Light chain-bridged bispecific antibody

Abstract

This invention describes a novel format of monomeric bispecific fusion protein with immune activating property for clinical therapies. A bispecific fusion protein includes a first targeting domain with a specificity for a first target of interest; a bridging domain derived from a constant region of a light chain or heavy chain of an immunoglobulin, which may be a human immunoglobulin; and a second targeting domain with a specificity for a second target of interest. The bispecific fusion protein may further include a linker fused to the N-terminus or the C-terminus of the bridging domain. The first targeting domain is fused to the bridging domain and the second targeting domain is fused to the bridging domain or the linker. The linker may include a GGGGS sequence. The first target of interest may be CD20, Her2 / neu, or EpCAM, and the second targeting domain is a T-lymphocyte activating domain.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to Provisional Application Serial No. 61 / 580,491, filed December 27, 2011, the disclosure of which is incorporated herein by reference in its entirety. technical field [0003] The present invention relates to methods of preparing bispecific or multispecific biomolecules, such as bispecific antibodies, and products thereof. Background of the invention [0004] Combining biomolecules with different functions may result in new molecules with desired or improved properties. For example, recent advances in multispecific antibodies, including bispecific antibodies and bispecific tumor-targeting T-lymphocyte engagers, have demonstrated multiple Specific molecules often deliver enhanced efficacy in tumor therapy. [0005] For example, a bispecific antibody (BsAb) can be composed of fragments of two different binding domains (ie, variable regions) from different antibodies. Two different bin...

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Problems solved by technology

However, such fusions may cause incompatibility between fusion partners due to different biological and / or physiological properties of the fusion partners

Additionally, physiological constraints, including the permeability of renal filtration or circulation pathways, may also challenge the design of medically available multiple-specific tumor-targeting molecules

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