Hybrid nuclease molecules and methods for treating an immune-related disease or disorder in a mammal, and a pharmaceutical composition for treating an immune-related disease in a mammal.

The present disclosure relates to the use of 2-((4S)-6-(4-chlorophenyl)-1-methyl-4H-benzo[c]isoxazolo[4,5-e]azepin-4-yl)acetamide, and pharmaceutically acceptable salts thereof, for treating myelofibrosis.

The invention relates to novel compounds of the general formula (I),

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with Het-2 being an optionally substituted bicyclic heteroaryl of the formula

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pharmaceutical compositions comprising them and the use thereof as medicaments, in particular for the use as ferroportin inhibitors, more particularly for the use in the prophylaxis and/or treatment of diseases caused by a lack of hepcidin or iron metabolism disorders, such as particularly iron overload states such as in particular thalassemia and hemochromatosis.

The invention relates to novel compounds of the general formula (I),

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with Het-2 being an optionally substituted bicyclic heteroaryl of the formula

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pharmaceutical compositions comprising them and the use thereof as medicaments, in particular for the use as ferroportin inhibitors, more particularly for the use in the prophylaxis and/or treatment of diseases caused by a lack of hepcidin or iron metabolism disorders, such as particularly iron overload states such as in particular thalassemia and hemochromatosis.

In one aspect, the disclosure relates to pharmaceutical compositions comprising 2′-deoxycytidine analogs, oral and other dosage formulations containing the same, and methods of making the same. In another aspect, the disclosure relates to methods of treating hematological disorders and diseases associated with abnormal cell proliferation using the same. In a still further aspect, the disclosure relates to kits comprising 2′-deoxycytidine analogs useful for treating hematological disorders and diseases associated with abnormal cell proliferation. In still another aspect, the disclosure relates to methods for increasing fetal hemoglobin levels in a subject. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.

A method of treating a subject in need of a non-syngeneic cell or tissue graft is disclosed. The method comprising: (a) transplanting into a subject a dose of T cell depleted immature hematopoietic cells, wherein the T cell depleted immature hematopoietic cells comprise less than 5×10.sup.5 CD3.sup.+ T cells per kilogram body weight of the subject, and wherein the dose comprises at least about 5×10.sup.6 CD34+ cells per kilogram body weight of the subject; and subsequently (b) administering to the subject a therapeutically effective amount of cyclophosphamide, wherein the therapeutically effective amount comprises 25-200 mg per kilogram body weight, thereby treating the subject.

The present application features antibodies that bind to human neonatal Fc receptor (FcRn). These anti-FcRn antibodies are useful, e.g., to promote clearance of autoantibodies in a subject, to suppress antigen presentation in a subject, to block an immune response, e.g., block an immune complex-based activation of the immune response in a subject, and to treat immunological diseases (e.g., autoimmune diseases) in a subject. These anti-FcRn antibodies are also useful, e.g., to decrease pathogenic antibody transport across the placenta of a pregnant subject, to increase pathogenic antibody catabolism in a pregnant subject, and to treat an antibody-mediated enhancement of viral disease in a fetus or a neonate.

The present invention provides methods and compositions for treating thyroid-related medical conditions. Many thyroid-related medical conditions exist that go undiagnosed and untreated. These conditions may be prevented and treated with reduced folates and vitamin B12. Administration of reduced folates and vitamin B12 will prevent or treat cerebrospinal folate deficiency, which is linked to thyroid-related medical conditions. Administration of reduced folates and vitamin B12 will also prevent or treat conditions associated with masked megaloblastic anemia and hypothyroidism, and other conditions brought upon through improper thyroid function. Additionally, it is commonplace to treat many thyroid conditions with anti-thyroid drugs or thyroid stimulating drugs. This practice alone is also responsible for causing, or not beneficially addressing, adverse conditions that can be prevented or treated through the methods and compositions discussed herein.

Provided herein are heterocyclic compounds of Formula (I), pharmaceutical compositions containing such a compound and their therapeutic uses, methods for their preparation, intermediate compounds, pharmaceutical compositions containing such a compound, and their therapeutic uses.

The present disclosure provides methods and compositions for genetically modifying hematopoietic stem and progenitor cells (HSPCs), in particular by replacing the HBA1 or HBA2 locus in the HSPCs with a transgene encoding a therapeutic protein.