Abstract: Biomaterials that support cell attachment and growth are provided. In one aspect, biomaterials are provided comprising a first polymer matrix comprising reactive amino moieties and a second polymer matrix that interpenetrates with the first polymer matrix, where the second polymer matrix comprises a poly(alkylene oxide) comprising two or more alkylene oxide oligomers joined by gamma-thioether carbonyl linkages. In another aspect, biomaterials are provided comprising at least one biopolymer comprising amino groups, thiol groups, and bifunctional modifiers connecting at least some of the amino groups to at least some of the thiol groups; and at least one poly(alkylene oxide) cross-linked to at least two thiol groups of the biopolymer. The biomaterials may further comprise a pharmacologically active agent or cells. Methods of administering such biomaterials to a patient in need thereof are also provided.

Abstract: The present invention relates to polypeptides and their uses as apelin inhibitors. More particularly, the present invention relates to a polypeptide comprising the sequence as set forth in SEQ ID NO:1 wherein at least one arginine residue at position 18, 19, 22 or 23 has been substituted or deleted.

Abstract: This invention is directed to a chorionic gonadotrophin carboxy terminal peptide (CTP) modified dual GLP-1/Glucagon receptor agonist, and methods of producing and using the same. In one embodiment, the present invention provides a CTP-modified polypeptide comprising a dual GLP-1/Glucagon receptor agonist and at least one chorionic gonadotrophin carboxy terminal peptide (CTP) attached to the amino terminus or carboxy terminus of said agonist.

Abstract: The invention relates to novel polypeptide analogs of GLP-1 and exendin-4. The polypeptide, in a preferred embodiment, is insulinotropic and long-acting. Preferably, the polypeptide's insulinotropic effect is comparable to or exceeds the effect of an equimolar amount of GLP-1 or exendin-4. The invention also relates to a method of treating a subject with diabetes, comprising administering to the subject the polypeptide of the invention in an amount that has an insulinotropic effect. The invention also relates to methods of using GLP-1, exendin-4, and polypeptide analogs thereof for neuroprotective and neurotrophic effects.

Abstract: An aqueous composition having increased protein stability is obtained by: a. determining a pH at which the protein has stability at the desired temperature; b. adding to the composition at least one displacement buffer wherein the displacement buffer has a pKa that is at least 1 unit greater or less than the pH of step (a); and c. adjusting the pH of the composition to the pH of step (a); wherein the aqueous composition does not comprise a conventional buffer at a concentration greater than about 2 mM and wherein the conventional buffer has a pKa that is within 1 unit of the pH of step (a).

Abstract: Disclosed herein are an in situ-forming, bioadhesive hydrogel and the medical uses thereof. Being formed by in situ crosslinking through an enzymatic reaction, the hydrogel has an advantage over conventional bioadhesive hydrogels in terms of biocompatibility. In addition, the in situ-forming bioadhesive hydrogel has excellent biocompatibility and mechanical strength and has excellent tissue adhesiveness thanks to modification with/without dopa derivatives. The hydrogel finds a variety of applications in the biomedical field, including bioadhesives or hemostats, implant substances for tissue regeneration and augmentation, carriers for delivering biologically active materials or drugs, etc.

Abstract: The present invention provides, among other things, methods and compositions for treating or preventing fibrotic diseases, disorders or conditions based on Angiotensin (1-7) polypeptides, and analogs or derivatives thereof. In some embodiments, compositions and methods for treating or preventing pulmonary fibrosis, pulmonary hypertension, chronic obstructive pulmonary disease (COPD), asthma, cystic fibrosis, kidney fibrosis, liver fibrosis, systemic sclerosis, post-surgical adhesions, accelerating wound healing, and reducing or preventing scar formation are provided.

Abstract: Reversible pegylated drugs are provided by derivatization of free functional groups of the drug selected from amino, hydroxyl, mercapto, phosphate and/or carboxyl with groups sensitive to mild basic conditions such as 9-fluorenylmethoxycarbonyl (Fmoc) or 2-sulfo-9-fluorenylmethoxycarbonyl (FMS), to which group a PEG moiety is attached. In these pegylated drugs, the PEG moiety and the drug residue are not linked directly to each other, but rather both residues are linked to different positions of the scaffold Fmoc or FMS structure that is highly sensitive to bases and is removable under physiological conditions. The drugs are preferably drugs containing an amino group, most preferably peptides and proteins of low or medium molecular weight. Similar molecules are provided wherein a protein carrier or another polymer carrier replaces the PEG moiety.

Abstract: Provided herein are methods of reducing and/or inhibiting A deposition or A plaque formation in the brain, and/or inhibiting or slowing the progression of disorders mediated by A deposition or A plaque formation using therapeutically effective amounts of amylin agonist compounds or pharmaceutical compositions comprising amylin agonist compounds. As demonstrated herein, amylin and amylin analog administration improves cognition, including memory. Also provided herein are non-invasive, inexpensive amylin or amylin analog challenge assays and methods and kits thereof for detecting the presence of plaques comprising A? peptide in the brain, and for identifying individuals at increased risk for Alzheimer's disease (AD) and/or amnestic mild cognitive impairment.

Abstract: A breath-powered, dry powder inhaler, a cartridge, and a pulmonary drug delivery system are provided. The dry powder inhaler can be provided with or without a unit dose cartridge for using with the inhaler. The inhaler and/or cartridge can be provided with a drug delivery formulation comprising, for example, a diketopiperazine and an active ingredient, including, peptides and proteins such as insulin and glucagon-like peptide 1 for the treatment of diabetes and/or obesity. The dry powder inhaler is compact; can be provided in various shapes and sizes, colors, and comprises a housing, a mouthpiece, a cartridge placement area, and a mechanism for opening and closing the medicament cartridge. The device is easy to manufacture, provides a pre-metered single unit dose, it is relatively easy to use, and can be reusable or disposable.

Abstract: The present invention includes compositions and methods for the integration of a non-allergenic nanocellulose into a wound bed. The composition may be formed into a wide variety of implants, e.g., a suture, a sheet, a compress, a bandage, a band, a prosthesis, a fiber, a woven fiber, a bead, a strip, a clasp, a prosthesis, a catheter, a screw, a bone plate, a pin, a bandage or combinations thereof.

Abstract: The present invention relates to extended recombinant polypeptide (XTEN) compositions, conjugate compositions comprising XTEN and XTEN linked to cross-linkers useful for conjugation to pharmacologically active payloads, methods of making highly purified XTEN, methods of making XTEN-linker and XTEN-payload conjugates, and methods of using the XTEN-cross-linker and XTEN-payload compositions.

Abstract: The invention relates to biopolymer-gel based depot systems for prolonged and/or controlled release delivery of biologically active agents, methods for the manufacture of the biopolymer based gel-depots which include a biologically active agent, and uses of such biopolymer gel-depots in therapy. The biopolymer-gel based depot systems comprise a biocompatible polyaminosaccharide and/or protein; a biocompatible phosphate and/or sulphonamide compound; a biologically active agent; an aqueous insoluble alkaline earth metal phosphate; and a biocompatible glycan and/or proteoglycan.

Abstract: A polypeptide and polynucleotides comprising at least two carboxy-terminal peptides (CTP) of chorionic gonadotrophin attached to a non-human peptide-of-interest are disclosed. Pharmaceutical compositions comprising the non-human polypeptides and polynucleotides of the invention and methods of using both human and non-human polypeptides and polynucleotides are also disclosed.

Abstract: The present invention relates generally to a method of modulating graft functionality. More specifically, the present invention relates to a method of downregulating the onset or progression of graft dysfunction by downregulating the functional level of activin. The method of the present invention is useful, inter alia, in the treatment and/or prophylaxis of conditions characterised by graft dysfunction, such as the primary graft dysfunction associated with organ transplantation.

Abstract: This invention provides a method of promoting bone healing by locally administering a vanadium-based insulin mimetic agent to a patient in need thereof. The invention also provides a new use of insulin-mimetic vanadium compounds for manufacture of medicaments for accelerating bone-healing processes. In addition, the invention also encompasses a bone injury treatment kit suitable for localized administration of insulin-mimetic vanadium compounds or compositions thereof to a patient in need of such treatment.

Abstract: Methods for facilitating joint immobilization or fusion using selective estrogen receptor modulator (SERM) such as raloxifene are disclosed. The SERM may be administered systemically or locally. In conjunction with SERM, other therapeutic agents such as calcium, vitamin D, bone morphogenetic protein may be administered simultaneously. The method can similarly be applied to facilitate bone repair, bone healing, and connective tissue healing processes in a patient.

Abstract: The present invention provides methods and kits for treating diseases and conditions associated with impaired pancreatic function. The present invention further provides methods of stimulating islet cell neogenesis and stimulating islet cell differentiation from progenitor cells.

Abstract: The present invention relates to novel peptidic inhibitors of signal transmission from G?s- to G?i-coupled receptor cascades and methods for their use.

Abstract: Provided are methods relating to the use of CDP-therapeutic agent conjugates for the treatment of a disease or disorder, e.g., autoimmune disease, inflammatory disease, central nervous system disorder, cardiovascular disease, or metabolic disorder. Also provided are CDP-therapeutic agent conjugates, particles comprising CDP-therapeutic agent conjugates, and compositions comprising CDP-therapeutic agent conjugates.

Abstract: An interventional medical device and manufacturing method thereof, the interventional medical device comprising a stent body (1); the stent body (1) is provided with a drug releasing structure on the surface, the drug in the drug releasing structure being a drug for inhibiting adventitial fibroblast proliferation. When the interventional medical device is implanted into a human body, the drug for inhibiting the adventitial fibroblast proliferation can be slowly released into vessel wall cells in contact with the stent body (1), thus inhibiting the proliferation of the adventitial fibroblasts, promoting vascular compensatory expansion, and reducing the incidence rate of instent restenosis.

Abstract: The present invention relates to the use of an antagonist of kisspeptin in the manufacture of a medicament for the treatment of a condition induced and/or worsened by kisspeptin activity in an individual. The invention also provides certain defined peptide molecules, which may act as an antagonist of kisspeptin, which are of use in treating a condition induced and/or worsened by kisspeptin activity in an individual. In addition, the invention provides methods of identifying and/or using antagonists of kisspeptin and/or the defined peptides, and pharmaceutical compositions thereof.

Abstract: A combination of compounds is described for the treatment and/or prevention of skin conditions linked to hypopigmentation. Also described, is a combination product that includes at least one prostaglandin receptor agonist and at least one MC1R receptor agonist, as a medicament for use simultaneously, separately or spread out over time for the treatment and/or prevention of skin conditions linked to hypopigmentation, such as vitiligo.

Abstract: This invention provides long-acting, superactive analogs of glycoprotein hormones demonstrating enhanced bioactivity both in vitro and in vivo as compared to wild type counterparts. The analogs are particularly useful for treating subjects showing low receptor expression or poor receptor responsiveness, and for the treatment of any condition associated with glycoprotein hormone activity.

Abstract: Peptide-peptidase inhibitor conjugate molecules are disclosed. These conjugate molecules are useful as agents for the treatment and prevention of metabolic and cardiovascular diseases, disorders, and conditions. Such diseases, conditions and disorders include, but are not limited to, hypertension, dyslipidemia, cardiovascular disease, eating disorders, insulin-resistance, obesity, and diabetes mellitus of any kind, and other diabetes-related disorders.

Abstract: Methods and materials for diagnosing and treating heart conditions (e.g., heart failure) and kidney conditions (e.g., kidney failure) are described.

Abstract: This disclosure relates to a method of generating conditionally active biologic proteins from wild type proteins, in particular therapeutic proteins, which are reversibly or irreversibly inactivated at the wild type normal physiological conditions. For example, evolved proteins are virtually inactive at body temperature, but are active at lower temperatures.

Abstract: Described are methods for diagnosing and predicting the risk of pregnancy loss in a subject based on the presence of an aberrant humoral response to three proteins, Apolipoprotein B-100, alpha2macrogloblin (alpha2M), and fibronectin. The presence or a detectable level of maternal IgG antibodies to trophoblast-derived fibronectin and/or ApoB-100, and/or the absence or a non-detectable level of antibodies specifically binding to alpha2M is associated with a history of RPL and an increased risk of pregnancy loss. Also described are methods for identifying subjects at risk of pregnancy loss, selecting subjects for participation in a clinical study, and methods of decreasing the risk of pregnancy loss in a subject which include detecting the presence or absence of antibodies to one or more of trophoblast-derived ApoB-100, alpha2M, and fibronectin. Also provided are kits that contain ApoB-100, alpha2M, and fibronectin.

Abstract: The invention features methods of diagnosing a subject as having, or at risk of developing ALS by determining the frequency of Gems in cells obtained from the subject. These methods include diagnosing the severity or monitoring the progression of ALS by determining the Gem frequency in a subject. Also, the invention features methods of identifying compounds useful for the treatment of ALS as well as methods for the treatment of ALS.

Abstract: Provided herein are methods for prophylactic treatment of renal disorders comprising administration of adrenocorticotropic hormone (ACTH), or fragment, analog, complex or aggregate thereof, or any combination thereof, to an individual suspected of having, predisposed to, or at risk of developing a renal disorder

Abstract: Methods are provided herein for enhancing the effectiveness of medical therapies by administering agents that suppress a biological damage response that is inducible by the medical therapy administered to a subject. In certain embodiments, a method is provided for administering an anti-senescent cell agent that suppresses a biological response comprising cellular senescence that is induced by the medical therapy.

Abstract: The present disclosure relates to the use of angiotensin II in therapeutic methods for the treatment of renal failure, especially renal failure associated with cirrhosis.

Abstract: The present invention relates to novel analogs of PYY that have an improved therapeutic profile when compared to native human PYY. These novel PYY analogs are useful in the treatment of obesity, diabetes, and other disorders.

Abstract: Disclosed herein is a novel hemostatic patch that may be used to control and/or arrest bleeding in patients. The patch offers an effective but also minimally invasive way to control and/or arrest bleeding in a patient. The patch comprises a mucoadhesive and a compound that causes vasoconstriction. In a preferred aspect, the patch comprises chitosan and Neuropeptide Y. Also disclosed are methods of using the novel hemostatic patch.

Abstract: Disclosed are embryonic stem cells and motor neurons derived from mice carrying transgenic alleles of the normal or mutant human SOD1 gene. Also disclosed are in vitro systems employing such SOD1 transgenic motor neurons for the study of neural degenerative disease.

Abstract: The present invention provides new uroguanylin derivatives that are useful for the treatment of gastrointestinal disorders. The present invention also provides compositions and methods of treating gastrointestinal disorders and pharmaceutical compositions for accomplishing the same. In some embodiments, these pharmaceutical compositions include oral dosage forms.

Abstract: The present invention provides a method of ameliorating inflammation, inhibiting proinflammatory cytokine and/or chemokine expression and treating various diseases and/or conditions incidental to the onset of inflammation, in a subject in need of treatment for such conditions, by administering select analogous of native hGhrelin.

Abstract: A method of treating a disease or condition in which up-regulating GAGs is therapeutically beneficial is disclosed. The method comprises locally administering to a subject a therapeutically effective amount of an agent capable of down-regulating activity or expression of a component of the renin-angiotensin system.

Abstract: The present invention relates to fibronectin-based scaffold domain proteins that bind to myostatin. The invention also relates to the use of these proteins in therapeutic applications to treat muscular dystrophy, cachexia, sarcopenia, osteoarthritis, osteoporosis, diabetes, obesity, COPD, chronic kidney disease, heart failure, myocardial infarction, and fibrosis. The invention further relates to cells comprising such proteins, polynucleotides encoding such proteins or fragments thereof, and to vectors comprising the polynucleotides encoding the proteins.

Abstract: Work described herein provides, in one embodiment, a method for increasing proliferation or replication of pancreatic beta cells in a subject in need thereof, comprising administering to said subject an effective amount of an agent that increases the level or activity of hepatocellular carcinoma-associated protein TD26 (TD26), thereby increasing proliferation or replication of pancreatic beta cells. Such an agent may function by, for example, increasing the level of active TD26 in the subject or by increasing the functional activity of TD26 in the subject.

Abstract: In the past decade a great deal of structural information for class A-GPCRs (G protein-coupled receptors) has emerged. However, the structural and electronic basis of ligand selectivity for closely related receptor subtypes such as the angiotensin receptors AT1aR and AT2R, which present completely diverse biological functions in response to the same ligand, is poorly understood. In order to monitor complex responses in biosystems it is useful to have ligands that present a gradient in terms of selectivity. In this study we present an efficient method to tune ligand selectivity for the two angiotensin II receptor subtypes, AT1aR and AT2R, by controlling aromatic-prolyl interactions in angiotensin II, through alternation of aromatic electronics. On the basis of this strategy, an AT2R selective and high affinity agonist analogue (Ki=3 nM) was obtained.

Abstract: According to this invention, compositions and methods for increasing the extent of penetration of a biologically active substance into the tissues and organs are proposed, the methods comprising administration of the biologically active substance in combination with one or more chaotropic agents, e.g., ammonium sulfate.

Abstract: Disclosed is the use of angiotensin-(1-7) peptide as an anti-cancer and chemoprevention therapeutic. Embodiments of the present invention comprise methods and compositions to prevent cancer or to reduce the risk of cancer in an individual comprising administering to the individual a pharmaceutically effective amount of an agonist for the angiotensin-(1-7) receptor to inhibit at least one of formation of a tumor (tumorigenesis), the proliferation of tumor cells, the growth of tumor cells, or metastasis of tumor cells in the individual. Cancers treated using the methods and compositions described herein may include cancers having an angiotensin-(1-7) receptor, including, but not limited to, breast cancer, colon cancer, glioblastoma, and lung cancer.

Abstract: The invention provides pharmaceutical compositions, methods for the treatment of and related diagnostics and computer-implementable systems that relate to, the treatment of a variety of metabolic syndromes, including hyperlipidemia, weight gain, obesity, insulin resistance, hypertension, atherosclerosis, fatty liver diseases and certain chronic inflammatory states. In an additional aspect of the invention, compositions and methods of treatment are calibrated to the ileal brake response to surgical intervention e.g. RYGB, as both activate the ileal brake, which acts in the gastrointestinal tract and the liver of a mammal to control metabolic syndrome manifestations and thereby reverse or ameliorate the cardiovascular damage (atherosclerosis, hypertension, lipid accumulation, and the like) resulting from progression of metabolic syndrome.

Abstract: Provided herein are methods of treatment of migraine headaches comprising administration of adrenocorticotropic hormone (ACTH), or fragment, analog, complex or aggregate thereof, or any combination thereof, to an individual in need thereof.

Abstract: This invention is related to bone fillers, hard tissue supporting films and three dimensional scaffolds that contains composite particle of inorganic compound/water soluble polymer (such as ?-TCP/Gelatin), that can lead to bone regeneration and release an antibacterial or bioactive agent at the defect area. The bone regenerative hard tissue supporting films and scaffolds were obtained by addition of antibacterial or bioactive agent loaded composite particles into biodegrable polymer (such as PCL) matrix.

Abstract: The present invention encompasses methods, compositions, and devices for treating an ocular disease, disorder or condition in a mammal. The invention includes polypeptides that possess anti-inflammatory, anti-apoptotic, immune modulatory and anti-tumorigenic properties, and their application in the treatment of eye disease, particularly diseases of the retina. In particular aspects, the invention includes administration of a therapeutic polypeptide such as a stanniocalcin family member protein for the treatment of an eye disease. Also included are fusion proteins and cells stimulated or modified to express the therapeutic polypeptides as set forth herein.

Abstract: The present invention relates to muscle repair promoters for local application that contain a colony-stimulating factor (CSF) as an active ingredient. The muscle repair promoters of the present invention exhibit their effect at low doses, particularly when they are administered intramuscularly.

Abstract: Method for preparing an oxidized polysaccharide-protein composition, by (a) oxidizing a polysaccharide with an oxidizing agent to form an oxidized polysaccharide where less than 20% of the oxidized units are comprised of alpha-hydroxy aldehyde units, (b) reacting the oxidized polysaccharide with a protein to form a composition comprising an oxidized polysaccharide-protein conjugate, and (c) maintaining the oxidized polysaccharide-protein conjugate composition by placing it in an environment where the temperature is less than 8° C. The oxidized polysaccharide and the protein are conjugated via one or more imine bonds, the oxidized polysaccharide-protein composition is soluble in aqueous solvent, and the composition is capable of releasing the protein.

Abstract: The present invention generally relates to compositions and methods for transdermal delivery, treatment of skin, and improving the appearance of skin. In some cases, the composition may include nitric oxide and/or peptides. The nitric oxide and/or peptide may be present within a first phase comprising a lecithin, such as phosphatidylcholine. In certain embodiments, the lecithin is present in liposomes, micelles, or other vesicles containing nitric oxide, peptides, or both. The composition can take the form of a gel, a cream, a lotion, an ointment, a solution, a solid “stick,” etc., that can be rubbed or sprayed onto the skin. Other aspects of the present invention are generally directed to methods of making or using such compositions, methods of promoting such compositions, kits including such compositions, or the like.