Abstract: The present disclosure relates to variant CBH I polypeptides that have reduced product inhibition, and compositions, e.g., cellulase compositions, comprising variant CBH I polypeptides. The variant CBH I polypeptides and related compositions can be used in variety of agricultural and industrial applications. The present disclosure further relates to nucleic acids encoding variant CBH I polypeptides and host cells that recombinantly express the variant CBH I polypeptides.

Abstract: A flavin-binding glucose dehydrogenase (FAD-GDH), which in addition to having high substrate specificity and adequate desirable heat stability, is suitable for efficient production, preferably using E. coli, yeast or molds and the like as host cells. The FAD-GDH has amino acid substitutions at positions equivalent to one or more locations selected from the group consisting of position 213, position 368 and position 526 in the amino acid sequence described in SEQ ID NO: 8. The FAD-GDH is acquired from a culture by inserting a gene encoding the FAD-GDH into host cells such as E. coli. A preferable example of the FAD-GDH is FAD-GDH, in which a signal peptide region present in an N-terminal region has been deleted from the amino acid sequence of Mucor-derived FAD-GDH, and which has the aforementioned amino acid substitutions. The FAD-GDH can be preferably used in clinical diagnosis.

Abstract: The present invention relates to polypeptides having xylanase activity, catalytic domains, and carbohydrate binding domains, and polynucleotides encoding the polypeptides, catalytic domains, and carbohydrate binding domains. The present invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides, catalytic domains, and carbohydrate binding domains.

Abstract: Disclosed are novel acyl-CoA synthetases and novel acyltransferases, nucleic acid molecules encoding the same, recombinant nucleic acid molecules and recombinant host cells comprising such nucleic acid molecules, genetically modified organisms (microorganisms and plants) comprising the same, and methods of making and using the same. Also disclosed are genetically modified organisms (e.g., plants, microorganisms) that have been genetically modified to express a PKS-like system for the production of PUFAs (a PUFA PKS system or PUFA synthase), wherein the organisms have been modified to express an acyl-CoA synthetase, to express an acyl transferase, to delete or inactivate a fatty acid synthase (FAS) expressed by the organism, to reduce competition for malonyl CoA with the PUFA synthase or to increase the level of malonyl CoA in the organism, and in one aspect, to inhibit KASII or KASIII.

Abstract: Provided are isolated polypeptides having xylanase activity, catalytic domains and cellulose binding domains, and polynucleotides encoding the polypeptides, catalytic domains or cellulose binding domains. Also provided are nucleic acid constructs, vectors and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides, catalytic domains or cellulose binding domains.

Abstract: The present disclosure relates to novel lipocalin muteins which bind to PCSK9. The disclosure also provides corresponding nucleic acid molecules encoding lipocalin muteins and methods for producing lipocalin muteins as well as their encoding nucleic acid molecules.

Abstract: Bacteria that run the beta oxidation cycle in reverse anabolic direction are provided, along with many novel primers to start the reverse cycle, pathways to make such primers, and a large variety of products produced thereby. Methods for making desired product by using such primers in the reverse pathway are also disclosed.

Abstract: The present invention is directed to antibodies and fragments thereof having binding specificity for HGF. Another embodiment of this invention relates to the antibodies described herein, and binding fragments thereof, comprising the sequences of the VH, VL and CDR polypeptides described herein, and the polynucleotides encoding them. The invention also contemplates conjugates of anti-HGF antibodies and binding fragments thereof conjugated to one or more functional or detectable moieties. The invention also contemplates methods of making said anti-HGF antibodies and binding fragments thereof. Embodiments of the invention also pertain to the use of anti-HGF antibodies, and binding fragments thereof, for the diagnosis, assessment and treatment of diseases and disorders associated with HGF.

Abstract: The invention relates to an isolated nucleic acid sequence comprising a promoter, which is a native sequence of Pichia pastoris comprising the nucleic acid sequence of pCS1 of SEQ ID NO:1, or a functionally active variant thereof which is a size variant, a mutant or hybrid of SEQ ID NO:1, or a combination thereof, expression constructs and recombinant host cells comprising the promoter, and a method of producing a protein of interest under the control of the promoter. It further relates to a method to identify a constitutive promoter from eukaryotic cells, and an isolated nucleic acid sequence comprising a promoter which when operatively linked to a nucleotide sequence encoding a protein of interest directs the expression thereof in a host cell at an expression level that is higher than under control of the native pGAP promoter at high and low growth rates.

Abstract: The present invention is directed to antibodies and fragments thereof (especially chimeric and humanized) having binding specificity for HGF and their use in therapy and diagnosis. These antibodies inhibit or block HGF-associated activities including HGF's effects on cell proliferation, invasion, angiogenesis, metastasis and fibrosis. Particularly the antibodies may be used as a monotherapy or in combination therapies in treating cancer, other proliferative disorders and other conditions wherein inhibition of HGF and/or the HGF/HGF-R (c-met) interaction is desired.

Abstract: [Problem] An object of the present invention is to provide an anti-human IL-23R antibody having excellent activity and/or cross-reactivity compared to conventional IL-23R antibodies, and means for using the antibody to prevent or treat various diseases in which human IL-23R is involved in pathogenesis. [Means for Solution] An anti-human IL-23R antibody comprising a heavy-chain variable region consisting of the amino acid sequence shown by SEQ ID NO:5, 9, 13, 17, 21, 25 or 29 and a light-chain variable region consisting of the amino acid sequence shown by SEQ ID NO:7, 11, 15, 19, 23, 27 or 31.

Abstract: Methyl-lysine affinity reagents created by engineering the 3×MBT methyl-lysine binding domain repeat of lethal (3) malignant brain tumor-like protein 1 (L3MBTL1) are disclosed. In particular, the invention relates to affinity reagents and affinity chromatography media comprising the 3×MBT domain repeat and methods of using such affinity reagents in detection, purification, and proteomic profiling of methylated proteins and peptides.

Abstract: The present invention provides Fibroblast Growth Factor Receptor-Like (FGFR-L) polypeptides and nucleic acid molecules encoding the same. The invention also provides selective binding agents, vectors, host cells, and methods for producing FGFR-L polypeptides. The inventio further provides pharmaceutical compositions and methods for the diagnosis, treatment, amelioration, and/or prevention of diseases, disorders, and conditions associated with FGFR-L polypeptides.

Abstract: The present disclosure relates to polypeptides, including fusions thereof, nucleic acids, vectors, host cells, immunodiagnostic reagents, kits, and immunoassays for use detecting the presence of HCV antibodies. More specifically, the present invention describes specific NS3 antigens that can be used for the detection of anti-HCV antibodies.

Abstract: The present invention relates to systems and methods for propagating yeast using a feedstock material such as starch and one or more enzymes (e.g., an enzyme cocktail) to break down the feedstock material into one or more monosaccharides at a sufficient rate so that the yeast can use the monosaccharides as a carbon source for producing more yeast cells while not producing an undue amount of alcohol.

Abstract: The present invention relates to the field of G protein coupled receptor (GPCR) structural biology and signaling. In particular, the present invention relates to binding domains directed against and/or specifically binding to GPCR:G protein complexes. Also provided are nucleic acid sequences encoding such binding domains and cells expressing or capable of expressing such binding domains. The binding domains of the present invention can be used as universal tools for the structural and functional characterization of G-protein coupled receptors in complex with downstream heterotrimeric G proteins and bound to various natural or synthetic ligands, for investigating the dynamic features of G protein activation, as well as for screening and drug discovery efforts that make use of GPCR:G protein complexes.

Abstract: Provided herein are compositions and methods for improved production of acetyl-CoA and acetyl-CoA derived compounds in a host cell. In some embodiments, the host cell is genetically modified to comprise a heterologous nucleotide sequence encoding a phosphoketolase (PK), and a functional disruption of an endogenous enzyme that converts acetyl phosphate to acetate. In some embodiments, the host cell further comprises a heterologous nucleotide sequence encoding a phosphotransacetylase (PTA). In some embodiments, the enzyme that converts acetyl phosphate to acetate is a glycerol-1-phosphatase. In some embodiments, the glycerol-1-phosphatase is GPP1/RHR2. In some embodiments, the glycerol-1-phosphatase is GPP2/HOR2. The compositions and methods described herein provide an efficient route for the heterologous production of acetyl-CoA-derived compounds, including but not limited to, isoprenoids, polyketides, and fatty acids.

Abstract: Provided are binding polypeptides (e.g., antibodies), and drug conjugates thereof, comprising an Fc domain with an altered glycosylation profile and reduced effector function. In particular embodiment, the Fc domain comprises: an asparagine residue at amino acid position 298, according to EU numbering; and a serine threonine residue at amino acid position 300, according to EU numbering. Also provided are nucleic acids encoding the antigen-binding polypeptides, recombinant expression vectors and host cells for making such antigen-binding polypeptides. Methods of using the antigen-binding polypeptides disclosed herein to treat disease are also provided.

Abstract: The present invention is related to methods of propagating one or more organisms by using a carbon source that includes xylose (e.g., xylose syrup from pretreating lignocellulosic feedstock) and/or a nutrient source that includes a stillage component (e.g., thin stillage derived from a corn-to-ethanol process) in the propagation medium. The organisms include those that can convert one or more monosaccharides into an alcohol via fermentation, such as yeast. The present invention is also directed to related compositions.

Abstract: Disclosed are immunogens including a recombinant RSV F protein stabilized in a prefusion conformation. Also disclosed are nucleic acids encoding the immunogens and methods of producing the immunogens. Methods for generating an immune response in a subject are also disclosed. In some embodiments, the method is a method for treating or preventing a RSV infection in a subject by administering a therapeutically effective amount of the immunogen to the subject.

Abstract: Provided herein are glycerol-3-phosphate dehydrogenase (GPD) enzymes with increased KM for NADH and GPD enzymes with substantially the same affinity for NADH and NADPH and/or are feedback inhibited by glycerol-3-phosphate. Also provided herein are recombinant microorganisms comprising a heterologous gene encoding GPD and a deletion or disruption in an endogenous gene encoding GPD. Also provided are recombinant microorganisms comprising a heterologous gene encoding GPD and a butanol biosynthetic pathway. Further provided are methods of producing butanol comprising providing the recombinant microorganisms described herein and contacting the recombinant microorganism with at least one fermentable carbon substrate under conditions wherein butanol is produced.

Abstract: Methods of screening for dihydroxy-acid dehydratase (DHAD) variants that display increased DHAD activity are disclosed, along with DHAD variants identified by these methods. Such enzymes can result in increased production of compounds from DHAD requiring biosynthetic pathways. Also disclosed are isolated nucleic acids encoding the DHAD variants, recombinant host cells comprising the isolated nucleic acid molecules, and methods of producing butanol.

Abstract: Antibody variants having decreased or increased ability to mediate CDC due to modifications at the C-terminus of their heavy chains are described. Methods of generating such antibodies, as well as nucleotide constructs and host cells suitable for the production of said antibodies are also described.

Abstract: An object of the present invention is to provide a method for converting the coenzyme dependency of enzymes of the medium-chain dehydrogenase/reductase (MDR) family. A further object of the present invention is to provide enzyme variants of the MDR family whose coenzyme dependency is converted by the conversion method and a method for enzymatically producing optically active alcohols using the enzymes. The present inventors developed a novel enzyme conversion method for converting the coenzyme dependency of enzymes of the MDR family, rationally designed enzyme variants that are altered by the enzyme conversion method to be able to use NADPH as a coenzyme from a useful enzyme of the MDR family that uses NADH as a coenzyme, and actually provide variants having such an ability.

Abstract: Described is a method for the enzymatic production of butadiene which allows to produce butadiene from crotyl alcohol. Also described are enzyme combinations and compositions containing such enzyme combinations which allow the enzymatic conversion of crotyl alcohol into butadiene. Furthermore, the invention relates to microorganisms which have been genetically modified so as to be able to produce butadiene from crotyl alcohol. Moreover, the invention relates to a method for the enzymatic production of crotyl alcohol from crotonyl-Coenzyme A. The obtained crotyl alcohol can be further converted into butadiene as described herein. Also described are enzyme combinations which allow to convert crotonyl-Coenzyme A into crotyl alcohol as well as (micro)organisms which express such enzyme combinations.

Abstract: The disclosure provides TNF-like ligand 1a (TL1a)-binding proteins comprising an antigen binding domain of an antibody which binds specifically to TL1a and inhibits interaction of TL1a and Death Receptor 3 (DR3) and which does not inhibit the interaction of TL1a and Decoy Receptor 3 (DcR3). The disclosure also provides uses of the TL1a-binding proteins.

Abstract: The present invention relates to glucoamylase variants having improved thermostability. The present invention also relates to polynucleotides encoding the variants; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the variants.

Abstract: Disclosed herein are methods of producing alcohol esters during a fermentation by providing alcohol-producing microorganisms which further comprise an engineered polynucleotide encoding a polypeptide having lipase activity.

Abstract: The present invention relates to nanobodies specifically directed against VCAM-1 and to their use in medical imaging and in diagnostic, prognostic and treatment methods.

Abstract: The present invention provides genetically modified eukaryotic host cells that produce isoprenoid precursors or isoprenoid compounds. A subject genetically modified host cell comprises increased activity levels of one or more of mevalonate pathway enzymes, increased levels of prenyltransferase activity, and decreased levels of squalene synthase activity. Methods are provided for the production of an isoprenoid compound or an isoprenoid precursor in a subject genetically modified eukaryotic host cell. The methods generally involve culturing a subject genetically modified host cell under conditions that promote production of high levels of an isoprenoid or isoprenoid precursor compound.

Abstract: This document describes biochemical pathways for producing pimelic acid, 7-hydroxyheptanoic acid, 7-aminoheptanoic acid, heptamethylenediamine or 1,7-heptanediol by forming two terminal functional groups, comprised of carboxyl, amine or hydroxyl group, in a C7 aliphatic backbone substrate. These pathways, metabolic engineering and cultivation strategies described herein rely on the CoA-dependent elongation enzymes or analog enzymes associated with the carbon storage pathways from polyhydroxyalkanoate accumulating bacteria.

Abstract: The present invention provides novels genes encoding methyl butenol (MBO) synthase, methy butenol synthases and their use in methyl butenol production.

Abstract: Provided are isolated polypeptides having cellobiohydrolase activity, catalytic domains and cellulose binding domains, and polynucleotides encoding the polypeptides, catalytic domains or cellulose binding domains. Also provided are nucleic acid constructs, vectors and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides, catalytic domains or cellulose binding domains.

Abstract: The present invention provides and includes monoclonal antibodies (mAbs) preferentially selective for HER2 antigens, hybridoma lines that secrete these HER2 antibodies or antibody fragments, and the use of such antibodies and antibody fragments to detect HER2 antigens, particularly those expressed by cancer cells. The present invention also includes antibodies that are specific for or show preferential binding to a soluble or secreted form of HER2. The present invention also includes an antibody or antibody fragment that is capable of reducing the activity of HER2 in at least one form, including a soluble form or a secreted form. The present invention further includes chimeric antibodies, processes for producing monoclonal and chimeric antibodies or monoclonal or chimeric antibodies, and their therapeutic uses, particularly in the detection of cancer most preferentially in human breast, stomach, and colon.

Abstract: Recombinant microorganisms, plants, and plant cells are disclosed that have been engineered to express a zeaxanthin cleavage dioxygenase alone or in combination with recombinant genes encoding UDP-glycosyltransferases (UGTs). Such microorganisms, plants, or plant cells can produce compounds from saffron such as crocetin, crocetin dialdehyde, crocin, or picrocrocin.

Abstract: Provided are multispecific binding proteins and methods for using these multispecific binding proteins to modulate the activation state of immune cells, such as T-cells (e.g., cytotoxic T-cells). Also provided are methods of modulating an immune response (e.g., cell killing by cytotoxic T-cells) in a subject (e.g., a human subject). Also provided are nucleic acids, expression vectors and host cells encoding the multispecific binding proteins.

Abstract: The invention relates to multispecific antibody constructs comprising Fab fragments having mutations at the interface of the CH1 and CL domains, said mutations preventing heavy/light chain mispairing.

Abstract: The present invention is directed to variant squalene synthase enzymes, including Saccharomyces cerevisiae squalene synthase enzymes, and to nucleic acid molecules encoding these variant enzymes. These variant enzymes produce squalene at a lower rate than the wild-type enzyme, allowing more farnesyl pyrophosphate to be utilized for production of isoprenoid compounds, while still producing sufficient squalene to allow the S. cerevisiae cells to grow without the requirement for supplementation by sterols such as ergosterol. These variant enzymes, therefore, are highly suitable for the efficient production of isoprenoids.

Abstract: Embodiments of the present invention relate to methods for the biosynthesis of di- or trifunctional C7 alkanes in the presence of isolated enzymes or in the presence of a recombinant host cell expressing those enzymes. The di- or trifunctional C7 alkanes are useful as intermediates in the production of nylon-7, nylon-7,x, nylon-x,7, and polyesters.

Abstract: Recombinant microorganisms, plants, and plant cells are disclosed that have been engineered to express a mutant AROM polypeptide and/or mutant catechol-O-methyltransferase polypeptide alone or in combination with one or more vanillin biosynthetic enzymes or UDP-glycosyltransferases (UGTs). Such microorganisms, plants, or plant cells can produce vanillin or vanillin beta-D-glucoside.

Abstract: Engineered multivalent and multispecific binding proteins, methods of making, and their uses in the prevention, diagnosis, and/or treatment of disease are provided.

Abstract: The present invention provides methods of designing and generating glycerol dehydrogenase (GlyDH) variants that have altered function as compared to a parent polypeptide. The present invention further provides nucleic acids encoding GlyDH polypeptide variants having altered function as compared to the parent polypeptide. Host cells comprising polynucleotides encoding GlyDH variants and methods of producing lactic acids are also provided in various aspects of the invention.

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

Abstract: Cell lines having genetically modified glycosylation pathways that allow them to carry out a sequence of enzymatic reactions, which mimic the processing of glycoproteins in humans, have been developed. Recombinant proteins expressed in these engineered hosts yield glycoproteins more similar, if not substantially identical, to their human counterparts. The lower eukaryotes, which ordinarily produce high-mannose containing N-glycans, including unicellular and multicellular fungi are modified to produce N-glycans such as Man5GlcNAc2 or other structures along human glycosylation pathways.

Abstract: Provided are protein, nucleic acid, and cellular libraries of multivalent binding proteins (e.g., DVD-Fab or DVD-Ig molecules) and the use of these libraries for the screening of multivalent binding proteins using cell surface display technology (e.g., yeast display).

Abstract: The invention relates generally to polypeptides, such as antibody molecules, that demonstrate high stability and solubility. In particular, the invention relates to polypeptides comprising paired VL and VH domains that demonstrate soluble expression and folding in a reducing or intracellular environment. The invention also relates to polynucleotides encoding such polypeptides, to libraries of such polypeptides or polynucleotides, and to methods of using such polypeptides in research, diagnostic and therapeutic applications.

Abstract: Nucleic acid compositions encoding rapidly maturing fluorescent proteins, as well as non-aggregating versions thereof (and mutants thereof) as well as the proteins encoding the same, are provided. The proteins of interest are proteins that are fluorescent, where this feature arises from the interaction of two or more residues of the protein. The subject proteins are further characterized in that, in certain embodiments, they are mutants of wild type proteins that are obtained either from non-bioluminescent Cnidarian, e.g., Anthozoan, species or are obtained from Anthozoan non-Pennatulacean (sea pen) species. In certain embodiments, the subject proteins are mutants of wild type Discosoma sp. “red” fluorescent protein. Also of interest are proteins that are substantially similar to, or mutants of, the above specific proteins. Also provided are fragments of the nucleic acids and the peptides encoded thereby, as well as antibodies to the subject proteins and transgenic cells and organisms.

Abstract: Provided herein are cells, vectors and viruses in association with a mutant polypeptide that has emerged in response to a therapeutic or prophylactic agent; compositions comprising such cells, vectors and viruses and methods for their use in eliciting an immune response to the mutant polypeptide. In some examples, the immune response is a cellular immune response.

Abstract: Disclosed are isolated polypeptides having cellobiohydrolase activity, catalytic domains, carbohydrate binding domains and polynucleotides encoding the polypeptides, catalytic domains or carbohydrate binding domains. Furthermore, nucleic acid constructs, vectors and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides, catalytic domains or carbohydrate binding domains are disclosed.

Abstract: The present invention provides a novel phosphatidic acid phosphatase gene. The object of the present invention can be solved by providing a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 1, SEQ ID NO: 4, or SEQ ID NO: 5; a protein comprising the amino acid sequence set forth in SEQ ID NO: 2; and mutants thereof.