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.

The present disclosure provides recombinant nucleic acids comprising one or more polynucleotides encoding a polypeptide (e.g., an inhaled therapeutic polypeptide, such as a human alpha-1-antitrypsin polypeptide); viruses comprising the recombinant nucleic acids; compositions and formulations comprising the recombinant nucleic acids and/or viruses; methods of their use (e.g., for delivering the polypeptide to one or more cells of the respiratory tract and/or for the treatment of a disease affecting the lungs, such as alpha-1-antitrypsin deficiency); and articles of manufacture or kits thereof.

The present invention relates to binding fusion protein compositions comprising targeting moieties linked to extended recombinant polypeptide (XTEN), binding fusion protein-drug conjugate compositions, and XTEN-drug conjugate compositions, isolated nucleic acids encoding the compositions and vectors and host cells containing the same, and methods of using such compositions in treatment of diseases, disorders, and conditions.

A novel method of treating and preventing bacterial diseases is provided. In particular, the present invention relates to compositions and methods for inhibition of Gram negative, Gram positive and acid fast bacilli in general and tuberculosis (TB), Mycobacterium avium complex (MAC), and anthrax in particular. Thus, the invention relates to modulation of cellular activities, including macrophage activity, and the like. More particularly, the present invention relates to the inhibitory compounds comprising naturally occurring and man-made inhibitors of serine protease.

Disclosed herein are compositions and methods for modulating the production of a protein in a target cell. The compositions and methods disclosed herein are capable of ameliorating diseases associated with protein or enzyme deficiencies.

Described herein are compositions and methods for modulation of gene expression in the liver including modulation of PCSK9, TTR, SERPINA1, KLKB1 and/or HAO1.

Described herein are compositions and methods for modulation of gene expression in the liver including modulation of PCSK9, TTR, SERPINA1, KLKB1 and/or HAO1.

A method for producing a modified cryo-poor precipitate that can be utilized in chromatography without intervening precipitation steps is provided. While thawing frozen plasma at low temperature a precipitating compound (e.g. a salt of an organic acid) is added in small amounts. The resulting modified cryo-poor plasma has a reduced tendency to foul chromatography media, permitting direct application to such media without the need for additional precipitation steps. The resulting modified cryoprecipitate has a higher content of cold-insoluble proteins (such as clotting factors), and can be resolubilized and processed further.

The present invention relates to modified serpins for use in the treatment of bradykinin-mediated diseases. The modified serine protease inhibitors (serpins) have mutations in one or more of the P4, P3, P2, P1 and P1 residues of their reactive center loop, which mutations increase the serpin's inhibition of plasma kallikrein (PK) as compared to the corresponding unmodified serpin. The mutations in the modified serpins of the invention further ensure that serpins display substantially no inhibition of at least thrombin and activated protein C. A modified serpin of the invention further preferably shows increased inhibition of at least one of an active form of Factor XII (FXII) and plasmin as compared to the corresponding unmodified serpin, and, preferably, the serpin inhibits at least one of an active form of FXII and PK stronger than they are inhibited by C1 esterase inhibitor. Preferably the modified serpin is a modified 1-antitrypsin. The invention further pertains to nucleic acid molecule encoding the modified serpins of the invention, e.g. a gene therapy vector, and to pharmaceutical compositions comprising the modified serpins of the invention or such gene therapy vectors.

The invention relates to methods and compositions directed at obtaining a non-natively glycosylated recombinant human alpha-1 antitrypsin (A1AT) peptides that are glycosylated in a non-native configuration that confer enhanced biologic activities.