Anti-PD-1 antibodies, method for producing same and method for using same
The present invention relates to biotechnology and comprises isolated monoclonal antibodies, in particular human monoclonal antibodies, which specifically bind to PD-1 with high affinity. The antibodies according to the invention may be chimeric, humanized or human antibodies, or antigen-binding fragments thereof, and may be used as a medicinal agent in oncology and immuno-oncology, for treating diseases associated with various cell proliferation or development disorders. The invention also relates to methods for producing said antibodies and a method for treating human diseases using said antibodies.
1. An antibody, having the ability to bind to a human PD-1 receptor, comprising:
a heavy chain variable domain that comprises H-CDR1, H-CDR2, H-CDR3 sequences, wherein H-CDR1 comprises an amino acid sequence corresponding to SEQ ID NO: 1, H-CDR2 comprises an amino acid sequence corresponding to SEQ ID NO: 2 and H-CDR3 comprises an amino acid sequence corresponding to SEQ ID NO: 3;
a light chain variable domain that comprises L-CDR1, L-CDR2, L-CDR3 sequences, wherein L-CDR1 comprises an amino acid sequence corresponding to SEQ ID NO: 4, L-CDR2 comprises an amino acid sequence corresponding to SEQ ID NO: 5 and L-CDR3 comprises an amino acid sequence corresponding to SEQ ID NO: 6.
2. The antibody according to claim 1 , characterized in that the antibody contains:
the heavy chain variable domain comprising an amino acid sequence corresponding to SEQ ID NO:7, and
the light chain variable domain comprising an amino acid sequence corresponding to SEQ ID NO:8.
3. The antibody according to claim 1 , characterized in that the antibody is one of the following human isotypes: IgG1, IgG2, IgG3 and IgG4.
4. The antibody according to claim 1 , which binds to human PD-1 and has a heavy chain sequence that corresponds to SEQ ID NO 9.
5. The antibody according to claim 1 , which binds to human PD-1 and has a light chain sequence that corresponds to SEQ ID NO 10.
6. A method for preparing the antibody according to claim 1 , comprising: producing a host cell comprising a nucleic acid molecule encoding the antibody according to claim 1 , culturing the host cell under conditions sufficient to produce the antibody, and isolating and purifying the obtained antibody.
7. A pharmaceutical composition comprising the antibody according to claim 1 , in combination with one or more pharmaceutically acceptable excipients, diluents or vehicles.
8. A method of inhibiting the biological activity of PD-1 in a subject in need of such inhibition, comprising administering an effective amount of the antibody according to claim 1 .
9. A method for treating a PD-1 mediated oncological and immuno-oncological disease in a patient in need of such treatment, which comprises administering the antibody according to claim 1 .
10. The antibody according to claim 1 , characterized in that the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 7.
11. The antibody according to claim 1 , wherein an Fc constant portion comprises one or more mutations at respectively one or more of the positions 228, 233, 234 and 235 in the Fc constant portion that reduce or abolish any of effector functions ADCC, ADCP or CDC, as compared to the natural sequence.
12. An isolated nucleic acid encoding the antibody as defined in claim 1 .
13. An expression vector comprising the isolated nucleic acid molecule according to claim 12 .
14. A host cell comprising the nucleic acid molecule according to claim 12 .
15. A method for producing a host cell, comprising transfecting a suitable stem cell with an expression vector as defined in claim 13 .
16. A method for treating a PD-1 mediated oncological and immuno-oncological disease in a patient in need of such treatment, comprising administering the pharmaceutical composition according to claim 7 .