Antibody derivatives

Abstract

The invention relates inter alia to a bivalent, bispecific construct comprising an anti-IL-6 antibody, or derivative thereof, and an anti-IL-23 antibody, or derivative thereof and its use in therapy. The invention also relates to useful anti-IL-6 antibodies and anti-IL-23 antibodies.

Description

RELATED APPLICATIONS[0001]The present application is a Continuation of co-pending PCT Application No. PCT / EP2011 / 065697 filed Sep. 8, 2011, which in turn, claims priority from U.S. Provisional Application Ser. No. 61 / 381,789, filed Sep. 10, 2010. Applicants claim the benefits of 35 U.S.C. §120 as to the PCT application and priority under 35 U.S.C. §119 as to the said U.S. Provisional application, and the entire disclosures of both applications are incorporated herein by reference in their entireties.[0002]This disclosure relates to novel antibody derivatives, methods for preparing them, compositions containing them, and their use in therapy.INTRODUCTIONBispecific Antibodies[0003]Monospecific antibodies, such as the naturally-occurring IgG, have two identical antigen binding paratopes, as they are made of two identical heavy chains and two identical light chains. Bispecific antibodies are engineered immunoglobulin derivatives that have two different binding paratopes, usually directe...

AI Technical Summary

Benefits of technology

The patent text discusses the need for stable and effective bispecific antibodies for therapeutic purposes. The issue is that these molecules can become inactive or degraded quickly in the body. One solution is to create molecules that have disulfide bridges between the different domains to improve stability. However, this method can also reduce production yield. The patent proposes a new approach that addresses this issue and produces high-quality antibodies suitable for therapeutic application.

Problems solved by technology

The widespread development of bispecific antibodies has been hampered by the difficulty of producing materials of sufficient quality and in sufficient quantity for in vivo preclinical and clinical studies.

However, a marked reduction in production yield has been reported for these disulfide-stabilized bispecific diabodies in E-coli.

Providing such therapies in the form of a bispecific construct (e.g. one that is specific for IL-6 and IL-23 (and optionally IL-12 as well) represents a significant challenge.

While many efforts have been made to create bispecific antibodies, all efforts to date have failed to create such stable molecules with long in vivo residence times. Moreover, the many efforts to create bispecifics through genetic fusion methods have not succeeded in creating readily manufactured molecules that are stable and high affinity.

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