Human immunodeficiency virus neutralizing antibodies and methods of use thereof
The invention provides broadly neutralizing antibodies directed to epitopes of Human Immunodeficiency Virus, or HIV. The invention further provides compositions containing HIV antibodies used for prophylaxis, and methods for diagnosis and treatment of HIV infection.
1. An isolated bispecific anti-HIV antibody or antigen binding portion thereof, comprising a first antigen-binding arm and a second antigen-binding arm,
wherein the first antigen-binding arm and the second antigen-binding arm bind specifically to different epitopes or molecules,
wherein the first antigen-binding arm comprises
the CDR1, CDR2, and CDR3 regions of the sequence of SEQ ID NO: 892, and the CDR1, CDR2 and CDR3 regions of the sequence of SEQ ID NO: 906, wherein the CDR1, CDR2, and CDR3 regions of the sequence of SEQ ID NO: 892 are DYFIH (SEQ ID NO: 1139), WINPKTGQPNNPROFQG (SEQ ID NO: 1140), and QRSDYWDFDV (SEQ ID NO: 1141), respectively; and the CDR1, CDR2, and CDR3 regions of the sequence of SEQ ID NO: 906 are QANGYLN (SEQ ID NO: 1142), DGSKLER (SEQ ID NO:1143), and QVYEF (SEQ ID NO: 1144), respectively.
2. The isolated bispecific anti-HIV antibody or antigen binding portion thereof of claim 1 , wherein the first antigen-binding arm comprises the respective sequences set forth in a sequence set of SEQ ID NOs: 892 and 906.
3. The isolated bispecific anti-HIV antibody or antigen binding portion thereof of claim 1 , wherein the antibody is a human antibody, a humanized antibody, or a chimeric antibody.
4. The isolated bispecific anti-HIV antibody or antigen binding portion thereof of claim 1 , wherein the antibody is a recombinant antibody.
5. An isolated nucleic acid comprising a sequence encoding the isolated bispecific anti-HIV antibody of claim 1 , or antigen binding portion thereof.
6. A vector comprising the nucleic acid of claim 5 .
7. A cultured cell comprising the vector of claim 6 .
8. A method for making a bispecific anti-HIV antibody or a fragment thereof, comprising
obtaining the cultured cell of claim 7 ;
culturing the cell in a medium under conditions permitting expression of a polypeptide encoded by the vector and assembling of an antibody or fragment thereof; and
purifying the antibody or fragment from the cultured cell or the medium of the cell.
9. A pharmaceutical composition comprising (i) at least one bispecific anti-HIV antibody of claim 1 and (ii) a pharmaceutically acceptable carrier.
10. The pharmaceutical composition of claim 9 , further comprising a second therapeutic agent.
11. The pharmaceutical composition of claim 10 , wherein the second therapeutic agent comprises a second anti-HIV antibody or antigen binding portion thereof.
12. The pharmaceutical composition of claim 10 , wherein the second therapeutic agent comprises an antiviral agent.
13. The pharmaceutical composition of claim 12 , wherein the antiviral agent is selected from the group consisting of a non-nucleoside reverse transcriptase inhibitor, a protease inhibitor, an entry or fusion inhibitor, and an integrase inhibitor.
14. A method of or treating an HIV infection or an HIV-related disease comprising the steps of:
identifying a patient in need of such or treatment, and
administering to said patient the pharmaceutical composition of claim 9 .
15. A method of or treating an HIV infection or an HIV-related disease comprising the steps of:
identifying a patient in need of such or treatment, and
administering to said patient a therapeutically effective amount of at least one isolated bispecific anti-HIV antibody or antigen binding portion thereof of claim 1 .
16. The method of claim 15 , further comprising administering to said patient a second therapeutic agent.
17. The method of claim 16 , wherein the second therapeutic agent comprises a second anti-HIV antibody or antigen binding portion thereof.
18. The method of claim 16 , wherein said second therapeutic agent comprises an antiviral agent.
19. The method of claim 18 , wherein the antiviral agent is selected from the group consisting of a non-nucleoside reverse transcriptase inhibitor, a protease inhibitor, an entry or fusion inhibitor, and an integrase inhibitor.
20. A kit comprising:
a pharmaceutically acceptable dose unit of a pharmaceutically effective amount of at least one bispecific anti-HIV antibody of claim 1 , and
a pharmaceutically acceptable dose unit of a pharmaceutically effective amount of an anti-HIV agent.
21. The kit of claim 20 , wherein the two pharmaceutically acceptable dose units take the form of a single pharmaceutically acceptable dose unit.
22. The kit of claim 21 , wherein the anti-HIV agent is selected from the group consisting of a non-nucleoside reverse transcriptase inhibitor, a protease inhibitor, an entry or fusion inhibitor, and an integrase inhibitor.