Abstract: Provided herein are Complement Factor I (CFI) variants that exhibit at least one improved characteristic relative to a wild type CFI. CFI variants of the disclosure can exhibit tunable specificity and activity. Also included are CFI-containing fusion constructs comprising at least one domain of CFI, for example, wild type full length CFI fused to human serum albumin. Also included are methods of making and using such CFI variants and fusion constructs. The CFI variants and fusion constructs provided herein may be useful for treating a disease or condition associated with dysregulation of the complement system or a deficiency of CFI.

Abstract: Provided herein are modified FVII polypetides, and modified FVIIa polypeptides, and methods of treatment of acute and episodic bleeding with modified FactorVIIa polypeptides. To effect treatment and use, in some embodiments, the modified polypeptides are subcutaneously administered to provide on-demand treatment. In some embodiments, the on-demand treatment is provided in a multiple dosing regimen over a twenty-four hour period. The subcutaneous administration of the modified polypeptides of the disclosure exhibit increased coagulant activity, potency, bioavailablilty and prolonged duration.

Abstract: AAV vectors that encode a modified Factor IX (FIX) polypeptide for gene therapy for treatment of hemophilia B are provided. The modified FIX polypeptide has increased potency compared to the wild-type FIX polypeptide. The nucleic acid encoding the modified FIX polypeptide includes a portion of an intron. The AAV vectors were generated and selected to infect islet cells, but were found to effectively transduce hepatocytes upon systemic administration, and to express high levels of FIX polypeptide. Relatively low doses of the AAV vectors can be administered to achieve a therapeutic effect. The gene therapy treatment can result in normal or near normal coagulation pharmacokinetics and normal levels of FIX, or mild hemophilia B. Combining an AAV vector with improved properties for transducing hepatocytes, and modified FIX polypeptides with enhanced potency, improves transgene expression and effectively lowers the viral dose needed to achieve therapeutically relevant FIX activity levels.

Abstract: The present invention relates to thrombin sensitive coagulation Factor X (FX), as well as use thereof in medicine. In particular the invention relates to FX molecules comprising 2 to 10 amino acid modifications in the activation peptide N-terminally of the FX “IVGG” motif as well as compositions comprising such molecules and use thereof. Such molecules may be useful in connection with convenient and patient friendly treatment regimens in treatment and prophylaxis of haemophilia.