The present invention relates to heterodimeric Relaxin fusion polypeptides, in particular to heterodimeric Relaxin 2 fusion polypeptides and uses thereof. Thus, the invention provides Relaxin fusion polypeptides, nucleic acid molecules, vectors, host cells, pharmaceutical compositions and kits comprising the same and uses of the same including methods of treatment. The polypeptides and compositions of the invention may be useful, in particular, in the treatment of cardiovascular diseases, for example for the treatment of heart failure.

Disclosed herein is a method for diagnosing a renal allograft recipient's risk for developing fibrosis of the allograft and allograft loss. The method includes determining the expression levels of certain microRNAs, which have been determined to be predictive of an allograft recipient's risk. Also disclosed herein is a method of treating a renal allograft recipient to inhibit fibrosis of the allograft and allograft loss, as well as kits for use in the methods disclosed herein.

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.

A pharmaceutical composition for treatment of persons afflicted of heart failure with preserved ejection fraction (HFPEF), diastolic heart failure (DHF) or diastolic dysfunction (DF), the composition comprising a therapeutically effective amount of a compound capable of specific binding to the relaxin receptor (RXFP1) present on fibroblasts, fibromyoblasts, endothelial cells, endocardial cells, and cardiomyocytes in the cardiac muscle to increase the heart's stroke volume at lower end-diastolic pressure.

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.

In alternative embodiments, the invention provides methods for treating, ameliorating or protecting (preventing) an individual or a patient against a disease, an infection or a condition responsive to an increased paracrine polypeptide level in vivo comprising: providing a paracrine polypeptide-encoding nucleic acid or gene operatively linked to a transcriptional regulatory sequence; or an expression vehicle, a vector, a recombinant virus, or equivalent, having contained therein a paracrine-encoding nucleic acid or gene, and the expression vehicle, vector, recombinant virus, or equivalent can express the paracrine-encoding nucleic acid or gene in a cell or in vivo; and administering or delivering the paracrine polypeptide -encoding nucleic acid or gene operatively linked to a transcriptional regulatory sequence, or the expression vehicle, vector, recombinant virus, or equivalent, to an individual or a patient in need thereof, thereby treating, ameliorating or protecting (preventing) the individual or patient against the disease, infection or condition responsive to an increased paracrine polypeptide level.

Growth differentiation factor 15 (GDF-15) is a stress-responsive cytokine known to be associated with adverse events in heart failure patients. The use of serelaxin has been shown to affect GDF-15 levels at baseline and decreases in GDF-15 levels over time. Measuring GDF-15 levels allows a healthcare provider to accurately predict pulmonary load in patients with pulmonary congestion.

In an acute care setting, rapid onset of the therapeutic effects of medication is highly desirable. The invention provides in-line filters suitable for rapid delivery of a positively charged protein therapeutic via intravenous administration.

The present invention relates to relaxin or a homologue or variant thereof for use in a method of treating an inflammatory condition, for example an autoimmune inflammatory condition. The invention also relates to the treatment of an inflammatory condition, for example an autoimmune inflammatory condition comprising administering to a subject in need thereof a relaxin, or a homologue or variant thereof. Such conditions may be CNS conditions or be organ specific.

The present invention relates to relaxin or a homologue or variant thereof for use in a method of treating an inflammatory condition, for example an autoimmune inflammatory condition. The invention also relates to the treatment of an inflammatory condition, for example an autoimmune inflammatory condition comprising administering to a subject in need thereof a relaxin, or a homologue or variant thereof. Such conditions may be CNS conditions or be organ specific.