Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: A pharmaceutical composition for treatment for of r afflicted or in risk of becoming of impaired glucose tolerance (IGT) and/or type-2 it comprising an effective amount of relaxin for protecting beta-cells and beta-cell function against the effects of high blood glucose (glucotoxicity). Treatment of persons of disglycaemias, and protection of beta cells of the islets of Langerhans and beta-cell function in patients having type-2 diabetes, is diclosed.

Abstract: The disclosure provides, inter alia, methods of improving sperm function and related methods of fertilization, together with preparations of activated or potentiated sperm. The disclosure additionally provides articles of manufacture suitable for performing the methods provided by the invention. The methods provided by the disclosure, in some embodiments entail energy depletion with subsequent staged reintroduction of different energy sources.

Abstract: 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.

Abstract: The application discloses new biomarkers for hypertensive disorders of pregnancy and particularly preeclampsia; methods for the diagnosis, prediction, prognosis and/or monitoring said disorders based on measuring said biomarkers; and kits and devices for measuring said biomarker and/or performing said methods.

Abstract: A method for identifying a kidney transplant recipient at an increased risk of developing interstitial fibrosis or tubular atrophy which comprises obtaining a post-transplant urine sample from the kidney transplant recipient; measuring the level of clusterin in the urine sample; comparing the level of clusterin in the patient sample to the level of clusterin in a control sample from the urine of a non-fibrotic kidney transplant recipient; diagnosing a kidney transplant recipient with a clusterin level that is significantly higher than the clusterin level in the control as being at an increased risk of developing interstitial fibrosis or tubular atrophy.

Abstract: This document provides methods and materials related to genetic variations associated with endometriosis. For example, this document provides methods for using such genetic variations to assess risk of, or susceptibility of developing or diagnosing endometriosis.

Abstract: The subject application relates to methods for treating a placental syndrome, wherein relaxin is administered during the late secretory/luteal (LS) phase of the menstrual cycle in women who have a propensity for developing the placental syndrome. In certain embodiments, administration of relaxin continues beyond the LS phase and into pregnancy.

Abstract: The present invention is based, at least in part, on the identification of a pharmaceutical container formed, at least in part, of a glass composition which exhibits a reduced propensity to delaminate, i.e., a reduced propensity to shed glass particulates. As a result, the presently claimed containers are particularly suited for storage of pharmaceutical compositions and, specifically, a pharmaceutical solution comprising a pharmaceutically active ingredient, for example, LUCENTIS® (ranibizumab), BEXSERO® (meningococcal group B vaccine [rDNA, component, adsorbed]), AIN457 (secukinumab) or RELAXIN® (serelaxin).

Abstract: A process for preparing human relaxin-2 having the following amino acid sequence: A chain: (SEQ?ID?NO:?1) pGlu-Leu-Tyr-Ser-Ala-Leu-Ala-Asn-Lys-Cys-Cys-His- Val-Gly-Cys-Thr-Lys-Arg-Ser-Leu-Ala-Arg-Phe-Cys B chain: (SEQ?ID?NO:?2) Asp-Ser-Trp-Met-Glu-Glu-Val-Ile-Lys-Leu-Cys-Gly- Arg-Glu-Leu-Val-Arg-Ala-Gln-Ile-Ala-Ile-Cys-Gly- Met-Ser-Thr-Trp-Ser; comprising the following steps: providing the amino acids necessary for the synthesis of the A and B chains with usual protective groups, wherein the cysteines are employed as trityl-protected amino acids (L-Cys(Trt)-OH); effecting a chromatographic purification of the individual chains A and B after the solid state synthesis; followed by the simultaneous folding and combination of the individual chains A and B in ammonium hydrogencarbonate buffer at pH 7.9 to 8.4; and subsequent purification of the relaxin-2 formed.

Abstract: Human H3 preprorelaxin, human H3 prorelaxin, human H3 relaxin, human relaxin analogues having a modified A chain and/or a modified B chain are described. Also described are nucleic acid sequences encoded human H3 preprorelaxin, human H3 prorelaxin, human H3 relaxin, human relaxin analogues. Also described are methods for the treatment of conditions responsive to administration of H3 relaxin or analogues thereof.

Abstract: The present invention relates to the use of one or more Relaxin proteins in methods for diagnoses and treatment of multiple sclerosis. The invention also provides compositions for use in diagnosing or treating multiple sclerosis as well as the methods themselves. Kits for carrying out the methods are also described.

Abstract: The subject invention provides methods for recruitment of bone marrow-derived cells, including bone marrow-derived endothelial cells (BMDEC), and increasing their function by administration of relaxin. The methods of the invention can be used in, for example, treating 5 conditions amenable to treatment by recruitment of bone marrow-derived cells, such as BMDEC and bone marrow-derived angio-osteogcnic progenitor cell.

Abstract: Disclosed in certain embodiments is a method of treating a cardiovascular indication comprising administering a natriuretic peptide to a patient in need thereof within 24 hours of clinical assessment of the patient.

Abstract: Modified relaxin polypeptides and their uses thereof are provided

Abstract: The present invention provides Relaxin fusion polypeptides A-L-B with a non-wild type array of the Relaxin A-chain and Relaxin B-chain, wherein the A- and B-chains are connected by a linker peptide. The invention further provides Relaxin fusion polypeptides with extended half-life. Furthermore, the invention provides nucleic acid sequences encoding the foregoing fusion polypeptides, vectors containing the same, pharmaceutical compositions and medical use of such fusion polypeptides.

Abstract: The invention provides a synthetic polypeptide of Formula I? (SEQ ID NO: 1): X1-X2-X3-R—X5-X6-X7-X8-X9-X10-X11-X12-X13??I or an amide, an ester or a salt thereof, wherein X1, X2, X3, X5, X6, X7, X8, X9, X10, X11, X12 and X13 are defined herein. The polypeptides are agonist of the APJ receptor. The invention also relates to a method for manufacturing the polypeptides of the invention, and its therapeutic uses such as treatment or prevention of acute decompensated heart failure (ADHF), chronic heart failure, pulmonary hypertension, atrial fibrillation, Brugada syndrome, ventricular tachycardia, atherosclerosis, hypertension, restenosis, ischemic cardiovascular diseases, cardiomyopathy, cardiac fibrosis, arrhythmia, water retention, diabetes (including gestational diabetes), obesity, peripheral arterial disease, cerebrovascular accidents, transient ischemic attacks, traumatic brain injuries, amyotrophic lateral sclerosis, burn injuries (including sunburn) and preeclampsia.

Abstract: The present invention provides Relaxin fusion proteins, wherein a linker connects the carboxy-terminus of Relaxin with a proteinaceous half-life extending moiety and the linker comprises a protease cleavage site. Therefore, the invention provides Relaxin fusion polypeptides with extended half-life whereby the fusion protein by itself serves as a depot for release of the biologically active Relaxin. Furthermore, the invention provides nucleic acid sequences encoding the foregoing fusion polypeptides, vectors containing the same, cells expressing the Relaxin fusion polypeptides, pharmaceutical compositions and medical use of such fusion polypeptides.

Abstract: Modified relaxin polypeptides and their uses are provided. In one aspect, the disclosure provides a relaxin polypeptide comprising one or more non-naturally encoded amino acids. The polypeptide may be linked to a linker, polymer, or biologically active molecule. The serum half-life of the relaxin polypeptide may be enhanced relative to the unconjugated form. In another aspect, the disclosure provides methods of treating a patient having a disorder modulated by relaxin.

Abstract: 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.

Abstract: Modified relaxin polypeptides and their uses are provided. In one aspect, the disclosure provides a relaxin polypeptide comprising one or more non-naturally encoded amino acids. The polypeptide may be linked to a linker, polymer, or biologically active molecule. The serum half-life of the relaxin polypeptide may be enhanced relative to the unconjugated form. In another aspect, the disclosure provides methods of treating a patient having a disorder modulated by relaxin.

Abstract: The present disclosure relates to methods of modulating aquaporin channels. Particularly, the disclosure provides methods of modulating aquaporin channels in a tissue of a mammal by administering relaxin.

Abstract: The present invention provides methods for increasing arterial compliance. The methods generally involve administering to an individual in need thereof an effective amount of relaxin. The present invention further provides methods of increasing arterial compliance in individuals who have Type 1 or Type 2 diabetes. The present invention further provides methods of increasing arterial compliance in perimenopausal, menopausal, and post-menopausal women. The present invention further provides methods of increasing arterial compliance in individuals who have or who are at risk of developing age-associated arterial stiffness.

Abstract: The present invention relates to biologically active single chain relaxin polypeptides comprising a relaxin B chain derived from relaxin-3, the polypeptides being truncated by one or more amino acids at the C-terminus of the relaxin-3 B chain. Typically the single chain relaxin polypeptides are antagonists of the RXFP3 receptor, and in some embodiments are selective antagonists of the RXFP3 receptor.

Abstract: Insl5 has been found to be orexigenic, i.e. it increases appetite. Insl5, or a derivative or fragment thereof that retains the ability to bind to the GPR100 receptor, or an Insl5 antibody, are useful in therapy, in particular to treat anorexia nervosa, bulimia, cachexia or wasting disease.

Abstract: The present invention relates to biologically active relaxin polypeptides comprising a relaxin A chain and a B chain derived from a relaxin superfamily member, wherein the A chain comprises no intra-chain disulphide bonds. In particular embodiments the modified polypeptides comprise relaxin-3 derived A and B chains, and truncations of the A and/or B chains from the N-termini and/or C-termini. In particular embodiments the polypeptides of the invention are selective agonists or antagonists of the RXFP3 receptor.

Abstract: The present disclosure relates to methods for treating human subjects afflicted with chronic heart failure. The methods described herein employ administration of relaxin.

Abstract: The invention relates to methods for modulating PPAR-? activity using relaxin or agonists thereof. The result is wide range of new therapeutic regimens for treating, inhibiting the development of, or otherwise dealing with, a multitude of illnesses and conditions, including small vessel disorders of the brain and those associated with increased blood-brain barrier permeability, cognitive disorders such as Alzheimer's disease, vascular dementia, epilepsy, stroke, CADASIL and migraine.

Abstract: The present disclosure relates to methods for assessing increased risk of preeclampsia in a pregnant woman. The methods described herein employ measuring relaxin levels, and optionally measuring C-reactive protein levels in a biological sample of a pregnant woman. The disclosure further encompasses methods of reducing risk of preeclampsia through administration of a pharmaceutical formulation of relaxin to a pregnant woman.

Abstract: The present disclosure relates to methods for detecting an increased risk of preeclampsia, determining the presence of preeclampsia, reducing the likelihood that preeclampsia will develop and treating preeclampsia. It also provides methods of measuring relaxin levels in a biological sample of a pregnant woman.

Abstract: Human relaxin analogs, polypeptide compositions related thereto, as well as nucleotide compositions encoding the same, are provided.

Abstract: 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.

Abstract: The disclosure pertains to methods of reducing decompensation through acute intervention including in subjects afflicted with acute decompensated heart failure. Particularly, the disclosure provides methods for treating acute cardiac decompensation by administering a pharmaceutically effective amount of relaxin.

Abstract: The disclosure pertains to methods of reducing decompensation through acute intervention including in subjects afflicted with acute decompensated heart failure. Particularly, the disclosure provides methods for treating acute cardiac decompensation by administering a pharmaceutically effective amount of relaxin.

Abstract: Human relaxin analogs, polypeptide compositions related thereto, as well as nucleotide compositions encoding the same, are provided.

Abstract: The present disclosure relates to methods of modulating aquaporin channels. Particularly, the disclosure provides methods of modulating aquaporin channels in a tissue of a mammal by administering relaxin.

Abstract: The disclosure pertains to methods of reducing decompensation through acute intervention including in subjects afflicted with acute decompensated heart failure. Particularly, the disclosure provides methods for treating acute cardiac decompensation by administering a pharmaceutically effective amount of relaxin.

Abstract: The present disclosure relates to methods for assessing increased risk of preeclampsia in a pregnant woman. The methods described herein employ measuring relaxin levels, and optionally measuring C-reactive protein levels in a biological sample of a pregnant woman. The disclosure further encompasses methods of reducing the risk of preeclampsia and treating it, once it has occurred by administering a pharmaceutical formulation of relaxin to a pregnant woman.

Abstract: It is described the preparation of Insulin like peptides, of chimeric Insulin like peptides and of their derivatives by the random combination of their chains A and their chains B and the pharmaceutical application of the obtained products.

Abstract: The chimeric polypeptide R3(B?23-27)R/I5 is described, which is a high-affinity antagonist for GPCR1 35 and GPCR1 42 over LGR7.

Abstract: The present invention relates to the discovery that relaxin is associated with the development or maturation of body tissues. Knockouts of the gene encoding relaxin result in various abnormalities in the development of various tissues. The present invention provides methods of modulating apoptosis by administering a relaxin agonist or antagonist to a subject.

Abstract: Effective devices and methods using an antifibrotic agent are provided for treating fibrosis or treating normal fibrous tissue. The devices and methods comprise an antifibrotic agent to degrade shrink, relax or stretch at least a portion of the fibrotic tissue. In some embodiments, the methods and devices are configured to immediately release an effective amount of the antifibrotic agent within 24 hours. In some embodiments, when the device comes in contact directly or indirectly with an activator, the antifibrotic agent will be immediately released from the depot. In some embodiments, the depot provides sustained release of the antifibrotic agent over a period of up to one year to treat fibrous tissue.

Abstract: The present invention relates to a device consisting of cross-linked nanofibrillary fibrin supported on and rooted to a microporous nonwoven fabric consisting of a biocompatible synthetic polymer material. An active ingredient is advantageously dispersed in the fibrin layer. The fibrin layer does not have a haemostatic function, but is suitable for retaining the active ingredient and releasing it with controlled kinetics. The device forming the object of the invention, preferably in the form of patches, is useful for in vitro cell cultures or for treating tissues damaged by wounds or necrosis, such as cardiac walls bearing the sequelae of infarction, or a tissue damaged by a diabetic ulcer.

Abstract: Modified relaxin polypeptides and their uses thereof are provided

Abstract: The disclosure pertains to methods of reducing decompensation through acute intervention including in subjects afflicted with acute decompensated heart failure. Particularly, the disclosure provides methods for treating acute cardiac decompensation by administering a pharmaceutically effective amount of relaxin.

Abstract: The disclosure pertains to methods of reducing decompensation through acute intervention including in subjects afflicted with acute decompensated heart failure. Particularly, the disclosure provides methods for treating acute cardiac decompensation by administering a pharmaceutically effective amount of relaxin.

Abstract: A therapeutic or bioeffecting film delivery system which includes nanoparticles having actives bound to or associated with the nanoparticles and which when administered allow the active to perform a therapeutic or bioeffecting function.