Abstract: Methods are provided for determining the amount of an IGF-I and/or IGF-II protein in a sample using high resolution/high accuracy mass spectrometry. The methods generally comprise enriching an IGF-I and/or IGF-II protein in a sample, ionizing an IGF-I and/or IGF-II protein from the sample to generate IGF-I and/or IGF-II protein ions, and determining the amount of IGF-I and/or IGF-II protein ions with high resolution/high accuracy mass spectrometry.

Abstract: Compositions and methods for the inhibiting human growth hormone (hGH), and treating or preventing hGH-mediated disorders, using a S1H peptide having the amino acid sequence of [SEQ ID NOs: 1-25], or a variant thereof, are described.

Abstract: The present invention provides compositions comprising a Fc-containing protein wherein substantially all the Fc domains have a C-terminal lysine. Further provided are host cell for producing said compositions, methods of making said host cells and compositions, and method of use thereof.

Abstract: Antibody-based binding agents derived from human and camelid immunoglobulins are described, as well as strains of yeast engineered to secrete the binding agents, and methods of treating and preventing Clostridium difficile infections using the engineered strains of yeast. These binding agents recognize and bind with specificity to Clostridium difficile toxin A and/or toxin B and in some cases exhibit toxin neutralizing activity. The binding agents include camelid VHH peptide monomers, linked groups of VHH peptide monomers, VHH peptide monomers joined to antibody Fc domains, and VHH peptide monomers joined to IgG antibodies.

Abstract: An antenna structure includes a metal mechanism element, a ground element, a first radiation element, a second radiation element, and a dielectric substrate. The metal mechanism element has a slot. A notch is formed on an edge of the metal mechanism element. The notch and the slot are connected to each other. The ground element is coupled to the metal mechanism element. The first radiation element has a feeding point. The second radiation element is coupled to the first radiation element and includes a first extension portion. The second radiation element extends across the slot. The first extension portion is parallel to the slot. A vertical projection of the first extension portion at least partially overlaps the slot. The dielectric substrate is adjacent to the metal mechanism element. The first radiation element and the second radiation element are disposed on the dielectric substrate.

Abstract: The present invention discloses a method for treating wounds and for accelerating the healing of wounds by administering an effective amount of a pharmaceutical composition containing type VII collagen protein, mini-C7 protein, variants thereof or any combinations thereof. The pharmaceutical composition may be administered through a variety of routes including intravenous injection, topical application, or oral ingestion. The method may further include administering a genetically modified fibroblast capable of expressing type VII collagen protein, miniC7 protein, variants thereof or small growth factors to achieve synergistic healing effect.

Abstract: Described herein are modified fibroblast growth factors (FGFs), pharmaceutical compositions, ophthalmic formulations, and medicaments that include such modified FGFs, and methods of using such modified FGFs to treat ocular diseases, disorders, or conditions.

Abstract: Herein is reported a method for producing a fusion-polypeptide comprising the seeps of a) cultivating a mammalian cell comprising a nucleic acid encoding a variant fusion-polypeptide wherein the amino acid sequence of the fusion-polypeptide has been modified by replacing in a pro-fusion-polypeptide the endogenous protease cleavage site between the pro-peptide and the fusion-polypeptide with an exogenous (with respect to the origins of the parts of the fusion-polypeptide) or artificial protease cleavage site, and b) recovering the fusion-polypeptide or fusion-pro-polypeptide from the cell or the cultivation median and thereby producing the (recombinant) fusion-polypeptide.

Abstract: Provided herein are methods and arrangements and related cell-free biomolecular breadboards configured to design, build, implement, debug, and/or test a genetic circuit to be operated in a target environment, by testing in a cell-free system under conditions of the target environment, molecular components of the genetic circuit and/or combinations thereof to select the molecular components and/or combinations thereof of a genetic circuit operative in the target environment.

Abstract: An insulin analogue comprises an insulin A-chain polypeptide and an insulin B-chain polypeptide. The A-chain polypeptide contains a Glu substitution at a position corresponding to position A8, and an Ala, Glu, Gln, His, Tyr, Phe or Trp substitution at a position A13, relative to wild type insulin. The B-chain polypeptide contains a cyclohexanylalanine substitution at position B24, relative to wild type insulin. The analogue may be an analogue of a mammalian insulin, such as human insulin. A nucleic acid encoding such an insulin analogue is also provided. A method of lowering the blood sugar of a patient comprises administering a physiologically effective amount of the insulin analogue or a physiologically acceptable salt thereof to a patient.

Abstract: A new approach to targeting imaging agents to macrophage-rich sites of interest is disclosed. Compositions of the invention are rHDL and HDL-like liposomal compositions, protein constituents of which, apolipoproteins A-I and/or A-II or fragments thereof are used not only as structural but also as targeting agents. This is achieved by certain controlled chemical or enzymatic modification of apolipoproteins A-I or A-II or fragments thereof. Such modification converts these apolipoproteins to substrates for macrophage scavenger receptors and results in the improvement of contrast agent-(HDL/modified apolipoprotein)-particle association with macrophages and/or absorption (uptake) by macrophages when compared to that of the contrast agent-(HDL/apolipoprotein)-particle constructed with non-modified naturally occurring apo A-I.

Abstract: The invention belongs to the technical field of polypeptide preparation methods, and in particular relates to a preparation method of a liraglutide intermediate polypeptide GLP-1 (7-37). In the preparation method, main steps include constructing recombinant liraglutide engineered bacteria via E. coli to induce expression of a liraglutide intermediate fusion protein in the form of inclusion bodies, and performing denaturation, renaturation, enzyme digestion, separation and purification to obtain the liraglutide intermediate polypeptide GLP-1 (7-37). The invention alters expression pattern into the expression of the intracellular insoluble inclusion bodies by changing a signal peptide of the recombinant sequence to increase significantly expression level. The liraglutide intermediate polypeptide prepared by the invention has a purity up to 87% or more and a yield of more than 85%.

Abstract: An integrated circuit (IC) device includes a semiconductor substrate having a via hole extending through at least a part thereof, a conductive structure in the via hole, a conductive barrier layer adjacent the conductive structure; and a via insulating layer interposed between the semiconductor substrate and the conductive barrier layer. The conductive barrier layer may include an outer portion oxidized between the conductive barrier layer and the via insulating layer, and the oxidized outer portion of the conductive barrier layer may substantially surrounds the remaining portion of the conductive barrier layer.

Abstract: The present disclosure relates to compositions and methods useful for the production of heterologous proteins with reduced O-mannosylation in filamentous fungal cells, such as Trichoderma cells. More specifically, the invention provides a PMT-deficient filamentous fungal cell comprising a) at least a first mutation that reduces an endogenous protease activity compared to a parental filamentous fungal cell which does not have said first mutation, and, b) at least a second mutation in a PMT gene that reduces endogenous O-mannosyltransferase activity compared to a parental filamentous fungal cell which does not have said second mutation, wherein said filamentous fungal cell is selected from the group consisting of Trichoderma, Neurospora, Myceliophthora or Chrysosporium cell.

Abstract: The use of two tandem microfiltration (MF) steps in a process for making recombinant insulin is described. The two MF steps in a single downstream purification unit operation reduce both soluble and insoluble impurities and exchange the insulin product into a suitable buffer for downstream purification.

Abstract: Disclosed are messenger RNA molecules and related compositions incorporating a 4?-thio modification in the furanose ring of at least one nucleotide residue, and methods of using these mRNAs to produce an encoded therapeutic protein in vivo and to treat or prevent diseases or disorders. In certain embodiments, the 4?-thio modified mRNA provides for enhanced stability and/or reduced immunogenicity in in vivo therapies.

Abstract: A composition comprising a synthetic growth factor analogue comprising a non-growth factor heparin binding region, a linker and a sequence that binds specifically to a cell surface receptor and an osteoconductive material where the synthetic growth factor analogue is attached to and can be released from the osteoconductive material and is an amplifier/co-activator of osteoinduction.

Abstract: Provided herein are methods for refolding proteins that are denatured. Exemplary methods comprise solubilizing the denatured protein with a denaturing agent, e.g., a chaotropic agent, and renaturing the protein using a buffer exchanging system, e.g., tangential flow filtration (TFF).

Abstract: A peptide comprising an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, according to the present invention, shows proliferation and differentiation promotion of osteoblast and proliferation and activation promotion of periodontal ligament fibroblast. A peptide, according to the present invention, increases BMP signaling such as SMAD1/5/8 phosphorylation and increases the growth of osteoblast and the expression of a differentiation marker such as COL1A1, BSP and ALP, thereby ultimately showing osteoblast activation. A peptide, according to the present invention, promotes the growth of periodontal ligament fibroblast by means of PI3K and Akt phosphorylation and increases the expression of an activation marker such as COL1A1 and DSPP, thereby ultimately showing periodontal tissue regeneration activation. Provided are a composition for preventing or treating bone diseases and a composition for preventing or treating periodontal diseases, the compositions comprising the aforementioned peptide.

Abstract: The invention discloses a promoter which can be induced to express in acidic conditions, and relates to the field of bioengineering technology. The promoters of the invention are separated from A. niger and can actuate and/or regulate the expression of the effectively connected nucleic acids in A. niger. In the invention the expression of the promoters is studied in A. niger, and it is indicated that some promoters show weak expression, and some show strong activity. The invention provides an effective method and new thought for organic acids production by fungi or other products produced by fermentation under acidic conditions.

Abstract: A polypeptide and polynucleotides encoding same comprising one carboxy-terminal peptide (CTP) of chorionic gonadotrophin attached to an amino terminus of a cytokine and two carboxy-terminal peptides (CTP) of chorionic gonadotrophin attached to a carboxy terminus of a cytokine 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 a conjugate containing at least one kidney-selective carrier molecule and at least one active compound which has a protective action for the kidney against nephrotoxic active compounds, to a process for the preparation of the conjugate, to the use thereof for the protection of the kidney against nephrotoxic active compounds, and to a medicament comprising the conjugate.

Abstract: The invention relates to growth hormone compounds with a protracted profile. The effect is obtained by linking an albumin binding residue via a hydrophilic spacer to growth hormone variants. Further described are methods of preparing and using such compounds. These growth hormone compounds are based on there altered profile considered particular useful in therapy.

Abstract: The invention discloses a composition comprising at least one long chain polyunsaturated fatty acid, at least one probiotic and a mixture of oligosaccharides, said mixture containing at least one N-acetylated oligosaccharide, at least one sialylated oligosaccharide and at least one neutral oligosaccharide, for use in the promotion of healthy bone growth and/or in the prevention and/or treatment of bone disease. Said bone disease is in particular osteomalacia, rickets, osteopenia or osteoporosis. Preferably the composition is a nutritional composition.

Abstract: This invention relates to a compound that induces or activates telomerase activity based on the nucleotide sequence of the GSE 24.2 fragment of dyskerin or the protein or peptide sequence encoded by said nucleotide sequence. Another part of the invention relates to vectors that comprise said sequence and cells transformed thereby, and pharmaceutical compositions that contain all these elements. These compositions may be used in the treatment of diseases from the following group: ageing or acceleration of ageing, neurodegenerative diseases and dyskeratosis congenita.

Abstract: The present invention relates to an insulin conjugate having improved in vivo duration and stability, which is prepared by covalently linking insulin with an immunoglobulin Fc region via a non-peptidyl polymer, a long-acting formulation comprising the same, and a preparation method thereof. The insulin conjugate of the present invention maintains in vivo activity of the peptide at a relatively high level and remarkably increases the serum half-life thereof, thereby greatly improving drug compliance upon insulin treatment.

Abstract: The present invention provides a method of maintaining a gram negative bacterium plasmid without the use of antibiotic selection pressure. Further, the invention relates to the drugless plasmids produced including drugless plasmids containing a heterologous gene. The invention also provides formulations and/or compositions comprising the drugless plasmids comprising a heterologous gene, formulations and/or compositions comprising a protein or an immunogen expressed using the drugless plasmids, and methods of administering such formulations and/or compositions to a host. The invention relates to gram negative bacteria containing the drugless plasmids.

Abstract: The screening method of the present invention is useful for screening drugs such as insulin secretagogues having an insulin secretagogue activity with minimized side effects (hypoglycemia induction, etc.). The transformant in which a polynucleotide encoding the fusion protein used for the screening method is introduced, the screening kit comprising the transformant, etc. are also useful for screening excellent drugs.

Abstract: The purpose of the present invention is to provide fragments of humanized anti-EGFR antibody substituted-lysine light-chain or heavy-chain variable regions, and single-chain antibodies, etc, comprising the same, having sufficient binding activity (affinity) with target cells, and having the ability to undergo various site-specific and uniform chemical modifications. The present invention pertains to a humanized variable region on the light-chain or heavy-chain of antibody 528 against human epidermal cell growth factor receptor 1 (Her-1), said variable region comprising the amino acid sequence represented by SEQ ID NO: 2 or SEQ ID NO: 4, wherein fragments of humanized anti-EGFR antibody lysine-substituted light-chain variable regions are formed by substituting a different amino acid for all of the lysine residues, or all of the lysine residues except for the lysine residue(s) of one specified moiety.

Abstract: The present invention relates to an isolated mutant eubacterium comprising at least one mutation resulting in a substitution of at least one amino acid in the beta-subunit of the RNA-polymerase encoded for by the rpoB-gene providing an altered production of a product of interest when said production of a product of interest is compared to the production of the same product in an isogenic wild type strain grown at identical conditions, wherein the substitution of at least one amino acid occurs at any of positions 469, 478, 482, 485, or 487 of SEQ ID NO:2, or at the equivalent positions in any eubacterial RNA-polymerase beta-subunit family member. Another aspect of the invention relates to a process for producing at least one product of interest in a mutant eubacterium and to a use of the mutant eubacterium according to the invention for producing at least one product of interest.

Abstract: Disclosed herein are embodiments for a novel method of producing an organic compound, including harvesting at least one organic compound from an organism or cell line genetically engineered with a gene for at least one proton-pump protein.

Abstract: The invention concerns the field of cell culture technology. It concerns RNA having a specific sequence, expression vectors encoding said RNA, production host cell lines comprising said RNA, and methods of producing recombinant biopharmaceutical products using engineered host cell with altered levels of said RNAs, such as small non-coding RNAs, preferably microRNAs (miRNAs). The invention also relates to engineered host cells with altered levels in one or more of said RNAs. Those cell lines have improved secretion and/or growth characteristics in comparison to control cell lines.

Abstract: The present invention provides methods for the high-level production of recombinant human erythropoietin (rhuEPO) derivative, asialoerythropoietin (asialo-rhuEPO), in plants. The methods for producing asialo-rhuEPO comprise making a plant or at least one plant cell that comprises a promoter that drives expression in a plant cell operably linked to a polynucleotide encoding a human erythropoieting fusion protein and a promoter that drives expression in a plant cell operably linked to a polynucleotide encoding N-glycosylation modification enzyme, particularly a mammalian ?1,4-galactosyltransferase. The present invention further provides plants, plant cells, and seeds that have been genetically modified to produce high levels of asialo-rhuEPO. Additionally, provided are methods for purifying asialo-rhuEPO from plant tissues.

Abstract: The disclosure relates to a process of obtaining a fully folded two chain insulin glargine that require no further processing to make it functionally active. The present disclosure discloses a surprising effect of over expression of Kex2p intracellularly under the control of inducible FLD1 promoter in the host Pichia pastoris to produce two chain functional glargine secreted directly in the medium. The schematic diagram of how the two chains are made inside the host Pichia pastoris and secretes into the medium.

Abstract: The invention provides materials and methods for the treatment of obesity and excess weight, diabetes, and other associated metabolic disorders. In particular, the invention provides novel glucagon analogue peptides effective in such methods. The peptides may mediate their effect by having increased selectivity for the GLP-1 receptor as compared to human glucagon.

Abstract: A plastid transformation vector for stably transforming a plastid genome, comprising, as operably-linked components, a first flanking sequence, a DNA sequence coding for synthetic insulin-like growth factor-1 (IGF-1s) (SEQ ID NO. 1) or a substantially homologous DNA sequence of IGF-1s, which is capable of expression in the plastid genome, and a second flanking sequence.

Abstract: The invention herein provides isolated antibodies that bind to VEGF. The invention further provides methods of making anti-VEGF antibodies, and polynucleotides encoding anti-VEGF antibodies.

Abstract: The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotides, primary transcripts and mmRNA molecules.

Abstract: The present invention relates to lower eukaryotic host cells having modified oligosaccharides which may be modified further by heterologous expression of a set of glycosyltransferases, sugar and sugar nucleotide transporters to become host-strains for the production of mammalian, e.g., human therapeutic glycoproteins. The process provides an engineered host cell which can be used to express and target any desirable gene(s) involved in glycosylation. Host cells with modified lipid-linked oligosaccharides are created or selected. N-glycans made in the engineered host cells exhibit GnTIV, GnTV, GnT VI or GnTIX activity, which produce multiantennary N-glycan structures and may be modified further by heterologous expression of one or more enzymes, e.g., glycosyltransferases, sugar, sugar nucleotide transporters, to yield human-like glycoproteins. For the production of therapeutic proteins, this method may be adapted to engineer cell lines in which any desired glycosylation structure may be obtained.

Abstract: The present invention provides non-human mammalian cell lines that are deficient in CMP-Neu5Ac hydroxylase (Cmah) and/or glycoprotein alpha-1,3-galactosyltransferase (Ggta1). Also provided are methods for using the cells disclosed herein for producing recombinant proteins with human-like patterns of glycosylation.

Abstract: The present invention relates to polypeptides and their uses as apelin inhibitors. More particularly, the present invention relates to a polypeptide comprising the sequence as set forth in SEQ ID NO:1 wherein at least one arginine residue at position 18, 19, 22 or 23 has been substituted or deleted.

Abstract: The present invention relates to the identification of novel nucleic acid sequences, designated herein as 7p, 8k, 7E, 9G, 8Q and 203, in a host cell which effect protein production. The present invention also provides host cells having a mutation or deletion of part or all of the gene encoding 7p, 8k, 7E, 9G, 8Q and 203, which are presented in FIG. 1, and are SEQ ID NOS.: 1-6, respectively. The present invention also provides host cells further comprising a nucleic acid encoding a desired heterologous protein such as an enzyme.

Abstract: Novel transcription units that may be used in expression vectors. The transcription unit allow antibodies to be produced whose gain in productivity is not linked to a particular antigenic target antibody and therefore by extrapolation to a given recombinant protein, nor linked to the culture medium.

Abstract: The present disclosure describes recombinant human chorionic gonadotropin (hCG) and methods for the production thereof. The recombinant hCG can include ?2,3, ?2,6, and, optionally, ?2,8 sialylation. The recombinant hCG can be produced in a human cell line such as a PER.C6® cell line.

Abstract: The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotides, primary transcripts and mmRNA molecules.

Abstract: A method for recognizing and evaluating the presence and function of GnRH receptors on tumor cells including those originating in the brain and/or nervous system and/or the meninges and/or reactive neuroglia cells and/or primitive neuroectodermal tumor cells and/or on Kaposi sarcoma is provided. Furthermore, a method for reducing degenerate GnRH-positive tumor cells and/or for decreasing cellular replication of the above GnRH-positive tumor cells comprising administering to a cell or to a subject a replication decreasing amount of a GnRH agonist and/or GnRH antagonist and/or an erythropoietin agonist, and/or a thrombopoietin agonist, and/or a endothelin antagonist and/or a gonadotropin inhibiting hormone agonist is also provided. Furthermore, a diagnostic kit for detecting GnRH receptors on tumor cells according to the present methods is disclosed.

Abstract: The present invention relates to compositions comprising glucose regulating peptides linked to extended recombinant polypeptide (XTEN), isolated nucleic acids encoding the compositions and vectors and host cells containing the same, and methods of making and using such compositions in treatment of glucose regulating peptide-related diseases, disorders, and conditions.

Abstract: New methods for the production of recombinant polypeptides from inclusion bodies are disclosed. Modulation of the cell culture conditions positively affects the yield of the recombinant polypeptide in active form. In one aspect, the methods comprise (a) cultivating a host cell at a first temperature, the host cell comprising a nucleic acid encoding a recombinant polypeptide, (b) lowering the cultivation temperature from the first temperature to a second temperature, and (c) cultivating the host cell at the second temperature.

Abstract: The present disclosure describes recombinant follicle stimulating hormone (FSH) and methods for the production thereof. The recombinant FSH can include ?2,3, ?2,6, and, optionally, ?2,8 sialylation. The recombinant FSH can be produced in a human cell line such as a PER.C6® cell line.

Abstract: The invention relates to variants and fusions of fibroblast growth factor 19 (FGF19), variants and fusions of fibroblast growth factor 21 (FGF21), fusions of fibroblast growth factor 19 (FGF19) and/or fibroblast growth factor 21 (FGF21), and variants or fusions of fibroblast growth factor 19 (FGF19) and/or fibroblast growth factor 21 (FGF21) proteins and peptide sequences (and peptidomimetics), having one or more activities, such as glucose lowering activity, and methods for and uses in treatment of hyperglycemia and other disorders.