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CN-120718149-B - PD-1 antibodies and uses thereof

CN120718149BCN 120718149 BCN120718149 BCN 120718149BCN-120718149-B

Abstract

The present disclosure provides a PD-1 antibody and uses thereof. The PD-1 antibodies or antigen-binding portions provided by the present disclosure have high affinity for human PD-1 proteins and are capable of binding to human PD-1 with a Kd value of 0.9x10 ‑8 M. And has strong binding specificity, and does not generate cross reaction with human CTLA-4 positive cells (3T 3 cells which over-express human CTLA-4) and human PD-1 negative cells (such as Raji cells). Based on the characteristics, the PD-1 antibody or antigen binding portion provided by the disclosure can be used for detecting human PD-1 protein, and can be singly or jointly applied to tumor immunotherapy with other methods, namely, can be effectively applied to preparation of medicines for treating tumors, infectious diseases, autoimmune diseases, anti-immune rejection and the like.

Inventors

  • YUAN XIANGFEI
  • LU YANG
  • Tian Wencong
  • ZHANG XIANG
  • ZHANG YANJUN

Assignees

  • 天津市中西医结合医院（天津市南开医院）
  • 中国医学科学院血液病医院(中国医学科学院血液学研究所)
  • 天津市人民医院

Dates

Publication Date
20260505
Application Date
20250626

Claims (11)

  1. 1. An isolated antibody or antigen-binding portion that specifically binds to a human programmed death receptor 1 (PD-1) protein, comprising: a Complementarity Determining Region (CDRH) of a heavy chain variable region CDRH1 shown in SEQ ID No. 1, a heavy chain variable region CDRH2 shown in SEQ ID No. 2 and a heavy chain variable region CDRH3 shown in SEQ ID No. 3, and Complementarity Determining Region (CDRL) of the light chain variable region CDRL1 of the light chain variable region shown as SEQ ID No. 4, CDRL2 of the light chain variable region shown as SEQ ID No. 5 and CDRL3 of the light chain variable region shown as SEQ ID No. 6.
  2. 2. The isolated antibody or antigen-binding portion of claim 1, wherein the antibody or antigen-binding portion comprises: The heavy chain variable region as shown in SEQ ID No. 7 or an amino acid sequence having more than 90% identity to said heavy chain variable region, and/or The light chain variable region as shown in SEQ ID No. 8 or an amino acid sequence having more than 90% identity to the light chain variable region.
  3. 3. The antibody or antigen-binding portion of claim 1 or 2, wherein the antibody is a chimeric or humanized antibody.
  4. 4. The isolated antibody or antigen-binding portion of claim 1 or 2, wherein the antibody is one or more selected from the group consisting of IgG1, igG2, igG3, and IgG 4.
  5. 5. The isolated antibody or antigen-binding portion of claim 4, wherein the antibody is IgG1.
  6. 6. The antibody or antigen-binding portion of claim 1 or 2, wherein the antigen-binding portion is a Fab, fab ', F (ab') 2 , fd, dAb, or single chain antibody scFv.
  7. 7. An isolated polynucleotide encoding an antibody or antigen binding portion according to any one of claims 1 to 6.
  8. 8. The polynucleotide according to claim 7, wherein the polynucleotide sequence encoding the heavy chain variable region is shown in SEQ ID No. 9 and the polynucleotide sequence encoding the light chain variable region is shown in SEQ ID No. 10.
  9. 9. A carrier, characterized in that, the vector comprises the polynucleotide of claim 7 or 8.
  10. 10. A cell comprising an antibody or antigen binding portion according to any one of claims 1 to 6, a polynucleotide according to claim 7 or 8, or a vector according to claim 9.
  11. 11. Use of an antibody or antigen binding portion according to any one of claims 1 to 6 for the preparation of a product for detecting the presence or level of human PD-1 molecules in a sample.

Description

PD-1 antibodies and uses thereof Technical Field The present disclosure relates to the field of biological medicine, in particular, the disclosure relates to PD-1 antibodies and uses thereof. Background Immunotherapy, which now utilizes the principles of immunological techniques to treat cancer, is rapidly becoming an accepted treatment for cancer following surgery, chemotherapy and radiation therapy. Among them, monoclonal antibodies targeting immune checkpoints, such as cytotoxic T lymphocyte-associated protein 4 (CTLA-4), programmed death receptor 1 (PD-1), programmed death ligand 1 (PD-L1), etc., have made a major breakthrough in cancer immunotherapy. PD-1, also known as CD279, is an important immunosuppressive molecule that regulates the immune system and promotes immune tolerance by inhibiting the activity of T cells. It can prevent autoimmune diseases, but also can prevent the immune system from killing cancer cells, so PD-1 has become a hot target for developing tumor immunotherapeutic drugs. Currently, 3 PD-1 mab inhibitors have been marketed worldwide, namely Keytruda from moxadong, opdivo from bavish precious, and Libtayo from sirofine/regenerator, respectively. In recent years, two domestic PD-1 monoclonal antibodies, LOQTORZI (monarch organism) and TEVIMBRA (Baiji Shenzhou) were marketed in the United states. The indications of the medicine span various solid tumors such as non-small cell lung cancer, melanoma, colorectal cancer, nasopharyngeal carcinoma and the like, and the range of the indications is continuously expanding. These all demonstrate that PD-1 antibodies have very good clinical utility. According to the data of clinical experiments, PD-1 monoclonal antibodies are treated by the method, partial patients do not respond to the treatment, and various monoclonal antibodies have side effects with different degrees. At present, the mechanism of non-response of most patients to treatment is not clear, and new anti-human PD-1 antibodies are still needed, so that a new idea is provided for treatment. Disclosure of Invention The technical problems to be solved are as follows: in one aspect of the present disclosure, a PD-1 antibody is provided that addresses the lack of desirable anti-human PD-1 antibodies in the prior art. The antibody or antigen binding portion thereof is capable of competitively binding to a human PD-1 protein molecule and blocking the binding of PD-L1/PD-L2 to PD-1. The technical scheme is as follows: an isolated antibody or antigen binding portion that specifically binds to a human programmed death receptor 1 (PD-1) protein, comprising: a Complementarity Determining Region (CDRH) of a heavy chain variable region selected from at least one of the amino acid sequences shown as SEQ ID No. 1, SEQ ID No. 2 or SEQ ID No. 3, and/or A Complementarity Determining Region (CDRL) of the light chain variable region selected from at least one of the amino acid sequences set forth in SEQ ID No. 4, SEQ ID No. 5 or SEQ ID No. 6. In some embodiments, the antibody or antigen binding portion may comprise: a heavy chain variable region CDRH1 as shown in SEQ ID No. 1, a heavy chain variable region CDRH2 as shown in SEQ ID No. 2 and a heavy chain variable region CDRH3 as shown in SEQ ID No. 3, and/or A light chain variable region CDRL1 as shown in SEQ ID No. 4, a light chain variable region CDRL2 as shown in SEQ ID No. 5 and a light chain variable region CDRL3 as shown in SEQ ID No. 6. In some embodiments, the antibody or antigen binding portion may comprise: The heavy chain variable region as shown in SEQ ID No. 7 or an amino acid sequence having more than 90% identity to said heavy chain variable region, and/or The light chain variable region as shown in SEQ ID No. 8 or an amino acid sequence having more than 90% identity to the light chain variable region. In the present disclosure, the above sequences having greater than 90% identity (identity) refer to sequences having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% identity to the heavy chain variable region/light chain variable region. In the present disclosure, the above antibody or antigen binding portion is capable of preventing the binding of PD-1 to its ligand PD-L1/PD-L2, releasing the inhibition of T cells, thereby restoring or enhancing the function of T cells. In some embodiments, the antibody may be a mammalian-derived antibody, e.g., murine, rabbit, sheep, horse, monkey, pig, camel, shark, chicken, etc. In other embodiments, the antibody may be a chimeric antibody or a humanized antibody. In some embodiments, the antibody may be IgG, igA, igM, igD or IgE. Preferably, in some embodiments, the antibody may be of the IgG type. Further, in some embodiments, the antibody may be one or more selected from IgG1, igG2, igG3, or IgG 4. Preferably, the antibody may be IgG1. In some embodiments, the antibody is a monoclonal antibody. In some embodiments, the antibody