This invention relates to the treatment of Pulmonary Hypertension with heart failure with preserved ejection fraction (PH-HFpEF). More specifically, embodiments of the invention provide compositions and methods useful for the treatment of PH-HFpEF employing the use of levosimendan.

Methods and compositions are provided for extending the half-life of a therapeutic agent. One or more half-life extending moieties may be attached to a therapeutic agent, thereby extending the half life of the therapeutic agent. The modified therapeutic agents (mTAs) comprising one or more half-life extending moieties attached to a therapeutic agent may be used to treat a disease or condition in a subject in need thereof.

The present invention relates to a novel gene delivery system and recombinant adenovirus including the relaxin-encoding sequence to enhance transduction efficiency of transgenes, a pharmaceutical anti-tumor composition including the recombinant adenovirus, a pharmaceutical composition having improved tissue penetration potency and a pharmaceutical composition for treating a disease or disorder associated with accumulation of excess extracellular matrix.

The present disclosure teaches a method for treating airways disease including ameliorating symptoms of airway inflammation, airway remodeling and airway hyper-responsiveness. The method comprises the administration of an anti-fibrotic agent together with amnion epithelial cells or their functional equivalents or exosomes.

The subject invention relates to methods for improving a subject's vasculature to normalize maternal hemodynamics, particularly in subjects attempting to conceive via assisted reproductive technologies, and comprises increasing relaxin levels in a subject or increasing any one or more of: relaxin synthesis, relaxin receptor synthesis, relaxin binding to the relaxin receptor, or relaxin receptor activity.

The subject invention relates to methods for improving a subject's vasculature to normalize maternal hemodynamics, particularly in subjects attempting to conceive via assisted reproductive technologies, and comprises increasing relaxin levels in a subject or increasing any one or more of: relaxin synthesis, relaxin receptor synthesis, relaxin binding to the relaxin receptor, or relaxin receptor activity.

The present invention provides methods for treating a stiffened joint in a subject that comprise administering relaxin, e.g., a PEGylated relaxin-2, to the subject. The relaxin may be administered intra-articularly as a sustained release formulation. The present invention also provides sustained release formulations in the form of a hydrogel for administering polypeptides that are covalently attached to a polymer, e.g., PEG.

The present disclosure generally relates to modified relaxin polypeptides, such as modified human relaxin 2 polypeptides, comprising a non-naturally encoded amino acid which is linked to a pharmacokinetic enhancer, and therapeutic uses of such polypeptides, such as for the treatment of cardiovascular conditions (such as heart failure) and/or conditions relating to fibrosis.

Modified relaxin polypeptides and their uses thereof are provided. Exemplary embodiments provide relaxin polypeptides which include one or more amino acid substitutions with natural or non-naturally encoded amino acids, and/or linkage to a water-soluble polymer, such as polyethylene glycol. Additionally, use of said relaxin polypeptides for treatment of disease, such as heart failure, is also provided.

The present invention provides methods for treating a stiffened joint in a subject that comprise administering relaxin, e.g., a PEGylated relaxin-2, to the subject. The relaxin may be administered intra-articularly as a sustained release formulation. The present invention also provides sustained release formulations in the form of a hydrogel for administering polypeptides that are covalently attached to a polymer, e.g., PEG.