Abstract: The invention provides a method for increasing the stability and/or activity of a polypeptide at low pH and/or elevated temperatures. The invention further provides a method for increasing the melting temperature of a polypeptide. Also provided are paleoenzymologically reconstructed thioredoxin polypeptides having activity at higher temperatures and/or lower pH than extant thioredoxin polypepetides, as well as paleoenzymologically reconstructed thioredoxin polypeptides having higher melting temperatures than extant thioredoxin polypepetides.

Abstract: Engineered fusion proteins comprising photochromic protein domains are disclosed. In particular, the inventors have constructed fusion proteins containing photoswitchable photochromic fluorescent protein domains linked to selected proteins and shown that such fusion proteins can be used to control the activity or localization of selected proteins with light.

Abstract: Provided herein are methods and recombinant expression systems for the production of recombinant glycoproteins that have increased sialic acid content and contain predominantly alpha2-6 sialic acid linkages. Also provided herein are recombinant glycoproteins that have an increased in vivo circulatory half-life. One potential application of the glycoproteins described herein is for the treatment and prophylaxis of poisoning by neurotoxins.

Abstract: Disclosed are a novel expression vector for efficient expression of recombinant proteins in mammalian cells, a mammalian cell transformed with the vector, and a method for production of the mammalian cell. The expression vector includes a gene expression regulatory site, and a gene encoding the protein downstream thereof, and an internal ribosome entry site further downstream thereof, and a gene encoding a glutamine synthetase further downstream thereof.

Abstract: The present invention relates to humanized antibodies that specifically bind to CXCR5 and can, for example, inhibit CXCR5 function. The invention also includes uses of the antibodies to treat or prevent CXCR5 related diseases or disorders.

Abstract: The present invention provides an expression vector for the production of proteins and peptides comprising a promoter operably linked to gene of interest, TPL and VA genes I and II, matrix attachment regions (MARs)/SARs, and antibiotic marker. The vector is transfected in suitable host cell.

Abstract: Polypeptides comprising at least one carboxy-terminal peptide (CTP) of chorionic gonadotrophin attached to the carboxy terminus but not to the amino terminus of a coagulation factor and polynucleotides encoding the same are disclosed. Pharmaceutical compositions comprising the polypeptides and polynucleotides of the invention and methods of using and producing same are also disclosed.

Abstract: In certain aspects, the present invention provides compositions and methods for increasing red blood cell and/or hemoglobin levels in vertebrates, including rodents and primates, and particularly in humans.

Abstract: The invention generally features compositions and methods based on the structure-based design of alpha 1-3 N-Acetylgalactosaminyltransferase (alpha 3 GalNAc-T) enzymes from alpha 1-3galactosyltransferase (a3Gal-T) that can transfer 2?-modified galactose from the corresponding UDP-derivatives due to substitutions that broaden the alpha 3Gal-T donor specificity and make the enzyme a3 GalNAc-T.

Abstract: Disclosed are useful constructs and methods for the expression of proteins using primary translation products that are processed within a recombinant host cell. Constructs comprising a single open reading frame (sORF) are described for protein expression including expression of multiple polypeptides. A primary translation product (a pro-protein or a polyprotein) contains polypeptides such as inteins or hedgehog family auto-processing domains, or variants thereof, inserted in frame between multiple protein subunits of interest. Also disclosed are independent aspects of conducting efficient expression, secretion, and/or multimeric assembly of proteins such as immunoglobulins.

Abstract: A fusion protein comprising factor VII (FVII) and transferrin according to the present invention has an improved specific activity of FVII compared to existing FVII fusion proteins comprising other fusion partners than transferrin, and thus can be effectively used in a therapy using FVII.

Abstract: Disclosed is a modified iduronate-2-sulfatase (IDS) gene constructed by inserting the nucleotide of SEQ ID NO: 2 into a wild-type IDS gene. In addition to being negatively charged, the improved IDS enzyme encoded by the modified gene exhibits a sufficient retention time in blood to target the bone, so that it is more effective for treating Hunter syndrome.

Abstract: An in vitro system for generating sequence, and thus structural, diversity in proteins is described. The system can be constructed using appropriately selected nucleic acid molecules that encode regions of a selected protein or proteins and recombination signal sequences (RSS). The selected protein(s) can be, for example, immunoglobulin (Ig) V, D, J and/or C regions, regions of a non-immunoglobulin (non-Ig) protein, or a combination of Ig regions and non-Ig regions. Assembly of such appropriately selected components and their introduction into suitable recombination-competent host cells allows for recombination between the RSS sequences and introduction of sequence and structural diversity into the protein(s).

Abstract: A process for high expression of protein of interest using an expression vector. The process comprises at least the following regulatory elements: a) a CMV promoter, or a functional variant thereof, b) an intron, c) TPL or a functional variant thereof, d) VA gene or a functional variant thereof, and e) a bovine growth hormone polyadenylation sequence or a functional variant thereof.

Abstract: The present invention relates to a trimeric fusion protein comprising three polypeptide chains, wherein each polypeptide chain comprises a eukaryotic collagen or collagen-like domain and a prokaryotic or viral trimerisation domain (PVTD). Also provided is a fusion polypeptide comprising a eukaryotic collagen or collagen-like domain and a PVTD. A suitable PVTD of a fusion polypeptide or protein of the invention is preferably derived from a collagen-like protein sequence found in the genome of the E. coli strain O157:H7 and other E. coli strains, and in bacteriophages or prophages infecting these strains or embedded in their genomes. A PVTD mediates trimerisation of collagen or collagen like polypeptides.

Abstract: The present invention relates to nucleic acid fragments and constructs comprising genomic nucleotide sequences from the promoter region of a 60S ribosomal protein L32 gene (RPL32), for the production of a gene product of interest in a eukaryotic, preferably mammalian, host cell in the presence of a stringent selectable marker. The invention further relates to host cells comprising the nucleic acid constructs, to methods for generating the host cells and to methods for producing a gene product of interest using the host cells.

Abstract: The present invention provides a novel expression vector which comprises a gene of interest, a nuclear anchoring element, and at least one inverted repeat element, preferably two inverted repeat elements. The expression vector is an episomal vector capable of transfecting a mammalian cell. The present invention further provides a method for enhancing gene expression by transfecting the expression vector to a mammalian cell, preferably a human cell.

Abstract: The present invention relates to animal protein-free cell culture media comprising polyamines and a plant- and/or yeast-derived hydrolysate. The invention also relates to animal protein-free culturing processes, wherein cells can be cultivated, propagated and passaged without adding supplementary animal proteins in the culture medium. These processes are useful in cultivating cells, such as recombinant cells or cells infected with a virus, and for producing biological products by cell culture processes.

Abstract: The present disclosure provides methods and compositions for diagnosis and for providing a prognosis of a cancer patient by assessing CK2 alpha 1 pseudogene (CSNK2A1P) status. The present disclosure also provides polypeptide, polynucleotide, host cell, and transgenic animal compositions associated with CSNK2A1P.

Abstract: Disclosed are methods and isolated cells useful for the improved production of function fXa derivative protein that acts as a fXa inhibitor antidote. One aspect relates to an isolated cell comprising the r-Antidote polynucleotide and Furin polynucleotide. Another aspect relates to a method for preparing the cleaved two-chain r-Antidote by expressing, in a cell, the pre-processed r-Antidote polypeptide and a Furin polypeptide.

Abstract: Novel collectin related molecules i.e., a novel collectin gene comprising a nucleotide sequence set out in SEQ ID NO: 1, and a novel collectin comprising an amino acid sequence set out in SEQ ID NO: 2, which are expected to exhibit anti-bacterial, anti-viral activity or the like especially in human body, and methods in which these molecules are used are provided.

Abstract: The present invention relates to novel chimeric molecules of ficolin-associated polypeptides, such as fusion polypeptides for the use in the treatment of conditions associated with inflammation, apoptosis, autoimmunity, coagulation, thrombotic or coagulopathic related diseases. The present invention further relates to nucleic acid molecules encoding such fusion polypeptides, vectors and host cells used in the production of the fusion polypeptides.

Abstract: The present invention relates to a fusion protein having a TAL (transcription activator-like) effector (TALE) domain and a nucleotide cleavage domain, and more particularly, to the TAL effector nuclease comprising a TAL (transcription activator-like) effector (TALE) domain and a nucleotide cleavage domain, wherein the TALE domain includes one or more TALE-repeat modules, each of the TALE-repeat modules recognizing a single specific nucleic acid, and a use thereof.

Abstract: Chimeric clotting factors which localize the therapeutic to sites of coagulation (e.g., by being targeted to platelets or being activatable at sites of coagulation), have reduced clearance rates, have improved manufacturability, have reduced thrombogenicity, have enhanced activity, or have more than one of these characteristics are described as are methods for making chimeric clotting factors and methods for improving hemostasia using these clotting factors.

Abstract: The present invention includes the complete genome sequence for the methanogen, Methanobrevibacter ruminantium, including polynucleotides which encode M. ruminantium polypeptides or peptides, as well as polynucleotides from non-coding regions. Also included are the encoded M. ruminantium polypeptides and peptides, and antibodies directed to these peptides or polypeptides, in addition to expression vectors and host cells for producing these peptides, polypeptides, polynucleotides, and antibodies. The invention further includes methods and compositions for detecting, targeting, and inhibiting microbial cells, especially methanogen cells such as M. ruminantium cells, using one or more of the disclosed peptides, polypeptides, polynucleotides, antibodies, expression vectors, and host cells.

Abstract: Disclosed is a composition of matter involving a recombinant fusion protein comprising a a pharmacologically active protein partner, and a small pharmacologically inactive protein domain partner of human origin, such as but not limited to, a 10th fibronectin III domain, a SH3 domain, a SH2 domain, a CH2 domain of IgG1, a PDZ domain, a thrombospondin repeat domain, an ubiquitin domain, a leucine-rich repeat domain, a villin headpiece HP35 domain, a villin headpiece HP76 domain, or a fragment or modification of any of these. Also disclosed are nucleic acids (e.g., DNA constructs) encoding the fusion protein, expression vectors and recombinant host cells for expression of the fusion protein, and pharmaceutical compositions containing the recombinant fusion protein and a pharmaceutically acceptable carrier, and method of producing a pharmacologically active recombinant fusion protein.

Abstract: Human G-protein chemokine receptor polypeptides and DNA (RNA) encoding such polypeptides and a procedure for producing such polypeptides by recombinant techniques is disclosed. Also disclosed are methods for utilizing such polypeptides for identifying antagonists and agonists to such polypeptides and methods of using the agonists and antagonists therapeutically to treat conditions related to the underexpression and overexpression of the G-protein chemokine receptor polypeptides, respectively. Also disclosed are diagnostic methods for detecting a mutation in the G-protein chemokine receptor nucleic acid sequences and detecting a level of the soluble form of the receptors in a sample derived from a host.

Abstract: The invention concerns the field of cell culture technology. It concerns production host cell lines with increased expression of ribosomal RNA (rRNA) achieved through reducing expression of NoCR proteins, especially of TIP-5. Those cell lines have improved secretion and growth characteristics in comparison to control cell lines. The invention further concerns a method of producing proteins using the cells generated by the described method.

Abstract: The present invention relates to fibronectin based scaffold domain proteins that bind PCSK9. The invention also relates to the use of the innovative proteins in therapeutic applications to treat atherosclerosis, hypercholesterolemia and other cholesterol related diseases. The invention further relates to cells comprising such proteins, polynucleotides encoding such proteins or fragments thereof, and to vectors comprising the polynucleotides encoding the innovative protein.

Abstract: The present invention relates to a nucleic acid molecule encoding a chimeric protein having the biochemical activity of a surface active protein, wherein said chimeric protein comprises: (a) an N-terminal portion of a first surface active protein, wherein the N-terminal portion is devoid of between 0 and 10 of the most N-terminal amino acids of the mature first surface active protein; and, C-terminally thereof, (b) a C-terminal portion of a second surface active protein, wherein the C-terminal portion is devoid of between 0 and 10 of the most C-terminal amino acids of the mature second surface active protein. The present invention further relates to a vector, a non-human host and a method for the production of a chimeric protein having the biochemical activity of a surface active protein. In addition, the present invention relates to a chimeric protein encoded by the nucleic acid molecule of the invention and a composition comprising the chimeric protein.

Abstract: The present invention relates to fluorescent proteins, in particular green fluorescent proteins (GFPs), with increased activity in cells, and thus increased signal strength. A further aspect of the present invention relates to the use of peptides for increasing the expression and/or stability of a protein in a cell.

Abstract: There is provided a method to increase the production of a desired protein in a microorganism by introduction of slowly translated codons in the encoding DNA gene sequence capable of slowing down the translation speed of the ribosomes moving along the mRNA, whereby the ribosomes protect the mRNA from being enzymatically degraded. This increases the stability of the mRNA transcript and thus results in an increased production of the desired protein. Moreover, there is provided a method of decreasing the half-life of a mRNA transcript from a gene encoding a peptide.

Abstract: The present invention relates to human secreted polypeptides, and isolated nucleic acid molecules encoding said polypeptides, useful for diagnosing and treating diseases, disorders, and/or conditions (such as immune, cardiovascular, cancer, and other proliferative diseases, disorders, and/or conditions) related to said human secreted proteins. Antibodies that bind these polypeptides are also encompassed by the present invention. Also encompassed by the invention are vectors, host cells, and recombinant and synthetic methods for producing said polynucleotides, polypeptides, and/or antibodies. The invention further encompasses screening methods for identifying agonists and antagonists of polynucleotides and polypeptides of the invention. The present invention further encompasses methods and compositions for inhibiting or enhancing the production and function of the polypeptides of the present invention.

Abstract: The present invention provides nucleic acid molecules encoding novel red fluorescent proteins from Entacmaea quadricolor and mutants thereof. Also of interest are proteins that are substantially similar to the novel red fluorescent proteins. In addition, host cells, stable cell lines and transgenic organisms comprising the nucleic acid molecules encoding the novel red fluorescent proteins are provided. The subject proteins and nucleic acid compositions find use in a variety of different applications and methods, particularly for labeling of biomolecules, cells, or cell organelles. Finally, kits for use in such methods and applications are provided.

Abstract: Engineered multivalent and multispecific binding proteins that bind two different (e.g., nonoverlapping) epitopes of the same receptor or two different receptors expressed on the same cell are provided, along with methods of making and uses in the prevention, diagnosis, and/or treatment of disease.

Abstract: Provided herein are methods and compositions for expressing a modified polypeptide in a host cell, wherein the modified polypeptide comprises a terminal mannose at an N-linked glycosylation site of the polypeptide. The methods and compositions used herein involve the use of RNA effector molecules (e.g., siRNA, dsRNA etc) administered to a host cell to modify the expression of target genes involved in protein glycosylation (e.g., Mgat1, Mgat4, SLC35A1, SLC35A2 or GNE).

Abstract: The present invention relates to potato virus NIa protease variants or fragments thereof, polynucleotides encoding them, and methods of making and using the foregoing.

Abstract: The invention concerns the field of protein production and cell culture technology. CERT is identified as a novel in vivo PKD substrate. Phosphorylation on serine 132 by PKD decreases the affinity of CERT towards its lipid target phosphatidylinositol 4-phosphate at Golgi membranes and reduces ceramide transfer activity, identifying PKD as a regulator of lipid homeostasis. The present invention shows that CERT in turn is critical for PKD activation and PKD dependent protein cargo transport to the plasma membrane. The interdependence of PKD and CERT is thus a key to the maintenance of Golgi membrane integrity and secretory transport.

Abstract: The invention concerns the prevention and treatment of complement-associated eye conditions, such as choroidal neovascularization (CNV) and age-related macular degeneration (AMD), by administration of Factor D antagonists.

Abstract: The present invention relates to the culture of animal cells in serum-free culture medium. The present invention provides particular dipeptides that can improve recombinant protein production and cell viability in such cultures, especially in the absence of peptones.

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: Described are parvovirus variants derived, e.g., from H-1PV, showing higher anti-tumor potential compared to the wild type parvovirus, wherein said variant is characterized by (a) an amino acid substitution, alteration or addition, preferably substitution at position Lys96 of NS-2 and/or position Leu103 of NS-2 (together with a amino acid substituion at position Tyr595 of NS-1 in the latter case), or (b) an in-frame deletion in the parvovirus genome, preferably a deletion resulting in a large amino acid deletion in both the central part (aa 96-133) of NS-2 and the C-terminal part (aa 587-624) of NS-1. The present invention also relates to the use of said parvovirus variants for cancer therapy.

Abstract: Methods for increasing viability and production of secreted proteins in fed batch eukaryotic cell culture are disclosed.

Abstract: The present application provides fibronectin based scaffold proteins associated with improved stability. The application also relates to stable formulations of fibronectin based scaffold proteins and the use thereof in diagnostic, research and therapeutic applications. The application further relates to cells comprising such proteins, polynucleotides encoding such proteins or fragments thereof, and to vectors comprising such polynucleotides.

Abstract: Provided are mRNA translational enhancer elements (TEEs), e.g., SEQ ID NOs:1-35. Also provided are translational enhancer polynucleotides that comprise one or more of the specific TEEs exemplified herein or their variants, homologs or functional derivatives. Further provided are expression vectors comprising such TEEs or translational enhancer polynucleotides, as well as host cells and expression systems that harbor such vectors.

Abstract: Modified Factor IX (FIX) polypeptides and uses thereof are provided. Such modified FIX polypeptides include FIXa and other forms of FIX. Among the modified FIX polypeptides provided are those that have altered activities, typically altered procoagulant activity, including increased procoagulant activities. Hence, such modified polypeptides are therapeutics.

Abstract: The invention concerns the field of protein production and cell culture technology. CERT is identified as a novel in vivo PKD substrate. Phosphorylation on serine 132 by PKD decreases the affinity of CERT towards its lipid target phosphatidylinositol 4-phosphate at Golgi membranes and reduces ceramide transfer activity, identifying PKD as a regulator of lipid homeostasis. The present invention shows that CERT in turn is critical for PKD activation and PKD dependent protein cargo transport to the plasma membrane. The interdependence of PKD and CERT is thus a key to the maintenance of Golgi membrane integrity and secretory transport.

Abstract: Disclosed are NgR proteins and biologically active Nogo (ligand) protein fragments. Also disclosed are compositions and methods for modulating the expression or activity of the Nogo and NgR protein. Also disclosed are peptides which block Nogo-mediated inhibition of axonal extension. The compositions and methods of the invention are useful in the treatment of cranial or cerebral trauma, spinal cord injury, stroke or a demyelinating disease.

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: The invention relates to a set of genetic constructs which allow the efficient and reproducible introduction of a specific nucleotide sequence at a fixed position in the genome by generating a double strand break at a specific position in the genome using a meganuclease and so stimulating a homologous recombination event at this locus between the genomic site and a transfected donor sequence. The present invention also relates to methods using these constructs and to these materials in the form of a kit.