Abstract: Agents which bind to cell surface receptors; methods to manufacture such agents; therapeutic compositions comprising such agents; and screening methods to identify novel agents.

Abstract: The present invention relates to the use of a composition comprising (a) at least three different amino acids, (b) at least two different amino acids and a saponin or (c) at least one dipeptide or tripeptide for stabilizing biomolecules immobilized on a solid carrier. The invention furthermore relates to a method for producing stabilized biomolecules, comprising embedding the biomolecules in the composition according to the invention and a method of producing a solid carrier having biomolecules attached thereto. The invention furthermore relates to a solid carrier producible or produced by the method of the invention and a method of diagnosing a disease using the carrier of the invention.

Abstract: The invention relates to stable pharmaceutical compositions comprising a therapeutic peptide derivatized with a property-modifying group, wherein the property-modifying group is conjugated to the peptide by use of a linker comprising an oxime bond.

Abstract: The invention relates to vascular endothelial growth factor (VEGF) in which the alanine at AA position 111 is replaced by proline. The arginine at AA position 110 may moreover be replaced by another amino acid. The invention also relates to derivatives of the VEGF according to the invention, nucleic acids, expression systems, medicaments and the use of the VEGF mutants of the invention for the treatment of chronic wounds.

Abstract: The invention relates to an isolated amino acid that can act as an antagonist to FGF signaling, comprising at least a portion of the FGF protein amino acid sequence, and including a mutation in either a) the integrin ?v?3 binding region of FGF-1; or b) the FGFR binding region of FGF-1.

Abstract: The present invention provides useful means in an expansion culture system for a hematopoietic cell (hematopoietic stem cell, hematopoietic progenitor cell). Specifically, the present invention provides a composition for expanding a hematopoietic cell (hematopoietic stem cell, hematopoietic progenitor cell) containing recombinant human serum albumin; a serum-free medium for expanding a hematopoietic cell containing a basal medium and recombinant human serum albumin; a method of expanding a hematopoietic cell comprising culturing a hematopoietic cell in a serum-free medium containing recombinant human serum albumin, and a culture of a hematopoietic cell that can be obtained by the expansion method.

Abstract: Formulations of modified human growth hormone polypeptides are provided.

Abstract: The invention provides synthetic heparin-binding growth factor analogs having two peptide chains each branched from a branch moiety, such as trifunctional amino acid residues, the branch moieties separated by a first linker of from 3 to about 20 backbone atoms, which peptide chains bind a heparin-binding growth factor receptor and are covalently bound to a non-signaling peptide that includes a heparin-binding domain, preferably by a second linker, which may be a hydrophobic second linker. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

Abstract: Fusion protein for immunocastration (Sequences 1a and 1b) that comprises the primary amino acid sequence of the gonadotrophin-liberating protein fused to a theoretical sequence: NH2-QHWSYGLRPGGPPFSGGGGPPFSA-COOH??Sequence 1a NH2-GPPFSGGGGPPFSAQHWSYGLRPG-COOH;??Sequence 1b DNA sequences coding for said fusion protein; vaccine comprising said fusion protein; use of the fusion protein for mammal immunocastration; process for producing the vaccine; process for preparing the fusion protein that comprises fusing the amino acid sequence of the gonadotrophin-liberating hormone (GnRH-I) to a theoretical glycosilable sequence having immunogenic activity that does not include pathogen or “carrier” protein sequences in its structure.

Abstract: A Tat-based tolerogen composition comprising at least one immunogenic antigen coupled to at least one human immunodeficiency virus (HIV) trans-activator of transcription (Tat) molecule wherein the immunogenic antigen can be a foreign or endogenous antigen or fragments thereof. Additionally methods of suppressing organ transplant rejection and methods of treating autoimmune diseases are provided.

Abstract: Purified genes encoding a T cell surface antigen from a mammal, reagents related thereto including purified proteins, specific antibodies, and nucleic acids encoding this antigen are provided. Methods of using said reagents and diagnostic kits are also provided.

Abstract: The present invention relates to a fusion protein or peptide, the in vivo half-life of which is increased by maintaining in vivo sustained release, and to a method for increasing in vivo half-life using same. A fusion protein or peptide according to the present invention has excellent in vivo stability by binding a physiologically active protein or physiologically active peptide to an alpha-1 antitrypsin or alpha-1 antitrypsin mutant with one or more amino acids mutated to maintain the in vivo sustained release and to significantly increase the half-life thereof in blood (T1/2) compared to an inherent physiologically active protein or physiologically active peptide. Thus, a fusion protein or peptide according to the present invention can be useful in developing a sustained-release preparation of a protein or peptide drug.

Abstract: An isolated conformational isomer of a bifunctional chelating agent of the formula (I): wherein the variables Q1 and Q2 are as defined in the description of the present application. Also described is a complex of the above chelating agent to an ion of a stable or radioactive metal; a conjugate of the complex covalently attached to a biological carrier; and a pharmaceutical composition containing the conjugate.

Abstract: This invention describes a novel agent for the targeted control of a mammalian cell activity, in particular the agent is used to control the interaction of particular cell types with their external environment. The agent has applications as a pharmaceutical for the treatment of a variety of disorders. An agent according to the invention comprises three Domains B, T and E linked together in the following manner: Domain B-Domain T-Domain E where Domain B is the Binding Domain which binds the agent to a Binding Site on the cell which undergoes endocytosis to produce an endosome, Domain T is the Translocation Domain which translocates the agent (with or without the Binding Site) from within the endosome across the endosomal membrane into the cytosol of the cell, Domain E is the Effector Domain which inhibits the ability of the Recyclable Membrane Vesicles to transport the Integral Membrane Proteins to the surface of the cell.

Abstract: A fusion protein comprising at least one IGF1 variant component and a fusion component (F), and, optionally, a signal sequence, exhibits improved stability relative to the native IGF1 or IGF2 polypeptide. The fusion component (F) may be a multimerizing component, such as an immunoglobulin domain, in particular, the Fc domain of IgG or a heavy chain of IgG. IGF1 variants were shown to have improved ability to increase muscle mass in a subject suffering from muscle atrophy caused by cachexia, immobilization, aging, chronic disease, cancer, hereditary condition, an atrophy-causing agent, and the like. IGF1 variants are also effective in decreasing blood glucose in a subject suffering from diabetes or hyperglycemia.

Abstract: Method for increasing half-life of compounds in plasma and novel derivatives of such compounds.

Abstract: The present invention provides isolated polypeptides having VEGF antagonist activity, pharmaceutical compositions and methods of treatment of subjects having a disease or disorder associated with VEGF activity or subjects having tumors expressing a VEGF receptor. The polypeptides of the invention include polypeptides comprising a portion of SEQ ID NO: 1 having VEGF antagonist activity, polypeptides comprising SEQ ID NO: 2 or a portion thereof having VEGF antagonist activity, and a polypeptide having the structure of formula (I), set forth above. The present invention further includes analogs and derivatives of these polypeptides having VEGF antagonist activity.

Abstract: Mutants of human FGF-1 are disclosed having increased stability and mitogenic potency. In the FGF-1 polypeptide, primarily residue 12 is substituted with threonine and/or residue 134 is substituted cysteine, valine or threonine to render the polypeptide more stable and/or to increase its mitogenecity.

Abstract: Mutants of human FGF-1 are disclosed having increased stability and mitogenic potency. In the FGF-1 polypeptide, primarily residue 12 is substituted with cysteine and/or residue 134 is substituted cysteine, valine or threonine to render the polypeptide more stable and/or to increase its mitogenecity.

Abstract: Disclosed herein are non-natural amino acids and polypeptides that include at least one non-natural amino acid, and methods for making such non-natural amino acids and polypeptides. The non-natural amino acids, by themselves or as a part of a polypeptide, can include a wide range of possible functionalities, but typical have at least one aromatic amine group. Also disclosed herein are non-natural amino acid polypeptides that are further modified post-translationally, methods for effecting such modifications, and methods for purifying such polypeptides. Typically, the modified non-natural amino acid polypeptides include at least one alkylated amine group. Further disclosed are methods for using such non-natural amino acid polypeptides and modified non-natural amino acid polypeptides, including therapeutic, diagnostic, and other biotechnology uses.

Abstract: The present invention relates to methods of using zFGF5 compositions to proliferate chondrocytes and their progenitors, and to induce deposition of cartilage. zFGF5 compositions are disclosed for treating disorders associated with chondrocytes, such as cartilage injuries and defects. In addition, methods for treating neurological disorders, such as stroke, are disclosed, and methods for using zFGF5 compositions to stimulate growth of cells associated with neurological injury and disease are disclosed.

Abstract: Compositions and methods for inducing the deposition of elastin in skin by administering compositions including a mineralocorticoid, such as, for example, aldosterone and, optionally, a secondary active agent for enhancing or modulating the effect of the mineralocorticoid are described herein.

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. Also disclosed are therapeutic methods for using the cysteine variants of the invention.

Abstract: Methods of making Apo-2 ligand and formulations of Apo-2 ligand using divalent metal ions are provided. Such divalent metal ions include zinc and cobalt which improve Apo-2 ligand trimer formation and stability. The crystal structure of Apo-2 ligand is also provided, along with Apo-2 ligand variant polypeptides identified using oligonucleotide-directed mutagenesis.

Abstract: Methods for producing modified polypeptides containing amino acid analogues are disclosed. The invention further provides purified dihydrofolate reductase polypeptides, produced by the methods of the invention, in which the methionine residues have been replaced with homoallylglycine, homoproparglycine, norvaline, norleucine, cis-crotylglycine, trans-crotylglycine, 2-aminoheptanoic acid, 2-butynylglycine and allylglycine.

Abstract: The present invention provides methods for reducing and/or evaluating the immunogenic potential of a therapeutic protein preparation. The present invention further provides pharmaceutical compositions of therapeutic proteins and methods of treatment with the same, the compositions having low immunogenic potential and/or improved efficacy. The invention achieves these goals by evaluating therapeutic protein preparations for subvisible protein particulates, which can contribute significantly to the overall immunogenic potential of the protein preparation. Further, by maintaining the content of such subvisible protein particulates to below an immunogenic threshold level, the resulting pharmaceutical composition is less likely to result in a loss of tolerance (e.g., upon repeated administration), thereby improving both the safety and efficacy profile of the therapeutic.

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 are provided for the diagnosis and treatment of patients with increased risk of preeclampsia. The methods involve measuring levels of TGF-?3, receptors of cytokines of the TGf? family, or HIF-1?.

Abstract: Stabilized radiopharmaceutical formulations are disclosed. Methods of making and using stabilized radiopharmaceutical formulations are also disclosed. The invention relates to stabilizers that improve the radiostability of radiotherapeutic and radiodiagnostic compounds and formulations containing them. In particular, it relates to stabilizers useful in the preparation and stabilization of targeted radiodiagnostic and radiotherapeutic compounds, and, in a preferred embodiment, to the preparation and stabilization of radiodiagnostic and radiotherapeutic compounds that are targeted to the Gastrin Releasing Peptide Receptor (GRP-Receptor).

Abstract: Compositions for treating nervous system conditions. In at least one embodiment of a stem cell conditioned medium of the present disclosure, the stem cell comprises a cell culture supernatant containing at least one factor capable of exerting effective neuroprotection to treat a mammalian neural injury or insult, the cell culture supernatant produced by culturing at least one mammalian adipose stem cell to produce the at least one factor.

Abstract: The present invention provides methods and compositions for increasing the growth rates, alleviating the symptoms, or improving the metabolism of human patients having insulin-like growth factor-1 deficiency (IGFD). The invention relates to methods comprising administering insulin-like growth factor-I to a patient having a height which, at the time of treatment or prior to initial treatment with IGF-1, is at least about 2 standard deviations below normal for a subject of the same age and gender, a blood level of insulin-like growth factor-I that, and at the time of treatment or prior to initial treatment with IGF-1, is below normal mean levels, usually at least about 1 standard deviations below normal mean levels, for age and gender.

Abstract: The present invention is directed to an isolated peptide comprising or consisting of an amino acid sequence with an amino acid identity of at least 90% compared to mature human BMP2 with SEQ ID No. 1, characterized in that said amino acid sequence comprises at least two amino acid substitutions characterized in that a first amino acid substitution occurs at a position corresponding to N59, S88, E94, V99, K101 and/or N102 of SEQ ID No. 1 and to uses thereof.

Abstract: The present invention relates to a method of treating chronic wounds using calreticulin. In particular, the invention relates to the treatment of chronic diabetic wounds using topical application of calreticulin to a patient in need of such treatment.

Abstract: Provided herein are compositions and methods that inhibit expression of Adam12 gene products, such as ADAM12 mRNA and/or ADAM12 polypeptides, as a therapeutic approach for the treatment of, or promotion of healing of, wounds.

Abstract: The present invention relates to a target-activated cell/tissue-penetrating peptide for delivery of impermeable compounds (Target Activated Cell/tissue Translocation peptide for Impermeable Compound Strategy (TACTICS)), and the use thereof, and more particularly to a target-activated cell/tissue-penetrating peptide, which comprises (a) a protein transduction domain (PTD), (b) a masking domain and (c) a spacer having a cleavage site specific for a target cell/tissue enzyme and is provided with target selectivity so as to penetrate specifically into a target tissue, and to a conjugate of the peptide with a drug or drug-containing particles for imaging or therapeutic applications.

Abstract: The present disclosure relates to amphiphilic compounds, self assembling compositions formed from the amphiphilic compounds and methods of making such compositions.

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: The invention relates to novel designer osteogenic proteins having altered affinity for a cognate receptor, nucleic acids encoding the same, and methods of use therefor. More preferably, the novel designer osteogenic proteins are designer BMPs and have altered affinity for a cognate BMP receptor. The designer BMPs demonstrate altered biological characteristics and provide potential useful novel therapeutics.

Abstract: Mutants of human FGF-1 are disclosed having increased stability and mitogenic potency. In the FGF-1 polypeptide, primarily residue 12 is substituted with valine and residue 134 is substituted cysteine or threonine to render the polypeptide more stable and/or to increase its mitogenecity.

Abstract: The present invention provides fibroblast growth factor variants demonstrating enhanced receptor subtype specificity and/or affinity. Preferred embodiments include both variants having enhanced activity that act as improved agonists and variants having reduced activity that act as antagonists. Methods of utilizing preferred FGF variants in preparation of medicaments for the treatment of skeletal disorders including skeletal dysplasia, osteoporosis and enhancing bone fracture healing and cartilage healing processes are provided.

Abstract: A dimer comprising a mutated neublastin polypeptide coupled to a polymer is disclosed. Such dimers exhibit prolonged bioavailability and, in preferred embodiments, prolonged biological activity relative to wild-type forms of neublastin.

Abstract: Provided herein are ligand dimers, compositions thereof, as well as methods of their use. The ligand dimers provided can comprise at least one ligand to a Her receptor and can be used to force dimerization of specific receptor pairs. The forced dimerization of specific receptor pairs can be used to control (e.g., promote or inhibit) signaling, and, therefore, the ligand dimers provided can also be used in various forms of treatment in which such signaling control is beneficial to a subject. It follows that methods for controlling signaling are provided as are various methods of treatment.

Abstract: Peptides that specifically bind erythrocytes are described. These are provided as peptidic ligands having sequences that specifically bind, or as antibodies or fragments thereof that provide specific binding, to erythrocytes. The peptides may be prepared as molecular fusions with therapeutic agents, tolerizing antigens, or targeting peptides. Immunotolerance may be created by use of the fusions and choice of an antigen on a substance for which tolerance is desired. Fusions with targeting peptides direct the fusions to the target, for instance a tumor, where the erythrocyte-binding ligands reduce or entirely eliminate blood flow to the tumor by recruiting erythrocytes to the target.

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 invention relates to materials and methods of conjugating a water soluble polymer to an oxidized carbohydrate moiety of a therapeutic protein comprising contacting the oxidized carbohydrate moiety with an activated water soluble polymer under conditions that allow conjugation. More specifically, the present invention relates to the aforementioned materials and methods wherein the water soluble polymer contains an active aminooxy group and wherein an oxime or hydrazone linkage is formed between the oxidized carbohydrate moiety and the active aminooxy group on the water soluble polymer, and wherein the conjugation is carried out in the presence of a nucleophilic catalyst.

Abstract: Derivatives of Fibroblast Growth Factor 21 which have improved properties for treating diabetes can be prepared by a recombinant process.

Abstract: Use of a growth hormone protein and polynucleotides encoding same comprising an amino-terminal carboxy-terminal peptide (CTP) of chorionic gonadotrophin and two carboxy-terminal chorionic gonadotrophin CTPs attached to the growth hormone in methods of inducing growth or weight gain, method of increasing insulin-like growth factor (IGF-1) levels, and methods of reducing the dosing frequency of a growth hormone in a human subject are disclosed. Pharmaceutical compositions comprising the growth hormone and polynucleotides encoding the growth hormone of the invention and methods of using same are also disclosed.

Abstract: The present invention provides methods for promoting hair growth and/or treating or preventing hair loss (alopecia) by contacting the cells with a TGF-? antagonist or inhibitor either alone or in combination with other alopecia-inhibiting compounds.

Abstract: The invention provides HGF/Met modulators comprising HGF having mutations in regions that affect HGF function, and antagonists that target said regions. The invention further provides methods of identifying, making and using these modulators.

Abstract: The invention relates to composition and a method of using the composition for modulating proliferation, invasiveness, the expression of a biomarker of an abnormal cell, of reducing the risk of a patient cell becoming abnormal, or of modulating proliferation of a carcinoma-associated fibroblast or of a tumor-associated macrophage. The invention also relates to a method of culturing the composition to produce molecules that modulate abnormal cell proliferation, invasiveness, or metastasis. The composition comprises a biocompatible matrix and cells engrafted thereon.