Abstract: Methods and compositions are provided for treating a mammal having inflammation by protecting or enhancing a responsive cell, tissue, organ or body part exhibiting or associated with the inflammation, by systemic or local administration of a composition comprising a tissue protective cytokine. The invention also encompasses combination treatments comprising administering a composition comprising a tissue protective cytokine of the invention and administering at least one anti-inflammatory or least one immunomodulatory agent.

Abstract: The present invention refers to a system for inducing an immune response against transformed, infected, or diseased tissue comprising a device for removing only components present in blood or plasma having a molecular weight of 120,000 daltons or less, having an inlet and outlet for connection to a pump and tubing to recirculate the blood or plasma of a patient through the device. Further, the present invention refers to methods of inducing an immune response against transformed, infected, or diseased tissue comprising administering to a patient blood, plasma, or a blood fraction from which only components having a molecular weight of 120,000 daltons or less have been removed, whereby administration of said blood, plasma, or blood fraction induces an immune response against transformed, infected, or diseased tissue in the patient until the transformed, infected, or diseased tissue is reduced in amount.

Abstract: In certain aspects, the present invention provides compositions and methods for increasing red blood cell and/or hemoglobin levels in vertebrates, including rodents and primates, and particularly in humans.

Abstract: A method for delivering a biologic to a human, comprising administering said biologic parenterally into the perispina! space of said human without direct intrathecal injection and positioning said human in a Trendelenburg position.

Abstract: There is disclosed a molecular composition(s) of a novel tissue protective erythropoietin (EPO) binding receptor protein complex, termed NEPOR. Presence of NEPOR components on a tumor allows EPO to impinge on the survival of associated cells thereby enhancing tumor progression and negatively effecting patient survival. Presence of NEPOR represents a prognostic biomarker for poorer patient outcome. Thus, methods are provided for stratifying patients having a tumor as suitable (i.e. NEPOR not present) or non-suitable (i.e., NEPOR present) for EPO treatment, comprising: (a) isolating a tissue sample from an individual who is receiving or is a candidate for receiving erythropoietin, (b) determining the level of expression of the NEPOR gene(s) (mRNA) and/or the presence of the NEPOR gene product (protein) from the isolated tissue, and (c) correlating the presence of an NEPOR gene expression product or the presence of NEPOR protein to a physiological response to the treatment with erythropoietin.

Abstract: Modified animal erythropoietin polypeptides and uses thereof are provide.

Abstract: This invention relates to a combination of erythropoietin glycoisoforms, wherein such glycoisoforms may include a quantity of sialic acid ranging from 4 to 10 molecules of sialic acid per molecule of erythropoietin. The combination of glycoisoforms can be used for the treatment or prevention of sepsis, and used to prepare a pharmaceutical composition including such combination. The invention also encompasses a cell line producing a combination of erythropoietin glycoisoforms, procedures to obtain the cell line, a procedure to produce such a combination of glycoisoforms, and methods of treatment and prevention of sepsis.

Abstract: Described herein is a cell tissue gel cross-linked with a cross-linking agent, and a quenching agent bound to a reactive group of the cross-linking agent.

Abstract: Disclosed is a preparation for transnasal application, which has improved fluidability. Specifically disclosed is a preparation for transnasal application, which comprises at least a complex comprising: a fluidability-improving component comprising a first crystalline cellulose (A) having specified powder properties, tricalcium phosphate (B) having specified powder properties, and a second crystalline cellulose (C) having specified powder properties or a starch (D) having specified powder properties; and a physiologically active substance.

Abstract: The present invention refers to an angiogenesis-inducing protein, a composition containing it and the uses of said protein.

Abstract: Methods for increasing and maintaining hematocrit in a mammal comprising administering a hyperglycosylated analog of erythropoietin are disclosed. An analog may be administered less frequently than an equivalent molar amount of recombinant human erythropoietin to obtain a comparable target hematocrit and treat anemia. Alternatively, a lower molar amount of a hyperglycosylated analog may be administered to obtain a comparable target hematocrit and treat anemia. Also disclosed are new hyperglycosylated erythopoietin analogs, methods of production of the analogs, and compositions comprising the analogs.

Abstract: The present invention relates to peptide compounds that are agonists of the erythropoietin receptor (EPO-R). The invention also relates to therapeutic methods using such peptide compounds to treat disorders associated with insufficient or defective red blood cell production. Pharmaceutical compositions, which comprise the peptide compounds of the invention, and dosages are also provided.

Abstract: The invention relates to a human or veterinary pharmaceutical composition (B) for the stimulation of stem cells, comprising at least two stem-cells-stimulating-agents and at least one pharmaceutically acceptable excipient.

Abstract: The disclosure relates to treating muscle wasting-associated disorders in a patient, using a therapeutically effective amount of an antagonist of Fbxo40, wherein the antagonist reduces the expression, level or activity of Fbxo40. The Fbxo40 antagonist increases muscle mass, or prevents, limits or reduces muscle mass loss, in the patient. The Fbxo40 antagonist can be a low molecular weight (LMW) compound, a protein, an antibody, or an inhibitory nucleic acid, such as a siRNA. The disclosure also relates to methods of screening for antagonists of Fbxo40, and methods of diagnosing or monitoring levels of muscle mass maintenance, loss or increase.

Abstract: The invention provides a pharmaceutical composition comprising a mixture of: (a) an active macromolecular principle; and (b) a non-conjugated bile acid or salt; and (c) an additive chosen from propyl gallate, butyl hydroxy anisole (BHA) and analogues and derivatives thereof, or mixtures thereof.

Abstract: A method of stabilizing an aqueous protein or antibody formulation is disclosed herein. Additionally, stable pharmaceutical formulations are contemplated which comprise a biologically active protein, a destabilizing concentration of preservative and a stabilizing concentration of osmolyte.

Abstract: The present invention relates to a compound which is a polysaccharide derivative of EPO, or of an EPO like protein, wherein the polysaccharide is anionic and comprises between 2 and 200 saccharide units. The present invention also relates to pharmaceutical compositions comprising the novel compounds, and methods for making the novel compounds.

Abstract: Effective dosing regimens for neural stem cell proliferating and differentiating agents, kits comprising effective dosing regimens for neural stem cell proliferating and differentiating agents, and uses thereof are provided herein. Such kits and methods can be utilized acutely or chronically to treat a neurodegenerative disease or condition. Furthermore, the compositions and methods can be used continuously or intermittently in various dosing regimens.

Abstract: The invention generally relates to compositions and methods of their use. More specifically, the invention relates to the use of a compound in modulating erythropoiesis in a subject by mediating the activity and/or quantity of a member present in the LPA3-mediated signaling pathway, such as lysophosphatidic acid receptor subtype 3 (LPA3).

Abstract: The present application refers to cells, e.g. mesenchymal stem cells or mesenchymal stromal cells, or any further suitable cell, encoding and secreting a neuroprotective factor, an anti-angiogenic factor and/or any other protein or protein-like substance suitable for (intraocular) treatment of eye diseases. Such eye diseases include glaucoma and other optic nerve disorders, retinal diseases, particularly retinitis pigmentosa (RP), age-related macular degeneration (AMD) and diabetic retinopathy, etc. The cells used herein are encapsulated in a (spherical) microcapsule, preferably comprising a core and at least one surface layer, to prevent a response of the immune system of the patient to be treated. The present application also refers to the use of these (spherical) microcapsule(s) or such factors for (intraocular) treatment of eye diseases as defined herein (for the preparation of a (pharmaceutical) composition) for the treatment of such eye diseases.

Abstract: A procedure for the production of erythropoietin (EPO), in particular recombinant human EPO (rhEPO) with a defined composition of glycoforms in a highly pure form, i.e., with a high amount of O-glycosylated EPO isoforms is provided.

Abstract: Modified erythropoietin (EPO) polypeptides and other modified therapeutic polypeptides are provided. The EPO polypeptides and other therapeutic polypeptides are modified to exhibit physical properties and activities that differ from the unmodified EPO polypeptides and other unmodified therapeutic polypeptides, respectively. Nucleic acid molecules encoding these polypeptides also are provided. Also provided are methods of treatment and diagnosis using the polypeptides.

Abstract: An object of the invention is to provide a pharmaceutical composition that contains erythropoietin as the active ingredient and has, when administered in humans and/or animals, a hematopoietic effect that lasts for not less than seven days. The invention provides a pharmaceutical composition containing, in an amount equal to not less than 50% of the total erythropoietin, erythropoietin to which two or more water-soluble long-chain molecules are added. The invention also provides a pharmaceutical composition containing erythropoietin to which a water-soluble long-chain molecule is added, wherein the water-soluble long-chain molecule has a molecular weight of not less than 30 kDa. The invention further provides a pharmaceutical composition containing erythropoietin to which a water-soluble long-chain molecule is added, wherein the water-soluble long-chain molecule has a branched chain.

Abstract: The invention discloses particulate complexes composed of chitosan, poly-glutamic acid, and at least one bioactive agent, wherein equal moles of the positively charged chitosan and the negatively charged poly-glutamic acid substrate form an electrostatic network enabling improved loading the bioactive agent.

Abstract: The present invention concerns methods and compositions for forming cytokine-antibody complexes using dock-and-lock technology. In preferred embodiments, the cytokine-MAb DNL complex comprises an IgG antibody attached to two AD (anchor domain) moieties and four cytokines, each attached to a DDD (docking and dimerization domain) moiety. The DDD moieties form dimers that bind to the AD moieties, resulting in a 2:1 ratio of DDD to AD. The cytokine-MAb complex exhibits improved pharmacokinetics, with a significantly longer serum half-life than either naked cytokine or PEGylated cytokine. The cytokine-MAb complex also exhibits significantly improved in vitro and in vivo efficacy compared to cytokine alone, antibody alone, unconjugated cytokine plus antibody or cytokine-MAb DNL complexes incorporating an irrelevant antibody.

Abstract: The present invention concerns methods and compositions for forming PEGylated complexes of defined stoichiometry and structure. In preferred embodiments, the PEGylated complex is formed using dock-and-lock technology, by attaching a target agent to a DDD sequence and attaching a PEG moiety to an AD sequence and allowing the DDD sequence to bind to the AD sequence in a 2:1 stoichiometry, to form PEGylated complexes with two target agents and one PEG moiety. In alternative embodiments, the target agent may be attached to the AD sequence and the PEG to the DDD sequence to form PEGylated complexes with two PEG moieties and one target agent. In more preferred embodiments, the target agent may comprise any peptide or protein of physiologic or therapeutic activity. The PEGylated complexes exhibit a significantly slower rate of clearance when injected into a subject and are of use for treatment of a wide variety of diseases.

Abstract: The present invention provides a method of increasing neural stem cell numbers or neurogenesis by using a pheromone, a luteinizing hormone (LH) and/or a human chorionic gonadotrophin (hCG). The method can be practiced in vivo to obtain more neural stem cells in situ, which can in turn produce more neurons or glial cells to compensate for lost or dysfunctional neural cells. The method can also be practiced in vitro to produce a large number of neural stem cells in culture. The cultured stem cells can be used, for example, for transplantation treatment of patients or animals suffering from or suspected of having neurodegenerative diseases or conditions.

Abstract: There is disclosed a molecular composition(s) of a novel tissue protective erythropoietin (EPO) binding receptor protein complex, termed NEPOR. Presence of NEPOR components on a tumour allows EPO to impinge on the survival of associated cells thereby enhancing tumour progression and negatively effecting patient survival. Presence of NEPOR represents a prognostic biomarker for poorer patient outcome. Thus, methods are provided for stratifying patients having a tumour as suitable (i.e. NEPOR not present) or non-suitable (i.e., NEPOR present) for EPO treatment, comprising: (a) isolating a tissue sample from an individual who is receiving or is a candidate for receiving erythropoietin, (b) determining the level of expression of the NEPOR gene(s) (mRNA) and/or the presence of the NEPOR gene product (protein) from the isolated tissue, and (c) correlating the presence of an NEPOR gene expression product or the presence of NEPOR protein to a physiological response to the treatment with erythropoietin.

Abstract: This invention relates to a conjugate of a polymer moiety and an interferon-? moiety, an erythropoietin moiety, or a growth hormone moiety.

Abstract: A method for recognizing and evaluating the presence and function of GnRH receptors on tumor cells including those originating in the brain and/or nervous system and/or the meninges and/or reactive neuroglia cells and/or primitive neuroectodermal tumor cells and/or on Kaposi sarcoma is provided. Furthermore, a method for reducing degenerate GnRH-positive tumor cells and/or for decreasing cellular replication of the above GnRH-positive tumor cells comprising administering to a cell or to a subject a replication decreasing amount of a GnRH agonist and/or GnRH antagonist and/or an erythropoietin agonist, and/or a thrombopoietin agonist, and/or a endothelin antagonist and/or a gonadotropin inhibiting hormone agonist is also provided. Furthermore, a diagnostic kit for detecting GnRH receptors on tumor cells according to the present methods is disclosed.

Abstract: The present invention provides methods of forming a solid, biodegradable implant in-situ in a body by administering a liquid pharmaceutical composition comprising an effective amount of a biocompatible, water-insoluble, biodegradable polymer and an effective amount of a therapeutic peptide covalently modified with one or more lipophilic or amphiphilic moieties, which are dissolved or dispersed in a biocompatible, water-soluble organic solvent. This invention also provides related compositions and methods.

Abstract: Compositions and methods for treating type 2 diabetes and its sequelae by intravenous or subcutaneous administration of formulations of synthesized curcumin (diferuloylmethane) and concomitantly one or more anti-diabetic agents to human subjects are disclosed herein. The composition of the present invention may be used to: (i) treat patients with diabetes in advanced stages with evidence of any or all encephalopathy, retinopathy, nephropathy, pancreatitis or neoplasias; (ii) treat patients with diabetic disease status without symptomatic or pathologic evidence of associated sequelae but requiring better glycemic control than that offered by standard of care anti-diabetic; and (iii) patients with objective signs or symptoms of sequelae from diabetes of anti-diabetic drugs. One three-drug combination of the present invention includes a slow release PLGA-curcumin and an oral gliptin (DPP-4)-inhibitor or any incretin-mimetic and metformin.

Abstract: Methods for producing proteins and glycoproteins in Pichia pastoris that lack detectable cross binding activity to antibodies made against host cell antigens are described. In particular, methods are described wherein recombinant Pichia pastoris strains that do not display a ?-mannosyltransferase 2 activity with respect to an N-glycan or O-glycan and do not display at least one activity selected from a ?-mannosyltransferase 1, 3, and 4 activity to produce recombinant proteins and glycoproteins. These recombinant Pichia pastoris strains can produce proteins and glycoproteins that lack detectable ?-mannosidase resistant ?-mannose residues thereon and thus, lack cross binding activity to antibodies against host cell antigens. Further described are methods for producing bi-sialylated human erythropoietin in Pichia pastoris that lack detectable cross binding activity to antibodies against host cell antigens.

Abstract: The present invention relates to a method of treating a neurological condition in a mammal by administering at least one hematopoietic growth factor.

Abstract: The present invention relates to compositions and methods for the preparation, stabilization, and/or storage of active agents, particularly therapeutic proteins and polypeptides such as Interleukin-2.

Abstract: The present invention provides unstructured recombinant polymers (URPs) and proteins containing one or more of the URPs. The present invention also provides microproteins, toxins and other related proteinaceous entities, as well as genetic packages displaying these entities. The present invention also provides recombinant polypeptides including vectors encoding the subject proteinaceous entities, as well as host cells comprising the vectors. The subject compositions have a variety of utilities including a range of pharmaceutical applications.

Abstract: The present invention provides compositions comprising isolated human collagen, isolated human elastin and a pharmaceutically acceptable carrier wherein the human elastin is substantially insoluble in water with a molecular weight greater than 100 kDa. The present invention further provides methods and kits for soft tissue augmentation.

Abstract: Modified erythropoietin (EPO) polypeptides and other modified therapeutic polypeptides are provided. The EPO polypeptides and other therapeutic polypeptides are modified to exhibit physical properties and activities that differ from the unmodified EPO polypeptides and other unmodified therapeutic polypeptides, respectively. Nucleic acid molecules encoding these polypeptides also are provided. Also provided are methods of treatment and diagnosis using the polypeptides.

Abstract: Organic compounds showing the ability to inhibit viral glycoprotein (GP)-mediated entry of a filovirus into a host cell are disclosed. The disclosed filovirus entry inhibitor compounds are useful for treating, preventing, or reducing the spread of infections by filovirus including the type species Marburg virus (MARV) and Ebola virus (EBOV). Preferred inhibitors of the invention provide therapeutic agents for combating the Ivory Coast, Sudan, Zaire, Bundibugyo, and Reston Ebola virus strains.

Abstract: An improved thrombopoietin mimetic, the bis-(monoethanolamine) salt of 3?-[(2Z)-[1-(3,4-dimethylphenyl)-1,5-dihydro-3-methyl-5-oxo-4H-pyrazol-4-ylidene]hydrazino]-2?-hydroxy-[1,1?-biphenyl]-3-carboxylic acid.

Abstract: Injectable depot gel compositions and kits that provide an excipient for modulating a release rate and stabilizing beneficial agents are provided. Methods of administering and preparing such systems are also provided. The gel compositions comprise biodegradable, bioerodible polymers and water-immiscible solvents in amounts effective to plasticize the polymers and form gels with the polymers. Suitable excipients include pH modifiers, reducing agents, and antioxidants.

Abstract: A pharmaceutical composition comprising a mixture of: (c) an active macromolecular principle; (d) an aromatic alcohol absorption enhancer chosen from propyl gallate, butylated hydroxy toluene (BHT), butylated hydroxy anisole (BHA) and analogues and derivatives thereof, or mixtures thereof; and (d) a biguanide or a pharmaceutically acceptable salt thereof, capable of increasing the solubility of the aromatic alcohol absorption enhancer in an aqueous medium, wherein the aromatic alcohol absorption enhancer is present in an amount by weight greater than or equal to that of the active principle.

Abstract: The present invention provides a method of increasing neural stem cell numbers or neurogenesis by using a pheromone, a luteinizing hormone (LH) and/or a human chorionic gonadotrophin (hCG). The method can be practiced in vivo to obtain more neural stem cells in situ, which can in turn produce more neurons or glial cells to compensate for lost or dysfunctional neural cells. The method can also be practiced in vitro to produce a large number of neural stem cells in culture. The cultured stem cells can be used, for example, for transplantation treatment of patients or animals suffering from or suspected of having neurodegenerative diseases or conditions.

Abstract: In the present invention a method for purifying erythropoietin comprising at least one chromatography step using a stationary phase containing hydroxyapatite is reported. The method comprises the following steps i) the erythropoietin in a solution containing Calcium-ions is brought into contact with a stationary phase containing hydroxyapatite equilibrated with a solution containing Calcium-ions and namely under conditions under which the erythropoietin binds to the stationary phase containing hydroxyapatite, ii) a solution is passed over the stationary phase containing hydroxyapatite from i) which contains less Calcium-ions than the previous solution and the erythropoietin is not detached from stationary phase containing hydroxyapatite, and iii) a further solution which contains less than 0.5 mM Calcium-ions is passed over the stationary phase containing hydroxyapatite from ii) whereby the erythropoietin is detached from the stationary phase containing hydroxyapatite.

Abstract: Method for treatment and/or prophylaxis of schizophrenia and related psychoses of a human being, erythropoietin being administered to the human being.

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 relates to the use of inclusion bodies as vehicles for therapeutic protein delivery. This method is applicable to the delivery of therapeutic proteins to intracellular locations. In addition, the invention also relates to the administration of a cell or a pharmaceutical composition comprising inclusion bodies formed by therapeutic proteins. These inclusion bodies formed by therapeutic proteins could be used for the treatment of different diseases.

Abstract: The teachings provided herein generally relate to the preparation and uses of compositions comprising extracts of Astragalus membranaceus. The extracts are prepared from Astragalus membranaceus and can comprise, for example, an acid-modified arabinogalactan protein composition having an arabinose:galactose ratio ranging from about 3.5:1 to about 5.0:1, from about 5% to about 10% rhamnose, from about 15% to about 20% galactose, and from about 10% to about 15% glucose. The compositions can be used in the treatment of idiopathic thrombocytopenic purpura and the formulation of medicaments for such treatments.

Abstract: The present invention discloses the signaling pathway involved in erythroid repression by iron deficiency. Further disclosed is a non-toxic small-molecule compound which potently reverses the erythroid repression caused by iron deficiency. The present invention further encompasses novel compounds for inhibition of red cell production, useful, for example, in the treatment of polycythemia vera, a malignancy causing uncontrolled red cell production. These inhibitory compounds also promote megakaryocytic lineage commitment and may therefore be useful for augmentation of platelet production. The present invention further discloses isocitrate reversal of iron deprivation.

Abstract: Methods and compositions are provided for protecting or enhancing a responsive cell, tissue, organ or body part function or viability in vivo, in situ or ex vivo in mammals, including human beings, by systemic or local administration of a tissue protective cytokine.