Abstract: Described herein are bacteriochlorins comprising an annulated isocyclic ring such as a compound Formula I: or a metal conjugate thereof, wherein: R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, and Z are each as defined herein. Also described are methods and intermediates for the synthesis of bacteriochlorins comprising an annulated isocyclic ring, and methods of using such bacteriochlorins for, among other things, diagnostic and therapeutic purposes such as, e.g., luminescent compounds in flow cytometry, and/or as active agents in photodynamic therapy (PDT).

Abstract: The present invention is directed to 6,6-fused heteroarylpiperidine ether compounds which are allosteric modulators of the M4 muscarinic acetylcholine receptor. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which M4 muscarinic acetylcholine receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which M4 muscarinic acetylcholine receptors are involved.

Abstract: The present application relate to process for preparation of tetrahydrofuran compound of formula II, 4-Methylene tetrahydrofuran compound of formula V and tetrahydropyran compound of formula IX which are useful as intermediates for the preparation of halichondrin B analogues such as Eribulin or its pharmaceutically acceptable salts.

Abstract: Disclosed are a method for preparing 2-(cyclohexenylidene) malonic acid derivatives and uses thereof. In this method, an olefin and a 2-substituted malonic acid derivative are used as starting materials to prepare the 2-(cyclohexenylidene) malonic acid derivative in the presence of a catalyst through cyclization reaction. This method has the following advantages: (1) the method can be very efficiently used for the synthesis of highly sterically-hindered 2-(2,6-disubstituted cyclohexenylidene) malonic acid derivatives; (2) the reaction yield is high, the reaction conditions are mild, and the wastes are less, favorable for industrial production. More importantly, the present invention extends the further use of 2-(cyclohexenylidene)malonic acid derivatives in organic synthesis, especially in the synthesis of 2-aryl malonic acid derivatives and their corresponding drugs such as Pinoxaden.

Abstract: Object of the present invention is an improved process for the preparation of cyclopropyldiketopiperazines and thereof key intermediates.

Abstract: Provided herein are myeloid cell leukemia 1 protein (Mcl-1) inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula I, and pharmaceutically acceptable salts thereof and pharmaceutical compositions containing the compounds. The compounds and compositions provided herein may be used, for example, in the treatment of diseases or conditions, such as cancer.

Abstract: A polyfluoroalkyl phosphoric acid ester represented by the general formula [CnF2n+1(CH2CF2)a(CF2CF2)b(CH2CH2)cO]mP(O)(OH)3?m [I] n: 1 to 6, a: 1 to 4, b: 1 to 3, c: 1 to 3, m: 1 to 3) or a salt thereof. The polyfluoroalkyl phosphoric acid ester represented by the general formula [I] is produced by subjecting a polyfluoroalkyl alcohol represented by the general formula CnF2n+1(CH2CF2)a(CF2CF2)b(CH2CH2)cOH [II] (n: 1 to 6, a: 1 to 4, b: 1 to 3, c: 1 to 3) to a dehydration condensation reaction with phosphoric acid. The polyfluoroalkyl phosphoric acid ester can be easily synthesized without passing through dialkyl ester as in the case of phosphonic acid, and used for a mold-releasing agent comprising the same or a salt thereof as an active ingredient.

Abstract: The present invention relates to an improved process for the preparation of tetrofosmin or acid addition salt thereof. The present invention also relates to the process for the preparation of tetrofosmin disulfosalicylate salt. Further the present invention also provides the polymorphic form J of disulfosalicylate salt of tetrofosmin.

Abstract: The present invention provides mito-honokiol compounds, pharmaceutical compositions thereof, and methods of using the mito-honokiol compounds in the treatment of cancer.

Abstract: Though 3?,5?-cyclic diadenylic acid was conventionally provided only as a freeze-dried product, a solid material other than a freeze-dried product and a manufacturing method thereof is provided. By a step of adding acid to an aqueous solution of 3?,5?-cyclic diadenylic acid so as to lower pH to 1 to 3, an inclusion compound of 3?,5?-cyclic diadenylic acid can be obtained. Said manufacturing method is an extremely simple and easy method and does not need a special machine or the like.

Abstract: A phosphoramidochloridate morpholino monomer of the following formula is provided:

Abstract: Tetradentate and octahedral metal complexes suitable for use as phosphorescent or delayed fluorescent and phosphorescent emitters in display and lighting applications.

Abstract: Disclosed are a crystal form of a dapagliflozin intermediate and a preparation method therefor, and specifically disclosed are a crystal form of the dapagliflozin intermediate (2S,3R,4S,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyOphenyl)-2-ethoxy-6-(methylhydroxyl) tetrahydro-2H-pyran-3,4,5-triol and a preparation method therefor. The advantages thereof lie in that an intermediate can be highly purified to obtain a sample with a purity of 99.3% or more, which has an important significance for improving the quality of the dapagliflozin, and the preparation process is simple and suitable for industrial production.

Abstract: The present invention relates to novel salts and crystalline forms of (S)-2-ethylbutyl 2-(((S)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino)propanoate having the structure: for use in treating viral infections. One crystalline form of the compound can be characterized by an X-ray powder diffraction (XRPD) pattern having peaks at 22.3°, 16.9°, and 16.2° 2-?±0.2° 2-?. In some embodiments, the viral infection is caused by a virus selected from the group consisting of Arenaviridae, Coronaviridae, Filoviridae, Flaviviridae, and Paramyxoviridae.

Abstract: Unusual and unexpectedly stable aqueous suspension formulation and water dispersible dry composition of Formula I compounds. It causes little or no injection site irritation and has superior properties over non-aqueous formulations. It stimulates autophagy, enhance innate immunity, down-regulates unproductive inflammation and exerts a Th1 immune bias. It demonstrates better efficacy in both in vitro and in vivo models.

Abstract: The present invention relates generally to compositions and methods for treating cancer and hypercortisolism. Provided herein are substituted steroidal derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of glucocorticoid receptors. Furthermore, the subject compounds and compositions are useful for the treatment of cancer.

Abstract: Compositions of the inventive concept provide a therapeutic protein with less than 2% contamination by the therapeutic protein in denatured form. Such compositions provide enhanced specific activity and improved stability on storage and/or in serum than corresponding therapeutic protein preparations resulting from conventional isolation methods.

Abstract: The present invention relates to novel compounds which effectively inhibit the melanin synthesis in human melanocytes and are thus suitable for the treatment of senile lentigines, for smoothening skin color irregularities and/or for lightening natural skin color.

Abstract: The present invention discloses retro-inverso peptides and pharmaceutical composition containing them. The peptides of the invention prevent key events occurring during the metastatic process, i.e. invasion of the extracellular matrix, formation of a capillary network, and the entry into bloodstream. They are therefore useful in the treatment of diseases and conditions that are sustained by an increase of cell motility, cell invasion, and/or angiogenesis, such as tumors and chronic inflammation.

Abstract: Disclosed herein are compounds for the treatment of neurodegenerative diseases and compositions comprising the same.

Abstract: The invention relates to the chemistry of peptides, pharmacology and medicine, and specifically to a new group of peptides having the property of stimulating sexual and genital function and having increased storage stability. For this purpose, peptides of general formula (I) are proposed: A-Thr-Lys-Hyp-B-C-D-X, (SEQ ID NO: 8), in which A is 0, Met, Met(0), Thr, Ala, His, Phe, Lys, Gly; B is 0, Gly, Asp, Trp, Gln, Asn, Tyr, Hyp, Arg; C is 0, Arg, Phe, Tyr, Gly, His, Hyp, Lys; D is 0, Val, Gly, Tyr, Trp, Phe, His; X is OH, OCH3, NH2; where 0 is the absence of an amino acid residue, provided that if A?0, then B and/or C and/or D?0, if B?0, then C and/or D?0, excluding the tetrapeptides, as well as the peptides Phe-Thr-Lys-Hyp-Gly, (SEQ ID NO: 9), Thr-Lys-Hyp-Hyp-Arg (SEQ ID NO: 10) and Thr-Lys-Hyp-Arg-Gly (SEQ ID NO: 11).

Abstract: A peptide derived from the copine 7 protein and having both cell permeability and bone tissue regeneration ability, and a use of the peptide, are described. The peptide has excellent bone tissue regeneration ability and is therefore useful for treating a disease requiring bone regeneration, such as osteoporosis. Particularly, by also having cell permeability, the peptide does not require the attachment of a separate peptide or addition of another preparation for the cell permeation thereof and thus can be conveniently applied in orthopedics and the like requiring various surgical regeneration treatments.

Abstract: The present invention is related to novel cytotoxic agents, derivatives of Amanita toxins of Formula (I), wherein , -----, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, X, L, m, n and Q are defined herein, the preparation and the therapeutic uses in the targeted treatment of cancers, autoimmune disorders, and infectious diseases.

Abstract: The present disclosure provides compositions and methods for the generation of an antibody or immunogenic composition, such as a vaccine, through epitope focusing by variable effective antigen surface concentration. Generally, the composition and methods of the disclosure comprise three steps: a “design process” comprising one or more in silico bioinformatics steps to select and generate a library of potential antigens for use in the immunogenic composition; a “formulation process”, comprising in vitro testing of potential antigens, using various biochemical assays, and further combining two or more antigens to generate one or more immunogenic compositions; and an “administering” step, whereby the immunogenic composition is administered to a host animal, immune cell, subject or patient. Further steps may also be included, such as the isolation and production of antibodies raised by host immune response to the immunogenic composition.

Abstract: An amino acid-specific binder selectively binds to a binding amino acid. A binder complex selectively identifies the binding amino acid and includes an adjunct attached to the amino acid-specific binder. The adjunct includes a taggant, protein, substrate, or chemical modifier. Selectively identifying an N-terminal amino acid includes anchoring a C-terminal end; contacting an N-terminal amino acid of the anchored analyte with the binder complex; selectively binding when the N-terminal amino acid includes the binding amino acid; producing, by the taggant of the tagged complex, a taggant signal; detecting the taggant signal; and identifying the N-terminal amino acid based on the taggant signal.

Abstract: Variant factor H binding proteins that can elicit antibodies that are bactericidal for at least one strain of Neisseria meningitidis, compositions comprising such proteins, and methods of use of such proteins, are provided.

Abstract: Fusion proteins containing a targeting sequence, an exosporium protein, or an exosporium protein fragment that targets the fusion protein to the exosporium of a Bacillus cereus family member are provided. Recombinant Bacillus cereus family members expressing such fusion proteins are also provided. Genetically inactivated Bacillus cereus family members and recombinant Bacillus cereus family members that overexpress exosporium proteins are also provided. Seeds coated with the recombinant Bacillus cereus family members and methods for using the recombinant Bacillus cereus family members (e.g., for stimulating plant growth) are also provided. Various modifications of the recombinant Bacillus cereus family members that express the fusion proteins are further provided. Fusion proteins comprising a spore coat protein and a protein or peptide of interest, recombinant bacteria that express such fusion proteins, seeds coated with such recombinant bacteria, and methods for using such recombinant bacteria (e.g.

Abstract: This invention provides polypeptides that were identified as interacting with Vip3 toxin. This invention also provides a method of identifying agents that bind to Vip3 interacting polypeptides, which agents may act as insecticidal agent, cytotoxic agents and/or modulate the activity of Vip3 interacting polypeptides.

Abstract: As a calcium indicator protein having an excellent fluorescent characteristic and calcium reactivity, there is provided DNA in which one of a nucleotide sequence derivative of a calmodulin-binding sequence (ckkap sequence) of calcium/calmodulin-dependent protein kinase kinase and a nucleotide sequence encoding a calcium-binding sequence (CaM sequence) of calmodulin is linked to a 5? end of a nucleotide sequence encoding a fluorescent protein, and the other nucleotide sequence is linked to a 3? end of the nucleotide sequence encoding the fluorescent protein. The calcium indicator protein encoded by this DNA, which based on the derivative of the ckkap sequence as a binding domain for the calcium-bound CaM sequence, exhibits a fluorescent characteristic and calcium reactivity superior to those of conventional calcium indicator proteins.

Abstract: A polynucleotide comprising a nucleotide sequence encoding the retinitis pigmentosa GTPase regulator ORF15 isoform (RPGRORF15), wherein the RPGRORF15-encoding nucleotide sequence has been codon optimised to increase fidelity of replication of the sequence.

Abstract: This disclosure concerns compositions and methods for increasing the expression of a polynucleotide of interest. Some embodiments concern novel transactivation polypeptides and variants thereof that have been identified in plants, and methods of using the same. Particular embodiments concern the use of at least one DNA-binding polypeptide in a fusion protein to target at least one transactivation polypeptide or variant thereof to a specific binding site on a nucleic acid comprising the polynucleotide of interest, such that its expression may be increased.

Abstract: The present invention provides for recombinant Endo-S mutants that exhibit reduced hydrolysis activity and increased transglycosylation activity for the synthesis of glycoproteins wherein a desired sialylated oxazoline or synthetic oligosaccharide oxazoline is added to a core fucosylated or nonfucosylated GlcNAc-protein acceptor. Such recombinant Endo-S mutants are useful for efficient glycosylation remodeling of IgG1-Fc domain to provide different antibody glycoforms carrying structurally well-defined Fc N-glycans.

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: The present disclosure provides recombinant polypeptides, homodimeric and heterodimeric proteins comprising the recombinant polypeptides, nucleic acid molecules encoding the recombinant polypeptides, and vectors and host cells comprising the nucleic acid molecules. The present disclosure also provides compositions comprising the recombinant polypeptides and methods of making and using the recombinant polypeptides.

Abstract: The present disclosure provides binding-triggered transcriptional switch polypeptides, nucleic acids comprising nucleotide sequences encoding the binding-triggered transcriptional switch polypeptides, and host cells genetically modified with the nucleic acids. The present disclosure also provides chimeric Notch receptor polypeptides, nucleic acids comprising nucleotide sequences encoding the chimeric Notch receptor polypeptides, and host cells transduced and/or genetically modified with the nucleic acids. The present disclosure provides transgenic organisms comprising a nucleic acid encoding a binding triggered transcriptional switch polypeptide and/or a chimeric Notch receptor polypeptide of the present disclosure. Binding triggered transcriptional switch polypeptides and chimeric Notch receptor polypeptides of the present disclosure are useful in a variety of applications, which are also provided.

Abstract: The present invention describes compositions and methods for priming protective immunity in the presence of pre-existing maternal antibody. In some embodiments, the invention contemplates simultaneously masking vaccines to avoid antibody neutralization while targeting those vaccines to specific cell types in order to elicit an enhanced immune response. In other embodiments, vectors that recruit and activate specific antigen-presenting cells may further enhance the efficacy of those immune responses.

Abstract: Described herein are compositions and methods for the prevention and treatment of ebolavirus infection certain embodiments of the present invention, monoclonal antibodies substantially similar to those described herein, as well as affinity matured variants thereof, alone or in combination, provide therapeutic efficacy in a patient against multiple species of ebolavirus.

Abstract: The invention provides a method for obtaining a broadly neutralizing antibody (bNab), including screening memory B cell cultures from a donor PBMC sample for neutralization activity against a plurality of HIV-1 species, cloning a memory B cell that exhibits broad neutralization activity; and rescuing a monoclonal antibody from that memory B cell culture. The resultant monoclonal antibodies may be characterized by their ability to selectively bind epitopes from the Env proteins in native or monomeric form, as well as to inhibit infection of HIV-1 species from a plurality of clades. Compositions containing human monoclonal anti-HIV antibodies used for prophylaxis, diagnosis and treatment of HIV infection are provided. Methods for generating such antibodies by immunization using epitopes from conserved regions within the variable loops of gp120 are provided. Immunogens for generating anti-HIV1 bNAbs are also provided. Furthermore, methods for vaccination using suitable epitopes are provided.

Abstract: Human phoenixin peptides, analogs and mimetics useful in production of anti-phoenixin antibodies, diagnostic screening and assays, and in modulating cellular concentration of cAMP, and treatment of disorders related to cAMP or Ca2+ concentration in cells, modulating hypertension and cardiovascular function, modulating gonadotrophs and gastric emptying.

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 or 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 mainly addresses the problem of providing an antibody against semaphorin 3A protein, said antibody enabling effective prevention and/or treatment of a disease, in which Sema 3A protein participates, such as a neurodegenerative disease, autoimmune disease, inflammatory disease, cancer, infectious disease, etc. or disseminated intravascular coagulation syndrome. An anti-Sema 3A antibody comprising CDRs having specific amino acid sequences (SEQ ID NOS: 1-6, 60-62, 64-66, 68-70, 72-74, 76-78, 80-82, 84-86 and 88-90) enables effective prevention and/or treatment of a disease, in which Sema 3A protein participates, such as a neurodegenerative disease, autoimmune disease, inflammatory disease, cancer, infectious disease, etc. or disseminated intravascular coagulation syndrome and, therefore, remarkably ameliorates symptoms associated with such a disease.

Abstract: The present invention provides for recombinant Endo-S mutants (named Endo-S glycosynthases) that exhibit reduced hydrolysis activity and increased transglycosylation activity for the synthesis of glycoproteins wherein a desired sugar chain is added to a fucosylated or nonfucosylated GlcNAc-IgG acceptor. As such, the present invention allows for the synthesis and remodeling of therapeutic antibodies thereby providing for certain biological activities, such as, prolonged half-life time in vivo, less immunogenicity, enhanced in vivo activity, increased targeting ability, and/or ability to deliver a therapeutic agent.

Abstract: The combination of a first binding site specifically binding to a target associated with an eye disease and a second binding site specifically binding to a target influencing the retention in the eye a multispecific binder provides for improved intravitreal retention compared to a monospecific binder. The second binding site specifically binds to a compound/molecules found in the extracellular matrix (ECM) in vitreous humor/retina. This compound of the extracellular matrix has to be present in amounts allowing a sufficient loading/dose of the drug to be bound. It has been found that collagen, especially collagen II, is a suitable compound in the ECM in the vitreous humor for this purpose. Thus, herein is reported a multispecific binder comprising a first binding site specifically binding to a therapeutic ocular target, and a second binding site specifically binding to collagen II.

Abstract: The invention provides anti-Tau antibodies and methods of using the same.

Abstract: The present invention provides a monoclonal antibody or an antigen-binding portion thereof having increased binding affinity to cytoplasmic PCNA and blocks its interaction with NKp44. The present invention further provides use of the antibody or an antigen-binding portion thereof in the treatment of diseases associated with elevated expression of NKp44, such as cancer.

Abstract: The present invention relates to bispecific antibodies having activity against a vascular endothelial growth factor (VEGF) and an angiopoietin (ANG), and methods of making and using such bispecific antibodies.

Abstract: The invention relates to an isolated immunoglobulin heavy chain polypeptide and an isolated immunoglobulin light chain polypeptide that bind to interleukin-33 (IL-33). The invention provides an IL-33-binding agent that comprises the aforementioned immunoglobulin heavy chain polypeptide and immunoglobulin light chain polypeptide. The invention also provides related vectors, compositions, and methods of using the IL-33-binding agent to treat a disorder in a mammal that is responsive to IL-33 inhibition.

Abstract: There is disclosed an improved ADC (antibody drug conjugate) type composition having at least two different drug payloads conjugated to a single targeting protein. More specifically, the present disclosure attaches a first drug conjugate to a dual Cysteine residue on a targeting protein and a second drug conjugate with a different drug to a Lys residue on the targeting protein.

Abstract: The present disclosure provides antibodies and antigen-binding fragments capable of binding PAR2. In some embodiments, the anti-PAR2 antibodies or antigen-binding fragments thereof bind PAR2 in a pH-dependent manner. The disclosure further provides methods for making and using the antibodies and antigen-binding fragments.

Abstract: The invention provides antibodies against the antigen containing the Dsg2 extracellular domain 2. Also provided is the method of using the antibodies in treatment or prevention of a cancer.