Abstract: A method of producing a protein of interest (POI) by culturing a recombinant eukaryotic cell line comprising an expression construct comprising a regulatable promoter and a nucleic acid molecule encoding a POI under the transcriptional control of said promoter, comprising the steps a) cultivating the cell line with a basal carbon source repressing the promoter, b) cultivating the cell line with a limited amount of a supplemental carbon source de-repressing the promoter to induce production of the POI at a transcription rate of at least 15% as compared to the native pGAP promoter, and c) producing and recovering the POI; and further an isolated regulatable promoter and a respective expression system.

Abstract: Compositions of small molecules, matrices, and isolated cells including methods of preparation, and methods for differentiation, trans-differentiation, and proliferation of animal cells into the osteoblast blast cell lineage were described. Examples of osteogenic materials that were administered to cells or co-cultured with cells are represented by compounds of Formula II, IV, and VI independently or preferably in combination with a matrix to afford bone cells. Small molecule-stimulated cells were also combined with a matrix, placed with a cellular adhesive or material carrier and implanted to a site in an animal for bone repair. Matrix pretreated with compounds of Formula II, IV, and VI were also used to cause cells to migrate to the matrix that is of use for therapeutic purposes.

Abstract: The invention provides nitrile-containing protease inhibitors caged to ruthenium compounds. The nitrile-caged ruthenium compounds provide inactivated inhibitors that can be delivered to surface or site for activation, for example, but exposure to light. The invention also provides methods for delivering protease inhibitors to subjects for the therapeutic treatment of conditions such as cancer.

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

Abstract: The present invention provides the use of recombinant plasminogen activator inhibitor-1 (PAI-1) isoform 23 in methods of increasing plasmin activity, inhibiting angiogenic vasa vasorum, promoting plaque regression and treating atherosclerosis by administering to a subject in need of treatment an effective amount of recombinant plasminogen activator inhibitor type isoform 23 (rPAI-123). In some embodiments, rPAI-123 is set forth in SEQ ID NOs:5-8. In other embodiments, rPAI-123 is administered at a dose in the range of approximately 2.5 ?g/kg/day to 20 ?g/kg/day. In further embodiments, the effective amount achieves a ratio of rPAI-123 to PAI-1 is in the range of approximately 1:2 to 3:1.

Abstract: The present invention discloses a sensor chip for screening a topoisomerase inhibitor and a screening method thereof. The sensor chip comprises topoisomerase I and a biochip. The topoisomerase I is immobilized on the biochip, and the topoisomerase I has DNA catalytic activity. This provides a rapid screening method for topoisomerase I inhibitors.

Abstract: The present invention relates to an improved method for the serum-free production of an immortalized human cell line stably transfected under serum-free conditions with a specific vector carrying the gene coding for the protein of interest. Furthermore the invention relates to a production cell line obtained by said method, a production method for said protein of interest utilizing said production cell line, and the specific vector carrying the gene of interest itself.

Abstract: The present invention relates to a method for increased production of a secreted, recombinant protein product through the introduction of molecular chaperones in a mammalian host cell. The present invention also relates to a mammalian host cell with enhanced expression of a secreted recombinant protein product by coexpressing at least one chaperone protein.

Abstract: The present invention relates to the provision of a DNA sequence of the major grass pollen allergen Lol p 4. The invention also encompasses fragments, new combinations of partial sequences and point mutants having a hypoallergenic action. The recombinant DNA molecules and the derived polypeptides, fragments, new combinations of partial sequences and variants can be utilised for the therapy of pollen-allergic diseases. The proteins prepared by recombinant methods can be employed for in vitro and in vivo diagnosis of pollen allergies.

Abstract: The methods and compositions described herein are based, in part, on the discovery of a polypeptide of soluble CD23 (sCD23) that binds and sequesters IgE. Thus, the sCD23 peptides, polypeptides and derivatives described herein are useful for treating conditions or disorders involving increased IgE levels such as e.g., allergy, anaphylaxis, inflammation, lymphoma, and certain cancers.

Abstract: The present invention relates to the field of insect pests control, using methods and compositions which comprise of alpha-amylase analogous mutant inhibitors (?AIs). More specifically, the invention provides new ?AIs analogous mutant molecules for controlling insect pests, in particular boll weevils (Anthonomus grandis), partially or totally presenting reduction of the amylolytic activity of the digestive enzymes in the intestinal lumen of the insect. Other aspects of the invention include gene constructs containing the nucleic acid molecules that code for the alpha-amylase inhibitors, heterologous expression methods of the new molecules in the active form, and the use of these molecules for controlling insect pests. The invention also provides analogous synthetic genes optimized for their transformation and expression in plants.

Abstract: The present invention relates to methods for inhibiting myostatin, a regulator of muscle mass, for muscle enhancement (including inducing hypertrophy and/or hyperplasia) as well as improving muscle function (including decreasing atrophy and/or increasing endurance, force and/or strength). Some of the methods involve delivering genes to cells using viral vectors such as a recombinant Adeno-associated virus (rAAV), lentivirus or equine-associated virus, or using other delivery techniques known in the art in order to inhibit myostatin. Examples of genes to be delivered are genes encoding proteins such as Follistatin, Follistatin-related gene-1 (FLRG-1), growth differentiation factor associated protein-1 (GASP-1) and myostatin precursor propeptide. In other methods of the invention, expression of proteins such as activin IIb and myostatin is inhibited by oligonucleotide techniques to effect muscle enhancement.

Abstract: A hypoglycemic effect enhancer for enhancing the activity of an ?-glucosidase inhibitor, the enhancer comprising at least one kind of bacteria selected from the group consisting of bifidobacteria, lactic acid bacteria, saccharifying bacteria, and butyric acid bacteria.

Abstract: A method of producing ?-santalene by contacting at least one polypeptide with farnesyl pyrophosphate (FPP). This method may be carried out in vitro or in vivo to produce ?-santalene, a very useful compound in the fields of perfumery and flavoring. The present invention also provides the amino acid sequence of a polypeptide useful in the method of the invention. A nucleic acid encoding the polypeptide of the invention and an expression vector containing the nucleic acid are also disclosed, along with a non-human host organism or a cell transformed to be used in the method of producing ?-santalene.

Abstract: A recombinant filamentous fungal cell (e.g. Aspergillus) having one or more inactivated chromosomal genes is provided. The chromosomal genes in some embodiments correspond to derA, derB, htmA, mnn9, mnn10, ochA, dpp4, dpp5, pepAa, pepAb, pepAc, pepAd, pepF and combinations thereof. The recombinant fungal cells may include further inactivated chromosomal genes which correspond to pepA, pepB, pepC and pepD. The recombinant filamentous fungal cells may include a heterologous nucleic acid encoding a protein of interest. Also provided are methods of producing a protein of interest in said recombinant filamentous fungal cell.

Abstract: Compositions and methods are disclosed that relate to novel plasmin-inhibiting polypeptides that are structural variants of a human TFPI-2 Kunitz-type proteinase first inhibitor domain (KD1). The polypeptides are potent plasmin inhibitors and in certain embodiments have anti-fibrinolytic activity and/or decreased anti-coagulation activity relative to wild-type TFPI-2 KD1 and are not highly immunogenic. The plasmin-inhibiting polypeptides will find uses as anti-cancer agents, as antifibrinolytic agents, as protease inhibitors, and in other contexts.

Abstract: This invention relates to industrial production of proteins. More specifically, the invention relates to the res-DHFR surrogate marker, which corresponds to a fusion between DHFR and a protein conferring resistance to a toxic compound or conferring a metabolic advantage. The invention further relates to the use of res-DHFR for screening cells for high expression of a protein of interest. The invention is illustrated by the Puro-DHFR surrogate marker, which corresponds to a fusion between the puromycin N-acetyltransferase and dihydrofolate reductase (DHFR).

Abstract: Provided herein are methods for treating and preventing neurodegenerative disease in a mammal by administering an inhibitor of glutaminyl cyclase (QC). Neurodegenerative diseases treatable or preventable according to methods described herein include mild cognitive impairment (MCI), Alzheimer's disease, neurodegeneration in Down Syndrome, Familial British Dementia, and Familial Danish Dementia.

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 present invention refers to protein kinase inhibitors and more specifically to inhibitors of the protein kinase c-Jun amino terminal kinase. Additionally, the present invention provides JNK inhibitor sequences, chimeric peptides, nucleic acids encoding same as well as pharmaceutical compositions for treating pathophysiologies associated with JNK signaling.

Abstract: This invention provides for a novel means of incorporating non-native amino acids into preselected positions of a protein using a cell-free synthesis system. The methods involve the use of non-orthogonal, native isoaccepting sense tRNAs that are encoded by the genetic code. Such methods allow for numerous non-native amino acids to be incorporated through the use of sense codons without having to rely upon orthogonal tRNA-synthetase pairs.

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 provides improved fusion proteins for therapy of autoimmune and cardiovascular disease.

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: It is intended to provide an inhibitor for the formation of a ?-secretase complex which comprises a cholesterol synthesis inhibitor or a protein geranylgeranylation regulator as the active ingredient; and use of a cholesterol synthesis inhibitor or a protein geranylgeranylation regulator for producing the same. It is also intended to provide a method of screening a substance having an effect of inhibiting the formation of an active complex of ?-secretase which comprises assaying the activity of inhibiting cholesterol synthesis or quantifying cholesterol accumulated in lipid rafts in cells. It is also intended to provide a method of screening a cholesterol synthesis inhibitor, a protein geranylgeranylation regulator or an HMG-CoA reductase inhibitor which comprises assaying the effect of inhibiting the formation of an active complex of ?-secretase.

Abstract: A method for rapidly and highly sensitively measuring endotoxin is provided. Endotoxin is measured using an endotoxin-measuring agent comprising the proteins (1) to (3) below, each of which is a recombinant protein obtainable by being expressed using insect cells as a host: (1) a factor C derived from Tachypleus tridentatus, which factor C does not have a His-tag sequence at the C-terminus; (2) a factor B of a horseshoe crab; and (3) a proclotting enzyme of a horseshoe crab.

Abstract: The disclosure provides methods and compositions useful for culturing stem cell including embryonic stem cells, adult stem cells, and embryonic germ cells.

Abstract: This invention relates to molecules, particularly polypeptides, more particularly fusion proteins that include a serpin polypeptide or an amino acid sequence that is derived from a serpin and second polypeptide comprising of at least one the following: an Fc polypeptide or an amino acid sequence that is derived from an Fc polypeptide; a cytokine targeting polypeptide or a sequence derived from a cytokine targeting polypeptide; a WAP domain containing polypeptide or a sequence derived from a WAP containing polypeptide; and an albumin polypeptide or an amino acid sequence that is derived from a serum albumin polypeptide. This invention also relates to methods of using such molecules in a variety of therapeutic and diagnostic indications, as well as methods of producing and purifying such molecules.

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 present invention is directed to the use of a compound capable of reducing the uric acid level in a mammal for the prevention and/or the treatment of IL-I? driven lung pathology, particularly to treat lung inflammation such as chronic fibrosis, COPD and interstitial fibrosis and other IL-1? driven lung pathologies including those of autoimmune origin. Preferred compounds capable of reducing the uric acid level are selected from the group consisting of xanthine oxidase inhibitors, such as allopurinol, recombinant enzyme uricase and uricosuric compound capable of enhancing uric acid excretion, such as probenecid. The invention further relates to a method for identifying in vitro whether a patient presents an IL-1? driven lung pathology or is at risk to develop an IL-1? driven lung pathology, or for the screening of a compound for treating an IL-1? driven lung pathology.

Abstract: The invention relates to a filamentous fungal cell (e.g., Aspergillus sp.) comprising at least one inactivated protease gene chosen from apsB, a homolog of apsB, cpsA, a homolog cpsA, and combinations thereof. Nucleic acids and methods for making the inactivated mutant filamentous fungal cells are provided as well as methods for using the cells for the altered production of endogenous or heterologous proteins of interest.

Abstract: The invention provides an improved process for preparing romidepsin. The process involves producing, purifying, or storing romidepsin under conditions that prevent the formation of undesired adducts. Purifying romidepsin at an apparent pH lower than approximately 6.0 (e.g., between an apparent pH of 4.0 and 6.0) has been discovered to prevent the reduction of the disulfide bond of romidepsin and the subsequent formation of dimerized, oligomerized, or polymerized adducts. The invention also provides pharmaceutical compositions of monomeric romidepsin free of dimerized, oligomerized, or polymerized adducts.

Abstract: The current invention discloses novel methods for the inhibition of inducible nitric oxide synthesis (iNOS) and the production of NO. Methods of inhibiting the induction of proinflammatory cytokines are also described. Methods of treating various disease states, such as X-linked adrenoleukodystrophy, multiple sclerosis, Alzheimer's and septic shock using inhibitors of iNOS and cytokine induction are disclosed. The inhibitors include the exemplary compounds lovastatin, a sodium salt of phenylacetic acid (NaPA), FPT inhibitor II, N-acetyl cysteine (NAC), and cAMP.

Abstract: The invention relates to thrombin inhibitors derived from the salivary glands of haematophagous arthropods and in particular to bivalent and trivalent thrombin inhibitors that act by interacting with thrombin at two or three different sites.

Abstract: The present invention is to provide a polypeptide specifically inhibiting the activity of Akt (Protein Kinase B), the DNA thereof, the antibody thereof, an inhibitor of Akt activity or an antitumor agent, and the like. The polypeptide comprises polypeptides (SEQ ID NO: 1, 3, 5, 7, and 9 of the sequence listing) that contain an amino acid sequence corresponding to any of the position of amino acid residue 10-24 of human TCL1, amino acid residue 8-22 of human TCL1B, amino acid residue 5-19 of human MTCP1, and amino acid residue 9-24 of mouse or rat TCL1; and the derivatives. Further, the present invention includes DNA encording the polypeptide (SEQ ID NO: 2, 4, 6, 8 or 10 of the sequence listing), and the antibodies specifically binding to the polypeptides. The polypeptide of the present invention can be used for an inhibitor of Akt activity, an antitumor agent, or the like.

Abstract: The invention provides isolated nucleic acid molecules, designated PGC-1? nucleic acid molecules, which encode novel PGC-1 related coactivator molecules. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing PGC-1? nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a PGC-1? gene has been introduced or disrupted. The invention still further provides isolated PGC-1? proteins, fusion proteins, antigenic peptides and anti-PGC-1? antibodies. Diagnostic and therapeutic methods utilizing compositions of the invention are also provided.

Abstract: The present invention provides a telomerase activity inhibiting polypeptide. The expression of the polypeptide in tumor cells can inhibit significantly tumor cell telomerase activity, tumor cell growth, and lead to the death of such cells. The present invention further provides a preparation method for the polypeptide and an application thereof in targeted treatments of tumors.

Abstract: Vector constructs comprising the coding sequence for human C1 inhibitor are described. Expression of glycosylated recombinant human C1 inhibitor is achieved human cells in high yields.

Abstract: The various embodiments herein provide a cell growth inhibitor derived from p16INK4a gene comprising a C-terminal segment of the p16INK4a gene, two ankyrin repeats i.e. ankyrin III and ankyrin IV of the p16INK4a gene, two loops i.e. loop 2 and loop 3 of the p16INK4a gene and residues along with the loop 2 consisting Phe90, Glu88, Gly89, Asp92 and Asp84 residues. The cell growth inhibitor is a truncated form of the p16INK4a gene and encompasses 66-156 amino acids of a full length p16INK4a gene. The cell growth inhibitor has 42% growth inhibition at 24 hrs. The embodiments herein also provide a method of synthesizing the cell growth inhibitor using a polymer chain reaction method.

Abstract: The present invention relates to an efficient production method of xylitol by using the xylitol producing microorganism introduced with arabinose metabolic pathway to inhibit the production of arabitol, the byproduct, and instead to use arabinose only for cell metabolism in xylose/arabinose mixed medium. More precisely, to express efficiently L-arabinose isomerase (araA), L-ribulokinase (araB) and L-ribulose-5-phosphate 4-epimerase (araD) in Candida tropicalis, codon optimization was performed. Then, each gene was inserted in the gene expression cassette containing the glyceraldehyde-3-phosphate dehydrogenase promoter and the selection marker URA3, which was introduced into Candida sp. microorganism. As a result, arabitol, the byproduct interrupting the purification and crystallization of xylitol could be inhibited, making the production method of xylitol of the present invention more efficient.

Abstract: The present invention provides: (1) antiviral agents that act by reducing or inhibiting the activity of SR proteins, more specifically, (i) antiviral agents that act by enhancing dephosphorylation of SR proteins, and (ii) antiviral agents that act by inhibiting proteins that phosphorylate SR proteins; (2) antiviral agents that act by inhibiting the expression of SR proteins, and (3) antiviral agents that act by activating proteins that antagonize SR proteins. The present invention also provides compounds that inhibit SRPKs, which phosphorylate SR proteins. Such compounds inhibit the activity of SR proteins and have antiviral activities. Various new viruses including SARS have emerged, and thus the present invention provides long-lasting broad-spectrum antiviral agents applicable to new viruses.

Abstract: LSD1, a homolog of nuclear amine oxidases, functions as a histone demethylase and transcriptional co-repressor. LSD1 specifically demethylates histone H3 lysine 4, which is linked to active transcription. Lysine demethylation occurs via an oxidation reaction that generates formaldehyde. Importantly, RNAi inhibition of LSD1 causes an increase in H3 lysine 4 methylation and concomitant de-repression of target genes, suggesting that LSD1 represses transcription via histone demethylation. The results thus identify a histone demethylase conserved from S. pombe to human and reveal dynamic regulation of histone methylation by both histone methylases and demethylases.

Abstract: The present invention relates to isolated polypeptides having cellulolytic enhancing activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods for producing and using the polypeptides.

Abstract: This invention provides a method of preventing or treating in a subject contact dermatitis which comprises administering to the subject an amount of a compound capable of inhibiting the stem cell factor signaling pathway effective to prevent or treating contact dermatitis so as to thereby prevent or treat contact dermatitis in the subject. This invention also provides a method of preventing or treating in a subject hyperpigmentation, asthma, cutaneous inflammation, anaphylaxis and bronchospasm, mastocytosis, tumors which express activated kit, and conception.

Abstract: Methods for producing proteins and glycoproteins in Pichia pastoris that lack detectable cross binding activity to antibodies made against host cell antigens are described. In particular, methods are described wherein recombinant Pichia pastoris strains that do not display a ?-mannosyltransferase 2 activity with respect to an N-glycan or O-glycan and do not display at least one activity selected from a ?-mannosyltransferase 1, 3, and 4 activity to produce recombinant proteins and glycoproteins. These recombinant Pichia pastoris strains can produce proteins and glycoproteins that lack detectable ?-mannosidase resistant ?-mannose residues thereon and thus, lack cross binding activity to antibodies against host cell antigens. Further described are methods for producing bi-sialylated human erythropoietin in Pichia pastoris that lack detectable cross binding activity to antibodies against host cell antigens.

Abstract: The present disclosure relates to a method for producing heterologous protein including: (c) providing a host cell comprising a 2 ?m-family plasmid, the plasmid comprising a gene encoding a protein comprising the sequence of a chaperone protein and a gene encoding a heterologous protein; (d) culturing the host cell in a culture medium under conditions that allow the expression of the gene encoding the chaperone protein and the gene encoding a heterologous protein; (e) purifying the thus expressed heterologous protein from the cultured host cell or the culture medium.

Abstract: Antagonists of human proprotein convertase subtilisin-kexin type 9 (“PCSK9”) are disclosed. The disclosed antagonists are effective in the inhibition of PCSK9 function and, accordingly, present desirable antagonists for use in the treatment of conditions associated with PCSK9 activity. The present invention also discloses nucleic acid encoding said antagonists, vectors, host cells, and compositions comprising the antagonists. Methods of making PCSK9-specific antagonists as well as methods of using the antagonists for inhibiting or antagonizing PCSK9 function are also disclosed and form important additional aspects of the present disclosure.

Abstract: The invention provides a method for producing polypeptide protein products and nucleic acid products having reduced levels of antigenicity in an animal being treated with a biologic product. Somatic cells are isolated from an animal, transformed into pluripotent stem cells, transfected with a nucleic acid(s) of interest, and re-differentiated towards somatic cells known to be high level producers of the desired nucleic acid product. The invention can be used to derive a general cell line to treat populations, racial specific cell lines to treat ethnic groups, or patient specific cell lines to treat individuals. Additionally, the invention provides a method to allow induced pluripotent stem cells to be re-differentiated towards their somatic cell of origin so that the cells can be used to therapeutically treat an animal without resulting teratoma formation.

Abstract: The present invention relates to the design of trimeric polypeptides using polypeptide structural elements derived from the tetranectin protein family, and their use in rational de novo design and production of multi-functional molecules including the application of the multi-functional molecules in protein library technology, such as phage display technology, diagnostic and therapeutic systems, such as human gene therapy and imaging. The trimeric polypeptides being constructed as a monomer polypeptide construct comprising at least one tetranectin trimerising structural element (TTSE) which is covalently linked to at least one heterologous moiety, said TTSE being capable of forming a stable complex with two other TTSEs; or as an oligomer which is comprised of two monomer polypeptide constructs as mentioned above, and which comprises three TTSEs or a multiplum of three TTSEs, or which is comprised of three monomer polypeptide constructs.

Abstract: Methods and compositions are provided for assaying for enzymes capable of releasing an enzyme donor fragment (ED) conjugated to a nucleic acid strand bonded to a surface. Conveniently, the beads are magnetic allowing segregation of the beads during the determination. Upon addition of enzyme acceptor fragment (EA) and substrate to the assay mixture, the method allows for discrimination between ED free in solution and ED bound to the bead. The complexing of ED and EA provides an active ?-galactosidase enzyme. The method permits the assay of any substance involved in a pathway that can result in a reaction releasing the ED.