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. In more preferred embodiment the cytokine is G-CSF, erythropoietin or INF-?2b.

Abstract: Methods and compositions are provided for protecting or enhancing an erythropoietin-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 an erythropoietin receptor activity modulator, such as an erythropoietin or a modified erythropoietin.

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 polyethylene glycol-conjugated erythropoietin (PEG-conjugated EPO) prepared by PEG conjugation on the lysine residue at position 52 of native erythropoietin (native EPO). In order to achieve more sustained efficacy without losing physiological activities of native EPO, a glycoprotein rich in sugar chains, there has been a need to develop a PEG-conjugated EPO with significantly sustained efficacy by introducing a controlled number of PEG molecules at controlled positions. This PEG-conjugated EPO addresses such a need and provides more sustained efficacy.

Abstract: A polymeric prodrug composition including a hydrogel, a biologically active moiety and a reversible prodrug linker. The prodrug linker covalently links the hydrogel and the biologically active moiety at a position and the hydrogel has a plurality of pores with openings on its surface. The diameter of the pores is larger than that of the biologically active moiety at least at all points of the pore between at least one of the openings and the position of the biologically active moiety.

Abstract: Disclosed is a temperature- and pH-sensitive hydrogel composed of a poly(amidoamine) oligomer only. The hydrogel is prepared in a simple manner and is readily released from the body. Further disclosed are a method for preparing the hydrogel and a drug carrier using the hydrogel.

Abstract: Invented are non-peptide TPO mimetics. Also invented are novel processes and intermediates used in the preparation of the presently invented compounds. Also invented is a method of treating thrombocytopenia, in a mammal, including a human, in need thereof which comprises administering to such mammal an effective amount of a selected hydroxy-1-azobenzene derivative.

Abstract: A liquid composition in an osmotic drug delivery system and a dosage form in an osmotic drug delivery system is disclosed comprising an amphiphilic molecule, a non-aqueous liquid solvent, and a pharmaceutically active agent.

Abstract: Described are methods of modulating stem/progenitor cell recruitment involving molecules that agonize the formation of plasmin stimulating the recruitment of stem/progenitor cells, including hematopoietic and endothelial precursor cells. Conversely, antagonists of plasmin can inhibit recruitment of the stem cells. In addition, the identification of the uPA receptor (uPAR) as a retention signal for stem cells in their niche suggests a novel method for increased engraftment and isolation of multipotent stem cells.

Abstract: The present invention concerns methods and compositions for making and using bioactive assemblies of defined compositions, which may have multiple functionalities and/or binding specificities. In particular embodiments, the bioactive assembly is formed using dock-and-lock (DNL) methodology, which takes advantage of the specific binding interaction between dimerization and docking domains (DDD) and anchoring domains (AD) to form the assembly. In various embodiments, one or more effectors may be attached to a DDD or AD sequence. Complementary AD or DDD sequences may be attached to an adaptor module that forms the core of the bioactive assembly, allowing formation of the assembly through the specific DDD/AD binding interactions. Such assemblies may be attached to a wide variety of effector moieties for treatment, detection and/or diagnosis of a disease, pathogen infection or other medical or veterinary condition.

Abstract: Cosmetic and therapeutic compositions for skin care, containing a transgenic plant extract containing a growth factor, or a growth factor purified from transgenic plants, or a mixture of growth factors derived from transgenic plants as extracts or in purified form, for use in topical therapeutic and/or cosmetic applications. Importantly, this invention makes safer growth factors available for use for cosmetic and topical treatment. These growth factors do not carry the risk of unwanted contaminants and transmissible agents that can result from animals or animal cell based expression systems, and the recombinant growth factors that plant expression systems provide are post-translationally modified proteins.

Abstract: A liquid composition in an osmotic drug delivery system and a dosage form in an osmotic drug delivery system is disclosed comprising an amphiphilic molecule, a non-aqueous liquid solvent, and a pharmaceutically active agent.

Abstract: Anti-TNF antibodies, fragments and regions thereof which are specific for human tumor necrosis factor-? (TNF?) and are useful in vivo diagnosis and therapy of a number of TNF?-mediated pathologies and conditions, including ankylosing spondylitis, as well as polynucleotides coding for murine and chimeric antibodies, methods of producing the antibody, methods of use of the anti-TNF antibody, or fragment, region or derivative thereof, in immunoassays and immunotherapeutic approaches are provided.

Abstract: A method of reducing organ toxicity in a subject being administered a cytotoxic agent comprising concurrently administering with the cytotoxic agent erythropoietin (EPO), the EPO being administered in an amount effective to reduce pulmonary toxicity caused by the cytotoxic agent.

Abstract: The present invention relates to the use of Stem Cell Factor in the protection of multiprogenitor cells and in the prevention of chemotherapy-induced depletion of blood cells.

Abstract: A pharmaceutical dosage form comprises a solid dispersion product of at least one active ingredient dispersed in a polymeric binder composition, the polymeric carrier composition comprising a) a vinylpyrrolidone homopolymer, wherein at least 95% by weight of the vinylpyrrolidone homopolymer has a molecular weight distribution within the range of from 1000 to 13 000; and b) a vinylpyrrolidone copolymer having a weight-average molecular weight of from 5000 to 1 500 000. The dosage form is preferably prepared by a melt extrusion process. The polymeric carrier composition exhibits a high drug dissolution power and allows a reduction of the viscosity of the melt without deteriorating the mechanical properties and storage stability of the dosage form.

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: The invention relates to the use of haematopoietic growth factors, in particular erythropoietin (EPO) and thrombopoietin (TPO), or derivatives analogues or parts thereof, for promoting structural tissue regeneration.

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 erythropoietin analogs, methods of production of the analogs, and compositions comprising the analogs.

Abstract: The presently disclosed subject matter provides methods of diagnosing retinal disorders in subjects by measuring hemoglobin and modified hemoglobin in the subjects. The presently disclosed subject matter further provides methods of treating retinal disorders in subjects by decreasing hypoxia in retinal tissue of the subjects through modulation of hemoglobin levels and activities in the retinal tissue.

Abstract: The invention relates to covalent conjugates between endoperoxides and small peptides and organic compounds that bind to molecular cavities on the transferrin or lactoferrin receptor, and the use of compositions comprising these conjugates to treat cancer, hyperproliferative disorders, inflammatory diseases, and infections.

Abstract: The subject invention concerns materials and methods for treating a person or animal having cognitive impairment. In one embodiment, the method comprises administering an effective amount of one or more inflammatory mediator(s), for example, fms-related tyrosine kinase 3 (Flt3) ligand, interleukin-6 (IL-6), macrophage migration inhibitory factor (MIF), interleukin-1 (IL-1), interleukin-3 (IL-3), erythropoietin (EPO), vascular endothelial growth factor A (VEGF-A), hypoxia-inducible transcription factor (HIF-1alpha), insulin like growth factor-1 (IGF-1), tumor necrosis factor (TNF), granulocyte colony-stimulating factor (G-CSF), granulocyte/macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), Stem Cell Factor (SCF), Darbepoetin (ARANESP), and metalloproteinases, to an animal or person in need of treatment.

Abstract: This invention provides compositions comprising a protein, an absorption enhancer, a protease inhibitor, methods for treating diabetes mellitus, comprising administering same, and methods for oral administration of a protein with an enzymatic activity, comprising orally administering same.

Abstract: This disclosure provides peptides, polypeptides, fusion polypeptides, compositions, and methods for enhancing or increasing the stability of a polypeptide (e.g., Taq polymerase). Such peptides, polypeptides, fusion polypeptides, or compositions include polypeptides linked to a peptide tag that enhances the stability of the polypeptide. The peptides, polypeptides, fusion polypeptides, compositions may also enhance the activity, specificity, and/or fidelity of other polypeptides in a reaction mixture. The disclosure also provides methods of using such peptides, polypeptides, fusion polypeptides, compositions.

Abstract: The invention provides a pharmaceutical composition for oral drug delivery comprising a solid dosage form containing an effective amount of a therapeutic agent, a permeation enhancer and a pharmaceutically acceptable excipient and a bioadhesive layer containing a bioadhesive polymer, and optionally comprising an impermeable or semi-permeable layer having an opening capable of directing a unidirectional release of the therapeutic agent and the permeation enhancer from the solid dosage form. Methods of making and using the present pharmaceutical composition are also provided.

Abstract: Compositions and methods are provided for prophylactic or therapeutic treatment of a mammal for hearing or balance impairments involving neuronal damage, loss, or degeneration, preferably of spiral ganglion neurons, by administration of a therapeutically effective amount of one or more molecules having erythropoietin activity selected from EPO, or a biosimilar, a variant, or a mutant thereof; a protein or peptide mimetic of EPO; a small molecule mimetic of EPO and an erythropoiesis stimulating agent. Also provided are improved compositions and methods for treatments of ototoxicity requiring administration of a pharmaceutical having an ototoxic side-effect in combination with a therapeutically effective amount of a molecule having erythropoietin activity.

Abstract: A transmembrane fusion protein including ubiquitin or a ubiquitin-like protein, a membrane translocation sequence linked to the C-terminus of the ubiquitin or ubiquitin-like protein, and a biologically active molecule linked to the C-terminus of the membrane translocation sequence is disclosed herein. A polynucleotide encoding the transmembrane fusion protein, a recombinant expression vector including the polynucleotide sequence, a cell transformed by the recombinant expression vector, and a method of delivering the biologically active molecule into a cell using the transmembrane fusion protein are also disclosed.

Abstract: The present invention provides conjugates between Granulocyte Colony Stimulating Factor and PEG moieties. The conjugates are linked via an intact glycosyl linking group that is interposed between and covalently attached to the peptide and the modifying group. The conjugates are formed from both glycosylated and unglycosylated peptides by the action of a glycosyltransferase. The glycosyltransferase ligates a modified sugar moiety onto either an amino acid or glycosyl residue on the peptide. Also provided are pharmaceutical formulations including the conjugates. Methods for preparing the conjugates are also within the scope of the invention.

Abstract: The present invention provides therapeutic agents and compositions comprising elastic peptides and therapeutic proteins. Such peptides exhibit a flexible, extended conformation. In some embodiments, the therapeutic protein is a GLP-1 receptor agonist (e.g., GLP-1, exendin), insulin, or Factor VII/VIIa, including functional analogs. The present invention further provides encoding polynucleotides, as well as methods of making and using the therapeutic agents. The therapeutic agents have improvements in relation to their use as therapeutics, including, inter alia, one or more of half-life, clearance and/or persistence in the body, solubility, and bioavailability.

Abstract: A method of promoting wound healing or connective tissue reconstruction and a method of treating ischemia in a subject in need thereof are disclosed. The methods comprising topically administering to the subject about 10-30 mg per cm2 wound tissue of Erythropoietin and about 100-300 mg per cm2 wound tissue of Fibronectin, thereby promoting wound healing or connective tissue reconstruction or treating ischemia in the subject. Unit dosage forms, pharmaceutical compositions, cosmetic compositions and formulations comprising Erythropoietin and/or Fibronectin are also disclosed.

Abstract: Provided are lipidic particles comprising phosphatidylcholine, phosphatidylinositol and cholesterol. Also provided are compositions comprising the lipidic particles and having associated therewith therapeutic agents such as peptides, polypeptides or proteins. In these compositions, the therapeutic agents have reduced immunogenicity and/or longer circulating time. These compositions can be used for therapeutic administration of the peptides, polypeptides and/or proteins.

Abstract: The invention relates to the use of certain derivatives of D-mannopyranoside for controlling angiogenesis. These compounds have a pro-angiogenic activity, and can particularly be used for preparing a pharmaceutical composition for treating cardiovascular diseases or for treating muscular atrophy. The invention also relates to certain D-mannopyranoside derivatives, to a pharmaceutical or cosmetic composition containing said derivatives, and to the use of such a cosmetic composition for preventing and/or treating hair loss.

Abstract: Compositions and methods for mucosal delivery of agents are provided. The compositions are intended for administration to mucosal surface, such as oral, gastrointestinal and nasal mucosa. The compositions provided contain one or more mucoadhesive proteins and an agent to be delivered. Methods for delivery of agents using the compositions provided herein are also provided.

Abstract: The present invention relates to a method for the treatment and/or prophylaxis of multiple sclerosis, and to the use of erythropoietin for this purpose and for the manufacture of a medicament for the intermittent treatment and/or intermittent prophylaxis of multiple sclerosis.

Abstract: A system and method for producing a scaffold coated and/or impregnated with at least one bioactive agent. This is accomplished by culturing at least one cell in the same medium as a scaffold, but without physical contact between the at least one cell and the scaffold. The system includes a container having a surface defining an interior compartment. A medium is disposed within the interior compartment. At least one cell is disposed within the medium, the at least one cell being capable of producing at least one bioactive agent. Further, a scaffold is disposed within the medium. The scaffold is physically separated from the at least one cell such that there is no contact between the scaffold and the at least one cell. Thus, as the at least one cell produces at least one bioactive agent, such as a growth factor, the at least one bioactive agent enters the medium, and contacts and coats and/or impregnates the scaffold.

Abstract: Disclosed are methods, compositions of matter, and cells, useful for the treatment of autism, social integrative disorders, and various cognitive abnormalities. The invention discloses, inter alia, means of substantially ameliorating or reversing the progression of autism through the administration of autologous and/or allogeneic stem cells, alone or in combination with mobilization agents. The use of stem cells and cells naturally possessing or endowed with angiogenic and anti-inflammatory activity are disclosed for autism either alone or in combination with various therapeutic interventions.

Abstract: A method of making and using a monolithic alginate implant is described. The implant is formed by providing an uncrosslinked, highly pure and high molecular weight alginate solution and injecting the alginate solution into a patient at a predetermined site to form a gel body comprising the monolithic alginate implant. Spontaneous crosslinking of the monolithic alginate implant occurs at the predetermined site without the addition of an exogenous crosslinker. The implant may be used for treating medical conditions requiring support of sphincter musculature, reconstructive surgery, or cosmetic reconstruction, for the treatment of wrinkles on the hand, face, or décolleté, or for increasing volume, for example in the case of (HIV-induced) lipoatrophy of the breasts, and for the treatment of selected diseases, including gastrooesophageal reflux disease, urinary incontinence or vesicoureteral reflux disease.

Abstract: Disclosed herein are compositions and methods for the identification of a subject at risk for developing microvascular complications associated with diabetes such as diabetic nephropathy and diabetic retinopathy. Also disclosed is a therapeutic target for the prevention and treatment of microvascular complications associated with diabetes.

Abstract: Disclosed are fusion proteins comprising a biologically active molecule and an immunoglobulin (Ig) Fc domain which is linked to the biologically active molecule. The Fc domain is a hybrid human Fc domain of (i) IgG1, IgG2 or IgG4 or (ii) IgG4 and IgD. The hybrid Fc is useful as a carrier of biologically active molecules.

Abstract: Methods and materials are provided for the production of compositions of erythropoietin protein, wherein said compositions comprise a pre-selected N-linked glycosylation pattern as the predominant N-glycoform.

Abstract: The present invention relates to a stabilized solution comprising a hydrophobic protein, a method for the production thereof, and the stabilizing solution as a pharmaceutical, and the use thereof.

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: The invention relates to the use of haematopoietic growth factors, in particular erythropoietin (EPO) and thrombopoietin (TPO), or derivatives, analogues or parts thereof, for promoting structural tissue regeneration.

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 making and using bioactive assemblies of defined compositions, which may have multiple functionalities and/or binding specificities. In particular embodiments, the bioactive assembly is formed using dock-and-lock (DNL) methodology, which takes advantage of the specific binding interaction between dimerization and docking domains (DDD) and anchoring domains (AD) to form the assembly. In various embodiments, one or more effectors may be attached to a DDD or AD sequence. Complementary AD or DDD sequences may be attached to an adaptor module that forms the core of the bioactive assembly, allowing formation of the assembly through the specific DDD/AD binding interactions. Such assemblies may be attached to a wide variety of effector moieties for treatment, detection and/or diagnosis of a disease, pathogen infection or other medical or veterinary condition.

Abstract: The invention relates to peptides which bind to human FcRn and inhibit binding of the Fc portion of an IgG to an FcRn, thereby modulating serum IgG levels. The disclosed compositions and methods may be used for example, in treating autoimmune diseases and inflammatory disorders. The invention also relates to methods of using and methods of making the peptides of the invention.

Abstract: Catheter injectable depot compositions are provided that include a bioerodible, biocompatible polymer, a solvent having miscibility in water of less than or equal to 7 wt. % at 25° C., in an amount effective to plasticize the polymer and form a gel therewith, a thixotropic agent, and a beneficial agent. The solvent comprises an aromatic alcohol, an ester of an aromatic acid, an aromatic ketone, or mixtures thereof. The compositions are have substantially improved the shear thinning behavior and reduced injection force, rendering the compositions readily implanted beneath a patient's body surface by injection.

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: The present invention provides a method of increasing neural stem cell numbers or neurogenesis by using prolactin. 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 neurodegenerative diseases or conditions. In addition, since neural stem cells are a source for olfactory neurons, the present invention also provides methods of increasing olfactory neurons and enhancing olfactory functions.

Abstract: A sustained-release drug composition consisting essentially of microparticles of hyaluronic acid having a high molecular weight or an inorganic salt thereof and a protein or peptide drug encased in said microparticles, wherein the average size of said microparticles ranges from 0.1 to 40 ?m.