited under ATCC Accession No. PTA-13102. 
     
     
       4. The antibody drug conjugate of  claim 3 , wherein the antibody comprises a heavy chain consisting of the amino acid sequence of the heavy chain of an antibody produced by a Chinese Hamster Ovary (CHO) cell deposited under ATCC. Accession No. PTA-13102, and a light chain consisting of the amino acid sequence of a light chain of an antibody produced by a Chinese Hamster Ovary (CHO) deposited under ATCC. Accession No. PTA-13102. 
     
     
       5. The antibody drug conjugate of  claim 1 , wherein the fragment is an Fab, F(ab') 2 , Fv or scFv fragment. 
     
     
       6. The antibody drug conjugate of  claim 1 , wherein the antibody is a fully human antibody. 
     
     
       7. The antibody drug conjugate of  claim 1 , which the antibody is recombinantly produced. 
     
     
       8. A pharmaceutical composition that comprises a therapeutically effective amount of the antibody drug conjugate of  claim 1  and a pharmaceutically acceptable excipient in a human unit dose form. 
     
     
       9. The pharmaceutical composition of  claim 8 , wherein the composition is for treatment of glioblastoma cancer, lung cancer, bladder cancer, or breast cancer. 
     
     
       10. The pharmaceutical composition of  claim 8 , wherein the composition is administered in combination with radiation or a chemotherapeutic agent. 
     
     
       11. The pharmaceutical composition of  claim 8 , further comprising a chemotherapeutic agent in a human unit dose form. 
     
     
       12. A method of treating bladder cancer in a subject, comprising administering to said subject a therapeutically effective amount of an antibody drug conjugate of  claim 1 . 
     
     
       13. A method for treating bladder cancer in a subject, comprising administering to said subject an a therapeutically effective amount of a combination of an antibody drug conjugate of  claim 1  and radiation. 
     
     
       14. A method for treating bladder cancer in a subject, comprising administering to said subject an a therapeutically effective amount of a combination of an antibody drug conjugate of  claim 1  and a chemotherapeutic agent. 
     
     
       15. An anti-158P1D7 antibody or antigen binding fragment thereof, 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 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 in the light chain variable region sequence set forth in SEQ ID NO:8. 
     
     
       16. The antibody or antigen binding fragment of  claim 15 , wherein the antibody or antigen binding fragment thereof 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. 
     
     
       17. The antibody or antigen binding fragment of  claim 15 , wherein the fragment is an Fab, F(ab') 2 , Fv or scFv fragment. 
     
     
       18. The antibody or antigen binding fragment of  claim 15  further comprising a human IgG constant region and a human light chain constant region. 
     
     
       19. The antibody or antigen binding fragment of  claim 18 , wherein the IgG constant region is IgG2 and the light chain constant region is kappa. 
     
     
       20. The antibody or antigen binding fragment of  claim 19 , wherein the antibody or antigen binding fragment 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. 
     
     
       21. The antibody or antigen binding fragment of  claim 15 , wherein the antibody is a fully human antibody. 
     
     
       22. The antibody or antigen binding fragment of  claims 15 , wherein the antibody is recombinantly produced. 
     
     
       23. An antibody drug conjugate comprising the antibody or antibody binding fragment of  claim 15  conjugated to a cytotoxic agent. 
     
     
       24. The antibody drug conjugate of  claim 23 , wherein the cytotoxic agent is monomethyl auristatin E (MMAE). 
     
     
       25. The antibody drug conjugate of  claim 24 , wherein the antibody drug conjugate has the following structure: 
       
         
           
           
               
               
           
         
         wherein Ab-s- L- represents anti-158P1D7 antibody and p ranges from 1 to about 10. 
       
     
     
       26. A pharmaceutical composition that comprises a therapeutically effective amount of the antibody drug conjugate of  claim 23  and a pharmaceutically acceptable excipient in a human unit dose form. 
     
     
       27. The pharmaceutical composition of  claim 26 , wherein the composition is for bladder cancer treatment. 
     
     
       28. The pharmaceutical composition of  claim 27 , wherein the composition is administered in combination with radiation or a chemotherapeutic agent. 
     
     
       29. The pharmaceutical composition of  claim 28 , further comprising a chemotherapeutic agent in a human unit dose form. 
     
     
       30. A method of treating bladder cancer in a subject, comprising administering to said subject an a therapeutically effective amount of the antibody drug conjugate of  claim 23 . 
     
     
       31. A method for treating bladder cancer in a subject, comprising administering to said subject an a therapeutically effective amount of a combination of an antibody drug conjugate of  claim 24  and radiation. 
     
     
       32. A method for treating bladder cancer in a subject, comprising administering to said subject an a therapeutically effective amount of a combination of an antibody drug conjugate of  claim 25  and a chemotherapeutic agent. 
     
     
       33. The antibody or antigen binding fragment of claim 15, wherein said heavy chain variable region comprises CDRs consisting of the amino acid sequences of the CDRs in the heavy chain variable region sequence set forth in SEQ ID NO:7 according to Kabat numbering, and wherein said light chain variable region comprises CDRs consisting of the amino acid sequences of the CDRs in the light chain variable region sequence set forth in SEQ ID NO:8 according to Kabat numbering. 
     
     
       34. The antibody or antigen binding fragment of claim 15, wherein said light chain variable region comprises light chain CDR1, CDR2, and CDR3 having an amino acid sequence ranging from residues 24-39, from residues 55-61, and from residues 94-102, respectively, of SEQ ID NO: 8. 
     
     
       35. The antibody or antigen binding fragment of claim 15, wherein said heavy chain variable region comprises heavy chain CDR1 and CDR2 having an amino acid sequence ranging from residues 31-35, and from residues 50-66, respectively, of SEQ ID NO: 7. 
     
     
       36. The antibody or antigen binding fragment of claim 34, wherein said heavy chain variable region comprises heavy chain CDR1 and CDR2 having an amino acid sequence ranging from residues 31-35, and from residues 50-66, respectively, of SEQ ID NO: 7. 
     
     
       37. The antibody or antigen binding fragment of claim 15, wherein said heavy chain variable region comprises heavy chain CDR1, CDR2, and CDR3 having an amino acid sequence ranging from residues 31-35, from residues 50-66, and from residues 99-109, respectively, of SEQ ID NO: 7, and wherein said light chain variable region comprises light chain CDR1, CDR2, and CDR3 having an amino acid sequence ranging from residues 24-39, from residues 55-61, and from residues 94-102, respectively, of SEQ ID NO: 8. 
     
     
       38. The antibody drug conjugate of claim 23, wherein said heavy chain variable region of said antibody or antigen binding fragment thereof comprises CDRs consisting of the amino acid sequences of the CDRs in the heavy chain variable region sequence set forth in SEQ ID NO:7 according to Kabat numbering, and wherein said light chain variable region of said antibody or antigen binding fragment thereof comprises CDRs consisting of the amino acid sequences of the CDRs in the light chain variable region sequence set forth in SEQ ID NO:8 according to Kabat numbering. 
     
     
       39. The antibody drug conjugate of claim 23, wherein said light chain variable region of said antibody or antigen binding fragment thereof comprises light chain CDR1, CDR2, and CDR3 having an amino acid sequence ranging from residues 24-39, from residues 55-61, and from residues 94-102, respectively, of SEQ ID NO: 8. 
     
     
       40. The antibody drug conjugate of claim 23, wherein said heavy chain variable region of said antibody or antigen binding fragment thereof comprises heavy chain CDR1 and CDR2 having an amino acid sequence ranging from residues 31-35, and from residues 50-66, respectively, of SEQ ID NO: 7. 
     
     
       41. The antibody drug conjugate of claim 39, wherein said heavy chain variable region of said antibody or antigen binding fragment thereof comprises heavy chain CDR1 and CDR2 having an amino acid sequence ranging from residues 31-35, and from residues 50-66, respectively, of SEQ ID NO: 7. 
     
     
       42. The antibody drug conjugate of claim 23, wherein said heavy chain variable region of said antibody or antigen binding fragment thereof comprises heavy chain CDR1, CDR2, and CDR3 having an amino acid sequence ranging from residues 31-35, from residues 50-66, and from residues 99-109, respectively, of SEQ ID NO: 7, and wherein said light chain variable region of said antibody or antigen binding fragment thereof comprises light chain CDR1, CDR2, and CDR3 having an amino acid sequence ranging from residues 24-39, from residues 55-61, and from residues 94-102, respectively, of SEQ ID NO: 8. 
     
     
       43. The antibody drug conjugate of claim 23, comprising from about 3 to about 5 units of the cytotoxic agent per antibody or antigen binding fragment thereof. 
     
     
       44. The antibody drug conjugate of claim 24, comprising from about 3 to about 5 units of MMAE per antibody or antigen binding fragment thereof. 
     
     
       45. The antibody drug conjugate of claim 23, wherein the antibody or antigen binding fragment thereof is conjugated to the cytotoxic agent via an enzyme-cleavable linker unit. 
     
     
       46. The antibody drug conjugate of claim 45, wherein the enzyme-cleavable linker unit comprises a Val-Cit linker. 
     
     
       47. The antibody drug conjugate of claim 45, wherein the linker unit forms a bond with a sulfur atom of the antibody or antigen binding fragment thereof. 
     
     
       48. The antibody drug conjugate of claim 38, wherein the antibody or antigen binding fragment thereof is conjugated to the cytotoxic agent via an enzyme-cleavable linker unit; wherein the linker unit forms a bond with a sulfur atom of the antibody or antigen binding fragment thereof. 
     
     
       49. The antibody drug conjugate of claim 38, wherein the cytotoxic agent is MMAE; and wherein the antibody or antigen binding fragment thereof is linked to MMAE via a linker unit that has the formula: -A a -W w —Y y —; wherein -A- is a stretcher unit, a is 0 or 1; —W— is an amino acid unit, w is an integer ranging from 0 to 12; and —Y— is a spacer unit, y is 0, 1, or 2; wherein the stretcher unit has the structure of Formula I below; the amino acid unit is Val-Cit; and the spacer unit is a PAB group having the structure of Formula II below; 
       
         
           
           
               
               
           
         
       
       wherein the stretcher unit forms a bond with a sulfur atom of the antibody or antigen binding fragment thereof; and wherein the spacer unit is linked to MMAE via a carbamate group. 
     
     
       50. The antibody drug conjugate of claim 41, wherein the antibody or antigen binding fragment thereof is conjugated to the cytotoxic agent via an enzyme-cleavable linker unit; wherein the linker unit forms a bond with a sulfur atom of the antibody or antigen binding fragment thereof. 
     
     
       51. The antibody drug conjugate of claim 41, wherein the cytotoxic agent is MMAE; and wherein the antibody or antigen binding fragment thereof is linked to MMAE via a linker unit that has the formula: -A a -W w —Y y —; wherein -A- is a stretcher unit, a is 0 or 1; —W— is an amino acid unit, w is an integer ranging from 0 to 12; and —Y— is a spacer unit, y is 0, 1, or 2; wherein the stretcher unit has the structure of Formula I below; the amino acid unit is Val-Cit; and the spacer unit is a PAB group having the structure of Formula II below; 
       
         
           
           
               
               
           
         
       
       wherein the stretcher unit forms a bond with a sulfur atom of the antibody or antigen binding fragment thereof; and wherein the spacer unit is linked to MMAE via a carbamate group. 
     
     
       52. The antibody drug conjugate of claim 42, wherein the antibody or antigen binding fragment thereof is conjugated to the cytotoxic agent via an enzyme-cleavable linker unit; wherein the linker unit forms a bond with a sulfur atom of the antibody or antigen binding fragment thereof. 
     
     
       53. The antibody drug conjugate of claim 42, wherein the cytotoxic agent is MMAE; wherein the antibody or antigen binding fragment thereof is linked to MMAE via a linker unit that has the formula: -A a -W w —Y y —; wherein -A- is a stretcher unit, a is 0 or 1; —W— is an amino acid unit, w is an integer ranging from 0 to 12; and —Y— is a spacer unit, y is 0, 1, or 2; wherein the stretcher unit has the structure of Formula I below; the amino acid unit is Val-Cit, and the spacer unit is a PAB group having the structure of Formula II below; 
       
         
           
           
               
               
           
         
       
       wherein the stretcher unit forms a bond with a sulfur atom of the antibody or antigen binding fragment thereof; and wherein the spacer unit is linked to MMAE via a carbamate group. 
     
     
       54. The pharmaceutical composition of claim 26, comprising about 1 to about 5 mg/kg of the antibody drug conjugate. 
     
     
       55. The antibody drug conjugate of claim 1, comprising from about 3 to about 5 units of MMAE per antibody or antigen binding fragment thereof. 
     
     
       56. The antibody drug conjugate of claim 1, wherein the antibody or antigen binding fragment thereof is conjugated to MMAE via an enzyme-cleavable linker unit. 
     
     
       57. The antibody drug conjugate of claim 1, wherein the antibody or antigen binding fragment thereof is linked to MMAE via a linker unit that has the formula: -A a -W w —Y y —; wherein -A- is a stretcher unit, a is 0 or 1; —W— is an amino acid unit, w is an integer ranging from 0 to 12; and —Y— is a spacer unit, y is 0, 1, or 2. 
     
     
       58. The antibody drug conjugate of claim 57, wherein the stretcher unit has the structure of Formula I below; wherein the amino acid unit is Val-Cit; and wherein the spacer unit is a PAB group having the structure of Formula II below; 
       
         
           
           
               
               
           
         
        
       
     
     
       59. The antibody drug conjugate of claim 58, wherein the stretcher unit forms a bond with a sulfur atom of the antibody or antigen binding fragment thereof; and wherein the spacer unit is linked to MMAE via a carbamate group. 
     
     
       60. The method of claim 12, wherein the bladder cancer is advanced bladder cancer. 
     
     
       61. The method of claim 12, wherein the bladder cancer is metastatic bladder cancer. 
     
     
       62. The method of claim 12, wherein the subject is a human subject. 
     
     
       63. The method of claim 12, comprising administering about 1 to about 5 mg/kg of the antibody drug conjugate to the subject. 
     
     
       64. The method of claim 30, wherein the bladder cancer is advanced bladder cancer. 
     
     
       65. The method of claim 30, wherein the bladder cancer is metastatic bladder cancer. 
     
     
       66. The method of claim 30, wherein the subject is a human subject. 
     
     
       67. The method of claim 30, comprising administering about 1 to about 5 mg/kg of the antibody drug conjugate to the subject.

Cited by (0)

No later patents cite this yet.

References (0)

No backward citations on record.