Abstract: The invention is directed to bone morphogenetic proteins that have reduced immunogenicity. In particular, the invention is directed to human BMP-7 that has been modified to reduce immunogenicity through alteration of the amino acid sequence of wild-type BMP-7.

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 invention relates to the field of glycoprotein processing in transgenic plants used as cost efficient and contamination safe factories for the production of recombinant biopharmaceutical proteins or pharmaceutical compositions comprising these glycoproteins. The invention provides a plant comprising a functional mammalian enzyme providing mammalian GnTIII that is normally not present in plants, said plant additionally comprising at least a second mammalian protein or functional fragment thereof that is normally not present in plants.

Abstract: Targeted therapeutics that localize to a specific subcellular compartment such as the lysosome are provided. The targeted therapeutics include a therapeutic agent and a targeting moiety that binds a receptor on an exterior surface of the cell, permitting proper subcellular localization of the targeted therapeutic upon internalization of the receptor. Nucleic acids, cells, and methods relating to the practice of the invention are also provided.

Abstract: Targeted therapeutics that localize to a specific subcellular compartment such as the lysosome are provided. The targeted therapeutics include a therapeutic agent and a targeting moiety that binds a receptor on an exterior surface of the cell, permitting proper subcellular localization of the targeted therapeutic upon internalization of the receptor. Nucleic acids, cells, and methods relating to the practice of the invention are also provided.

Abstract: The present invention provides pharmaceutical compositions comprising a pharmaceutically acceptable excipient and a conjugate having a degradable linkage. The conjugates include at least one of each the following: an aromatic moiety comprising an ionizable hydrogen atom, a spacer moiety, and a water-soluble polymer. Methods for delivering such compositions are also provided.

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: The present invention provides modified, highly potent bone morphogenetic proteins. In particular, the present invention relates to the observation that BMP-6 and BMP-9 are less susceptible to inhibition by Noggin that are other members of the BMP subfamily of proteins. The present invention features chimeric bone morphogenetic proteins in which the middle portion of BMP-6 or BMP-9 replaces the middle portion of another BMP subfamily protein to cause resistance to inhibition by Noggin or other Noggin-like antagonists. Other embodiments of modified BMPs, compositions and methods of use are also included.

Abstract: A method is provided for increasing trafficking of endothelial progenitor cells to an ischemic myocardium in a subject's heart comprising administering to the subject's heart an amount of Stromal-Derived Factor-1 (SDF-1).

Abstract: Cosmetic and dermatologic compositions for skin care, containing a non-plant derived growth factor, purified from a host organisms or host cells such as bacterial, yeast, or animal cells, including insect cells, or a mixture of growth factors in purified form, for use in topical therapeutics, dermatology and cosmetics. Importantly this invention provides stabilized, safer growth factors available for use for cosmetic and topical treatment. Preferred composition comprises a non-plant derived growth factor and hyaluronic acid. The skin-care/dermatological compositions with stabilized growth factor do not carry the risk of unwanted breakdown products and the resulting loss of activity of the composition.

Abstract: A composition for treating a wound, wherein the composition can comprise therapeutically effective amount of an epidermal growth factor and a physiologically acceptable agent, wherein the physiologically acceptable agent comprises at least one of a stabilizer, a preservative, a thickening agent, carrier/diluent, and optionally pH regulating agent and humectant.

Abstract: The invention relates to modified soluble FGF receptor Fc fusions comprising a fusion of a soluble fragment or domain of the FGF receptor part (targeting or binding moiety) with an Fc region of an immunoglobulin part (effector function moiety), having improved biological activity including ADCC/CDC activities, compositions containing them, and method of producing such modified soluble FGF receptor Fc fusion molecules.

Abstract: The present invention is directed to fusion polypeptides comprising Klotho protein or an active fragment thereof and FGF23 or an active fragment thereof.

Abstract: This invention provides methods for extracting platelets, compositions obtained therefore, and methods for using the same.

Abstract: The NK1 fragment of hepatocyte growth factor (HGF) binds to and activates the Met receptor, a transmembrane receptor tyrosine kinase that plays a critical role in embryonic development and organ formation. The instant application discloses NK1 variant polypeptides which act as agonists or antagonists of HGF. Further disclosed are covalently linked NK1 variant polypeptides. Many of the disclosed variant polypeptides possess improved stability characteristics.

Abstract: Fluorescent phenyl xanthene dyes are described that comprise any fluorescein, rhodamine or rhodol comprising a particular C9 phenyl ring. One or both of the ortho groups on the lower C9 phenyl ring is ortho substituted with a group selected from alkyl, heteroalkyl, alkoxy, halo, haloalkyl, amino, mercapto, alkylthio, cyano, isocyano, cyanato, mercaptocyanato, nitroso, nitro, azido, sulfeno, sulfinyl, and sulfino. In one embodiment, halo and/or hydroxy groups are used. Optimal dyes contain a lower C9 phenyl ring in which both ortho groups are the same and the lower ring exhibits some form a symmetry relative to an imaginary axis running from the phenyl rings point of attachment to the remainder of the xanthene dye through a point para to the point of attachment. The phenyl xanthene dyes may be activated. Furthermore, the phenyl xanthene dyes may be conjugated to one or more substances including other dyes.

Abstract: The present invention provides a method for stable long-term storage of non-glycosylated recombinant human G-CSF, wherein an aqueous acetate or glutamate buffered G-CSF composition containing the non-glycosylated recombinant human G-CSF and sorbital is cooled to a temperature of ?15° C. or below to obtain a frozen G-CSF composition, which frozen composition is then stored in the frozen state and then increased in temperature to a temperature within the range of from 2° C. to 8° C. for a period of time adjusted to allow the composition to thaw and to obtain a liquid composition having a G-CSF content of at least 95% of the G-CSF content of the original composition.

Abstract: We disclose growth hormone [GH] fusion proteins that have increased in vivo stability and activity; nucleic acid molecules encoding said proteins and methods of treatment of growth hormone deficiency that use said fusion proteins. The GH fusion proteins comprise human GH covalently linked to the extracellular domain of Growth Hormone Receptor [GHR] either as a direct in-frame translational fusion or via a flexible peptide linker. The GH/GHR fusion proteins have exceptional pharmacokinetics and are potent growth hormone receptor agonists. The GH/GHR fusion proteins form head to tail dimers.

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 invention in suitable embodiments is directed to an isolated protein comprising one or more amino acid sequences, each amino acid sequence capable of being functionalized and/or attached in whole and/or in part to one or more or a plurality of elements of one or more types including to cargo elements, forming a composition of elements suitable for use as an in vivo and/or in vitro medicament to treat one or more biological species.

Abstract: This disclosure relates in part to synthesizing a cleavable proinsulin construct in transgenic plants by chloroplast expression.

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

Abstract: A cascade carrier linked prodrug is described comprising a biologically active moiety and a masking group having at least one nucleophile and being distinct from the carrier.

Abstract: The invention also relates to a method for of enhancing the acceptance and/or healing of a skin graft in a subject comprising stimulating angiogenesis and lymphangiogenesis with an effective amount of an isolated VEGF-D polypeptide.

Abstract: The disclosure provides nucleic acid molecules encoding chimeric polypeptides, chimeric polypeptides, pharmaceutical compositions comprising chimeric polypeptides, and methods for treating metabolic disorders such as diabetes and obesity using such nucleic acids, polypeptides, or pharmaceutical compositions.

Abstract: Provided is a new anti-inflammatory drug that produces an anti-inflammatory effect by modulating macrophage function. Specifically, a new anti-inflammatory drug that produces an anti-inflammatory effect through induction of M2 macrophages using activin species is provided.

Abstract: The present invention relates to growth hormone conjugates comprising a bile acid residue, said conjugation may occur through wt or mutant amino acid residues. The growth hormone polypeptide may be wt human growth hormone or a growth hormone variant.

Abstract: Modified glucagon peptides are disclosed having enhanced potency at the glucagon receptor relative to native glucagon. Further modification of the glucagon peptides by forming lactam bridges or the substitution of the terminal carboxylic acid with an amide group produces peptides exhibiting glucagon/GLP-1 receptor co-agonist activity. The solubility and stability of these high potency glucagon analogs can be further improved by modification of the polypeptides by pegylation, substitution of carboxy terminal amino acids, or the addition of a carboxy terminal peptide selected from the group consisting of SEQ ID NO: 26 (GPSSGAPPPS), SEQ ID NO: 27 (K-RNRNNIA) and SEQ ID NO: 28 (KRNR).

Abstract: Conjugate for targeting therapeutic or diagnostic agent or drug to cells or tissues in a body, e.g. areas of neoplastic growth or angiogenesis. Use of conjugate for in vivo diagnosis or therapy e.g. inhibiting tumor growth or metastasis, inhibiting angiogenesis and/or treating cancer. Conjugate comprises therapeutic or diagnostic agent as oligomeric protein e.g. heterodimeric protein, wherein first and second subunits of protein are each conjugated to a specific binding member e.g. an antibody fragment such as scFv. Subunits of oligomer may be conjugated to specific binding members as fusion proteins. Conjugate may comprise IL-12 heterodimer having two subunits, each subunit fused to scFv L19 or TN11 for targeting IL-12 to extracellular matrix components associated with neoplastic growth and angiogenesis.

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 relates to the identification of new proteins comprising fibroblast growth factor 21 (FGF21) and other metabolic regulators, including variants thereof, known to improve metabolic profiles in subjects to whom they are administered. Also disclosed are methods for treating FGF21-associated disorders, GLP-1-associated disorders, and Exendin-4-associated disorders, including metabolic conditions.

Abstract: The present invention relates to specific regions of the N-terminal portion of the VAR2CSA protein and to the use of such specific regions in the prevention of pregnancy-associated malaria. The invention also provides immunogenic compositions and vaccines that are useful for preventing malaria in pregnant women.

Abstract: The present invention provides compositions useful as prodrugs and methods for making the same. The compositions include a fusion protein having a first delivery domain and a second protein precursor domain linked together via a linker sequence. The delivery domain is a protein capable of facilitating entry to a target cells via the endocytotic pathway, such as transferrin. The protein precursor is a prohormone or a profactor, such as proinsulin. Methods of this invention include the steps of selecting a protein suitable as the delivery domain, constructing a vector to encode the fusion protein, and expressing the fusion protein in a suitable expression host. Also disclosed is a method for targeted-delivery of prodrugs to livers and a method of reducing hepatic glucose production.

Abstract: Leptin muteins, in particular leptin antagonists, with increased binding affinity to leptin receptor are provided. These compounds as well as pharmaceutical composition comprising them are useful for the treatment of any disorder in which a non-desirable or deleterious activity of endogenous leptin or an altered innate immune response is implicated.

Abstract: The present invention relates to compositions and methods for neuroprotection. In particular, provided herein are compositions (e.g., hepatocyte secretory factors) for alleviating and/or protecting against neuronal damage (e.g., resulting from stroke), and methods of use thereof.

Abstract: This invention provides information on differentially expressed genes in malignant tissue of gastric, colon and pancreatic adenocarcinomas as compared to their corresponding adjacent non-malignant tissues. These genes or their products can be used as targets in developing new strategies for the treatment and diagnosis of these gastrointestinal cancers.

Abstract: Mutant fibroblast growth factor (FGF) proteins having a polypeptide sequence with a high sequence identity to proteins encoded by members of the Fgf-1 subfamily of genes from a mammalian species, such as human, and with a specific amino acid substitution of an alanine at a position corresponding to amino acid position 66 of human FGF-1 with a cysteine and/or a specific amino acid substitution of a phenylalanine at a position corresponding to amino acid position 132 of human FGF-1 with a tryptophan (based on the 140 amino acid numbering scheme of human FGF-1) are provided. Other amino acid mutations or substitutions may be combined. Polynucleotide sequences encoding the mutant FGF proteins and host cells containing such polynucleotide sequences are provided. Methods of administering a mutant FGF protein to an individual to treat an ischemic condition or disease or a wound or tissue injury are also provided.

Abstract: The invention features compounds of the general formula: B-L-M where B is a binding agent capable of selectively binding to a nerve cell surface receptor and mediating absorption of the compound by the nerve cell; M is a moiety which performs a useful non-cytotoxic function when absorbed by a nerve cell, and can be a therapeutic moiety or an imaging moiety; and L is a linker coupling B to M. The invention also features methods of use of the compounds in, for example, treating conditions such as viral infections and pain, as well as in labeling nerve cells.

Abstract: The present disclosure is directed to methods, kits and compositions for preventing or treating age-related conditions or metabolic disorders. The fusion polypeptides of the disclosure include FGF23 or an active fragment thereof. In one embodiment, the fusion polypeptide comprises (a) a polypeptide comprising fibroblast growth factor 23 (FGF23), or a functionally active variant or derivative thereof, wherein FGF23 has a mutation at one or more of the positions Q156, C206 and C244; and (b) either a modified Fc fragment having decreased affinity for Fc-gamma-receptor and/or increased serum half-life, or a polypeptide comprising at least one extracellular subdomain of a Klotho protein, or a functionally active variant or derivative thereof; and, optionally (c) a linker. The Klotho fusion proteins are useful in the treatment and prevention of a variety of age-related conditions and metabolic disorders.

Abstract: Processes are provided for recovering and purifying refolded recombinant proteins produced in heterologous host cells, which includes the step of refolding the protein in a high pH buffer.

Abstract: The present invention provides a method comprising administering to a patient suffering from an endocrine disorder characterized by partial endogenous growth hormone activity or signaling an amount of insulin-like growth factor-1 (IGF-1) and an amount of growth hormone (GH) that in combination are effective to improve growth or metabolism in the patient, where the patient receives IGF-1 in a single daily administration and receives GH in a single daily administration, and where the single administrations are administered to the patient substantially contemporaneously each day.

Abstract: The present invention refers to a device, comprising a hollow body having at least one open end comprising at least one solid matrix binding, adsorbing, absorbing, chelating or retaining compounds which are not desired in a sample and preferably at least one barrier which is non-permeable for liquids and solids under ambience conditions, however, becomes liquid-permeable by applying an external force to said barrier, the use of such a device for isolating or purifying a biomolecule from a sample, a method for preparation of said device and a method for isolation or purification of any biomolecule using said device.

Abstract: Featured is T cell receptor complexes designed to redirect the immune system against various diseases. The T cell receptor complexes of the invention have been engineered to recognize target antigen in a functionally bispecific nature. Fusion protein complexes and protein conjugate complexes are comprised of high affinity antigen-specific TCR and biologically active proteins and/or effector molecules. Also featured is methods of production of T cell receptor fusion and conjugate complexes as well as therapeutic compositions for use of the complexes.

Abstract: A modular platform is provided for rapid preparation of various water-soluble prosthetic groups capable to efficiently introduce 18F into proteins with 18F labelling reagents.

Abstract: The invention relates to neublastin neurotrophic factor polypeptides, nucleic acids encoding neublastin polypeptides, and antibodies that bind specifically to neublastin polypeptides, as well as methods of making and methods of using the same.

Abstract: Provided are a G-CSF and water-soluble polymer conjugate, or a pharmaceutically acceptable salt thereof, comprising a water-soluble polymer, a protein, and a linking group; a method for preparing thereof; and a pharmaceutical composition comprising the same.

Abstract: Human growth hormone factor (GFR) containing pharmaceutical compositions are described, and more precisely, lyophilized compositions of hGRF stabilized by means of saccharose.

Abstract: The present disclosure provides for proprotein and activatable proprotein compositions. A proprotein contains a functional protein (i.e. a full length protein or functional fragment thereof) which is coupled to a peptide mask that inhibits the binding of the functional protein to its target or binding partner. An activatable proprotein contains a functional protein coupled to a peptide mask, and further coupled to an activatable linker, wherein in an non-activated state, the peptide mask inhibits binding of the functional protein to its target or binding partner and in an activated state the peptide mask does not inhibit binding of the functional protein to its target or binding partner. Proproteins can provide for reduced toxicity and adverse side effects that could otherwise result from binding of a functional protein at non-treatment sites if it were not inhibited from binding its binding partner. Proproteins can further provide improved biodistribution characteristics.

Abstract: The present invention is directed to a multimeric agent and a multimeric conjugate formed from this multimeric agent and a biologically active agent. Said multimeric conjugates have a longer life time in vivo and an increased avidity compared to the unmodified biologically agent. The present invention is further directed to a pharmaceutical or diagnostic composition containing said conjugate as well as to a method of its production. The invention additionally provides the use of said conjugates for the detection, determination, separation and/or isolation of a specific binding partner and for the diagnosis, prophylaxis and treatment of diseases in which the specific binding partner is directly or indirectly involved.