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EP-4190815-B1 - ANTI-PVRIG PROTEIN ANTIBODY OR ANTIBODY FRAGMENT, AND USE THEREOF

EP4190815B1EP 4190815 B1EP4190815 B1EP 4190815B1EP-4190815-B1

Inventors

  • TIAN, ZHIGANG
  • LI, YANGYANG
  • XIAO, WEIHUA
  • SUN, RUI
  • SUN, HAOYU

Dates

Publication Date
20260506
Application Date
20220307

Claims (10)

  1. An antibody or antibody fragment comprising a heavy chain variable region and a light chain variable region, the heavy chain variable region being selected from the group consisting of sequences set forth in SEQ ID NO: 9, SEQ ID NO: 15, SEQ ID NO: 18, SEQ ID NO: 21, SEQ ID NO: 24, SEQ ID NO: 27, SEQ ID NO: 30, and SEQ ID NO: 33, and the light chain variable region being a sequence set forth in SEQ ID NO: 36.
  2. The antibody or antibody fragment according to claim 1, comprising a heavy chain and a light chain, wherein an amino acid sequence of the heavy chain is a sequence set forth in SEQ ID NO: 10, SEQ ID NO: 16, SEQ ID NO: 19, SEQ ID NO: 22, SEQ ID NO: 25, SEQ ID NO: 28, SEQ ID NO:31, or SEQ ID NO: 34; and wherein an amino acid sequence of the light chain is a sequence set forth in SEQ ID NO: 37.
  3. An isolatable nucleic acid, encoding the antibody or antibody fragment according to claim 1 or 2.
  4. An expression vector, comprising the nucleic acid according to claim 3.
  5. A host cell, expressing the antibody or antibody fragment according to claim 1 or 2.
  6. The host cell according to claim 5, comprising the expression vector according to claim 4.
  7. A pharmaceutical composition, comprising the antibody or antibody fragment according to claim 1 or 2 and a pharmaceutically acceptable carrier.
  8. A pharmaceutical combination, comprising: (1) the antibody or antibody fragment according to claim 1 or 2, or the pharmaceutical composition according to claim 7; and (2) an antibody for cancer therapy other than (1).
  9. A method for inhibiting PVRIG protein activity in a sample in vitro, comprising contacting the sample with the antibody or antibody fragment according to claim 1 or 2, or the pharmaceutical composition according to claim 7.
  10. The antibody or antibody fragment according to any one of claims 1 to 2 or the pharmaceutical composition according to claim 7 for use in preventing or treating cancer.

Description

The present application claims priority to Chinese Patent Application No. 202110250342.9, filed on March 08, 2021. TECHNICAL FIELD The present disclosure relates to the field of pharmaceuticals, and more particularly to an anti-PVRIG protein antibody or antibody fragment and use thereof in cancer therapy. BACKGROUND Tumor cells evade surveillance of the immune system through a variety of mechanisms. The immune checkpoint pathway is used for the maintenance of self-tolerance and control of activated lymphocyte effector function, but cancer cells can utilize this pathway to avoid disruption. Recent reports indicate that PVRIG is a very important immune checkpoint. PVRIG is mainly expressed on activated T cells and NK cells and inhibits the effector function of T cells and NK cells by interacting with the ligand CD112 expressed on target cells or DC cells. CD112 is highly expressed on the surface of many kinds of tumor cells, so as to inhibit the function of the immune system through PVRIG signaling pathway and realize immune escape. It has been shown in researches that deletion of PVRIG may result in enhanced effector function of CD8+ T cells. In addition, the use of antibodies that block the binding of PVRIG to its ligand CD 112 can also be effective in restoring the function of tumor-infiltrating CD8+ T cells and inhibiting tumor growth. An antibody targeting human PVRIG has been in clinical trials, showing good therapeutic effects. CN107580500A is directed to anti-PVRIG antibodies and methods of using them. CN112433055A discloses a method for detecting the biological activity of a PVRIG antibody based on a reporter gene method. CN110088132A discloses anti-TIGIT antibodies, anti-PVRIG antibodies and combinations thereof. WO2018/017864A2 discloses agents that specifically bind PVRIG. US2017/088607A1 is directed to PVRIG polypeptides and their uses. Further improvements are needed for antibodies that target PVRIG. SUMMARY The present disclosure aims to provide an antibody or an antibody fragment with an enhanced anti-tumor function and use thereof. The provided antibody or antibody fragment is capable of effectively binding to PVRIG and is capable of blocking the binding of PVRIG to its ligand CD112. The provided antibody or antibody fragment have been verified to have high affinity to human PVRIG, and is effective in blocking the interaction between human PVRIG and CD112. In a first aspect, the present disclosure provides an antibody or antibody fragment including a heavy chain variable region and a light chain variable region, the heavy chain variable region being selected from the group consisting of sequences set forth in SEQ ID NO: 9, SEQ ID NO: 15, SEQ ID NO: 18, SEQ ID NO: 21, SEQ ID NO: 24, SEQ ID NO: 27, SEQ ID NO: 30, and SEQ ID NO: 33, and the light chain variable region being a sequence set forth in SEQ ID NO: 36. In a second aspect, the present disclosure provides an isolatable nucleic acid encoding any of antibodies or antibody fragments as described above. In a third aspect, the present disclosure provides an expression vector including the nucleic acid as described above. In a fourth aspect, the present disclosure provides a recombinant cell expressing any of antibodies or antibody fragments as described above. In a fifth aspect, the present disclosure provides a pharmaceutical composition including the antibody or antibody fragment as described above and a pharmaceutically acceptable carrier. In a sixth aspect, the present disclosure provides a pharmaceutical combination including: (1) the antibody or antibody fragment as described above, or the pharmaceutical composition as described above; and (2) an antibody for cancer therapy other than (1). In a seventh aspect, the present disclosure provides the antibody or antibody fragment as described above or the pharmaceutical composition as described above for use in preventing or treating cancer. In an eighth aspect, the present disclosure provides a method for inhibiting PVRIG protein activity in a sample in vitro, including contacting the sample with any of antibodies or antibody fragments as described above, or the pharmaceutical composition as described above. According to an embodiment of the present disclosure, the sample may be a cell sample. The antibody or antibody fragment provided by the present disclosure is capable of specifically bind to the PVRIG antigen and greatly enhancing the killing effect of human PBMC and exhibits good anti-tumor effects in mouse models. Additional features and advantages of the present disclosure will be set forth in the detailed description which follows. BRIEF DESCRIPTION OF DRAWINGS FIG. 1 is a graph showing the ELISA analysis results of binding of the murine antibody to human PVRIG according to an embodiment of the present disclosure;FIG. 2 is a graph showing the analysis results of binding of the murine antibody to human PVRIG on the surface of a cell membrane according to an embodiment of the present