Abstract: Described herein are methods for the manufacture of ceftolozane and related compounds, as well as compositions comprising the same.

Abstract: The present invention provides imidazopyridazine compounds or imidazothiadiazole compounds of Formula I having the structure: (I) wherein X1, X2, X3, X4, X5, Y, W, R1, R2, R3, R4, R5 and (II) are as defined herein, or a stereoisomer, tautomer, pharmaceutically acceptable salt, prodrug ester or solvate form thereof. These compounds are inhibitors of platelet aggregation and thus can be used as medicaments for treating or preventing thromboembolic disorders.

Abstract: The present invention relates to amido-substituted imidazopyridazine compounds of general formula (I): in which A, E, R2, R3, R4 and n are as defined in the claims, to methods of preparing said compounds, to intermediate compounds useful for preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of a hyper-proliferative and/or angiogenesis disorder, as a sole agent or in combination with other active ingredients.

Abstract: The present invention provides Bruton's Tyrosine Kinase (Btk) inhibitor compounds according to Formula (I), or pharmaceutically acceptable salts thereof, or to pharmaceutical compositions comprising these compounds and to their use in therapy. In particular, the present invention relates to the use of Btk inhibitor compounds of Formula (I) in the treatment of Btk mediated disorders.

Abstract: Described herein are compounds and compositions that modulate the activity of beta-lactamases. In some embodiments, the compounds described herein inhibit beta-lactamase. In certain embodiments, the compounds described herein are useful in the treatment of bacterial infections.

Abstract: This invention provides, among other things, novel compounds useful for treating protozoal infections, pharmaceutical compositions containing such compounds, as well as combinations of these compounds with at least one additional therapeutically effective agent.

Abstract: A furan-containing flame retardant molecule includes a furan moiety bonded to a phosphorus moiety via a phosphoryl linkage or via a phosphinyl linkage.

Abstract: Disclosed herein are compounds of formula (I): wherein: the groups R1, R2, R3, R4, R5, R6, R7, R8, R1?, R2?, R3?, R4?, R5?, R6?, R7?, R8?, R1?, R2?, R3?, R4?, R5?, R6?, R7?, R8? are defined herein; and at least one of the following conditions is satisfied: two radicals from at least one of the four following pairs of radicals are not the same radical: R1? and R8?, R2? and R7?, R3? and R6?, R4? and R5?, and two radicals from at least one of the four following pairs of radicals are not the same radical: R1? and R8?, R2? and R7?, R3? and R6?, R4? and R5?.

Abstract: Novel phosphorescent tetradentate platinum compounds of Formula I are provided. The complexes contain a dibenzo moiety, which allows for the creation of OLED devices with improved properties when compounds of Formula I are incorporated into such devices. Compounds of Formula I? that comprise two ligands that contain a 5-membered carbocyclic or heterocyclic ring, one of which contains an imidazole ring with a twisted aryl group attached to N?1 and a second aromatic ring that is attached to the platinum via a carbon atom. These compounds may be advantageously used in OLEDs.

Abstract: A method for purifying ?-nicotinamide mononucleotide (NMN) includes: sequentially microfiltrating and nanofiltrating a crude product solution containing NMN using membrane concentration devices to obtain a concentrated crude product solution; adjusting the concentrated crude product solution to pH 3-7 to obtain a loading solution, loading the loading solution onto a preparative reverse phase high performance liquid chromatographic column, and purifying by gradient elution using an octadecylsilane-bonded silica gel as a stationary phase, a hydrochloric acid solution at pH 3-7 as a mobile phase A, and 100% ethanol as a mobile phase B, to obtain a purified sample solution; concentrating the purified sample solution by nanofiltration and freeze drying in a vacuum freeze drier to obtain a purified NMN.

Abstract: The present disclosure encompasses solid state forms of Sofosbuvir, processes for their production, and pharmaceutical compositions thereof.

Abstract: The present invention is directed to a process for making Chloro-Substituted Nucleoside Phosphoramidate Compounds of formula (I): which are useful for the treatment and prophylaxis of HCV infection. The present invention is also directed to compounds that are useful as synthetic intermediates for making the compounds of formula (I).

Abstract: In this method, an oligonucleotide is prepared by using, as a synthesis unit, a novel nucleoside monomer compound represented by formula (I) [wherein X, R1, Y, Base, Z, Ar, R2, R3 and n are each as defined in Claim 1]. The novel nucleoside monomer compound is a nucleoside, the base moiety of which is substituted with an aromatic-hydrocarbon-ring-carbonyl or -thiocarbonyl group having at least one hydrophobic group. The method cars dispense with column-chromatographic purification in every reaction, and enables base elongation not only in the 3?-direction but also in the 5?-direction, thus attaining efficient liquid-phase mass synthesis of an oligonucleotide.

Abstract: A method for purifying a salt of reduced form of ?-nicotinamide adenine dinucleotide (NADH) includes: sequentially microfiltrating and nanofiltrating a reaction solution obtained after an enzymatic reaction, collecting a concentrate for use; adding an ion pair reagent to the concentrate, and purifying by gradient elution to obtain a purified filtrate using a reverse-phase chromatographic column as a stationary phase, a buffer solution as a phase A, and ethanol as a phase B; changing the cations in the purified filtrate into sodium ions to obtain a filtrate by using a cation exchange resin; and nanofiltrating the filtrate, and freeze drying in a vacuum freeze drier. The method results in an excellent purity and yield of a salt of NADH that meets requirements in industry.

Abstract: Compounds and methods of synthesizing oxysterols are provided. The compounds and methods provided allow the oxysterol to be safely produced at a high yield. The compounds and methods provided can produce the oxysterol in a stereoselective manner. The oxysterols of the current application can be used in effective amounts to grow bone.

Abstract: This invention provides a method of synthesizing new active compounds for pharmaceutical uses including cancer treatment, wherein the cancers comprise breast, leukocytic, liver, ovarian, bladder, prostatic, skin, bone, brain, leukemia, lung, colon, CNS, melanoma, renal, cervical, esophageal, testicular, spleenic, kidney, lymphatic, pancreatic, stomach and thyroid cancers. This invention is an anti-adhesion therapy which uses the compound as a mediator or inhibitor of adhesion proteins and angiopoietins. It inhibits excess adhesion and inhibits cell attachment. It modulates angiogenesis. The compounds also use as mediator of cell adhesion receptor, cell circulating, cell moving and inflammatory diseases.

Abstract: There is provided a process for producing proteins from the by-product streams arising from distillation processes, in particular the by-product stream known as “pot ale” or “burnt ale” and the use of such proteins as protein feed ingredients or food additives.

Abstract: The present invention relates to method for connecting a protein and a drug to a protein drug conjugate, wherein the drug is linked to the protein through a specific branched linker, said branched linker comprises a peptide chain and is derived from o-hydroxy p-amino benzylic alcohol, wherein the peptide chain is connected to the phenyl ring via the p-amino group, the drug is connected to the phenyl ring via the benzylic alcohol moiety, and the protein is connected to the phenyl ring via the o-hydroxy group; further to a process for the preparation of said protein-drug-conjugates via various intermediates, to the pharmaceutical use of such protein drug conjugates, such as methods of controlling the growth of undesirable cells, to pharmaceutical compositions comprising such protein drug conjugates, and to intermediates of the preparation of the protein drug conjugates.

Abstract: To provide a means for preventing, treating and/or controlling health damages, including food poisoning and infections, caused by a bacterium belonging to the genus Clostridium. The above object can be solved by a cyclic peptide containing the sequence Cys-Phe-Trp-Ala-His and/or a broth of Clostridium butyricum.

Abstract: We describe peptides and their uses for the treatment of autoimmune, inflammatory and metabolic diseases.

Abstract: The invention relates to novel pharmaceutically-useful peptides, in particular cyclic peptides that are agonists of the AngII type 2 receptor (AT2 receptor). The invention further relates to the use of such peptides as medicaments, to pharmaceutical compositions containing them, and to their production.

Abstract: A pharmaceutical composition for use in killing and/or inhibiting the growth and/or proliferation of a microorganism in a subject in need thereof, or for treating a subject afflicted with a microbial infection is disclosed. The composition comprises: (a) an effective amount of an isolated peptide, wherein the peptide comprises the arginine-rich carboxy-terminal region of hepatitis B virus core protein (HBc) and exhibits an antimicrobial activity; and (b) a pharmaceutically acceptable carrier. The peptide exhibits an activity against Gram-negative bacteria, Gram-positive bacteria, and/or fungi.

Abstract: Some embodiments of the invention include inventive polypeptides (e.g., mutant VP2 proteins) and virus-like particles made from the inventive polypeptides. Other embodiments of the invention include compositions for treating (e.g., preventing) parvovirus (e.g., erythrovirus or parvovirus B19) infection and other diseases. Further embodiments include methods for administering compositions to an animal. Other embodiments include treating (e.g., preventing) parvovirus (e.g., erythrovirus or parvovirus B19) infection and other diseases. Still other embodiments include nucleic acid sequences that encode the inventive polypeptides. Additional embodiments of the invention are also discussed.

Abstract: The present invention provides mutant adeno-associated virus (AAV) that exhibit altered capsid properties, e.g., reduced binding to neutralizing antibodies in serum and/or altered heparin binding and/or altered infectivity of particular cell types. The present invention further provides libraries of mutant AAV comprising one or more mutations in a capsid gene. The present invention further provides methods of generating the mutant AAV and mutant AAV libraries, and compositions comprising the mutant AAV. The present invention further provides recombinant AAV (rAAV) virions that comprise a mutant capsid protein. The present invention further provides nucleic acids comprising nucleotide sequences that encode mutant capsid proteins, and host cells comprising the nucleic acids. The present invention further provide methods of delivering a gene product to an individual, the methods generally involving administering an effective amount of a subject rAAV virion to an individual in need thereof.

Abstract: The present invention relates to methods and uses for screening anti-hepadnaviral substances, wherein the substances are screened for the capacity to inhibit covalently closed circular (ccc) DNA of a hepadnavirus, like hepatitis B virus. The methods and uses take advantage of cells comprising a nucleic sequence encoding a tagged hepadnavirus e antigen, like Hepatitis B virus e antigen (HBeAg). Furthermore, the present invention provides nucleic acid sequences encoding a tagged hepadnavirus e antigen and proteins encoded thereby. Also kits for use in the screening methods are provided.

Abstract: Provided is a preparation method for phycocyanin, including: adding chitosan to a suspension of cyanobacteria containing phycocyanin; and filtering the suspension.

Abstract: The present invention relates to compositions comprising Haemophilus influenzae Protein E and Pilin A. More particularly, the present application relates to fusion proteins and immunogenic compositions comprising Protein E and PilA, vaccines comprising such immunogenic compositions and therapeutic uses of the same.

Abstract: The present disclosure provides a method of producing enzyme-specific inhibitors or substrate binding partners comprising: identifying active site residues of the substrate in the enzyme substrate complex or in substrate binding partner-substrate complex; randomizing the active site residues to produce a combinatorial library of substrate variants; and selecting substrate variants that inhibit enzyme activity or bind substrate as substrate-specific binding partners. The present disclosure also provides ubiquitin enzyme specific inhibitors and ubiquitin variants that bind ubiquitin interaction motifs.

Abstract: Disclosed is a method for the production of three-dimensional silk products, wherein a three-dimensional silk product is treated with a silk solvent for a limited period of time so that a partial disintegration of the silk product is obtained whereafter the partially disintegrated silk product is re-stabilized with physical ?-sheet induction by a re-stabilizing solution.

Abstract: Disclosed are materials and methods for treating diseases of the mammalian eye, and in particular, Usher syndrome 1B (USH1B). The invention provides AAV-based, dual-vector systems that facilitate the expression of full-length proteins whose coding sequences exceed that of the polynucleotide packaging capacity of an individual AAV vector. In one embodiment, vector systems are provided that include i) a first AAV vector polynucleotide that includes an inverted terminal repeat at each end of the polynucleotide and a suitable promoter followed by a partial coding sequence that encodes an N-terminal portion of a full-length polypeptide; and ii) a second AAV vector polynucleotide that includes an inverted terminal repeat at each end of the polynucleotide and a partial coding sequence that encodes a C-terminal portion of a full-length polypeptide, optionally followed by a polyadenylation (pA) signal sequence.

Abstract: The invention provides compositions and methods for treating, preventing, and diagnosing diseases or conditions associated with an abnormal level or activity of biglycan; disorders associated with an unstable cytoplasmic membrane, due, e.g., to an unstable dystrophin associated protein complex (DAPC); disorders associated with abnormal synapses or neuromuscular junctions, including those resulting from an abnormal MuSK activation or acetylcholine receptor (AChR) aggregation. Examples of diseases include Amyotrophic Lateral Sclerosis (ALS), as well as muscular dystrophies, such as Duchenne's Muscular Dystrophy, Becker's Muscular Dystrophy, neuromuscular disorders and neurological disorders.

Abstract: Compositions and methods are disclosed for altering the binding affinity of calmodulin for ryanodine receptor 2 (RyR2). As disclosed herein, these therapeutic calmodulin (TCaM) proteins can be used to correct ryanopathies by prolonging the RyR2 refractory period. Therefore, also disclosed is a method for treating a ryanopathy-associated disease in a subject that involves administering to the subject a composition comprising a TCaM disclosed herein.

Abstract: A method of purifying a Growth Factor Protein in a purification sequence employing chromatography is provided. The method comprises performing at least one chromatography step using a multimodal resin, binding the Growth Factor Protein to the multimodal resin at a pH from 4 to 6.2, and eluting the Growth Factor Protein at a pH in the range of from 5.5 to 6.5. The elution of Growth Factor Protein is improved by addition of arginine and/or NaCl in the eluting buffer. Optionally the multimodal resin step is followed by a yeast derived affinity ligand resin step, which results in a purity of the product greater than 90%.

Abstract: The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

Abstract: Conjugated lysine-depleted variants of fragment crystallizable (Fc) regions of immunoglobulins are disclosed. Also disclosed are fusion proteins comprised of C-terminal targeting peptide sequences, fused to such lysine-depleted variant IgG-Fc domains. Polynucleotides encoding such proteins, compositions and kits containing such proteins, and methods of using such proteins are also disclosed.

Abstract: The application provides Fc fusion proteins having novel arrangements. In one embodiment, the application provides Fc fusion proteins comprising a 10F3 domain. In another embodiment, the application provides Fc fusion proteins comprising linkers derived from the naturally occurring C-terminal tail regions of membrane bound or secretory immunoglobulins.

Abstract: The invention concerns constructs and libraries comprising antibody surrogate light chain sequences. In particular, the invention concerns constructs comprising VpreB sequences, optionally partnered with another polypeptide, such as, for example, antibody heavy chain variable domain sequences, and libraries containing the same.

Abstract: Antibodies having Fab regions that specifically bind to Staphylococcus aureus protein A are capable of mediating opsinization of Staphylococcus aureus bacteria despite their expression of antibody-neutralizing protein A. These antibodies and antigen-binding fragments thereof can be used in methods of treating and/or preventing Staphylococcus aureus infections.

Abstract: The present invention is directed to antibodies and fragments thereof having binding specificity for CGRP. 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-CGRP antibodies and binding fragments thereof conjugated to one or more functional or detectable moieties. The invention also contemplates methods of making said anti-CGRP antibodies and binding fragments thereof. Embodiments of the invention also pertain to the use of anti-CGRP antibodies, and binding fragments thereof, for the diagnosis, assessment and treatment of diseases and disorders associated with CGRP.

Abstract: Antibodies that are agonists of sodium pump (Na+/K+ ATPase; NKA) activity are provided. In particular, antibodies that specifically bind epitopes on the beta-1 (?1) subunit of NKA are disclosed. These antibodies have the ability to increase the activity of the catalytic alpha subunit of NKA upon ?1 subunit binding. Due to their activity, the antibodies also have the ability to trigger a positive inotropic effect in cardiac tissues (i.e., increase cardiac contraction). The present invention thus includes, but is not limited to, NKA ?1 subunit peptide epitopes, antibodies that specifically bind the epitopes, methods of increasing NKA activity and cardiac contraction through administration of the peptide vaccines or the antibodies, and methods of treating and/or preventing heart disease through administration of the peptides or the antibodies.

Abstract: The present invention aims to provide a pharmaceutical composition for cancer treatment, which comprises a novel monoclonal antibody binding to SLC6A6 or its extracellular region and a chemotherapeutic agent conjugated therewith, as well as a therapeutic method in which the monoclonal antibody or a therapeutic agent composed of the monoclonal antibody conjugated with a chemotherapeutic agent is used in combination with a chemotherapeutic agent. The present invention provides a pharmaceutical composition comprising an antibody conjugate configured such that a monoclonal antibody having higher affinity than conventional antibodies and recognizing native SLC6A6 or a native polypeptide of an extracellular region of SLC6A6 is conjugated with an anticancer agent or the like having activity against cancer and other hyperproliferative diseases.

Abstract: A pharmaceutical composition comprising an active agent that causes reduction of the level of systemic immunosuppression in an individual for use in treating a disease, disorder, condition or injury of the CNS that does not include the autoimmune neuroinflammatory disease, relapsing-remitting multiple sclerosis (RRMS), is provided. The pharmaceutical composition is for administration by a dosage regimen comprising at least two courses of therapy, each course of therapy comprising in sequence a treatment session followed by an interval session of non-treatment.

Abstract: The present invention relates to antibodies that bind human programmed cell death 1 ligand 1 (PD-L1), and may be useful for treating solid and hematological tumors alone and in combination with chemotherapy and other cancer therapeutics.

Abstract: The present invention relates to antibodies targeted to BDCA2 that deplete plasmacytoid dendritic cells (pDC) and methods of using the antibodies to treat disorders associated with pDC.

Abstract: The present invention relates to methods and techniques for providing improved amino acid sequences that can be used as single antigen-binding domains. In particular, the invention relates to methods and techniques for providing improved amino acid sequences that can be used as single antigen-binding domains that comprise or essentially consist of at least one immunoglobulin sequence. More in particular, the amino acid sequences provided herein may comprise or essentially consist of at least one variable domain sequence or a suitable fragment thereof such as at least one light chain variable domain sequence (e.g. a VL-sequence) or a suitable fragment thereof or at least one heavy chain variable domain sequence (e.g. a VH-sequence or VHH sequence) or a suitable fragment thereof.

Abstract: The current disclosure provides binding polypeptides (e.g., antibodies), and effector moiety conjugates thereof (e.g., antibody-drug conjugates or ADCs), comprising a site-specifically engineered drug-glycan linkage within native or engineered glycans of the binding polypeptide. The current disclosure also provides 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: Endoglin has been identified to play a functional role as a regulator of TGF?1 signaling, particular in TGF?1-mediated calcineurin expression. The present invention features methods of reducing cardiac damage, particularly in a subject undergoing chemotherapy or radiation therapy by administering a composition that inhibits endoglin activity. The present invention also features methods of treating autoimmune diseases, inflammatory diseases, organ transplantation, and conditions association with oxidative stress related to TGF?1-mediated calcineurin expression and reactive oxygen species (ROS) production by administering a composition that inhibits endoglin activity. The present invention also features methods of treating fibrotic diseases by administering a composition that inhibits endoglin activity.

Abstract: The present disclosure relates to a monoclonal antibody specifically binding to human Long Interspersed Element-1 ORF2 encoded protein (L1-ORF2p) obtained from hybridoma chA1, and derivatives and uses thereof, including for prediction of response of cancer patients to NNRTI treatments. It also relates to a method for early detection of cell transformation in pre-neoplastic tissues of a human subject, comprising detecting in cells of a pre-neoplastic tissue sample from said subject the expression of L1-ORF2p, wherein the expression of L1-ORF2p indicates the presence of cell transformation in said pre-neoplastic tissues. It also relates to a method for detecting progression of colon adenoma in a human subject suffering from colon adenoma, based on detection of an increase of L1-ORF2p expression.

Abstract: The purpose of the present invention is to provide a monoclonal antibody that is useful in specifically assaying tartrate resistant acid phosphatase 5b (TRACP-5b). A hybridoma producing a monoclonal antibody against TRACP-5b, said monoclonal antibody showing higher reactivity with TRACP-5b than with tartrate resistant acid phosphatase 5a (TRACP-5a) and, therefore, being specific to TRACP-5b, is obtained by cell fusion using, as an antigen, human recombinant TRACP-5b purified from silkworm silk gland. By using this monoclonal antibody, TRACP-5b in a specimen can be highly sensitively and specifically detected.

Abstract: Disclosed are an anti-idiotype antibody that specifically binds to an idiotope site of an anti-c-Met antibody, the use of the anti-idiotype antibody for detecting the anti-c-Met antibody, and methods, polypeptides, polynucleotides, compositions, and vaccines related thereto.