Ang-2 Binding Complexes and Uses Thereof

Abstract

Complexes containing one or more modular recognition domains (MRDs) and MRDs attached to scaffold's including antibodies are described. The manufacture of these complexes are the use of these complexes to treat and diagnose diseases and disorders are also described.

Description

[0001]Related Applications U.S. 61 / 364,764, filed Jul. 15, 2010; U.S. 61 / 364,765, filed Jul. 15, 2010; U.S. 61 / 364,766, filed Jul. 15, 2010; U.S. 61 / 364,771, filed Jul. 15, 2010; U.S. 61 / 364,774, filed Jul. 15, 2010; U.S. 61 / 383,644, filed Sep. 16, 2010; U.S. 61 / 481,063, filed Apr. 29, 2011; U.S. 61 / 485,486, filed May 12, 2011; U.S. 61 / 485,484, filed May 12, 2011; U.S. 61 / 485,502, filed May 12, 2011; U.S. 61 / 485,505, filed May 12, 2011; and U.S. Ser. No. 13 / 184,485, filed Jul. 15, 2011 are herein incorporated by reference in their entireties.BACKGROUND OF THE INVENTION[0002]1. Field of the Invention[0003]The invention relates generally to complexes containing one or more modular recognition domains and includes complexes containing a scaffold such as an antibody. The invention also relates to methods of making these complexes and methods of treatment and diagnosis using these complexes.[0004]2. Background Art[0005]The development of bispecific or multi-specific molecules that target...

AI Technical Summary

Problems solved by technology

Although each of these molecules may bind one or more targets, they each present challenges with respect to retention of typical Ig function (e.g., half-life, effector function), production (e.g., yield, purity), valency, and simultaneous target recognition.

Unlike their fragment counterparts, engineering and production of recombinant IgG-like multi-specific, multi-valent molecules has been, however, rather technically challenging due to their large size (150-200 kDa) and structural complexity.

Success in the field, as judged by successful application in animal models, has been very limited.

However, RGD based reporter probes are problematic due to fast blood clearance, high kidney and liver uptake, and fast tumor washout.

Metastasis is the primary cause of morbidity and mortality in cancer.

Normally, angiogenesis is tightly regulated by pro- and anti-angiogenic factors, but in the case of diseases such as cancer, ocular noovascular disease, arthritis and psoriasis, the process can go awry.

The HER2 gene is overexpressed in 25% of invasive breast cancers, and is associated with poor prognosis and altered sensitivity to chemotherapeutic agents.

In normal adult cells, few ErbB2 molecules exist at the cell surface ˜20,000 per cell thereby limiting their signaling capacity and the likelihood of forming homo- and hetero-receptor complexes on the cell surface.

HERCEPTIN® induces rapid removal of ErbB2 from the cell surface, thereby reducing its availability to multimerize and ability to promote growth.

Overexpression of EGFR or expression of mutant forms of EGFR has been observed in many tumors, particularly epithelial tumors, and is associated with poor clinical prognosis.

An obstacle in the utilization of a catalytic antibody for selective prodrug activation in cancer therapy has been systemic tumor targeting.

However, the cost of developing and producing such therapies has limited their consideration as viable treatments for most indications.

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