Anti-PD-1 antibody and use thereof
This invention provides antibodies or functional fragments thereof that bind to PD-1 with high affinity. The invention provides nucleic acid molecules encoding the antibodies or the fragments thereof according to the present invention, expression vectors and host cells for expressing the antibodies or the functional fragments thereof according to the present invention, as well as methods for producing the antibodies or the functional fragments thereof according to the present invention. The present invention also provides immunoconjugates and pharmaceutical compositions comprising the antibodies or the functional fragments thereof according to the present invention. The present invention additionally provides methods for treating a plurality of diseases (comprising cancers, infectious diseases and inflammatory diseases) by using the antibodies or the functional fragments thereof disclosed herein.
1. An antibody or a functional fragment thereof that can bind to the programmed cell death 1 (PD-1) protein having an amino acid sequence of SEQ ID NO: 43, wherein the antibody or a functional fragment thereof comprises:
i) a heavy chain CDR1 having the amino acid sequence of Asp Tyr Glu Met His (SEQ ID NO: 1),
ii) a heavy chain CDR2 having the amino acid sequence of Val Ile Glu Ser Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe Lys Gly (SEQ ID NO: 2),
iii) a heavy chain CDR3 having the amino acid sequence of Glu Gly Ile Thr Thr Val Ala Thr Thr Tyr Tyr Trp Tyr Phe Asp Val (SEQ ID NO: 3),
iv) a light chain CDR1 having the amino acid sequence of Arg Ser Ser Gln Ser Ile Val His Ser Asn Gly Asn Thr Tyr Leu Glu (SEQ ID NO: 10),
v) a light chain CDR2 having the amino acid sequence of Lys Val Ser Asn Arg Phe Ser (SEQ ID NO: 11), and
vi) a light chain CDR3 having the amino acid sequence of Phe Gln Gly Ser His Val Pro Leu Thr (SEQ ID NO: 12).
2. The antibody or functional fragment thereof according to claim 1 , which comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO: 19, or an amino acid sequence having at least 95% sequence identity with SEQ ID NO: 19, and/or a light chain variable region having the amino acid sequence of SEQ ID NO: 22, or an amino acid sequence having at least 95% sequence identity with SEQ ID NO: 22.
3. The antibody or functional fragment thereof according to claim 1 , wherein the antibody or functional fragment thereof is a chimeric antibody or a humanized antibody.
4. The antibody or functional fragment according to claim 1 comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 35 or an amino acid sequence that has at least 95% sequence identity with SEQ ID NO: 35, and/or a light chain variable region comprising the amino acid sequence of SEQ ID NO: 37 or an amino acid sequence that has at least 95% sequence identity with SEQ ID NO: 37.
5. The antibody or functional fragment according to claim 1 , comprising a heavy chain variable region comprising SEQ ID NO: 35 or an amino acid sequence that has at least 95% sequence identity with SEQ ID NO: 35 and a light chain variable region comprising SEQ ID NO: 37 or an amino acid sequence that has at least 95% sequence identity with SEQ ID NO: 37.
6. A isolated nucleic acid molecule, which encodes said antibody or functional fragment thereof of claim 1 .
7. An expression vector, which comprises said nucleic acid molecule of claim 6 .
8. A host cell, which comprises said expression vector of claim 7 .
9. A method of producing the anti-PD-1 antibody or a functional fragment thereof of claim 1 , wherein the method comprises: culturing a host cell of claim 8 under conditions that allow production of said antibody or functional fragment thereof, and recovering said antibody or functional fragment thereof so produced.
10. An immunoconjugate, comprising said antibody or functional fragment thereof of claim 1 that is coupled with a therapeutic agent, wherein said therapeutic agent is a toxin, radioisotope, drug, or cytotoxic agent.
11. A pharmaceutical composition comprising the antibody or functional fragment thereof of claim 1 and a pharmaceutical carrier.