Anti PD-1 antibodies
The present invention relates to antibodies and antigen-binding fragments thereof that bind to PD-1, and to methods of using such antibodies and antigen-binding fragments. For example, the present invention provides humanized anti-PD-1 antibodies and methods of use thereof.
1. A method for treating an infectious disease in a subject in need thereof, the method comprising administering to the subject an antibody or fragment thereof that binds to PD-1, wherein the antibody or fragment thereof comprises:
(i) a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 115, 116, and 117, respectively, and a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 110, 111, and 112, respectively;
(ii) a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 55, 56, and 57, respectively, and a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 50, 51, and 52, respectively
(iii) a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 24, 25, and 26, respectively, and a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 19, 20, and 21, respectively;
(iv) a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 34, 35, and 36, respectively, and a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 29, 30, and 31, respectively;
(v) a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 45, 46, and 47, respectively, and a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 40, 41, and 42, respectively;
(vi) a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 65, 66, and 67, respectively, and a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 60, 61, and 62, respectively;
(vii) a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 75, 76, and 77, respectively, and a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 70, 71, and 72, respectively;
(viii) a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 85, 86, and 87, respectively, and a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 80, 81, and 82, respectively;
(ix) a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 95, 96, and 97, respectively, and a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 90, 91, and 92, respectively; or
(x) a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 105, 106, and 107, respectively, and a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 100, 101, and 102, respectively.
2. The method of claim 1 , wherein the antibody or fragment thereof comprises a light chain CDR1, CDR2, and CDR3 comprising an amino acid sequence according to SEQ ID NOs: 115, 116, and 117, respectively; and a heavy chain CDR1, CDR2, and CDR3 comprising an amino acid sequence according to SEQ ID NOs: 110, 111, and 112, respectively.
3. The method of claim 1 , wherein the antibody or fragment thereof comprises a light chain CDR1, CDR2, and CDR3 comprising an amino acid sequence according to SEQ ID NOs: 55, 56, and 57, respectively; and a heavy chain CDR1, CDR2, and CDR3 comprising an amino acid sequence according to SEQ ID NOs: 50, 51, and 52, respectively.
4. The method of claim 1 , wherein the antibody or fragment thereof is humanized.
5. The method of claim 1 , wherein the antibody or fragment thereof comprises
(i) a light chain variable region comprising SEQ ID NO: 33 and a heavy chain variable region comprising SEQ ID NO: 28;
(ii) a light chain variable region comprising SEQ ID NO: 54 and a heavy chain variable region comprising SEQ ID NO: 49;
(iii) a light chain variable region comprising SEQ ID NO: 64 and a heavy chain variable region comprising SEQ ID NO: 59;
(iv) a light chain variable region comprising SEQ ID NO: 104 and a heavy chain variable region comprising SEQ ID NO: 99;
(v) a light chain variable region comprising SEQ ID NO: 114 and a heavy chain variable region comprising SEQ ID NO: 109;
(vi) a light chain variable region comprising SEQ ID NO: 143 and a heavy chain variable region comprising SEQ ID NO: 141; or
(vii) a light chain variable region comprising SEQ ID NO: 152 and a heavy chain variable region comprising SEQ ID NO: 131.
6. The method of claim 1 , wherein the antibody or fragment thereof comprises a light chain variable region according to SEQ ID NO: 133 or 152 and a heavy chain variable region according to SEQ ID NO: 131.
7. The method of claim 1 , wherein the antibody or fragment thereof comprises a light chain variable region according to SEQ ID NO: 143 and a heavy chain variable region according to SEQ ID NO: 141.
8. The method of claim 1 , wherein the antibody or fragment thereof is selected from the group consisting of a monoclonal antibody, an scFv, a Fab fragment, an Fab′ fragment, and an F(ab)′ fragment.
9. The method of claim 1 , wherein the method further comprises administering the antibody or fragment thereof to the subject in combination with an additional therapeutic agent.
10. The method of claim 1 , wherein the infectious disease is caused by a bacterial or viral agent.
11. The method of claim 1 , wherein the infectious disease is associated with PD-L1 expression on infected cells and/or with PD-1 expression on T cells.
12. The method of claim 1 , wherein the infectious disease is associated with a chronic infection.
13. The method of claim 1 , wherein the infectious disease is selected from the group consisting of candidiasis, candidemia, aspergillosis, streptococcal pneumonia, streptococcal skin and oropharyngeal conditions, gram negative sepsis, tuberculosis, mononucleosis, influenza, respiratory illness caused by Respiratory Syncytial Virus, malaria, schistosomiasis, and trypanosomiasis.