USRE49908EActiveUtility

Bispecific binding proteins and uses thereof

89
Assignee: MEDIMMUNE LLCPriority: May 6, 2016Filed: Jun 30, 2021Granted: Apr 9, 2024
Est. expiryMay 6, 2036(~9.8 yrs left)· nominal 20-yr term from priority
Inventors:Srinath KasturiranganChangshou GaoGodfrey Jonah Anderson RaineyMichelle MorrowClaire Louise DobsonStacey DrabicDarren SchofieldGianluca CarlessoKristen PollizziYariv MazorMichael OberstScott HammondBrian LoboPrakash ManikwarJonathan SeamanSimon DovediRonald Herbst
C12N 15/63C07K 2317/55A61K 2039/505C12N 5/10C07K 2317/622C07K 2317/524C07K 2317/526C07K 2317/51C07K 2317/94C07K 2317/732C07K 2317/53C07K 2317/515C07K 2317/33C07K 16/2803C07K 16/2878C07K 16/2827C07K 16/2818C07K 2317/31C07K 2317/35C07K 2317/41C07K 2317/52C07K 2317/73C07K 2317/76C07K 2317/77C07K 2317/92A61K 39/395A61P 35/00
89
PatentIndex Score
1
Cited by
21
References
43
Claims

Abstract

The disclosure generally provides proteins that bind two epitopes (e.g., a first and a second epitope) and that are bivalent for binding to each of the first and second epitopes. The disclosure also provides for specific binding proteins, including antibodies, which bind to a target protein. The disclosure also provides compositions comprising such proteins, nucleic acid molecules encoding such proteins and methods of making such proteins. The disclosure provides methods of inducing an immune response in a subject as well as methods for treating or preventing cancer in a subject by administering the proteins, nucleic acid molecules and/or compositions to the subject.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
       1. A bispecific binding protein that binds to PD-1 and CTLA-4 comprising a first heavy chain comprising the amino acid sequence of SEQ ID NO: 9, a first light chain comprising the amino acid sequence of SEQ ID NO: 7, a second heavy chain comprising the amino acid sequence of SEQ ID NO: 12, and a second light chain comprising the amino acid sequence of SEQ ID NO: 4. 
     
     
       2. The protein of  claim 1  comprising an Fc region, wherein the Fc region is aglycosylated. 
     
     
       3. The protein of  claim 1  comprising an Fc region, wherein the Fc region is deglycosylated. 
     
     
       4. The protein of  claim 1  comprising an Fc region, wherein the Fc region has reduced fucosylation or is afucosylated. 
     
     
       5. A composition comprising the protein of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
       6. A nucleic acid molecule comprising a nucleotide sequence encoding a protein of  claim 1 . 
     
     
       7. A vector comprising the nucleic acid molecule of  claim 6 . 
     
     
       8. An isolated host cell comprising the vector of  claim 7 . 
     
     
       9. A method of treating or preventing cancer in a subject, the method comprising administering the protein of  claim 1  to the subject. 
     
     
       10. The method of  claim 9 , wherein the cancer is one or more of ovarian cancer, breast cancer, colorectal cancer, prostate cancer, cervical cancer, uterine cancer, testicular cancer, bladder cancer, head and neck cancer, melanoma, pancreatic cancer, renal cell carcinoma, and lung cancer. 
     
     
       11. A method of enhancing an immune response in a subject, the method comprising administering the protein of  claim 1  to the subject. 
     
     
       12. The nucleic acid molecule of  claim 6 , wherein the nucleotide encoding the protein of  claim 1  comprises a nucleotide sequence encoding a first heavy chain, comprising the nucleotide sequence of SEQ ID NO: 10; a nucleotide sequence encoding a first light chain, comprising the nucleotide sequence of SEQ ID NO: 8; a nucleotide sequence encoding a second heavy chain, comprising the nucleotide sequence of SEQ ID NO: 13; and a nucleotide sequence encoding a second light chain, comprising the nucleotide sequence of SEQ ID NO: 11. 
     
     
       13. A bispecific binding protein that binds to PD-1 and CTLA-4 comprising:
 (i) a first heavy chain comprising a VH1-CDR1, VH1-CDR2 and VH1-CDR3, wherein VH1-CDR1 comprises the amino acid sequence of residues 26-35 of SEQ ID NO: 9, wherein VH1-CDR2 comprises the amino acid sequence of residues 50-66 of SEQ ID NO: 9, and wherein VH1-CDR3 comprises the amino acid sequence of residues 99-111 of SEQ ID NO: 9;   (ii) a first light chain comprising a VL1-CDR1, VL1-CDR2, VL1-CDR3, wherein VL1-CDR1 comprises the amino acid sequence of residues 24-41 of SEQ ID NO: 7, wherein VL1-CDR2 comprises the amino acid sequence of residues 55-61 of SEQ ID NO: 7, and wherein VL1-CDR3 comprises the amino acid sequence of residues 94-100 of SEQ ID NO: 7;   (iii) a second heavy chain comprising a VH2-CDR1, VH2-CDR2 and VH2-CDR3, wherein VH2-CDR1 comprises the amino acid sequence of residues 26-35 of SEQ ID NO: 12, wherein VH2-CDR2 comprises the amino acid sequence of residues 50-66 of SEQ ID NO: 12, and wherein VH2-CDR3 comprises the amino acid sequence of residues 99-114 of SEQ ID NO: 12; and   (iv) a second light chain comprising a VL2-CDR1, VL2-CDR2 and VL2-CDR3, wherein VL2-CDR1 comprises the amino acid sequence of residues 24-34 of SEQ ID NO: 4, wherein VL2-CDR2 comprises the amino acid sequence of residues 50-56 of SEQ ID NO: 4, and wherein VL2-CDR3 comprises the amino acid sequence of residues 89-95 of SEQ ID NO: 4.   
     
     
       14. The protein of claim 13 comprising an Fc region, wherein the Fc region is aglycosylated. 
     
     
       15. The protein of claim 13 comprising an Fc region, wherein the Fc region is deglycosylated. 
     
     
       16. The protein of claim 13 comprising an Fc region, wherein the Fc region has reduced fucosylation or is afucosylated. 
     
     
       17. A composition comprising the protein of claim 13 and a pharmaceutically acceptable carrier. 
     
     
       18. A nucleic acid molecule comprising a nucleotide sequence encoding a protein of claim 13. 
     
     
       19. A vector comprising the nucleic acid molecule of claim 18. 
     
     
       20. An isolated host cell comprising the vector of claim 19. 
     
     
       21. A method of treating cancer in a subject, the method comprising administering the protein of claim 13 to the subject. 
     
     
       22. The method of claim 21, wherein the cancer is one or more of ovarian cancer, breast cancer, colorectal cancer, prostate cancer, cervical cancer, uterine cancer, testicular cancer, bladder cancer, head and neck cancer, melanoma, pancreatic cancer, renal cell carcinoma, and lung cancer. 
     
     
       23. A method of enhancing an immune response in a subject, the method comprising administering the protein of claim 13 to the subject. 
     
     
       24. A bispecific binding protein that binds to PD-1 and CTLA-4 comprising a first heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 51, a first light chain variable region comprising the amino acid sequence of SEQ ID NO: 49, a second heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 52, and a second light chain variable region comprising the amino acid sequence of SEQ ID NO: 54. 
     
     
       25. The protein of claim 24 comprising an Fc region, wherein the Fc region is aglycosylated. 
     
     
       26. The protein of claim 24 comprising an Fc region, wherein the Fc region is deglycosylated. 
     
     
       27. The protein of claim 24 comprising an Fc region, wherein the Fc region has reduced fucosylation or is afucosylated. 
     
     
       28. A composition comprising the protein of claim 24 and a pharmaceutically acceptable carrier. 
     
     
       29. A nucleic acid molecule comprising a nucleotide sequence encoding a protein of claim 24. 
     
     
       30. A vector comprising the nucleic acid molecule of claim 29. 
     
     
       31. An isolated host cell comprising the vector of claim 30. 
     
     
       32. A method of treating cancer in a subject, the method comprising administering the protein of claim 24 to the subject. 
     
     
       33. The method of claim 32, wherein the cancer is one or more of ovarian cancer, breast cancer, colorectal cancer, prostate cancer, cervical cancer, uterine cancer, testicular cancer, bladder cancer, head and neck cancer, melanoma, pancreatic cancer, renal cell carcinoma, and lung cancer. 
     
     
       34. A method of enhancing an immune response in a subject, the method comprising administering the protein of claim 24 to the subject. 
     
     
       35. The method of claim 10, wherein the cancer is melanoma. 
     
     
       36. The method of claim 10, wherein the cancer is renal cell carcinoma. 
     
     
       37. The method of claim 10, wherein the cancer is lung cancer. 
     
     
       38. The method of claim 22, wherein the cancer is melanoma. 
     
     
       39. The method of claim 22, wherein the cancer is renal cell carcinoma. 
     
     
       40. The method of claim 22, wherein the cancer is lung cancer. 
     
     
       41. The method of claim 33, wherein the cancer is melanoma. 
     
     
       42. The method of claim 33, wherein the cancer is renal cell carcinoma.  
     
     
       43. The method of claim 33, wherein the cancer is lung cancer.

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