Abstract: Compositions and methods for identifying patients at increased risk for PIGFD and ISS are disclosed.

Abstract: Improved host cells and culture methods involving overexpression of MAN1C1 activity to improve protein production are provided.

Abstract: The present invention provides methods and kits for assessing the state of oocyte maturation in a female mammal based on the level of PAPP-A found in the female's bodily fluid sample.

Abstract: A method for reducing or substantially preventing formation of a trisulfide derivative of a polypeptide in a liquid medium containing the polypeptide ijn question comprises stripping the liquid medium with a gas, suitably a chemically unreactive gas such as nitrogen or argon.

Abstract: The present invention provides methods of producing biologically active recombinant bFSH and methods of increasing reproduction in mammals, particularly bovine, using recombinant bFSH. Also provided are methods of producing single chain recombinant bFSH. The recombinant bFSH of the present invention increases superovulation, embryo development, and reproductive efficiency in cattle and other ungulates.

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: 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 invention provides methods for treating stroke and compositions for use in the same. The methods employ a chimeric peptide of an active peptide and an internalization peptide. The internalization peptide is a tat variant that promotes uptake of itself and a linked active peptide into a cell without substantial binding to N-type calcium channels. Use of the tat variant allows treating of stroke free of certain side effects associated with binding to N-type calcium channels. Tat variant peptides can also be linked to other active agent for use in treating other diseases.

Abstract: Provided are a means for the prevention and treatment of obesity and/or insulin resistance and, particularly, pharmaceutical drugs for the treatment of obesity and/or insulin resistance under the influence of FSTL3. Specifically, provided is an insulin resistance improving drug comprising an FSTL3 inhibitor as an active ingredient, particularly, the insulin resistance improving drug, wherein the FSTL3 inhibitor is one of (A) a substance specifically binding to FSTL3 to inhibit or suppress a function of FSTL3, (B) an inhibitor for expression of FSTL3, and (C) a competitor of FSTL3.

Abstract: A polypeptide comprising a G-CSF domain operably linked to a Tf domain, wherein the ability of the polypeptide to be transported into a cell expressing a TfR gene or the ability of the polypeptide to be transported across a cell expressing a TfR gene via transcytosis is higher than that of the G-CSF domain alone.

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

Abstract: 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: The present invention relates to a biosynthetic random coil polypeptide or a biosynthetic random coil polypeptide segment or biosynthetic conjugate, wherein said biosynthetic random coil polypeptide, said biosynthetic random coil polypeptide segment or said biosynthetic conjugate comprises an amino acid sequence consisting solely of proline and alanine amino acid residues, wherein said amino acid sequence consists of at least about 50 proline (Pro) and alanine (Ala) amino acid residues. Said at least about 50 proline (Pro) and alanine (Ala) amino acid residues may be (a) constituent(s) of a heterologous polypeptide or an heterologous polypeptide construct. Also uses and methods of use of these biosynthetic random coil polypeptides or polypeptide segments or said conjugates are described.

Abstract: A chimeric therapeutic polypeptide of a pre-existing therapeutic polypeptide is disclosed, as are a method of enhancing folded stabilization and a pharmaceutical composition of the glycosylated chimer. The pre-existing and chimeric polypeptides have substantially the same length, substantially the same amino acid residue sequence, and exhibit at least one tight turn containing a sequence of four to about seven amino acid residues in which at least two amino acid side chains extend on the same side of the tight turn and are within less than about 7 ? of each other. The chimeric therapeutic polypeptide has the sequon Aro-(Xxx)n-(Zzz)p-Asn-Yyy-Thr/Ser (SEQ ID NO:001) within that tight turn sequence such that the side chains of the Aro, Asn and Thr/Ser amino acid residues project on the same side of the turn and are within less than about 7 ? of each other. That sequon is absent from the pre-existing therapeutic polypeptide.

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

Abstract: The present invention provides methods and materials by which glycosylation of glycoproteins can be regulated. Methods include the monitoring and regulation of parameters such that a glycoprotein having a desired product quality is obtained.

Abstract: The following class of molecule is disclosed: a dimer containing a first neublastin polypeptide and a second neublastin polypeptide, wherein: (a) at least one of the polypeptides is glycosylated; (b) at least one of the polypeptides is conjugated at its N-terminus to a water-soluble synthetic polymer; and (c) neither of the polypeptides is conjugated to a water-soluble synthetic polymer at a position other than the N-terminus. Such dimers possess the biological activity of wild-type neublastin while displaying enhanced serum half-life and enhanced potency relative to wild-type neublastin.

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

Abstract: Disclosed is a newly identified secreted molecule, identified herein as “monocyte, granulocyte, and dendritic cell colony stimulating factor” (MGD-CSF), the polypeptide sequence, and polynucleotides encoding the polypeptide sequence. Also provided is a procedure for producing the polypeptide by recombinant techniques employing, for example, vectors and host cells. Additionally, procedures are described to modify the disclosed novel molecules of the invention to prepare fusion molecules. Also disclosed are methods for using the polypeptides and active fragments thereof for treatment of a variety of diseases, including, for example, cancer, autoimmune and inflammatory diseases, infectious diseases, and recurrent pregnancy loss.

Abstract: The present invention relates to a process for the purification of a glycoprotein comprising subjecting a liquid containing said glycoprotein to the steps of: a) reverse phase chromatography, b) size exclusion chromatography, and c) hydrophobic interaction chromatography. Also provided is a manufacturing process for producing a glycoprotein of interest.

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

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

Abstract: The present invention discloses methods to identify targets, pathways and molecules regulating purinosomes and their uses for treating pathophysiological disorders associated with purinosomes. Disclosed are methods related to both label-free cellular assays and fluorescence imaging to confirm the regulatory roles of various targets and molecules in purinosome dynamics. Disclosed are methods to classify molecules and the uses of these molecules for different indications. Specifically, the purinosome-disrupting molecules can be used for improved prevention and treatment of cancer development.

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

Abstract: The present invention relates to mutants of Fibroblast Growth Factor (FGF), particularly FGF-20 and FGF-21, which contain newly introduced N-linked or O-linked glycosylation site(s). The polynucleotide coding sequences for the mutants, expression cassettes comprising the coding sequences, cells expressing the mutants, and methods for producing the mutants are also disclosed. Further disclosed are pharmaceutical compositions comprising the mutants and method for using the mutants.

Abstract: The present invention is directed compositions for targeted delivery of RNA interference (RNAi) polynucleotides to cell in vivo. The pharmacokinetic modulator improve in vivo targeting compared to the targeting ligand alone. Targeting ligand-pharmacokinetic modulator targeting moiety targeted RNAi polynucleotides can be administered in vivo alone or together with co-targeted delivery polymers.

Abstract: Modified human leptin polypeptides and uses thereof are provided.

Abstract: The present disclosure relates to a method for preparing recombinant glycoproteins with high sialic acid content. More specifically, for UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE/MNK) enzyme where point mutation was induced by substituting arginine at position 263 by leucine only or by further substituting arginine at position 266 by glutamine, epimerase activity is constantly maintained, and overexpressed cells thereof experience an increase in intracellular cytidine monophosphate (CMP)-sialic acid content, irrespective of CMP-sialic acid concentration.

Abstract: The invention relates to the identification of new polypeptide and protein variants of fibroblast growth factor 21 (FGF21) that have improved pharmaceutical properties. Also disclosed are methods for treating FGF21-associated disorders, including metabolic conditions.

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

Abstract: The present invention provides methods and compositions for tissue regeneration without cell transplantation.

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: The present disclosure features therapeutic antibodies (e.g., TPO mimetic antibodies) and therapeutically-active fragments thereof as well as methods for preparing and using the antibodies and fragments. For example, the therapeutic antibodies and their fragments are useful in a variety of diagnostic and/or therapeutic applications such as methods for increasing platelet levels in a subject.

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

Abstract: Provided herein are glycosylated polypeptide compositions with substantially reduced Neu5Gc content. The glycosylated polypeptides compositions with substantially reduced Neu5Gc content can be obtained from cell sources cultured with Neu5Gc competitor or from non-human animal sources fed a diet supplemented with Neu5Gc competitor. Also provided herein are methods of treating a human subject with said compositions.

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: 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: A polypeptide and polynucleotides encoding same comprising at least two carboxy-terminal peptides (CTP) of chorionic gonadotrophin attached to an EPO peptide are disclosed. Pharmaceutical compositions comprising the polypeptide and polynucleotides of the invention and methods of using same are also disclosed.

Abstract: The present invention relates to compositions and methods for fusion protein separation utilizing a peptide linker comprising a novel thrombin cleavage site.

Abstract: Protease resistant modified interferon-beta polypeptides, and pharmaceutical compositions containing such modified interferon-beta polypeptides are provided. The modified interferon-beta polypeptides contain amino acid substitutions that confer increased resistance to proteolysis over unmodified IFN beta cytokine molecules. The present invention provides for pharmaceutical formulations suitable for oral, nasal and pulmonary administration, and the use of such formulations in the treatment of disease.

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: The present invention provides a method for preparing a site-specific physiologically active polypeptide conjugate in a high yield by treating a physiologically active polypeptide with a non-peptidyl polymer in the presence of an alcohol at a specific pH, which can be desirably employed in the development of long acting formulations of various peptide drugs having high in-vivo activity and markedly prolonged in-blood half-life.

Abstract: The present invention provides a method of producing polypeptide utilizing a fusion protein of A-B type in the following formula (I), by culturing transformed microorganism comprising DNA sequence encoding the desirable polypeptide; A-B (I). In the above formula (I), A is a fusion partner of 25 or more amino acid residues where aspartic and glutamic acid residues are incorporated to have a net negative charge of 30% or more, and B is the target protein to be produced. The target protein can be isolated from the fusion protein by employing enzymatic cleavage site etc. at the carboxyl-terminus of the fusion partner.

Abstract: Provided are methods of making carrier polypeptide that include incorporating a first unnatural amino acid into a carrier polypeptide variant, incorporating a second unnatural amino acid into a target polypeptide variant, and reacting the first and second unnatural amino acids to produce the conjugate. Conjugates produced using the provided methods are also provided. In addition, orthogonal translation systems in methylotrophic yeast and methods of using these systems to produce carrier and target polypeptide variants comprising unnatural amino acids are provided.

Abstract: Physically and chemically stable, water-soluble, amphiphilic polymer-PDGF complex, characterized in that the amphiphilic polymers include a hydrophilic polymeric backbone functionalized with hydrophobic substituents and hydrophilic groups.

Abstract: Formulations containing complexed human growth hormone crystals are described. Also described are needleless injection systems for crystalline proteins.

Abstract: The invention concerns human thrombopoietin and in particular modified forms of thrombopoietin (TPO) with improved properties. The improved proteins contain amino acid substitutions at specific positions within the TPO molecule. The invention provides modified TPO molecules, preferably fusion proteins comprising immunoglobulin constant regions and modified human TPO, with improved biological activity concomitant with reduced immunogenic potential in the protein. The improved proteins are intended for therapeutic use in the treatment of diseases in humans.

Abstract: This invention relates to a recombinant human G-CSF (rhG-CSF) dimer and its use in the treatment of neurological disorder. In particular, upon ischemic neural injury in animal, this invention can be used to protect neurons with the use of rhG-CSF dimer such that function of injured nerves can be restored. Serum half-life of G-CSF dimer of this invention is prolonged and the biological activity thereof is increased.