Abstract: The present invention describes fusion proteins based on cytokines, called bi-cytokines (BC), specifically formed by the binding of an IL2 agonist mutein with a type I interferon (IFN), linked by an Fc region of a mutant human IgG1 and a connector peptide. The combination of an IL2 agonist mutein and a type I IFN in the structure of the bi-cytokines gives surprising immunoregulatory properties to these molecules and a superior therapeutic effect than that of parental cytokines, or their combination, which makes them attractive and novel molecules for the treatment of cancer. Pharmaceutical compositions comprising as an active ingredient the fusion proteins object of this patent are also described.

Abstract: Disclosed is a product and process, wherein one adds a N-terminal Histamine-Maltose Binding Protein (“MBP”) tag to endonucleases, including restriction endonucleases like Hind III, and binds the tagged fusion protein to a solid support, preferably beads, once the enzyme has digested oligonucleotides in solution, in order to arrest further digestion. Preferred beads for binding the tagged enzyme are magnetic beads, which can easily be removed from solution by binding to a support and then removing it, or can be accumulated by magnetic attraction in a particular region. More preferred are magnetic beads bound to iminodiacetic acid or nitrilotriacetic acid.

Abstract: The present invention relates to plant-produced angiogenins, to related plant cells, plant calli, plants, seeds and other plant parts and products derived therefrom and to uses of plant-produced angiogenins. The present invention also relates to expression of angiogenin genes in plants and to related nucleic acids, constructs and methods.

Abstract: The invention relates to the field of medical biotechnology. Specifically, the present invention relates to a fusion protein containing an anti-interleukin-17 antibody and a tumor necrosis factor receptor extracellular region, a polynucleotide encoding the fusion protein, a vector comprising the polynucleotide, a host cell comprising the polynucleotide or the vector, and the use of the fusion protein for the treatment, prevention, and/or diagnosis of a related disease in an individual.

Abstract: Two long-acting recombinant porcine FSH (follicle-stimulating hormone) fusion proteins, comprising pFSH-Fc-1 and pFSH-Fc-2. ? subunit/? subunit is directly or indirectly fused on a Fc fragment by means of a linking component; the ? subunit/? subunit is combined with the ? subunit/? subunit by means of a Van der Waals force or the linking component. The porcine FSH fusion proteins can be prepared by an eukaryotic expression system based on a gene engineering technology. The two porcine FSH fusion proteins have a good medicinal effect and have a longer half-life period as compared with that of a natural porcine FSH; the two porcine FSH fusion proteins do not generate an undesirable effect on animals and can replace pregnant mare serum gonadotropin (PMSG) to be used in animal breeding production. The two porcine FSH fusion proteins can be used for preparation of medicines in the field of animal breeding.

Abstract: Fusion molecules composed of a type I interferon protein or portion thereof and a type III interferon protein or portion thereof, pharmaceutical compositions containing the fusion molecules, and methods for their use in inhibiting infection, inhibiting or treating cancer, inducing signaling of transcription of IFN-stimulated genes through an IFN-?R2 chain in a subject suffering from an infection which degrades or downregulates an IFN-?R1 chain, and treating various diseases or conditions are provided.

Abstract: Fusion Protein compositions comprising masked IFNs and methods of making masked IFNs are disclosed herein. Consequently, the masked IFNs can be fused to a Mab or binding fragment thereof and be administered to patients as a therapeutic modality and provide a method of treating cancer, immunological disorders and other disease.

Abstract: The present invention relates to an immunocytokine in which a human interferon-beta variant is conjugated to an antibody or a fragment thereof, and a method for preparing the same. The human interferon-beta variant has superior activity or functions compared with natural interferon-beta, and the productivity of the immunocytokine according to the present invention is excellent. In addition, the immunocytokine according to the present invention can be favorably used as a target therapeutic agent for multiple sclerosis or cancer since the immunocytokine express both of functions of the interferon-beta and characteristics of the antibody binding to a specific antigen.

Abstract: A method for cultivating a bacterial cell comprising the addition of an amino acid in an alkaline solution used for pH regulation. Also an aspect is a method for producing a polypeptide comprising the steps of a) providing a bacterial cell comprising a nucleic acid encoding the polypeptide, b) cultivating the provided cell, c) adjusting the pH value during the cultivating with a basic solution comprising an amino acid, d) recovering the polypeptide from the cell or the cultivation medium and thereby producing the polypeptide.

Abstract: Disclosed is a recombinant plasmid having a gene which encompasses at least the entire coding region of human fibroblast interferon messenger RNA and a method for preparing such plasmid.

Abstract: The invention provides extraction columns for the purification of an analyte (e.g., a biological macromolecule, such as a peptide, protein or nucleic acid) from a sample solution, as well as methods for making and using such columns. The columns typically include a bed of extraction media positioned in the column between two frits. In some embodiments, the extraction columns employ modified pipette tips as column bodies. In some embodiments, the invention provides methods of storing columns in a wet state.

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: A recombinant fusion interferon for animals. The recombinant fusion interferon comprises an animal interferon and a Fc region of an animal immunoglobulin G (IgG). The animal interferon and the Fc region of the animal immunoglobulin G can be further joined by a linker. A polynucleotide that encodes the recombinant fusion interferon for animals, a method for producing the recombinant fusion interferon, and the use of the recombinant fusion interferon.

Abstract: A codon optimized nucleic acid sequence for Interferon Alpha-2a is provided which can be used for expression of Interferon Alpha-2a in E. Coli.

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 relates to a process for the production of interferon beta, and to an interferon beta composition having a unique glycosylation pattern.

Abstract: The disclosure relates to a Gram negative bacterial cell that is transformed with a nucleic acid molecule that encodes a Gram positive twin-arginine translocase and including methods for the production of polypeptides.

Abstract: The present invention relates to processes for the production of peptides, and the peptides produced accordingly. Peptides produced according to the invention may be produced more efficiently than peptides produced according to prior art processes. The production process of the invention may lead to advantages in yield, purity, and/or price. Methods of marketing peptides are also disclosed.

Abstract: The invention relates to a chimeric monomer-dimer hybrid protein wherein the protein comprises a first and a second polypeptide chain, the first polypeptide chain comprising at least a portion of an immunoglobulin constant region and a biologically active molecule, and the second polypeptide chain comprising at least a portion of an immunoglobulin constant region without the biologically active molecule of the first chain. The invention also relates to methods of using and methods of making the chimeric monomer-dimer hybrid protein of the invention.

Abstract: The present disclosure relates to compositions and methods useful for the production of heterologous proteins in filamentous fungal cells.

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 a chimeric monomer-dimer hybrid protein wherein the protein comprises a first and a second polypeptide chain, the first polypeptide chain comprising at least a portion of an immunoglobulin constant region and a biologically active molecule, and the second polypeptide chain comprising at least a portion of an immunoglobulin constant region without the biologically active molecule of the first chain. The invention also relates to methods of using and methods of making the chimeric monomer-dimer hybrid protein of the invention.

Abstract: IFN-alpha mutants are obtained by substituting Cys for Tyr at position 85 or 86 in existing IFN-alpha. Their polyethylene glycol derivatives with high in vitro antiviral activity and prolonged in vivo half-life are also provided, wherein a polyethylene glycol moiety is covalently bound to the free Cys residue of an IFN-alpha mutant. The preparation methods of PEG derivatives of IFN-alpha mutants and medical compositions comprising the derivatives are also provided. The test results showed that the IFN-alpha mutants of the present invention are ready to prepare and have high activity; their polyethylene glycol derivatives have extended lifetime in the body and low clearance rate.

Abstract: A recombinant fusion interferon for animals. The recombinant fusion interferon comprises an animal interferon and a Fc region of an animal immunoglobulin G (IgG). The animal interferon and the Fc region of the animal immunoglobulin G can be further joined by a linker. A polynucleotide that encodes the recombinant fusion interferon for animals, a method for producing the recombinant fusion interferon, and the use of the recombinant fusion interferon.

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: The invention provides compositions and methods of identifying, modifying and producing modified target molecules, including therapeutic molecules by modification with non-natural amino acids. Certain aspects of the invention include methods of adding a chemical moiety to a target molecule, and the compositions resulting therefrom. Certain aspects of the invention also relate to kits for identifying, modifying and producing modified target molecules described herein.

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 current invention reports a method for the purification of a not-glycosylated, heterologous polypeptide, which has been recombinantly produced in a prokaryotic cell, wherein the method comprises three chromatography steps of which the first chromatography step selected from i) hydrophobic charge induction chromatography, or ii) hydrophobic interaction chromatography, or iii) affinity chromatography, or iv) ion exchange chromatography, the second chromatography step is selected from i) anion exchange chromatography, or ii) cation exchange chromatography, or iii) hydroxylapatite chromatography, or iv) hydrophobic interaction chromatography, and the a third chromatography step is selected from i) hydrophobic charge induction chromatography, or ii) anion exchange chromatography, or iii) cation exchange chromatography, or iv) hydrophobic interaction chromatography, whereby the first chromatography step is an affinity chromatography in case of polypeptides capable of interacting with metal ligands, the second c

Abstract: Disclosed are a method for rapid screening of suitable translational fusion partners (TFPs) capable of inducing expression or secretory production of non-producible proteins, which are difficult to produce in conventional recombinant production methods, from a variety of genetic sources, and protein secretion-inducing TFPs obtained using the method.

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

Abstract: A process for producing an interferon alpha 5 (IFNa5) protein by expression in an IFNa5 producing Escherichia coli host cell, wherein incorporation of an extra methionine residue in the N-terminal end of the polypeptide chain is minimized as well as the generation of its oxidized species is disclosed. The IFNa5 protein can be purified by an efficient process to render a biologically active IFNa5.

Abstract: The invention provides a method of increasing product yield per culture in a population of product-secreting cells bound to a scaffold, for example, a microcarrier, at least partially immersed in a culture medium in a bioreactor. The method comprising: semi-harvesting product by removing a volume of the culture medium with a first-secreted product concentration while leaving the scaffold with the bound cells in the bioreactor; re-feeding the cells by adding a fresh culture medium to increase the culture medium in the bioreactor to approximately the original volume; agitating the culture medium to allow the cells to grow and release a second-secreted product concentration; harvesting product by removing the culture medium with the second-secreted product concentration while leaving the scaffold with the bound cells behind. Also disclosed is a method of increasing virus yield per culture in a population of virus-infected cells bound to a microcarrier suspended in a culture medium.

Abstract: A glycosyl transferase from Chinese hamster and related methods are described.

Abstract: Methods and compositions described herein relate to processes for the production of deuterated peptides, and the deuterated peptides produced accordingly. Deuterated peptides produced according to methods and compositions described herein may be produced more efficiently than such peptides produced according to prior art processes. The production process of according to methods and compositions described herein may lead to advantages in yield, purity, and/or price for deuterated peptides. Methods of marketing deuterated peptides are also disclosed.

Abstract: A recombinant fusion interferon for animals. The recombinant fusion interferon comprises an animal interferon and a Fc region of an animal immunoglobulin G (IgG). The animal interferon and the Fc region of the animal immunoglobulin G can be further joined by a linker. A polynucleotide that encodes the recombinant fusion interferon for animals, a method for producing the recombinant fusion interferon, and the use of the recombinant fusion interferon.

Abstract: Disclosed is an interferon-? (IFN-?) fused protein having IFN-? fused to a cytoplasmic transduction peptide (CTP). The disclosure relates to a fused protein wherein a CTP, which binds well to cell-membrane barriers and enables translocation into the liver, is genetically fused to a human IFN-?, thereby enhancing the conjugation capacity of cell membranes and antiviral activity, inhibiting CTP transport into the cell nucleus, and enhancing the translocation and settlement of the fused protein into the liver and of transduction to the liver tissue. Accordingly, it is possible to develop protein-based medicines effective for preventing or treating various liver diseases associated with viral infection at low doses.

Abstract: The present invention relates to a hybrid promoter, in which a whole or a part of a CMV enhancer, a whole or a part of a ?-actin promoter, a whole or a part of a CMV promoter, and a whole or a part of a ?-actin intron are operably linked to each other, a recombinant vector comprising the same, a transformant transformed with the recombinant vector, a pharmaceutical composition comprising the recombinant vector or the transformant, and a method for preparing a target protein using the recombinant vector or the transformant. The hybrid promoter of the present invention is able to induce high expression of a target protein in a eukaryotic cell. Therefore, the hybrid promoter of the present invention can be effectively used for the development of an antibody or the production of a DNA vaccine.

Abstract: The invention provides compositions and methods of identifying, modifying and producing modified target molecules, including therapeutic molecules by modification with non-natural amino acids. Certain aspects of the invention include methods of adding a chemical moiety to a target molecule, and the compositions resulting therefrom. Certain aspects of the invention also relate to kits for identifying, modifying and producing modified target molecules described herein.

Abstract: This invention provides a set of methods for modulating protein spatial configuration. First, select the amino-acid codon for encoding the target protein according to host codon usage. Second, choose combinations which can modulate the spatial configuration and construct into different vectors which can transfect a series of hosts. Third, choose the vector promoter by monitoring a combination of base pairs after combining the code sequence of the promoter and the target protein. Finally, choose the appropriate expression host to express the target protein, refold and purify, measure the activity and spatial configuration.

Abstract: Novel chimeric moieties that show significant efficacy against cancers are provided. In certain embodiments the chimeric moieties comprise a targeting moiety attached to an interferon. In certain embodiments, the chimeric moieties comprise fusion proteins where an antibody that specifically binds to a cancer marker is fused to interferon alpha (IFN-?) or interferon beta (IFN-?).

Abstract: The invention relates to a nucleic acid molecule encoding a multimeric precursor which after transcription is specifically cleaved in vivo to form multiple copies of a protein of interest. The invention further relates to a cell comprising this nucleic acid molecule and a method for producing a protein of interest using this cell.

Abstract: This invention provides a recombinant interferon (rSIFN-co) and its equivalent with changed spatial configuration, high efficacy and low side effects. Therefore, high dose of rSIFN-co may be used. The cytotoxic effect of rSIFN-co is only one-eighth (?) of currently clinically available interferons but its anti-viral effect is approximately five to twenty (5-20) times higher, and when used in vivo it has a broader spectrum of clinical applications and longer biofeedback response. This invention further provides methods of using the recombinant interferon to treat proliferative disorders such as cancer or viral diseases.

Abstract: The invention relates to novel polyalkylene glycol compounds and methods of using them. In particular, compounds comprising a novel polyethylene glycol conjugate are used alone, or in combination with antiviral agents to treat a viral infection, such as chronic hepatitis C.

Abstract: The present invention discloses an improved process for the production of desired recombinant peptides from bacterial cells by using G-CSF as a novel fusion partner for their high level expression in these cells. The invention further provides an expression system comprising the fusion protein wherein the G-CSF is operatively linked to the peptide of interest via an enzymatic or chemical cleavage site which can be used to separate the fusion partner from the said peptide.

Abstract: This invention provides RNA, oligoribonucleotide, and polyribonucleotide molecules comprising pseudouridine or a modified nucleoside, gene therapy vectors comprising same, methods of synthesizing same, and methods for gene replacement, gene therapy, gene transcription silencing, and the delivery of therapeutic proteins to tissue in vivo, comprising the molecules. The present invention also provides methods of reducing the immunogenicity of RNA, oligoribonucleotide, and polyribonucleotide molecules.

Abstract: The invention relates to a chimeric monomer-dimer hybrid protein wherein said protein comprises a first and a second polypeptide chain, said first polypeptide chain comprising at least a portion of an immunoglobulin constant region and a biologically active molecule, and said second polypeptide chain comprising at least a portion of an immunoglobulin constant region without the biologically active molecule of the first chain. The invention also relates to methods of using and methods of making the chimeric monomer-dimer hybrid protein of the invention.

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

Abstract: This application relates to recombinant human interferon-like proteins. In one embodiment a recombinant protein created by gene shuffling technology is described having enhanced anti-viral and anti-proliferative activities in comparison to naturally occurring human interferon alpha 2b (HuIFN-?2b). The invention encompasses a polynucleotide encoding the protein and recombinant vectors and host cells comprising the polynucleotide. Preferably the polynucleotide is selected from the group of polynucleotides each having a sequence at least 93% identical to SEQ ID: No. 1 and the protein is selected from the group of proteins each having an amino acid sequence at least 85% identical to SEQ ID NO: 2. The proteins and compositions comprising the proteins can be used for treatment of conditions responsive to interferon therapy, such as viral diseases and cancer.

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 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.