Ang-2 Binding Complexes and Uses Thereof

Abstract

Complexes containing one or more modular recognition domains (MRDs) and MRDs attached to scaffolds 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]This is a Nonprovisional Application which claims the benefit under 35 U.S.C. §119(e) to Provisional Application Nos. 61 / 364,764, filed Jul. 15, 2010; 61 / 364,765, filed Jul. 15, 2010, 61 / 364,766, filed Jul. 15, 2010; 61 / 364,771, filed Jul. 15, 2010; 61 / 364,774, filed Jul. 15, 2010; 61 / 383,644, filed Sep. 16, 2010, 61 / 481,063, filed Apr. 29, 2011; 61 / 485,486, filed May 12, 2011; 61 / 485,484, filed May 12, 2011; 61 / 485,502, filed May 12, 2011; and 61 / 485,505, filed May 12, 2011, each of which is herein incorporated by reference in its entirety.REFERENCE TO SEQUENCE LISTING SUBMITTED ELECTRONICALLY[0002]The content of the electronically submitted sequence listing (Size: 79,196 bytes; and Date of Creation: Sep. 23, 2011) filed with the application is incorporated herein by reference in its entirety.BACKGROUND OF THE INVENTION[0003]1. Field of the Invention[0004]The invention relates generally to complexes containing one or more modular recognition domains and includes complexes con...

AI Technical Summary

Benefits of technology

[0059]The present invention also relates to a method of treating or preventing a disease or disorder in a subject in need thereof, comprising administering an antibody comprising an MRD to the subject. In one aspect, the disease is cancer. In another aspect, undesired angiogenesis in inhibited. In another aspect, angiogenesis is modulated. In yet another aspect, tumor growth is inhibited.

[0060]Certain embodiments provide for methods of treating or preventing a disease, disorder, or injury comprising administering a therapeutically effective amount of an antibody comprising an MRD (i.e., MRD-containing antibodies) to a subject in need thereof. In some embodiments, the disease, disorder or injury is cancer. In other embodiments, the disease, disorder or injury is a disorder of the immune system. In one embodiment, the disorder of the immune system is inflammation. In another embodiment, the disorder of the immune system is an autoimmune disease. In an additional embodiment, the disorder of the immune system is selected from the group consisting of: rheumatoid arthritis, Crohn's disease, systemic lupus erythematosus, inflammatory bowel disease, psoriasis, diabetes, ulcerative colitis, and multiple sclerosis. In one embodiment, the disease, disorder or injury is a metabolic disease. In another embodiment, the disease, disorder, or injury is an infectious disease. In specific embodiments, the infectious disease is human immunodeficiency virus (HIV) infection or AIDS, botulism, anthrax, or clostridium difficile. In other embodiments, the disease, disorder, or injury is neurological. In a specific embodiment, the neurological disease, disorder or injury is pain. In a more specific embodiment, the pain is, acute pain or chronic pain.

[0061]In another embodiment, a method of treatment or prevention comprising administering an additional therapeutic agent along with an antibody comprising an MRD is provided. In other embodiments, the methods of treatment or prevention comprise administering an antibody comprising more than one type of MRD.

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 neovascular 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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