Compositions and methods to mitigate or prevent an immune response to an immunogenic therapeutic molecule in non-human primates

Abstract

Methods and compositions for preventing an immune response to an immunogenic therapeutic agent [i.e. anti-drug antibody (ADA), a.k.a. anti-therapeutic antibody (ATA)] are disclosed. One of the disclosed methods comprises administering an effective amount of an immunosuppressant such as an IL-2 signaling pathway inhibitor, including an antagonist, super agonist or partial agonist to the cytokine IL-2, to the IL-2 receptor (IL-2R), or to IL-2R signal transduction molecules. Inhibitors can be in the form of antibodies or antibody fragments, peptide inhibitors, fusion molecule, small molecules, antibody / small molecule conjugates. Administration of a given inhibitor can decrease the incidence and / or magnitude of an immune response or prevent an immune response, including an antibody response, to a potentially immunogenic therapeutic agent in a non-human primate (NHP). Some of the disclosed methods produce a tolerizing effect in NHPs.

Description

RELATED APPLICATIONS[0001]This application claims priority under 35 U.S.C. 119 (e) to U.S. Provisional Patent Application Ser. No. 62 / 263,352, entitled “Compositions and Methods to Mitigate an Immune Response to an Immunogenic Therapeutic Agent in Non-Human Primates (NHP)”, filed Dec. 4, 2015, the disclosure of which is hereby incorporated by reference in its entirety.TECHNICAL FIELD[0002]The present invention is generally in the field of immunology and of modulating responses to immunogenic therapeutic agents.BACKGROUND OF THE INVENTION[0003]Biological medicinal products and therapeutic agents are a growing proportion of tested pharmaceutical drugs. Drug development and licensure entails the testing of these products in several animal species prior to their administration to humans. As non-human primates (NHP) are the species closest to man, they are generally the last animal species in which testing is performed before a drug is administered to humans.[0004]Biological medicinal pr...

AI Technical Summary

Benefits of technology

The patent text is about methods to reduce the risk and intensity of animal immune responses when giving therapeutic compositions to non-human primates (NHPs). Two main approaches are described: using immunosuppressants and inhibiting the IL-2 pathway. These methods can decrease the formation of antibodies against the therapeutic molecule, reducing the severity of the immune response and improving the safety and tolerability of the treatment. Overall, this patent text presents a way to make therapeutic compositions safer and more effective in NHPs.

Problems solved by technology

Because the immune system of different species can distinguish orthologous proteins as foreign, the preclinical testing of human therapeutic proteins in non-human species can be dramatically hampered by the animals' immune response to the protein, resulting in antibody-mediated alterations of the proteins' activity, bioavailability or toxicity.

Such antibodies may even trigger anaphylaxis or death of the animal.

Such ADA can also alter or mask the toxicity of the agent, resulting in misguided interpretations of the predicted safety profile of the product in humans.