Abstract: The invention relates to generation and use of cellular and humoral responses for the prevention and treatment of P. gingivalis related conditions and diseases.

Abstract: The present invention provides methods of dosing Factor VIII or Factor IX chimeric and hybrid polypeptides.

Abstract: The present disclosure provides POZ derivatives having a range of active functional groups allowing conjugation of POZ derivatives to a variety of target molecules under a wide range of reaction conditions to produce a hydrolytically stable target molecule-POZ conjugate. Furthermore, the present disclosure provides novel methods of synthesis for the disclosed POZ derivatives and hydrolytically stable target molecule-POZ conjugates created using the disclosed terminally activated monofunctional POZ derivatives. In one embodiment, the POZ derivative is a terminally activated monofunctional POZ derivative.

Abstract: Polypeptides comprising at least one carboxy-terminal peptide (CTP) of chorionic gonadotropin 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: An organophosphate scavenger is provided, with extended residence time in the mammalian circulation, which can be used in preventive and therapeutic treatment of organophosphate poisoning. The scavenger is a uniformly pegylated serine hydrolase, in which a part of lysine residues were replaced with other residues by site-directed mutagenesis. One part of lysine residues in the hydrolase amino acid sequence is selected for the PEG-coupling, and the other part for the replacement, wherein the selection should ensure that the hydrolase surface shows at least one free amino acid for PEG coupling for all possible views obtained by rotating a 3-D model generated for the hydrolase.

Abstract: Some aspects of this disclosure provide compositions, methods, and kits for improving the specificity of RNA-programmable endonucleases, such as Cas9. Also provided are variants of Cas9, e.g., Cas9 dimers and fusion proteins, engineered to have improved specificity for cleaving nucleic acid targets. Also provided are compositions, methods, and kits for site-specific nucleic acid modification using Cas9 fusion proteins (e.g., nuclease-inactivated Cas9 fused to a nuclease catalytic domain). Such Cas9 variants are useful in clinical and research settings involving site-specific modification of DNA, for example, genomic modifications.

Abstract: Some aspects of this disclosure provide compositions, methods, systems, and kits for controlling the activity and/or improving the specificity of RNA-programmable endonucleases, such as Cas9. For example, provided are guide RNAs (gRNAs) that are engineered to exist in an “on” or “off” state, which control the binding and hence cleavage activity of RNA-programmable endonucleases.

Abstract: This invention provides a homologous recombination-based nucleic acid molecular cloning method. According to the method of the present invention, a target DNA is cloned into a vector through homologous recombination by providing a linearized vector with both ends respectively added with a sequence (namely, a target DNA-specific homologous arm) homologous with sequences of both ends of the target DNA or a flank sequence thereof, or by utilizing a ligation fragment containing both the target DNA-specific homologous arm and a vector-specific homologous arm (a sequence homologous with a specific region of the vector). The method of the present invention is especially applicable to the cloning of a large DNA fragment and to the studies of single nucleotide polymorphism. The present invention further provides a related kit.

Abstract: Some aspects of this disclosure provide compositions, methods, systems, and kits for controlling the activity and/or improving the specificity of RNA-programmable endonucleases, such as Cas9. For example, provided are guide RNAs (gRNAs) that are engineered to exist in an “on” or “off” state, which control the binding and hence cleavage activity of RNA-programmable endonucleases. Some aspects of this disclosure provide gRNAs that modulate the activity of an RNA-programmable endonuclease based on the presence or absence of an extended DNA (xDNA).

Abstract: Some aspects of this disclosure provide compositions, methods, systems, and kits for controlling the activity and/or improving the specificity of RNA-programmable endonucleases, such as Cas9. For example, provided are guide RNAs (gRNAs) that are engineered to exist in an “on” or “off” state, which control the binding and hence cleavage activity of RNA-programmable endonucleases. Some aspects of this disclosure provide mRNA-sensing gRNAs that modulate the activity of RNA-programmable endonucleases based on the presence or absence of a target mRNA.

Abstract: Some aspects of this disclosure provide compositions, methods, and kits for improving the specificity of RNA-programmable endonucleases, such as Cas9. Also provided are variants of Cas9, e.g., Cas9 dimers and fusion proteins, engineered to have improved specificity for cleaving nucleic acid targets. Also provided are compositions, methods, and kits for site-specific recombination, using Cas9 fusion proteins (e.g., nuclease-inactivated Cas9 fused to a recombinase catalytic domain). Such Cas9 variants are useful in clinical and research settings involving site-specific modification of DNA, for example, genomic modifications.

Abstract: Low-copper click chemistry, 1.3-dipolar cycloadditions, and Staudinger ligations for modifying biomolecules is provided. Compositions, methods, and kits relating to low-copper click chemistry, 1.3-dipolar cycloadditions, and Staudinger ligations are also provided.

Abstract: Engineered transcriptional activator-like effectors (TALEs) are versatile tools for genome manipulation with applications in research and clinical contexts. One current drawback of TALEs is their tendency to bind and cleave off-target sequence, which hampers their clinical application and renders applications requiring high-fidelity binding unfeasible. This disclosure provides engineered TALE domains and TALEs comprising such engineered domains, e.g., TALE nucleases (TALENs), TALE transcriptional activators, TALE transcriptional repressors, and TALE epigenetic modification enzymes, with improved specificity and methods for generating and using such TALEs.

Abstract: Compositions and methods are provided for genome modification of a target sequence in the genome of a cell. The methods and compositions employ a guide polynucleotide/Cas endonuclease system to provide an effective system for modifying or altering target sites within the genome of a cell or organism. Once a genomic target site is identified, a variety of methods can be employed to further modify the target sites such that they contain a variety of polynucleotides of interest. Compositions and methods are also provided for editing a nucleotide sequence in the genome of a cell. Breeding methods and methods for selecting plants utilizing a two component RNA polynucleotide and Cas endonuclease system are also disclosed.

Abstract: The present disclosure relates to immunoglobulins and immunoglobulin conjugates with reduced oligomerization and efficient labeling and compositions, methods of generating such immunoglobulins and immunoglobulin conjugates and methods of using such immunoglobulin conjugates particularly in the treatment and prevention of disease.

Abstract: The present invention concerns methods and compositions for stably tethered structures of defined compositions, which may have multiple functionalities and/or binding specificities. Particular embodiments concern homodimers comprising monomers that contain a dimerization and docking domain attached to a precursor. The precursors may be virtually any molecule or structure, such as antibodies, antibody fragments, antibody analogs or mimetics, aptamers, binding peptides, fragments of binding proteins, known ligands for proteins or other molecules, enzymes, detectable labels or tags, therapeutic agents, toxins, pharmaceuticals, cytokines, interleukins, interferons, radioisotopes, proteins, peptides, peptide mimetics, polynucleotides, RNAi, oligosaccharides, natural or synthetic polymeric substances, nanoparticles, quantum dots, organic or inorganic compounds, etc. Other embodiments concern tetramers comprising a first and second homodimer, which may be identical or different.

Abstract: The present invention is related to the anti-PAX8 antibodies, kits, cocktails, and use of anti-PAX8 antibodies for detection of cancer.

Abstract: Disclosed herein are engineered cleavage half-domains; fusion polypeptides comprising these engineered cleavage half-domains; polynucleotides encoding the engineered cleavage half-domains and fusion proteins; and cells comprising said polynucleotides and/or fusion proteins. Also described are methods of using these polypeptides and polynucleotides, for example for targeted cleavage of a genomic sequence.

Abstract: Provided are compositions comprising newly identified protein fragments of aminoacyl-tRNA synthetases, polynucleotides that encode them and complements thereof, related agents, and methods of use thereof in diagnostic, drug discovery, research, and therapeutic applications.

Abstract: Provided are compositions comprising newly identified protein fragments of aminoacyl-tRNA synthetases, polynucleotides that encode them and complements thereof, related agents, and methods of use thereof in diagnostic, drug discovery, research, and therapeutic applications.

Abstract: A vector comprising a polynucleotide sequence encoding a polypeptide having an amino acid sequence of SEQ ID NO: 2 for detecting antibody against Toxocara spp. in a biological sample.

Abstract: The present invention relates to polymeric reagents and conjugates thereof, methods for synthesizing the polymeric reagents and conjugates, pharmaceutical compositions comprising the conjugates and methods of using the polymer conjugates including therapeutic methods where conjugates are administered to patients.

Abstract: The invention provides unique therapeutic and diagnostic antibodies, as well as their fragments, portions, derivatives, and variants thereof, that bind regions of the tau protein that contribute to the initiation and propagation of pathological tau-tau interactions, as well as methods of making them. The invention also relates to methods of using those antibodies for diagnostics, prevention, and treatment of Alzheimer's disease and related tauopathies. The present invention also provides a method for a prophylactic and therapeutic treatment of Alzheimer's disease and other neurodegenerative tauopathies. This method entails the injection of antibodies and/or peptide vaccines that elicits an immune response directed to pathological tau proteins and tau deposits in the brains of patients. Suitable vaccines represent a tau peptide carrying one or more of the tau therapeutic epitopes provided herein.

Abstract: Isolation or in vitro assembly of the Cas9-crRNA complex of the Streptococcus thermophilus CRISPR3/Cas system and use for cleavage of DNA bearing a nucleotide sequence complementary to the crRNA and a proto-spacer adjacent motif. Methods for site-specific modification of a target DNA molecule in vitro or in vivo using an RNA-guided DNA endonuclease comprising RNA sequences and at least one of an RuvC active site motif and an HNH active site motif; for conversion of Cas9 polypeptide into a nickase cleaving one strand of double-stranded DNA by inactivating one of the active sites (RuvC or HNH) in the polypeptide by at least one point mutation; for assembly of active polypeptide-polyribonucleotides complex in vivo or in vitro; and for re-programming a Cas9-crRNA complex specificity in vitro and using a cassette containing a single repeat-spacer-repeat unit.

Abstract: The present invention concerns methods and compositions for stably tethered structures of defined compositions with multiple functionalities and/or binding specificities. Particular embodiments concern stably tethered structures comprising a homodimer of a first monomer, comprising a dimerization and docking domain attached to a first precursor, and a second monomer comprising an anchoring domain attached to a second precursor. The first and second precursors may be virtually any molecule or structure, such as antibodies, antibody fragments, antibody analogs or mimetics, aptamers, binding peptides, fragments of binding proteins, known ligands for proteins or other molecules, enzymes, detectable labels or tags, therapeutic agents, toxins, pharmaceuticals, cytokines, interleukins, interferons, radioisotopes, proteins, peptides, peptide mimetics, polynucleotides, RNAi, oligosaccharides, natural or synthetic polymeric substances, nanoparticles, quantum dots, organic or inorganic compounds, etc.

Abstract: Microspheres are produced by contacting a solution of a macromolecule or small molecule in a solvent with an antisolvent and a counterion, and chilling the solution. The microspheres are useful for preparing pharmaceuticals, nutraceuticals, cosmetic products and the like of defined dimensions.

Abstract: The invention provides methods for the synthesis of oligosaccharides comprising an aminooxy group. The invention further provides oligosaccharides comprising an aminooxy group, methods for coupling oligosaccharides comprising an aminooxy group to glycoproteins, and oligosaccharide-protein conjugates. Also provided are methods of treating a lysosomal storage disorder in a mammal by administration of an oligosaccharide-protein conjugate.

Abstract: An inactive CRISPR/Cas system-based fusion protein and its applications in gene editing are disclosed. More particularly, chimeric fusion proteins including an inCas fused to a DNA modifying enzyme and methods of using the chimeric fusion proteins in gene editing are disclosed. The methods can be used to induce double-strand breaks and single-strand nicks in target DNAs, to generate gene disruptions, deletions, point mutations, gene replacements, insertions, inversions and other modifications of a genomic DNA within cells and organisms.

Abstract: Enzyme compositions with enhanced enzyme activity and/or thermophilic and psychrophilic stability are described. Additionally, methods and kits for making and using the enzyme compositions are provided.

Abstract: Methods, compositions and kits are disclosed directed at levetiracetam derivatives, immunogens, signal generating moieties, antibodies that bind levetiracetam and immunoassays for detection of levetiracetam.

Abstract: Neutralizing antibodies that specifically bind to HIV-1 gp120 and antigen binding fragments of these antibodies are disclosed. Nucleic acids encoding these antibodies, vectors and host cells are also provided. Methods for detecting HIV using these antibodies are disclosed. In addition, the use of these antibodies, antigen binding fragment, nucleic acids and vectors to prevent and/or treat an HIV infection is disclosed.

Abstract: The present invention relates to a binding molecule that specifically binds to two different epitopes of an antigen expressed on tumor cells, wherein the binding molecule comprises: (a) a first binding (poly)peptide that specifically binds to a first epitope of said antigen expressed on tumor cells, wherein said first binding (poly)peptide is a Fyn SH3-derived polypeptide; and (b) a second binding (poly)peptide that specifically binds to a second epitope of said antigen expressed on tumor cells. The present invention further relates to a nucleic acid molecule encoding the binding molecule of the invention, a vector comprising said nucleic acid molecule as well as a host cell or a non-human host transformed with said vector. The invention further relates to a method of producing a binding molecule of the invention as well as to pharmaceutical and diagnostic composition.

Abstract: Novel hybrid polymers are disclosed that have a structure represented by the following wherein Abiotic oligomer, Polypeptide, X, Y, and R1 are as described herein. The methods to prepare the hybrid polymers via novel oxazolidinyl compounds are also described.

Abstract: The present invention is related to a compound that includes a lysosomal enzyme and a targeting moiety, for example, where compound is a fusion protein including iduronate-2-sulfatase and Angiopep-2. In certain embodiments, these compounds, owning to the presence of the targeting moiety can crossing the blood-brain barrier or accumulate in the lysosome more effectively than the enzyme alone. The invention also features methods for treating lysosomal storage disorders (e.g., mucopolysaccharidosis Type II) using such compounds.

Abstract: Aspects of the disclosure include methods for analyzing an analyte composition by mass spectrometry employing a macroporous metal organic polymer matrix. In practicing methods according to certain embodiments an analyte composition is applied to a macroporous metal organic polymer matrix, a voltage is applied to the macroporous metal organic polymer matrix sufficient to produce and expel analyte ions from the macroporous metal organic polymer matrix and the analyte ions are analyzed by mass spectrometry. In other embodiments, a composition having biological macromolecules is applied onto a surface-modified macroporous metal organic polymer matrix and analytes produced by reaction (e.g., enzymatic cleavage of the biological macromolecules) at or near the surface of the macroporous metal organic polymer matrix are measured by mass spectrometry.

Abstract: The present invention provides polypeptides that bind to immunoglobulin G and methods for their use.

Abstract: The present invention relates to a transport protein which can be obtained by modifying the heavy chain of the neurotoxin formed by Clostridium botulinum wherein (i) the protein binds specifically to nerve cells with a higher or lower affinity as the native neurotoxin; (ii) the protein has an increased or reduced neurotoxicity compared to the native neurotoxin, the neurotoxicity being preferably determined in the hemidiaphragm assay; and/or (iii) the protein comprises a lower affinity against neutralizing antibodies compared to the native neurotoxin. The invention also relates to methods for producing the same and the use thereof in cosmetic and pharmaceutical compositions.

Abstract: The present invention relates to polypeptides and more particularly to Transcription Activator-Like Effector derived proteins that allow to efficiently target and/or process nucleic acids. Particularly, the present invention reports the characterization of TALE derived proteins that can efficiently target methylated DNA. The present invention more specifically relates to TALE derived proteins that allow activation of methylated promoters responsible for gene silencing.

Abstract: The present invention relates to a method for producing a product of a reaction catalysed by a nitrilase, which method comprises the steps (i) providing a microorganism comprising said nitrilase located on its surface, and/or a membrane preparation of said microorganism, and (ii) contacting the microorganism and/or the membrane preparation thereof with one or more nitrilase substrates under conditions compatible with nitrilase activity. The present invention further relates to a method for producing enantiomerically pure (R)-mandelic acid using the nitrilase-displaying whole cell biocatalyst or membrane preparation thereof for the conversion of racemic mandelonitrile.

Abstract: Ligand functionalized substrates, methods of making ligand functionalized substrates, and methods of using functionalized substrates are disclosed.

Abstract: The present invention relates to a method for the production of a compound of interest by microbial fermentation, wherein the microbial host cell used has been modified in its genome such that it results in a deficiency in the production of at least one non-ribosomal peptide synthase. The present invention further relates to a microbial host cell that has been modified in its genome such that it results in a deficiency in the production of at least one non-ribosomal peptide synthase. The invention further relates to a compound of interest.

Abstract: Provided are compositions comprising newly identified protein fragments of aminoacyl-tRNA synthetases, polynucleotides that encode them and complements thereof, related agents, and methods of use thereof in diagnostic, drug discovery, research, and therapeutic applications.

Abstract: The invention relates to materials and methods of conjugating a water soluble fatty acid derivative to a therapeutic protein comprising contacting the therapeutic protein with an activated water soluble fatty acid derivative under conditions that allow conjugation.

Abstract: A novel monoclonal antibody and like antigen-binding molecules against transmembrane protein with EGF-like and two follistatin-like domains 2 (TMEFE2) are provided with unique immunological and biological properties useful in the therapy of affective disorders such as depression and bipolar disorders as well as anxiety disorders. In addition, pharmaceutical compositions and kits comprising such antibody and derivatives thereof are described.

Abstract: The invention relates to constructs comprising a transmembrane protein pore subunit and a nucleic acid handling enzyme. The pore subunit is covalently attached to the enzyme such that both the subunit and enzyme retain their activity. The constructs can be used to generate transmembrane protein pores having a nucleic acid handling enzyme attached thereto. Such pores are particularly useful for sequencing nucleic acids. The enzyme handles the nucleic acid in such a way that the pore can detect its component nucleotides by stochastic sensing.

Abstract: There is provided a method of identifying candidate agents capable of modulating interaction between a first polypeptide and a second polypeptide, wherein the first polypeptide is ZO-2/TJP2 or a functional variant thereof and the second polypeptide is a Snail zinc finger transcription factor family member or a functional variant thereof.

Abstract: The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.

Abstract: The present invention provides methods for improving the specificity of nucleic acid amplification comprising incubating a nucleic acid molecule with a polymerase-Sso7 DNA binding domain conjugate and arginine, spermidine, or spermine. The present invention also provides reaction mixtures and kits for improving the specificity of nucleic acid amplification.

Abstract: Methods for synthesizing an ALP conjugate are provided. The methods may include activating a carboxyl group of the ALP with a carbodiimide, to generate an active ester; and adding the substance to be conjugated such that a synthetic reaction occurs between the active ester and the substance to be conjugated, to generate an ALP conjugate.

Abstract: Provided are human alpha-synuclein-specific autoantibodies as well as fragments, derivatives and variants thereof as well as methods related thereto. Assays, kits, and solid supports related to antibodies specific for ?-synuclein are also disclosed. The antibody, immunoglobulin chain(s), as well as binding fragments, derivatives and variants thereof can be used in pharmaceutical and diagnostic compositions for ?-synuclein targeted immunotherapy and diagnosis, respectively.