The University of Texas System

The Scripps Research Institute

Other

Peregrine Pharmaceuticals, Inc.

Massachusetts Institute of Technology

Ut Sw Medical Ctr at Dallas

Philip E Thorpe

Sophia Ran

Rolf A Brekken

Francis J Burrows

M Melina Soares

Thomas S Edgington

Steven W King

Boning Gao

Jin He

Xianming Huang

Alan J Schroit

Troy A Luster

Shelley P M Fussey

Shelley Pm Fussey

Shelley PM Fussey

Melina M Soares

Disclosed are surprising new methods and compositions for isolating extracellular microvesicles such as exosomes, particularly disease-related and phosphatidylserine (PS)-positive extracellular microvesicles as exemplified by tumor- and viral-derived exosomes. The methods of the invention are rapid, efficient, cost-effective and, importantly, are suitable for use with large volumes of biological fluids and produce antigenically intact extracellular microvesicles and exosomes. The methods and compositions are based on the surprising use of acetate buffers to isolate large quantities of extracellular microvesicles, particularly tumor-derived exosomes, from solution, without damaging their morphological or functional properties or antigenicity.

Methods and compositions for isolating exosomes

Disclosed are the surprising discoveries that aminophospholipids, such as phosphatidylserine and phosphatidylethanolamine, are stable and specific markers accessible on the luminal surface of tumor blood vessels, and that the administration of an anti-aminophospholipid antibody alone is sufficient to induce thrombosis, tumor necrosis and tumor regression in vivo. This invention therefore provides anti-aminophospholipid antibody-based methods and compositions for use in the specific destruction of tumor blood vessels and in the treatment of solid tumors. Although various antibody conjugates and combinations are thus provided, the use of naked, or unconjugated, anti-phosphatidylserine antibodies is a particularly important aspect of the invention, due to simplicity and effectiveness of the approach.

Treating macular degeneration using antibodies to aminophospholipids

Disclosed are new phosphatidylserine binding constructs with surprising combinations of properties, and a range of diagnostic and therapeutic conjugates thereof. The new constructs effectively bind phosphatidylserine targets in disease and enhance their destruction, and can also specifically deliver attached imaging or therapeutic agents to the disease site. Also disclosed are methods of using the new construct compositions, therapeutic conjugates and combinations thereof in tumor vasculature targeting, cancer diagnosis and treatment, and for treating viral infections and other diseases.

Constructs binding to phosphatidylserine and their use in disease treatment

Disclosed is the surprising discovery that aminophospholipids, such as phosphatidylserine and phosphatidylethanolamine, are specific, accessible and stable markers of the luminal surface of tumor blood vessels. The present invention thus provides aminophospholipid-targeted diagnostic and therapeutic constructs for use in tumor intervention. Antibody-therapeutic agent conjugates and constructs that bind to aminophospholipids are particularly provided, as are methods of specifically delivering therapeutic agents, including toxins and coagulants, to the stably-expressed aminophospholipids of tumor blood vessels, thereby inducing thrombosis, necrosis and tumor regression.

Cancer treatment kits comprising therapeutic antibody conjugates that bind to aminophospholipids

Disclosed are surprising discoveries concerning the role of anionic phospholipids and aminophospholipids in tumor vasculature and in viral entry and spread, and compositions and methods for utilizing these findings in the treatment of cancer and viral infections. Also disclosed are advantageous antibody, immunoconjugate and duramycin-based compositions and combinations that bind and inhibit anionic phospholipids and aminophospholipids, for use in the safe and effective treatment of cancer, viral infections and related diseases.

Compositions and methods comprising phosphatidylethanolamine-binding peptide derivatives

Cancer treatment kits using antibodies to aminophospholipids

Liposomes comprising duramycin and anti-viral agents

The invention embodies the surprising discovery that Tissue Factor (TF) compositions and variants thereof specifically localize to the blood vessels within a vascularized tumor following systemic administration. The invention therefore provides methods and compositions comprising coagulant-deficient Tissue Factor for use in effecting specific coagulation and for use in tumor treatment. The TF compositions and methods of present invention may be used alone, as TF conjugates with improved half-life, or in combination with other agents, such as conventional chemotherapeutic drugs, targeted immunotoxins, targeted coaguligands, and/or in combination with Factor VIIa (FVIIa) or FVIIa activators.

Tissue factor compositions and kits for coagulation and tumor treatment

Combinations kits and methods for treating viral infections using antibodies and immunoconjugates to aminophospholipids

Compositions comprising cell-impermeant duramycin derivatives

Methods, combinations and kits for treating viral infections using immunoconjugates and antibodies to aminophospholipids

Disclosed is the surprising discovery that aminophospholipids, such as phosphatidyserine and phosphatidylethanolamine, are specific, accessible and stable markers of the luminal surface of tumor blood vessels. The present invention thus provides aminophospholipid-targeted diagnostic and therapeutic constructs for use in tumor intervention. Antibody-therapeutic agent conjugates and constructs that bind to aminophospholipids are particularly provided, as are methods of specifically delivering therapeutic agents, including toxins and coagulants, to the stably-expressed aminophospholipids of tumor blood vessels, thereby inducing thrombosis, necrosis and tumor regression.

Targeting and imaging tumor vasculature using conjugates that bind to aminophospholipids

Combinations and kits for cancer treatment using selected antibodies to aminophospholipids

Disclosed are various compositions and methods for use in achieving specific blood coagulation. This is exemplified by the specific in vivo coagulation of tumor vasculature, causing tumor regression, through the site-specific delivery of a coagulant using a bispecific antibody.

Combined methods for tumor coagulation and tumor treatment

Liposomes coated with selected antibodies that bind to aminophospholipids

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Dallas, TX, United States of America

Philip E Thorpe