Invented by Julian Alexander Barden, Angus Gidley-Baird, Glenn Ronald Pilkington, Biosceptre Pty Ltd

The Market for Antibodies to Nonfunctional Oligomeric Receptors P2X7 and Methods of Using Them Introduction: Antibodies have revolutionized the field of medicine and biotechnology by providing targeted therapies for various diseases. One such area of interest is the market for antibodies targeting nonfunctional oligomeric receptors, specifically the P2X7 receptor. This article will explore the market potential for antibodies against P2X7 receptors and the various methods of using them in therapeutic applications. Understanding P2X7 Receptors: P2X7 receptors are a type of ion channel receptor found on the surface of immune cells, including macrophages and microglia. These receptors play a crucial role in the regulation of immune responses and inflammation. However, in certain conditions, such as chronic inflammatory diseases, the P2X7 receptors become overactive or nonfunctional, leading to dysregulated immune responses and tissue damage. Market Potential: The market for antibodies targeting nonfunctional P2X7 receptors is expected to witness significant growth in the coming years. This is primarily driven by the increasing prevalence of chronic inflammatory diseases, such as rheumatoid arthritis, Crohn’s disease, and multiple sclerosis. These conditions affect millions of individuals worldwide and often require long-term management. Antibodies targeting nonfunctional P2X7 receptors offer a promising therapeutic approach to modulate immune responses and alleviate disease symptoms. Therapeutic Applications: There are several methods of using antibodies against nonfunctional P2X7 receptors in therapeutic applications. Let’s explore a few of them: 1. Blocking P2X7 Receptor Activation: Antibodies can be designed to bind to the nonfunctional P2X7 receptors, preventing their activation and subsequent release of pro-inflammatory molecules. This approach helps in reducing inflammation and tissue damage associated with chronic inflammatory diseases. 2. Modulating Immune Responses: Antibodies can also be used to modulate immune responses by targeting nonfunctional P2X7 receptors. By binding to these receptors, antibodies can either enhance or suppress immune responses, depending on the desired therapeutic outcome. This approach has potential applications in autoimmune diseases and cancer immunotherapy. 3. Drug Delivery: Antibodies can be conjugated with therapeutic agents or nanoparticles to specifically target cells expressing nonfunctional P2X7 receptors. This targeted drug delivery approach enhances the efficacy of the therapeutic agent while minimizing off-target effects. It can be particularly useful in cancer treatment, where specific targeting is crucial for effective therapy. Challenges and Future Perspectives: Despite the promising potential of antibodies against nonfunctional P2X7 receptors, there are several challenges that need to be addressed. One major challenge is the development of antibodies with high specificity and minimal off-target effects. Additionally, the cost of antibody-based therapies and the regulatory approval process pose significant hurdles in the market adoption of these therapies. However, with advancements in antibody engineering technologies and increasing understanding of P2X7 receptor biology, these challenges can be overcome. The market for antibodies targeting nonfunctional P2X7 receptors is expected to witness substantial growth in the coming years, driven by the demand for more effective and targeted therapies for chronic inflammatory diseases. Conclusion: Antibodies targeting nonfunctional P2X7 receptors offer a promising therapeutic approach for chronic inflammatory diseases. The market potential for these antibodies is significant, driven by the increasing prevalence of such diseases globally. Various methods of using these antibodies, including blocking receptor activation, modulating immune responses, and targeted drug delivery, provide diverse therapeutic applications. Overcoming challenges related to specificity, cost, and regulatory approval will be crucial for the successful adoption of these therapies. As research and development in this field continue to progress, antibodies against nonfunctional P2X7 receptors hold great promise for improving patient outcomes and revolutionizing the treatment of chronic inflammatory diseases.

The Biosceptre Pty Ltd invention works as follows

The invention is a purinergic receptor, antibodies, and related fragments of antibodies that bind to said receptors. It also relates to the production of these antibodies and fragments as well as to their use for cancer diagnosis and therapy. The antibodies described in this article bind to P2X& non-functional receptors expressed by living cells.

Background for Antibodies to nonfunctional oligomeric receptors P2X7 and methods of using them

The specification does not acknowledge or suggest that the prior art is part of common knowledge in Australia, or in any other jurisdiction, or that a person with the necessary skills could be reasonably expected to ascertain, understand and regard this prior as relevant.

Purinergic (P2X receptors) are ATP-gated cation selective channels. Each receptor is composed of three monomers or subunits. Seven distinct genes that encode P2X monomers were identified to date: P2X1,P2X2,P2X3,P2X4,P2X5,P2X6, and P2X7.

P2X7 receptors have a special interest because they are only expressed by cells that can undergo programmed cell deaths, like thymocytes. It is known that P2X7 can be expressed in homeostasis. This includes erythrocytes.

This P2X7 receptor, which contains one or more monomers with a cis-isomerisation of Pro210 (according SEQ ID No: 1), and is devoid ATP binding functions, has been found in cells that cannot undergo programmed death, including preneoplastic and neoplastic cell types. This receptor isoform has been called a “non-functional” receptor. receptor.

Antibodies produced from immunisation using a peptide containing Pro210 in trans bind to P2X7 non-functional receptors. They do not bind P2X7-receptors that can bind ATP. These antibodies can be used to detect and treat some cancers, including haemopoietic and carcinoma.

WO02/057306A1″ and WO03/020762A1 discuss the use of monoclonal antibodies to distinguish between P2X7 functional receptors and P2X7 non-functional receptors.

It has been difficult to find serological reagents with the desired affinity that can bind to P2X7 non-functional receptors on living cells. In general, higher affinity reagents for cancer detection and treatment are desirable.

There is a requirement for improved reagents to bind P2X7, notably for new antibodies or fragments of antibodies that can discriminate between ATP-binding and non ATP-binding P2X7 on living cells. It is also necessary to develop antibodies and fragments that bind preferentially to P2X7 when expressed on living cells, but have a reduced ability to bind once the target cell is dead.

In one embodiment there is provided an antigen binding site for binding to a P2X7 receptor, the antigen binding site being defined by general formula 1:\nFR1-CDR1-FR2-CDR2-FR3-CDR3-FR4\nwherein:\nFR1, FR2, FR3 and FR4 are each framework regions;\nCDR1, CDR2 and CDR3 are each complementarity determining regions;\nwherein:\nCDR3 has an amino acid sequence of: (charged/polar/aromatic) (charged/aromatic)XXXY(aromatic/aliphatic)(charged/neutral)(neutral/aliphatic) (SEQ ID NO:48).\nX throughout the specification represents any amino acid.

In one embodiment there is provided an antigen binding site for binding to a P2X7 receptor, the antigen binding site being defined by general formula 2:\nFR1-CDR1-FR2-CDR2-FR3-CDR3-FR4\nwherein:\nFR1, FR2, FR3 and FR4 are each framework regions;\nCDR1, CDR2 and CDR3 are each complementarity determining regions;\nwherein:\nCDR3 has an amino acid sequence of: N(Y/F)XXXY(Y/F)EX (SEQ ID NO:49).

In one embodiment there is provided an antigen binding site for binding to a P2X7 receptor, the antigen binding site being defined by general formula 3:\nFR1-CDR1-FR2-CDR2-FR3-CDR3-FR4\nwherein:\nFR1, FR2, FR3 and FR4 are each framework regions;\nCDR1, CDR2 and CDR3 are each complementarity determining regions;\nwherein:\nCDR3 has an amino acid sequence of: N(Y/F)(neutral)(charged)(neutral)Y(Y/F)E(neutral) (SEQ ID NO:50).

In one embodiment there is provided an antigen binding site for binding to a P2X7 receptor, the antigen binding site being defined by general formula 4:\nFR1-CDR1-FR2-CDR2-FR3-CDR3-FR4\nwherein:\nFR1, FR2, FR3 and FR4 are each framework regions;\nCDR1, CDR2 and CDR3 are each complementarity determining regions;\nwherein:\nCDR3 has an amino acid sequence of: NFLESYFEA (SEQ ID NO:7).

In one embodiment there is provided an antigen binding site for binding to a P2X7 receptor, the antigen binding site being defined by general formula 5:\nFR1-CDR1-FR2-CDR2-FR3-CDR3-FR4\nwherein:\nFR1, FR2, FR3 and FR4 are each framework regions;\nCDR1, CDR2 and CDR3 are each complementarity determining regions;\nwherein:\nCDR3 has an amino acid sequence of: N(Y/F)(charged)(neutral)(charged)Y(Y/F)E(neutral) (SEQ ID NO:51).

In one embodiment there is provided an antigen binding site for binding to a P2X7 receptor, the antigen binding site being defined by general formula 6:\nFR1-CDR1-FR2-CDR2-FR3-CDR3-FR4\nwherein:\nFR1, FR2, FR3 and FR4 are each framework regions;\nCDR1, CDR2 and CDR3 are each complementarity determining regions;\nwherein:\nCDR3 has an amino acid sequence of: NYRGDYYET (SEQ ID NO:8).

In one embodiment there is provided an antigen binding site for binding to a P2X7 receptor, the antigen binding site being defined by general formula 7:\nFR1-CDR1-FR2-CDR2-FR3-CDR3-FR4\nwherein:\nFR1, FR2, FR3 and FR4 are each framework regions;\nCDR1, CDR2 and CDR3 are each complementarity determining regions;\nwherein:\nCDR3 has an amino acid sequence of: H(aromatic)XXXYYNI (SEQ ID NO:42).

In one embodiment there is provided an antigen binding site for binding to a P2X7 receptor, the antigen binding site being defined by general formula 8:\nFR1-CDR1-FR2-CDR2-FR3-CDR3-FR4\nwherein:\nFR1, FR2, FR3 and FR4 are each framework regions;\nCDR1, CDR2 and CDR3 are each complementarity determining regions;\nwherein:\nCDR3 has an amino acid sequence of: H(Y/F)(neutral)(charged)(charged)YYNI (SEQ ID NO:43).

In one embodiment there is provided an antigen binding site for binding to a P2X7 receptor, the antigen binding site being defined by general formula 9:\nFR1-CDR1-FR2-CDR2-FR3-CDR3-FR4\nwherein:\nFR1, FR2, FR3 and FR4 are each framework regions;\nCDR1, CDR2 and CDR3 are each complementarity determining regions;\nwherein:\nCDR3 has an amino acid sequence of: H(Y/F)(neutral)(charged)(neutral)YYNI (SEQ ID NO:44).

In one embodiment there is provided an antigen binding site for binding to a P2X7 receptor, the antigen binding site being defined by general formula 10:\nFR1-CDR1-FR2-CDR2-FR3-CDR3-FR4\nwherein:\nFR1, FR2, FR3 and FR4 are each framework regions;\nCDR1, CDR2 and CDR3 are each complementarity determining regions;\nwherein:\nCDR3 has an amino acid sequence of: HYSKEYYNI (SEQ ID NO:9).

In one embodiment there is provided an antigen binding site for binding to a P2X7 receptor, the antigen binding site being defined by general formula 11:\nFR1-CDR1-FR2-CDR2-FR3-CDR3-FR4\nwherein:\nFR1, FR2, FR3 and FR4 are each framework regions;\nCDR1, CDR2 and CDR3 are each complementarity determining regions;\nwherein:\nCDR3 has an amino acid sequence of: HFQRGYYNI (SEQ ID NO:10).

In one embodiment there is provided an antigen binding site for binding to a P2X7 receptor, the antigen binding site being defined by general formula 12:\nFR1-CDR1-FR2-CDR2-FR3-CDR3-FR4\nwherein:\nFR1, FR2, FR3 and FR4 are each framework regions;\nCDR1, CDR2 and CDR3 are each complementarity determining regions;\nwherein:\nCDR3 has an amino acid sequence of: (Y/N)(aromatic)XXXYY(charged)(neutral) (SEQ ID NO:52).

In one embodiment there is provided an antigen binding site for binding to a P2X7 receptor, the antigen binding site being defined by general formula 13:\nFR1-CDR1-FR2-CDR2-FR3-CDR3-FR4\nwherein:\nFR1, FR2, FR3 and FR4 are each framework regions;\nCDR1, CDR2 and CDR3 are each complementarity determining regions;\nwherein:\nCDR3 has an amino acid sequence of: (Y/N)(aromatic)(neutral)(neutral)(neutral)YYDV (SEQ ID NO:45).

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