Invented by Jackie Z. SHENG, Bo Liu, Gensun Biopharma Inc

The market for Anti-PD-1 antibodies and antigen-binding components thereof, as well as checkpoint regulator antagonists comprising, has witnessed significant growth in recent years. These innovative therapies have revolutionized the field of cancer treatment and hold immense potential for improving patient outcomes. Anti-PD-1 antibodies, also known as immune checkpoint inhibitors, are a class of drugs that work by blocking the programmed cell death protein 1 (PD-1) pathway. PD-1 is a protein found on the surface of immune cells that helps regulate the immune response. In certain cancers, tumor cells exploit the PD-1 pathway to evade detection and destruction by the immune system. By blocking PD-1, these antibodies unleash the immune system’s ability to recognize and attack cancer cells. The market for Anti-PD-1 antibodies has been driven by the increasing incidence of cancer worldwide. According to the World Health Organization (WHO), cancer is one of the leading causes of death globally, with approximately 9.6 million deaths in 2018. The rising prevalence of cancer, coupled with the limited efficacy of traditional treatments, has created a significant unmet need for novel therapies. Furthermore, the success of Anti-PD-1 antibodies in clinical trials has fueled the market growth. Key players in the pharmaceutical industry have invested heavily in research and development to bring these therapies to market. The U.S. Food and Drug Administration (FDA) has approved several Anti-PD-1 antibodies, including pembrolizumab (Keytruda) and nivolumab (Opdivo), for the treatment of various cancers, such as melanoma, lung cancer, and bladder cancer. In addition to Anti-PD-1 antibodies, the market for antigen-binding components thereof, such as single-domain antibodies and antibody fragments, is also expanding. These smaller antibody formats offer advantages over full-length antibodies, including improved tissue penetration and reduced immunogenicity. They can be used as standalone therapeutics or as building blocks for the development of novel antibody-based therapies. Checkpoint regulator antagonists, which encompass a broader range of immune checkpoint inhibitors beyond PD-1, are another segment driving market growth. These antagonists target other immune checkpoints, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and lymphocyte activation gene 3 (LAG-3), to enhance the immune response against cancer cells. Combination therapies involving Anti-PD-1 antibodies and checkpoint regulator antagonists have shown promising results in clinical trials, further fueling market expansion. The market for Anti-PD-1 antibodies and antigen-binding components thereof, as well as checkpoint regulator antagonists, is highly competitive. Key players in this market include pharmaceutical giants like Merck & Co., Inc., Bristol Myers Squibb Company, and Roche Holding AG. These companies are actively engaged in research and development activities to expand their product portfolios and gain a competitive edge. In conclusion, the market for Anti-PD-1 antibodies and antigen-binding components thereof, as well as checkpoint regulator antagonists, is witnessing rapid growth due to the increasing prevalence of cancer and the success of these therapies in clinical trials. With ongoing research and development efforts, these innovative treatments hold immense potential for improving patient outcomes and transforming the landscape of cancer treatment.

The Gensun Biopharma Inc invention works as follows

The disclosure includes checkpoint regulator antagonists which bind to TIGIT or PD-1, and/or PDL1. The checkpoint inhibitors are also disclosed, as well as methods for making and using them, including monospecific or bispecific antagonists.

Background for Anti-PD-1 antibodies and antigen-binding components thereof, as well as checkpoint regulator antagonists comprising the said

The host’s inability to eliminate cancerous cells remains a significant problem.” The use of monoclonal therapeutic antibodies to treat cancer is on the rise. However, resistance to these agents has been observed due to the different molecular pathways that underlie cancer growth and metastasis. Cancer cells can counteract the immunosurveillance of the immune system, despite the fact that the immune system is a primary mechanism for cancer prevention. There are natural control mechanisms that limit T cell activation to prevent collateral damages resulting from unrestrained activity of T cells. Tumor cells have exploited this process to evade the immune response. Immunotherapy aims to restore the ability of immune effectors, particularly T cells, in order to eliminate cancer.

The T cell Ig domain and ITIM (TIGIT protein) is an immunoregulator that can block the T cell immune response against cancer cells. TIGIT antagonists, and other immune-checkpoint antagonists, interfere (or inhibit) an immune-checkpoint regulator’s activity. As a result, signaling via the checkpoint receptor is either blocked or inhibited. Other immune checkpoint regulators are TIGIT and its ligands CD112, CD155; PD-1, PD-2, PD-3, TIM-3, Galectin-9, LAG-3, and its ligands including liver sinusoidal endothelial cells lectin (LSECtin), Galectin-3, and VISTA.

The need for better therapeutic binding antibodies or antagonists and ways to treat cancer and chronic viral infection with these reagents is evident. The medicines used in these improved methods of treating cancer and chronic viral infections may contain antibodies or fragments of antibodies that specifically bind TIGIT, PD-1, and/or PDL1 and reverse, or partially reverse, the TIGIT -, PD-1, and/or PDL1 mediated inhibition of anti-tumor, or anti-viral, immune responses.

The limitations of the host’s ability to eliminate cancerous cells create a need for more effective cancer treatments.

The

In some embodiments, an antibody or antigen-binding component thereof comprises: (1) A heavy chain variable area having an amino acid sequence which is approximately 80% to 100% identical to one of the following amino acids: SEQID NOS 107,109,111,113,115,117,119,121,123,125; (2) A light chain variable area having an amino acid sequence which is approximately 80% to 100% identical to another amino acid: SEQID NOS 108,110,112,114,116

The

In some embodiments, an antibody or antigen-binding component thereof comprises: (1) a variable heavy chain region with an amino-acid sequence that is approximately 80% to 100% identical to an amino-acid sequence selected from SEQID NOS 127, 129 131, 133 135 and 137, and (2) a variable light chain region with an amino-acid sequence that’s about 80% to 100% homologous an amino-acid sequence selected from SEQID NOS 128, 130 132 134 136

The

In some embodiments, an antibody or antigen-binding component thereof comprises: (1) a variable heavy chain region with an amino-acid sequence that is approximately 80% to 100% identical to an amino-acid sequence selected from SEQID NOS: 139 141, 143 145, 147 149, 151, 153 and (2) a variable light chain region with an amino-acid sequence that’s about 80% to 100% identical to an amino-acid sequence selected from SEQID NOS 140, 148 150 152

Another aspect of the current application relates a bispecific antigen, which comprises: a first domain antigen binding, which is the antigen-binding part of an anti-TIGIT antibody, anti PD-1 antibody or anti PD-L1 of the application; and a secondary domain antigen binding, which is the antigen bind portion of a different anti-TIGIT antibody, anti PD-1 antibody or anti PD-L1 of the application.

In one embodiment, the bispecific checkpoint inhibitor antagonist,TP-M2T8P5, comprises: (1) an amino acids sequence of the heavy chain that is approximately 80% to 100% identical to that in SEQ NO:155; (2) an amino acids sequence of the light chain that is approximately 80% to 100% identical to that in SEQ NO:156.

In another embodiment, the bispecific checkpoint inhibitor antagonist TP-M4T8P5 consists of: (1) a variable light chain region 2 and heavy chain variable 1 region (VL2/VH1) with an amino sequence that is approximately 80% to 100% identical to the sequence in SEQ NO:157; (2) a variable heavy chain region 2 and variable light chain region 1 region (VH2/VL1) with an amino sequence that’s about 80% to 100% similar to the sequence in SEQ NO:158.

In another embodiment, the bispecific checkpoint inhibitor antagonist TP-M6T8P5 consists of: (1) A heavy chain variable area with an amino sequence that is approximately 80% to 100% identical to that in SEQ NO: 159, (2) A light chain variable 2/light constant region (VL2/CL), which has an amino sequence that’s about 80% to 100% similar to that in SEQ NO: 160, and (3) a heavier chain variable 1/heavy constant region 1 (VH1/CH1), which contains an amino

In another embodiment, the bispecific checkpoint inhibitor antagonist TP-M6T8L8 consists of: (1) A heavy chain variable area with an amino sequence that is approximately 80% to 85% to 95% to 96% to 97% to 98% to 99% homologous/similar to that in SEQ NO: 162 (2) A light chain variable 2/light constant region (VL2/CL), which has an amino sequence that’s about 80% to 85% to 90% to 95% to 96% to 97% to

The amino acid sequence of the TP-M8T10P1 is approximately 80% to 100% identical to that in SEQ NO: 165. A light chain has an amino sequence that is approximately 80% to 100% similar to that in SEQ NO: 166.

In another embodiment, the bispecific checkpoint inhibitor antagonist TP-M9T10P1 is composed of: (1) A heavy chain with an amino acid composition that is approximately 80% to 100% identical to SEQ ID No: 167, and (2) A light chain with an amino acid composition that is approximately 80% to 100% identical to SEQID NO: 168.

The amino acid sequence of the TP-M9T10P5 is about 80% to 100% identical to that in SEQ NO: 169. It also contains a lighter chain with an amino sequence about 80% to 100% similar to that in SEQ NO: 170.

The amino acid sequence of the light chain variable region is approximately 80%, 85%, 90% 95% 96% 97% 98% 99% homologous with the amino acids sequence in SEQ NO: 172.

In another embodiment of a bispecific Checkpoint Regulator antagonist, TP M10T8L8 contains an amino acid scequence that is approximately 80%, 85% 90%, 95% 96% 97%, 99%, 98.9%, 99%, 99%, 98.9%, 99%, 99%, 999, % to about 100 % homologous with the amino acid scequence in SEQ ID No: 173.

In another embodiment, the bispecific checkpoint inhibitor TP-M14T8P5 consists of: (1) a heavy chains variable region 2 and heavy chains constant region 1, (VH2/CH1), with an amino sequence about 80% to 100% similar to that in SEQ NO:174; (2) variable light chain regions 1/heavy chains constant region 1, (VL1/CH1), with an amino sequence about 80% to 100% similar to that in SEQ NO:175; (3) light chain variable regions 2/light chain consistent

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