Serpin fusion polypeptides and methods of use thereof
This invention relates to molecules, particularly polypeptides, more particularly fusion proteins that include a serpin polypeptide or an amino acid sequence that is derived from a serpin and second polypeptide comprising of at least one the following: an Fc polypeptide or an amino acid sequence that is derived from an Fc polypeptide; a cytokine targeting polypeptide or a sequence derived from a cytokine targeting polypeptide; a whey acidic protein (WAP) domain containing polypeptide or a sequence derived from a WAP containing polypeptide; and an albumin polypeptide or an amino acid sequence that is derived from a serum albumin polypeptide. This invention also relates to methods of using such molecules in a variety of therapeutic and diagnostic indications, as well as methods of producing such molecules.
1. An isolated fusion protein comprising at least one alpha-1 antitrypsin (AAT) polypeptide operably linked to a second polypeptide, wherein the second polypeptide comprises a human serum albumin (HSA) polypeptide, and wherein the fusion protein comprises the amino acid sequence of SEQ ID NO: 30 or 31.
2. A method of inhibiting or downregulating aberrant serine protease expression or activity in a subject in need thereof, the method comprising administering an isolated fusion protein according to claim 1 .
3. The method of claim 2 , wherein the subject is a human.
4. The method of claim 2 , wherein the subject has a disease or disorder selected from the following: alpha-1 antitrypsin (AAT) deficiency, an infection, emphysema, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), allergic asthma, cystic fibrosis, cancers of the lung, ischemia-reperfusion injury, ischemia/reperfusion injury following cardiac transplantation, myocardial infarction, rheumatoid arthritis, septic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, psoriasis, type I diabetes, type II diabetes, pneumonia, sepsis, graft versus host disease (GVHD), a wound, systemic lupus erythematosus, and multiple sclerosis.
5. The method of claim 4 , wherein the infection is selected from a bacterial infection, a fungal infection, or a viral infection.