Abstract: The present invention is based upon the surprising discovery that Connective Tissue Growth Factor (CTGF) may act directly on the heart as a cardioprotective factor and provides CTGF for use in the treatment of a subject who has incurred or is incurring damage to the heart, wherein said CTGF is for administration during or after the heart-damaging event. The invention also relates to CTGF for use in protection of the heart during or after surgery or during ex vivo transportation or storage of an explanted heart.

Abstract: A polypeptide comprising a first protein domain, a second protein domain, and a dithiocyclopeptide spacer containing at least one protease cleavage site, wherein the dithiocyclopeptide is exogenous relative to the first or second protein domain, and wherein the first and second protein domains are operably linked by the dithiocyclopeptide. Also disclosed are methods of producing the polypeptide and delivering the protein domains into a cell.

Abstract: The present invention provides methods for reducing body weight in a mammal using Fibroblast Growth Factor-like (FGF-like) polypeptides and nucleic acid molecules encoding the same.

Abstract: Polypeptide growth factors, methods of making them, polynucleotides encoding them, antibodies to them, and methods of using them are disclosed. The polypeptides comprise an amino acid segment that is at least 90% identical to residues 46-163 of SEQ ID NO:2 or residues 235-345 of SEQ ID NO:2. Multimers of the polypeptides are also disclosed. The polypeptides, multimeric proteins, and polynucleotides can be used in the study and regulation of cell and tissue development, as components of cell culture media, and as diagnostic agents.

Abstract: An HGF precursor protein variant, in which a peptide structure comprises a sequence including a peptide chain X inserted between an ? chain of HGF or a polypeptide where 1 to 20 amino-acid residues from the C-terminus of the ? chain are deleted, and a ? chain of HGF or a polypeptide where 1 to 20 amino-acid residues from the N-terminus of the ? chain are deleted; wherein (i) the peptide chain X has an amino-acid sequence of at least two residues, (ii) the peptide chain X can be cleaved by a protease reaction or a chemical reaction, and (iii) a protein obtained by cleaving at least one site of the peptide chain X has HGF action.

Abstract: Biomaterials presenting synthetic peptides and methods of preparing biomaterials are disclosed. More particularly, the disclosure is directed to biomaterials including a substrate including a synthetic peptide thereon, wherein the synthetic peptide is selected from synthetic proteoglycan-binding peptides, synthetic glycosaminoglycan-binding peptides, and combinations thereof. The present disclosure is further directed to methods of preparing the biomaterials for use in sequestering endogenous proteoglycans and endogenous glycosaminoglycans, increasing stem cell proliferation, reducing spontaneous stem cell differentiation, and enhancing induced osteogenic differentiation of mesenchymal stem cells.

Abstract: A compound of the general formula X-[Q-W—(CH?CH)n—(CH2)2-L]m (I) in which X represents a polymer; Q represents a linking group; W represents an electron-withdrawing group; n represents 0 or an integer of from 1 to 4; L represents a leaving group; and m represent an integer of from 1 to 8. The compounds find use in the conjugation of biological molecules.

Abstract: The present invention generally provides methods for the site-specific modification of peptides, polypeptides, and proteins, e.g., granulocyte macrophage colony-stimulating factor, human superoxide dismutase, annexin, leptin, antibodies and the like, cytokines and chemokines, at their N-termini and at sites at which unnatural aminoacids have been introduced along the protein framework. The modifications described herein can be used for the synthesis and application of the adducts in radio-labeling, molecular imaging and protein therapeutic applications, and the treatment of disorders such as rheumatoid arthritis, lupus erythematosus, psoriasis, multiple sclerosis, type-1 diabetes, Crohn's disease, and systemic sclerosis, Alzheimer disease, cancer, liver disease (e.g., alcoholic liver disease), and cachexia.

Abstract: The object aims to form and maintain a cell, a tissue or an organ induced by differentiation. Disclosed is a composition for inducing the differentiation of a cell capable of being differentiated in a given direction to thereby produce a cell, a tissue or an organ through the further induction of the differentiation in the given direction. The composition comprises NELL-1 or a substance which can be altered so as to act as NELL-1 upon the differentiation. Also disclosed is a composition for maintaining a cell, a tissue or an organ produced by the induction of the differentiation.

Abstract: Novel growth hormone conjugates comprising a growth hormone compound (GH) and a growth hormone binding protein (GHBP) are disclosed. The invention also encompasses a novel derivatization method for producing stable, long-lasting conjugate (hGH-GHBP) by site specific conjugation. The novel GH-GHBP conjugates have an extended half-life in circulation that facilitates therapeutic use of the protein. The GH-GHBP conjugates exhibit pharmacological properties such as increased functional in vivo half-life, improved renal filtration, improved protease protection and albumin binding.

Abstract: The present invention provides a method and system for producing a NELL protein. The method and system comprise a CELL encoding a NELL protein or peptide and a non-insect secretory signal peptide.

Abstract: This invention is directed to methods for removing, preferably simultaneously and in one step, multiple impurities form crude culture samples, and, in particular, the removal of media components, protein, nucleic acids, lipids, and lipopolysaccharides to ultralow levels. Preferably the purification process comprises: (1) binding of the target substance containing one or more contaminants to a chromatography matrix; (2) washing the bound target substance with one or more buffers containing a synergistic combination of a lyotropic agent or organic solvent, a detergent, and a salt component; and (3) desorbing the target substance from the chromatography matrix, so that the eluate contains ultra low levels of contaminants. The reduction of impurities that can be achieved is preferably 91-99.9% as compared to the amount of impurities in the target substance before purification. The invention is also directed to the targets products that have been so purified.

Abstract: Disclosed herein is pyrroline-carboxy-lysine (PCL), a pyrrolysine analogue, which is a natural, biosynthetically generated amino acid, and methods for biosynthetically generating PCL. Also disclosed herein are proteins, polypeptides and peptides that have PCL incorporated therein and methods for incorporating PCL into such proteins, polypeptides and peptides. Also disclosed herein is the site-specific derivatization of proteins, polypeptides and peptides having PCL or pyrrolysine incorporated therein. Also disclosed herein is the crosslinking of proteins, polypeptides and peptides having PCL or pyrrolysine incorporated therein.

Abstract: Provided are a pharmaceutical composition for prevention and treatment of a neural disease including at least one selected from the group consisting of mesenchymal stem cells (MSCs), a culture solution of the MSCs, activin A, PF4, decorin, galectin 3, GDF15, glypican 3, MFRP, ICAM5, IGFBP7, PDGF-AA, SPARCL1, thrombospondin-1, WISP1, progranulin, IL-4, a factor inducing expression thereof, and any combination thereof, and a method therefor.

Abstract: The present invention provides enhanced methods of producing soluble, active fibroblast growth factor-20 (FGF-20), FGF-21, neurotrophin-3 (NT-3), growth hormone (GH), granulocyte colony stimulating factor (G-CSF), or glucocerebrosidase proteins in microorganisms that have an oxidizing environment.

Abstract: The invention provides methods and reagents for regulation of metabolic events, such as those mediated by adiponectin and adiponectin agonists. The invention also provides screening assays for identification of biologically active agents, diagnostic and therapeutic agents, and other methods and reagents.

Abstract: The present invention provides splice variants of myostatin that promote muscle growth, and include polynucleotides and polypeptide sequences, constructs comprising the sequences and compositions for regulating muscle growth and treating diseases associated with muscle tissue. The splice variants include the consensus sequence X1 I F L E X2 X3 X4 Q X5 C S I L X6 X7 X8 X9 X10 wherein X1 is I or L, X2 is V or L, X3 is Y, C, G or S, X4 is I or F, X5 is F or L, X6 is G or E, X7 is E or V, X8 is A or T, X9 is A or V and X10 is absent, F or L. The present invention also provides for the use of the present sequences in identifying animals with altered muscle mass, and for use in selective breeding programs to produce animals with altered muscle mass.

Abstract: The present invention provides a method of predicting pregnancy outcome in a subject by determining the amount of an early pregnancy associated molecular isoform of hCG in a sample. The present invention further provides a method for determining the amount of early pregnancy associated molecular isoforms of human chorionic gonadotropin (hCG) in a sample. The present invention also provides a diagnostic kit for determining the amount of early pregnancy associated hCG in a sample. The present invention additionally provides an antibody which specifically binds to an early pregnancy associated molecular isoform of human chorionic gonadotropin. Finally, the present invention provides methods for detecting trophoblast or non-trophoblast malignancy in a sample.

Abstract: The invention provides novel fragments of proBNP and NTproBNP, particularly useful in prognosing or diagnosing acute heart failure, chronic heart failure or sepsis.

Abstract: The growth hormone supergene family comprises greater than 20 structurally related cytokines and growth factors. A general method is provided for creating site-specific, biologically active conjugates of these proteins. The method involves adding cysteine residues to non-essential regions of the proteins or substituting cysteine residues for non-essential amino acids in the proteins using site-directed mutagenesis and then covalently coupling a cysteine-reactive polymer or other type of cysteine-reactive moiety to the proteins via the added cysteine residue. Disclosed herein are preferred sites for adding cysteine residues or introducing cysteine substitutions into the proteins, and the proteins and protein derivatives produced thereby.

Abstract: Provided are an aptamer having an inhibitory activity against NGF; a complex containing an aptamer having a binding activity or inhibitory activity against NGF and a functional substance (e.g., affinity substances, labeling substances, enzymes, drug delivery vehicles, drugs and the like); a medicament, a diagnostic agent, a labeling agent and the like containing an aptamer having a binding activity or inhibitory activity against NGF, or a complex containing the aptamer and the functional substance; and the like.

Abstract: The invention provides nucleic acid molecules encoding FGF21 mutant polypeptides, FGF21 mutant polypeptides, pharmaceutical compositions comprising FGF21 mutant polypeptides, and methods for treating metabolic disorders using such nucleic acids, polypeptides, or pharmaceutical compositions.

Abstract: We describe nucleic acid molecules that encode fusion polypeptides comprising GLP-1, or a receptor binding part thereof, linked directly or indirectly to a polypeptide that naturally binds GLP-1.

Abstract: The present invention relates to the field of recombinant protein production in bacterial hosts. It further relates to expression of soluble, active recombinant protein by using secretion signals to direct the protein to the periplasmic space of a bacterial cell. In particular, the present invention relates to a production process for obtaining soluble hG-CSF protein from a bacterial host.

Abstract: The present invention provides methods for reducing body weight in a mammal using Fibroblast Growth Factor-like (FGF-like) polypeptides and nucleic acid molecules encoding the same.

Abstract: The present invention relates an agent comprising FGF2 (Fibroblast Growth Factor-2 or basic Fibroblast Growth Factor (bFGF)) as an effective ingredient for treatment or prevention of Asthma and Chronic Obstructive Pulmonary Disease (COPD). Also, The present invention relates Th1 asthma and COPD mouse animal model induced by Ovalbumin and double strand RNA. The therapeutic agent comprising FGF2 of the present invention can be used for treatment or prevention for airway fibrosis, airway inflammation, airway hyperresponsiveness, airway remodeling, asthma and COPD. Also, Th1 asthma and COPD mice animal model induced by Ovalbumin and double strand RNA can be used for development of therapeutic agent for asthma and COPD.

Abstract: Novel protracted exendin-4 compounds and therapeutic uses thereof.

Abstract: Preparations of recombinant human growth hormone (hGH) are provided having a purity that comprises 2% or less of a peptide other than native human growth hormone (e.g., essentially free of multimeric forms) are disclosed. Active pharmaceutical ingredient (API) preparations of recombinant hGH suitable for commercial production of formulation grade recombinant hGH are provided. A stable Master Cell Bank of transformed E. coli is also disclosed, as well as methods for creating a transformed E. coli preparation that includes a Met-AsphGH encoding sequence. Improved manufacturing methods are also presented that are suitable for large scale production of highly purified preparations of recombinant human growth hormone.

Abstract: Disclosed are compositions and methods for increasing the longevity of a cell culture and permitting the increased production of proteins, preferably recombinant proteins, such as antibodies, peptides, enzymes, growth factors, interleukins, interferons, hormones, and vaccines. Cells transfected with an apoptosis-inhibiting gene or vector, such as a triple mutant Bcl-2 gene, can survive longer in culture, resulting in extension of the state and yield of protein biosynthesis. Such transfected cells exhibit maximal cell densities that equal or exceed the maximal density achieved by the parent cell lines. Transfected cells can also be pre-adapted for growth in serum-free medium, greatly decreasing the time required to obtain protein production in serum-free medium. In certain methods, the pre-adapted cells can be used for protein production following transfection under serum-free conditions. In preferred embodiments, the cells of use are SpESF or SpESF-X cells.

Abstract: The present invention is directed to stabilizing Bone Morphogenetic Protein in various lyophilized formulations and compositions. The present invention comprises formulations primarily including trehalose as an excipient for lyophilized compositions and their subsequent storage and reconstitution, and can also optionally include other excipients, including buffers and surfactants.

Abstract: A method for preserving a polypeptide comprises (i) providing an aqueous solution of one or more sugars, a polyethyleneimine and said polypeptide wherein the concentration of polyethyleneimine is 25 ?M or less based on the number-average molar mass (Mn) of the polyethyleneimine and the sugar concentration or, if more than one sugar is present, total sugar concentration is greater than 0.1 M; and (ii) drying the solution to form an amorphous solid matrix comprising said polypeptide.

Abstract: The present invention is directed to methods and compositions for making and using chimeric polypeptides that comprise a VEGFR-2 ligand. The chimeric molecules of the present invention retain VEGFR-2 binding activity and an enhanced angiogenic activity as compared to native VEGF-A.

Abstract: Methods of increasing the yield in plant expression of recombinant proteins comprising engineering glycosylation sites into cloned genes or cDNAs for proteins using codons that drive post-translational modifications in plants; and engineering the cloned genes or cDNAs to contain a plant secretory signal sequence that targets the gene products (protein) for secretion. The methods result in increased recombinant glycosylated protein yields. Proteins produced according to these methods are disclosed.

Abstract: There is provided the use of an inhibitor of phosphate transporter activity for the manufacture of a medicament for the prevention and/or treatment of non-viral damage to an epithelium, or of a condition caused or characterised by such damage. The inhibitor of phosphate transporter activity may optionally be a phosphono-carboxylic acid, or a pharmaceutically acceptable derivative of such an acid. There are also provided methods of treatment using such inhibitors, acids and derivatives.

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: The present invention provides formulations of cysteine knot proteins, including TGF-? superfamily proteins and bone morphogenic proteins that are pH stabilized. In particular, the present invention relates to the observation that certain buffers enhance the stability of cysteine knot proteins, including TGF-? superfamily proteins and bone morphogenic proteins. In particular, disclosed herein are liquid and lyophilized formulations prepared with a glycylglycine and tartaric acid buffers to stabilize the pH of the formulation.

Abstract: The invention relates to conjugated proteins, in particular but not exclusively, blood coagulation factors, to processes for preparing said conjugates, to pharmaceutical compositions comprising said conjugates and to the use of the conjugates in therapy, in particular but not exclusively, for the treatment of diseases alleviated by blood coagulation factors such as the prophylactic treatment of hemophilia.

Abstract: The present invention relates to the discovery of soluble isoforms of an Epidermal Growth Factor Receptor, or sErbB1 variants, the provision of the sequences of nucleic acids encoding these isoforms, purified recombinant proteins, novel antibodies specific for these isoforms, and the use of immunoassay and other protein assay techniques to measure the concentration of these protein isoforms in a patient biological sample in the femtomolar range. The present invention also provides methods for determining the presence of an ovarian carcinoma in the patient by assaying the concentration of soluble ErbB1 variants in a biological sample from a patient.

Abstract: Conjugates of hydroxyalkyl starch and a protein are provided herein. The conjugates are formed by a convalent linkage between the hydroxyalkyl starch or a derivative of the hydroxyalkyl starch and the protein. Methods of producing the conjugates and the use of the conjugates also are provided herein.

Abstract: An activatable functionalised Nth generation dendrimer having: a core comprising a first monomer having at least two carboxylic acid functional groups; and N successive generations, where N=0 to 10, wherein each generation comprises: a second monomer having at least two alcohol functional groups, wherein at least one alcohol group is bonded to a carboxylic acid group of the first monomer of the prior generation, and an additional first monomer attached to a second alcohol function group of said second monomer of that generation; and the final generation having attached thereto at said second alcohol functional group of said second monomer, a moiety having a dicarboxylic acid functional group, activatable by treatment with a carboxylic acid activating reagent such that reactivity of the carboxylic acid functional group is increased. The dendrimer, when activated, may be used in applications such as polymer crosslinking and/or nanoshell production.

Abstract: The present invention provides an agent for inhibiting alveolar airspace enlargement containing adiponectin or an agent for inhibiting alveolar wall destruction containing adiponectin. The pulmonary disease therapeutic agents of the present invention are highly safe drugs that possess an excellent effect of decreasing the deterioration of the pulmonary function, such as airflow limitation, and exhibit an extremely high effect of treating pulmonary disease accompanied by irreversible deterioration in pulmonary function, with fewer adverse side effects such as nausea, vomiting and gastric acid secretion.

Abstract: Modified FGF-21 polypeptides and uses thereof are provided.

Abstract: A method has for selectively acylating an amino group in a peptide or protein which has two or more reactive nucleophilic functional groups is described.

Abstract: The invention relates to genetically modified plants capable of producing a human recombinant protein Nerve Growth Factor, either in the form of pre-pro-protein or in the mature form and parts and differentiated and undifferentiated tissues thereof. The invention relates, also, to methods for the transformation of said plants in a transient way and methods for the transformation of said plants and tissues in a stable or transient way, methods for the recombinant protein purification from crude extract of proteins derived from plant tissue of said plants.

Abstract: The present invention is in the fields of medicine, public health, immunology, molecular biology and virology. The invention provides composition comprising a virus-like particle (VLP) linked to at least one antigen, wherein said antigen is NGF antigen. The invention also provides a process for producing the composition. The compositions of this invention are useful in the production of vaccines, in particular, for the treatment of pain. Moreover, the compositions of the invention induce efficient immune responses, in particular antibody responses.

Abstract: The invention generally relates to the use of leptin in the treatment of a leptin-responsive disease or condition in a non-lipodystrophic subject. More particularly, the invention is directed to the use of leptin in the treatment of a fatty liver disease in a non-lipodystrophic subject with a relative leptin deficiency. The invention includes methods for the treatment of nonalcoholic steatohepatitis (NASH), alcoholic fatty liver disease (AFLD), and nonalcoholic fatty liver disease (NAFLD) in a non-lipodystrophic subject. The invention includes the treatment of conditions ranging from ectopic lipid accumulation (steatosis) to cirrhosis.

Abstract: Novel polypeptides and polynucleotides encoding same are provided. Also provided methods and pharmaceutical compositions which can be used to treat various disorders such as cancer, immunological-related, blood-related and skin-related disorders using the polypeptides and polynucleotides of the present invention. Also provided are methods and kits for diagnosing, determining predisposition and/or prognosis of various disorders using as diagnostic markers the novel polypeptides and polynucleotides of the present invention.

Abstract: Non-natural amino acids and polypeptides with non-natural amino acids are disclosed. Further, polypeptides with non-natural amino acids that are subject to post-translational modification are disclosed. Additionally, methods of making, purifying, and using non-natural amino acids and polypeptides with non-natural amino acids are disclosed. The non-natural amino acids, by themselves or as part of a polypeptide, can include a wide range of possible functionalities, but typically have at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Uses for the non-natural amino acids and polypeptides with non-natural amino acids include diagnostic, therapeutic, and various biotechnology uses.

Abstract: The invention describes compositions of peptide analogs that are active in blood or cleavable in blood to release an active peptide. The peptide analogs have a general formula: A-(Cm)x-Peptide (SEQ ID NO: 76), wherein A is hydrophobic moiety or a metal binding moiety, e.g., a chemical group or moiety containing 1) an alkyl group having 6 to 36 carbon units, 2) a nitrilotriacetic acid group, 3) an imidodiacetic acid group, or 4) a moiety of formula (ZyHisw)p (SEQ ID NO: 50), wherein Z is any amino acid residue other than histidine, His is histidine, y is an integer from 0-6; w is an integer from 1-6; and p is an integer from 1-6; wherein if A has alkyl group with 6 to 36 carbon units x is greater than 0; and Cm is a cleavable moiety consisting of glycine or alanine or lysine or arginine or N-Arginine or N-lysine, wherein x is an integer between 0-6 and N may be any amino acid or none. The peptide analogs are complexed with polymeric carrier to provide enhanced half-life.

Abstract: An HGF precursor protein variant, in which a peptide structure comprises a sequence including a peptide chain X inserted between an ? chain of HGF or a polypeptide where 1 to 20 amino-acid residues from the C-terminus of the ? chain are deleted, and a ? chain of HGF or a polypeptide where 1 to 20 amino-acid residues from the N-terminus of the ? chain are deleted; wherein (i) the peptide chain X has an amino-acid sequence of at least two residues, (ii) the peptide chain X can be cleaved by a protease reaction or a chemical reaction, and (iii) a protein obtained by cleaving at least one site of the peptide chain X has HGF action.