Abstract: The present invention provides methods for the preparation of substituted heterocycle fused gamma-carbolines, such as the compound of Formula 2J, as shown below, intermediates useful in producing them and methods for producing such intermediates and such heterocycle fused gamma-carbolines, and as further defined herein.

Abstract: The present invention relates to a novel compound and a pharmaceutical composition for enhancing anticancer activity, which includes the same, and more particularly, to a pharmaceutical composition, which includes a compound represented by Formula 1 or a pharmaceutically acceptable salt thereof, thereby enhancing anticancer activity of an anticancer agent or radiation, and inducing proliferation inhibition and death of cancer cells, resulting in effectively treating cancer:

Abstract: The present disclosure relates to compounds having the structure of Formula (I) that serve as degraders (and/or inhibitors) of Bruton's tyrosine kinase (BTK). In the present disclosure, the said compounds, which contain a target protein (BTK) binding moiety and a E3 ubiquitin ligase (CRBN) binding moiety, are directed to bind to both the BTK and CRBN, such that the BTK is placed in close proximity to the E3 ligase to mediate ubiquitylation of the target protein followed by degradation of the target protein by the proteasome. The present disclosure provides methods for synthesizing the herein disclosed said compounds, and their pharmacological activities associated with degradation or inhibition of the target protein.

Abstract: The present invention relates to novel fused imidazo pyrazole derivatives of formula (I), and formula (II), and methods for preparation thereof, in the presence of a chitosan-Al2O3 nanocomposite film. The invention also relates to pharmaceutical compositions comprising compounds of the invention as active ingredients as well as the use of compounds of the invention for antimicrobial action.

Abstract: This invention provides an unexpectedly stable, highly crystalline form of the di-HCl salt of for advantageous therapeutic pharmaceutical efficacy and dosage form stability.

Abstract: The present invention aims to provide a method for improving the fluidity of a crystal nucleating agent for polyolefin resins without impairing other properties, and a polyolefin resin composition containing the crystal nucleating agent with improved fluidity and having excellent properties including transparency, and a molded article thereof. Adjustment to specific characteristics can improve the fluidity of a crystal nucleating agent for polyolefin resins, and the use of such a crystal nucleating agent having specific characteristics remarkably improves the workability during molding processing and provides a polyolefin resin composition excellent in properties such as transparency, and a molded article thereof.

Abstract: The invention provides a compound of formula (I): or a pharmaceutically acceptable salt thereof; wherein, A, B, ring C, R3, R4, R5, R6, and R7 have the meaning as described herein, and compositions containing such compounds and methods for using such compounds and compositions.

Abstract: Compounds, methods of use, and processes for making inhibitors of complement Factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof wherein R12 or R13 on the A group is an aryl, heteroaryl or heterocycle (R32) are provided. The inhibitors of Factor D described herein reduce the excessive activation of complement.

Abstract: 6,7-Dihydrothiazolo[5,4-c]pyridines substituted in the 5-position with heterocyclic rings are positive allosteric modulators of the muscarinic acetylcholine receptor M4 (mAChR M4) and may have use in treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction.

Abstract: The present description relates to compounds, forms, and pharmaceutical compositions thereof and methods of using such compounds, forms, or compositions thereof for treating or ameliorating Huntington's disease. In particular, the present description relates to substituted benzothiazole compounds of Formula (I), forms and pharmaceutical compositions thereof and methods of using such compounds, forms, or compositions thereof for treating or ameliorating Huntington's disease.

Abstract: The present invention relates to a compound of the formula (1), to the use of the compound in an electronic device, and to an electronic device comprising a compound of the formula (1). The present invention furthermore relates to a process for the preparation of a compound of the formula (1) and to a formulation comprising one or more compounds of the formula (1).

Abstract: Provided are compounds having a ligand LA of Formula I that are useful as emissive compounds in organic light emitting devices.

Abstract: The disclosure relates to novel compounds that include one or more aromatic boron-containing groups and methods of making the disclosed compounds. The present disclosure further relates to pharmaceutical compositions comprising the disclosed compounds, and their use in prevention and treatment of diseases and disorders.

Abstract: Borylated Amino Acid (“BAA”) compositions and methods of making BAAs are disclosed herein. Consequently, the BAAs can be administered to patients as a Neutron Capture Agent and provide a method of treating cancer, immunological disorders and other disease by utilizing a Neutron Capture Therapy modality.

Abstract: The subject invention provides catalytical compounds/complexes, compositions comprising such compound/complex, synthesis of the compounds/complexes, and methods of using such compounds/complexes as catalysts in, for example, RCM reactions. Specifically, the subject invention provides the synthesis of the first catalytically active V oxo alkylidene, VO(CHSiMe3)(PEt3)2Cl, which exhibits superior performance compared to other analogs.

Abstract: Lanthionine ketimine phosphonate (LK-P), lanthionine ketimine ester phosphonate (LKE-P), other lanthionine ketimine, lanthionine ketimine phosphonate, and lanthionine ketimine ester derivatives, methods of making and using the same, and methods of treatments are described.

Abstract: The invention comprises a process for the preparation of a GalNAc phosphoramidite epimer of the formula (I), wherein R1 is a hydroxy protecting group, n is an integer from 0 to 10 and m is an integer from 0 to 20, corresponding enantiomers and/or optical isomers thereof and the use of the process for the preparation of GalNAc-cluster oligonucleotide conjugates.

Abstract: A segment for use in synthesis of an oligonucleotide, represented by the following formula (I), a method for producing the same, and a method for synthesizing an oligonucleotide therefrom are provided. In formula (I), B is a protected/unprotected nucleoside base; R1 is a protecting group; R2, R3 and R4 are OCH2CH2CN, OCH2CH?CH2, etc.; R5 is a substituted/unsubstituted aliphatic group/aromatic group; X is a lone pair, O or S; Y is NHR6, a halogen, CN, etc., or a hydroxyl group protected with an acyl, ether or silyl protecting group; R6 is H, an aliphatic group or an aromatic group; Z is H, an alkyl, an O- or N-alkyl or a halogen, or forms a Z-Y bond with Y; and (m+n) is an integer of 2 or more and 23 or less.

Abstract: Steroid derivative regulators, a method for preparing the same, and uses thereof are described. Specifically, a compound of formula (I), a preparation method therefor, a pharmaceutical composition containing the compound, and uses thereof as a regulator the of GABAA receptor for treating depression, convulsion, Parkinson's disease, and nervous system diseases are described, wherein the substituents of the formula (I) are as defined in the description.

Abstract: The present disclosure provides a one-pot chemoenzymatic method for site-specific modification and conjugation of antibodies at their Fc glycan site to produce structurally well-defined antibody conjugates carrying defined drugs and other entities. The method is enabled by the discovery that certain endoglycosidases have the ability to both deglycosylate an antibody and to recognize selectively modified small disaccharide oxazolines for transglycosylation on antibodies without hydrolysis of the resulting products.

Abstract: The invention provides a process of purification of antibody or fusion protein from protein mixture comprising product and process related impurities. The process provides the use of hydroxyapatite chromatography for the separation of low molecular weight impurities and basic variants. In addition, invention further provides a scalable purification process to remove product and process related impurities.

Abstract: Production of modified influenza viral proteins in plants is described. More specifically, producing and increasing influenza virus-like particle (VLP) production in plants, wherein the VLPs comprise the modified influenza viral proteins, such as modified influenza hemagglutinin (HA) is described. The HA protein may comprise an amino acid sequence comprising at least one substitution when compared to a corresponding wildtype amino acid sequence. Further provided are nucleic acids encoding the modified HA protein. Furthermore, methods of producing an influenza virus like particle (VLP) and methods of increasing yield of production of an influenza virus like particle (VLP) in a plant, portion of a plant, or a plant cell, are also provided.

Abstract: The invention relates to pre-fusion RSV F protein and polypeptides that contain one or more amino acid mutations that stabilize the pre-fusion conformation or destabilize the post-fusion conformation. The invention also relates to methods for inducing an immune response to pre-fusion RSV F.

Abstract: The present invention relates to an mRNA sequence, comprising a coding region, encoding at least one antigenic peptide or protein of RSV infections Respiratory syncytial virus (RSV) or a fragment, variant or derivative thereof. Additionally the present invention relates to a composition comprising a plurality of mRNA sequences comprising a coding region, encoding at least one antigenic peptide or protein of RSV infections Respiratory syncytial virus (RSV) or a fragment, variant or derivative thereof. Furthermore it also discloses the use of the mRNA sequence or the composition comprising a plurality of mRNA sequences for the preparation of a pharmaceutical composition, especially a vaccine, e.g. for use in the prophylaxis or treatment of RSV infections Respiratory syncytial virus (RSV) infections. The present invention further describes a method of treatment or prophylaxis of RSV infections using the mRNA sequence.

Abstract: The present invention relates to chimeric papilloma virus L1 proteins and polynucleotides encoding thereof, and also to HPV virus-like particles and the preparation methods thereof. Said chimeric papilloma virus L1 protein comprises an N-terminal fragment derived from L1 protein of the first papilloma virus type, said N-terminal fragment maintains the immunogenicity of the L1 protein of the corresponding type of HPV; and a C-terminal fragment derived from L1 protein of the second papilloma virus type, said L1 protein of the second papilloma virus type has a better expression level and a better solubility compared to the L1 proteins of other HPV types; wherein said chimeric papilloma virus L1 proteins have the immunogenicity of the L1 proteins of the corresponding HPV types. Said chimeric papilloma virus L proteins have better expression amount and solubility for mass production of vaccines.

Abstract: The application relates to a dextran affinity tag and use thereof. The present application provides an affinity tag, which is a segment of dextran binding domain, and can purify a target protein by its affinity with the dextran. The affinity tag of the present application has the advantages of more efficient in preparation and purification, and can be widely used in industrial applications that require protein purification processes.

Abstract: The present invention relates to a novel process for purifying phycobiliproteins, in particular acid-pH-resistant phycobiliproteins, the resulting phycobiliproteins, and the uses thereof.

Abstract: The present disclosure provides compositions and methods for modulating transcription of mutant C9orf72 gene alleles in patients in need thereof, including patients having a C9orf72-related disease such as amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD).

Abstract: The present application relates to compositions and methods comprising polypeptides derived from MFG-E8 for treating and preventing fibrosis and other diseases.

Abstract: Provided is a CRY2 variant in which E279 and/or E281 having a negative charge in a N277SEGE281 sequence of SEQ ID NO: 1 is substituted with any one selected from the neutral amino acid group of alanine (A), isoleucine (I), leucine (L), valine (V), phenylalanine (F), methionine (M) and tryptophan (W), or in which S278 or G280 of a N277SEGE281 sequence of SEQ ID NO: 1 is substituted with any one selected from the bulky amino acid group of tryptophan (W) and phenylalanine (F).

Abstract: The present invention relates to hAM15-52 analogues with improved amylin receptor (hAMY3R) potency (hAMY3R-EC50?250 pM) and which are largely based on the sequence of the human adrenomedullin fragment hAM15-52. The invention further relates to hAM15-52 analogues that are selective amylin receptor (hAMY3R) agonists (hAMY3R-EC50?250 pM and an hAM1R-EC50?25 nM) and which are largely based on the sequence of the human adrenomedullin fragment hAM15-52. The hAM15-52 analogues according to the invention maintain the good physical stability of hAM15-52. The invention further relates to pharmaceutical compositions comprising such polypeptides and their use in the treatment of a medical condition such as obesity, NASH and/or diabetes.

Abstract: Methods and kits for the diagnosis of illnesses related to protocadherin 19 (PCDH19) protein deficiency or altered PCDH19 protein function are provided, as well as methods and kits for the identification of a predisposition to such illnesses and methods of screening subjects to identify carriers of such illnesses and methods and kits for the therapeutic or prophylactic treatment of PCDH19 deficiency or altered PCDH19 protein function. Further, nucleotide and amino acid sequences corresponding to a complete PCDH19 open reading frame (ORF), mutant sequences encoding non-functional PCDH19 mRNA or altered PCDH19 mRNA are described along with transformed cells and non-human transgenic animals comprising wild-type or mutant PCDH19 ORF nucleotide sequences.

Abstract: The present invention provides T-cells modified to express at least two chimeric antigen receptors, wherein one of the CARs binds specifically to an antigen selected from CD138, HER2 and CD24 and another CAR binds specifically a different antigen selected from CD 138, HER2 and CD24. Further, the invention provides pharmaceutical compositions comprising these CAR T-cells and their use in treatment of cancer, in particular, ovarian cancer, DNA constructs encoding said CARs and methods for preparation of T-cells expressing said CARs.

Abstract: The present disclosure provides compositions comprising anti-LMP2 TCR-T cell populations for the treatment of EBV-associated cancers and methods of making and using same.

Abstract: Disclosed herein are cells that are immune cells or precursor cells thereof, which cells recombinantly express a chimeric antigen receptor (CAR), and a dominant negative form of an inhibitor of a cell-mediated immune response of the immune cell, wherein the CAR binds to a cancer antigen. Also disclosed herein are T cells that recognize and are sensitized to a cancer antigen, which T cells recombinantly express a dominant negative form of an inhibitor of a T cell-mediated immune response. Additionally provided are methods of using such cells to treat cancer in a subject in need thereof.

Abstract: The present invention is directed to a novel targeted heterodimeric Fc fusion proteins comprising an IL-15/IL-15R? Fc fusion protein and an antigen binding domain Fc fusion proteins. In some instances, the antigen binding domain binds to CD8, NKG2A, or NKG2D.

Abstract: Provided are chimeric receptors for engineering cells for adoptive therapy, including T cells, and the genetically engineered cells. In some embodiments, the chimeric receptors, such as chimeric antigen receptors (CARs) are modified in a junction region by one or more amino acid modifications such that peptide fragments of such region exhibit a lower binding affinity for a human leukocyte antigen (HLA) and/or the region exhibits reduced immunogenicity, including following administration to a subject. In some aspects, also provided are methods and compositions for engineering and producing cells expressing such chimeric receptors, compositions containing the cells, and method for their administration to subjects. In some embodiments, features of the chimeric receptors and engineered cells containing the chimeric receptors result in methods that provide for increased or improved activity, efficacy and/or persistence.

Abstract: Provided herein are anti-neuraminidase agents useful for neutralization of influenza virus infection, and methods of use and manufacture thereof. In particular, compositions comprising anti-neuraminidase agents (e.g., antibodies) that are cross-reactive with multiple influenza strains are provided, as well as methods of treatment and prevention of influenza infection therewith.

Abstract: Disclosed herein are methods of treating or reducing incidence of migraine and/or at least one secondary symptom associated with refractory migraine in a subject having refractory migraine comprising administering to the subject a monoclonal antibody that modulates the CGRP pathway. Compositions for use in the disclosed methods are also provided. Antagonist antibody G1 and antibodies derived from G1 directed to CGRP are also described.

Abstract: Provided herein are antibody-peptide fusion proteins comprising an amyloid-reactive peptide linked to an antibody. Also provided herein are methods of treating amyloid-based diseases by administering an antibody-peptide fusion protein.

Abstract: A bispecific antibody according to an embodiment of the present disclosure specifically binds to IL-17A and TNF-?. The bispecific antibody according to the present invention or an antigen binding fragment thereof exhibits high specificity for IL-17A and TNF-? and more favorable neutralization property compared to monospecific antibody of a prior art, and, by quickly suppressing inflammation and an immune response by inhibiting simultaneously IL-17 and TNF-?, it has an advantage of improving the treatment effect with lower dose.

Abstract: Methods, agents, and compositions for promoting milk production in a mammal are provided. Agents useful for promoting milk production may include an agent that inhibits NOTCH4 activity. The agent may inhibit NOTCH4 activity by binding to ROBO2 and/or by binding to NOTCH4. The agent may inhibit NOTCH4 by competing with ROBO1 for binding to ROBO2, thereby making ROBO1 available to inhibit NOTCH4 activity. The agent may be a soluble ROBO1 extracellular domain or an anti-NOTCH4 antibody that inhibits NOTCH4 activity. The agent may be an RNAi construct that inhibits expression of NOTCH4 or an RNAi construct that inhibits expression of ROBO2. Also provided herein are transgenic mammals genetically modified for expression of a soluble ROBO1 extracellular domain; inhibition of expression of ROBO2; and/or inhibition of expression of NOTCH4. Methods for promoting milk production in such transgenic mammals by administering one or more of the agents disclosed herein are also provided.

Abstract: The invention provides agonistic anti-human VISTA antibodies and antibody fragments. These agonist antibodies and antibody fragments may be used to potentiate or enhance or mimic VISTA's suppressive effects on T cell immunity and thereby suppress T cell immunity. These agonist antibodies and antibody fragments are especially useful in the treatment of autoimmunity, allergy, inflammatory conditions, GVHD, sepsis and transplant recipients. Screening assays for identifying these agonists are also provided.

Abstract: The present disclosure provides stable liquid pharmaceutical formulations comprising anti-CD200 antibodies or antigen-binding fragments thereof, and articles of manufacture and kits containing the formulations. Also featured are methods of using the formulations in cancer and autoimmune therapies, and for preventing, delaying or treating cell, tissue, or organ transplant rejection.

Abstract: Methods of treating cancer and improving immunotherapies comprising decreasing soluble immune receptor levels are provided. Agents that bind membranal immune receptor and inhibit proteolytic cleavage of the receptor and agents that bind soluble immune receptor and that are neither receptor agonists nor antagonists are also provided, as are methods of producing these agents.

Abstract: The present invention relates to methods for upregulating immune responses using combinations of anti-RGMb and anti-PD-1 agents.

Abstract: The present invention relates to multi-specific antibodies comprising fine tuned combination of low affinity single binding domain fragments to selectively target double targets on cancer cell, and use thereof for therapy, such as for guided immunotherapy.

Abstract: The present disclosure provides an antibody for inducing immune tolerance, an induced lymphocyte, and a cell therapy agent therapeutic method using the induced lymphocyte. Specifically, the present disclosure provides an antibody that inhibits the interaction between CD80 and/or CD86 expressed on the surface of a certain cell and CD28 expressed on the surface of another cell, and substantially does not induce immune activation-induced cytokines. In a specific embodiment, the Fc portion of the antibody substantially does not produce the immune activation-induced cytokines.

Abstract: The presently disclosed subject matter provides for methods and compositions for treating a neoplasia (e.g., multiple myeloma). It relates to chimeric antigen receptors (CARs) that specifically target Fc Receptor-like 5 (FcRL5), e.g., domain 9 of FcRL5, and immunoresponsive cells comprising such CARs. The presently disclosed FcRL5-targeted CARs have enhanced immune-activating properties, including anti-tumor activity.

Abstract: The present invention provides MIC antibodies, antigen binding portions thereof and MIC binding agents thereof for use in the treatment of cancer.