Abstract: The present invention features bifunctional, soluble ecto-enzymes that are engineered to hydrolyze extracellular nucleotide triphosphates (e.g., ATP) to a nucleoside (e.g., adenosine), through the fusion of the ectodomains (ECD) of an ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) and a nucleotide monophosphatase (NMPAse), such as an ecto-5? nucleotidase (eN), alkaline phosphatase (ALP), or an acid phosphatase (AP). Also described are methods of use thereof, e.g. for limiting and decreasing inflammation and sequelae.

Abstract: In combination with conventional therapies (e.g., targeted therapy, chemotherapy, and angiogenesis inhibitors etc.), immunotherapies targeting checkpoint molecules have shown promise in the treatment of solid or liquid tumors. However, apoptotic regulatory T cells (Treg) induced by such therapies often become more suppressive in the tumor microenvironment (TME), through increased generation of adenosine tightly controlled by ectonucleotidases, viz. CD39 and CD73. CD39/ENTPD1, a novel checkpoint molecule, is highly expressed and activated on the tumor vasculature and infiltrating immune cells, promoting tumor growth. Deletion or blockade of CD39 enhances anti-tumor activity by augmenting anti-tumor immune responses and inhibiting tumor angiogenesis.

Abstract: The present invention relates to the treatment of disorders using heme oxygenase-1 and heme degradation products.

Abstract: The present invention relates to the treatment of disorders using heme oxygenase-1 and heme degradation products.

Abstract: Biologically active agents covalently linked to a polymer. The polymer is preferably a biodegradable polymer are provided. The biologically active agent is preferably a protein, such as an extracellular soluble protein, e.g., an extracellular enzyme. The enzyme can be an apyrase, e.g., NTPDase. Conjugates of the invention can be used as therapeutics in subjects. For example, a conjugate comprising an apyrase can be used for treating and preventing thrombosis, atherosclerotic plaque complications and vascular disorders.

Abstract: Biologically active agents covalently linked to a polymer. The polymer is preferably a biodegradable polymer are provided. The biologically active agent is preferably a protein, such as an extracellular soluble protein, e.g., an extracellular enzyme. The enzyme can be an apyrase, e.g., NTPDase. Conjugates of the invention can be used as therapeutics in subjects. For example, a conjugate comprising an apyrase can be used for treating and preventing thrombosis, atherosclerotic plaque complications and vascular disorders.

Abstract: The present invention relates to two ATP diphosphohydrolases (ATPDase enzymes) isolated from bovine aorta and pig pancreas, which enzymes have a molecular weight for their catalytic unit of about 78 and 54 Kilodaltons, respectively. A first process for obtaining a highly purified ATPDase is also an object of the present invention. This process has been successfully applied to the purification of both the pancreatic and the aorta enzymes and is deemed to work in the purification of any ATPDase. For both sources of enzymes, the process allows the specific activity of the enzyme to be increased by at least 10,000 fold when compared to the activity retrieved in the crude cell homogenates. The novel process involves an ion exchange chromatography step, a separation on an affinity column, followed by an electrophoresis under non-denaturing conditions.