Abstract: The present invention is directed to methods and compositions for the production of Fc-containing polypeptides having improved properties and comprising mutations at positions 243 and 264 of the Fc region.

Abstract: The present invention relates to pharmaceutical compositions and combinations comprising regorafenib or its hydrate, solvate, metabolite or pharmaceutically acceptable salt or a polymorph thereof and a PD-1/PD-L1(2) inhibitor for treating, preventing or managing diseases and conditions including hyperproliferative disorders such as cancer in humans and other mammals.

Abstract: The present invention relates to humanized antibodies that specifically bind to human BTN3A and their use in treating cancer and infectious disorders.

Abstract: Aspects of the disclosure relate to complexes and other aspects relate to formulations (e.g., aqueous, lyophilized forms) comprising such complexes comprising an oligonucleotide (e.g., useful for targeting DMPK) covalently linked to an antibody (e.g., anti-TfR1 antibody).

Abstract: The purpose of the present invention is to provide an agent for restoring a visual function or an agent for preventing the deterioration in a visual function, which has an excellent visual function restoring ability. The agent for regenerating a visual function or the agent for preventing the deterioration in a visual function according to the present invention contains, as an active ingredient, a chimeric protein having both an amino acid sequence for a microorganism-origin ion-transporting receptor rhodopsin and an amino acid sequence for an animal-origin G-protein-coupled receptor rhodopsin. The chimeric protein is preferably one in which an amino acid sequence for a cytoplasm-side second loop and/or a cytoplasm-side third loop in the amino acid sequence for the microorganism-origin ion-transporting receptor rhodopsin is substituted by an amino acid sequence for a cytoplasm-side second loop and/or a cytoplasm-side third loop in the G-protein-coupled receptor rhodopsin.

Abstract: The present invention relates to a cancer-specific tumor antigen neoepitope represented by any one of SEQ ID NOs: 1 to 184, an antigen-presenting cell loaded with the neoepitope, and a method for activating T cells for cancer treatment using the antigen-presenting cell. An antigen-presenting cell, that is, a dendritic cell, loaded with a cancer-specific tumor antigen epitope provided in the present invention enables rapid and effective induction of differentiation and proliferation of cancer antigen-specific T cells, preferably memory T cells, and the memory T cells thus activated can treat a cancerous or neoplastic condition or prevent recurrence, progression, or metastasis of cancer while avoiding the defense mechanism of cancer cells.

Abstract: Disclosed herein are polynucleic acid molecules, pharmaceutical compositions, and methods for treating facioscapulohumeral muscular dystrophy (FSHD).

Abstract: The present invention relates to methods for reducing soluble P-selectin and major thrombotic events in cancer patients.

Abstract: Provided herein are fusion proteins that comprise an enzyme replacement therapy enzyme and an Fc region, as well as methods of using such proteins to treat a lysosomal storage disorder. Methods for transporting agents across the blood-brain barrier are also provided herein.

Abstract: The invention is directed to a protein construct comprising a scaffold protein into which an IgE epitope containing motif is inserted or substituted. The protein construct may be used as an antigen, immunogen or vaccine to induce immune responses against IgE in a vaccinated subject thereby reducing the severity of allergic phenomena associated with IgE. The invention is also directed to a method for designing such a protein construct and expressing it using recombinant DNA methods.

Abstract: This application relates to a pharmaceutical composition for use in a method for treating and/or preventing a patient having ectopic ossification and/or brain tumor, wherein the patient has an active mutation in ALK2 protein which is responsible for ectopic ossification or brain tumor; an amino acid residue at position 330 of ALK2 is proline; and an active ingredient of this composition is an anti-ALK2 antibody or an antigen-binding fragment thereof comprising a property of binding to ALK2, a property of cross-linking ALK2, and a property of inhibiting BMP signal transduction.

Abstract: A method is used for treating bone metastasis diseases in subjects. The method preferably depends on whether the subject shows certain specific proteins levels in one or more body fluids prior to or during treatment. The treatment includes the administration of at least one pan ?v integrin inhibitor to a subject, a medicament for use in said new methods, and a method of predicting the outcome of a treatment with at least one pan ?v integrin inhibitor based on the specific protein levels in one or more body fluids of the subject.

Abstract: The present disclosure discloses a preparation method and use of a double-target fusion protein, and belongs to the technical field of medicines. According to the present disclosure, a novel fusion protein is obtained by transforming an FGF19 sequence and fusing the FGF19 sequence with GLP-1. Compared with wild-type FGF19 and GLP-1, the novel fusion protein has a more long-acting and stable effect, further reduces the carcinogenic risk of FGF19, and can better relieve liver damage and correct metabolic disorder, obesity, overweight, metabolic syndrome, diabetes, dyslipidemia and other diseases. Besides, in treatment, there are no side effects of gastrointestinal discomforts such as diet decline caused by GLP-1 treatment. Therefore, the double-target fusion protein has a wide application prospect.

Abstract: The invention relates to a method of removing immune suppression in a tumor microenvironment or stimulating an immune system against cancer cells, comprising administering to a subject a combination of a HDAC inhibitor and an NSAID in combination with an immune checkpoint inhibitor.

Abstract: Novel therapeutic agents, particularly those capable of activating (GPR)124/RECK/Frizzled/lipoprotein receptor-related protein (LRP)-mediated Wnt signaling, while not activating Frizzled/LRP-mediated Wnt signaling in the absence of RECK and/or GPR124. The agents are particularly useful for the prevention or treatment of neurovascular disorders or central nervous system (CNS) disorders including neurovascular dysfunction.

Abstract: A fusion protein is disclosed. The fusion protein of the invention comprises an Fc fragment of an immunoglobulin G and a bioactive molecule, wherein the Fc is a single chain Fc. The amino acids in the hinge of the Fc is mutated, substituted, or deleted so that the hinge of Fc cannot form disulfide bonds. Methods for producing and using the fusion protein of the invention are also provided.

Abstract: High affinity PD-1 mimic polypeptides are provided, which (i) comprise at least one amino acid change relative to a wild-type PD-1 protein; and (ii) have an increased affinity for PD-L1 relative to the wild-type protein. Compositions and methods are provided for modulating the activity of immune cells in a mammal by administering a therapeutic dose of a pharmaceutical composition comprising a high affinity PD-1 mimic polypeptide, which blocks the physiological binding interaction between PD-1 and its ligand PD-L1 and/or PD-L2.

Abstract: Disclosed is a molecule comprising: (a) a first domain, which comprises a targeting moiety; (b) a second domain, which comprises an albumin binding domain (ABD), (c) a third domain, which comprises a furin cleavage sequence (“FCS”), which FCS is cleavable by furin; and (d) a fourth domain, which comprises an optionally substituted Domain III from Pseudomonas exotoxin A (“PE”). Related nucleic acids, recombinant expression vectors, host cells, populations of cells, pharmaceutical compositions, methods of producing the molecule, methods of treating or preventing cancer in a mammal, and methods of inhibiting the growth of a target cell are also disclosed.

Abstract: This application relates to use of CD80 (B7-1) extracellular domain (ECD) polypeptides and CD80-ECD fusion molecules and their use in methods of increasing the number of central memory T cells or for treatment for cancer or for use in cancer vaccine compositions.

Abstract: The present invention relates to a PD-L1 antibody, antigen-binding fragments, and medical application thereof. Further, the present invention relates to chimeric antibodies and humanized antibodies comprising the CDR regions of the present PD-L1 antibody, as well as a pharmaceutical composition comprising the present PD-L1 antibody and the antigen-binding fragments thereof, and their use as anti-cancer drugs. In particular, the present invention relates to a humanized PD-L1 antibody and its use in preparation of a medicament for the treatment of PD-L1 mediated disease or disorder.

Abstract: The present invention provides constructs comprising a plurality of peptides capable of targeting at least two different extracellular tumor antigens and a toxin, optionally connected to an organic scaffold. Use of such constructs in treating cancer are provided as well. The invention also provides particular peptides binding certain extracellular tumor antigens as well as toxins having antitumor activity.

Abstract: The disclosure relates to chromatography ligands, e.g., chromatography ligands comprising at least two binding units and at least one spacer domain, wherein each binding unit comprises one or two immunoglobulin binding domains.

Abstract: The present disclosure provides derivatives of amino acids that have surface-active properties. The amino acid can be naturally-occurring or synthetic, or they may be obtained via a ring-opening reaction of a lactam, such as caprolactam. The amino acid may be functionalized to form a compound that is surface-active and have advantageous surfactant characteristics. The compounds of the present disclosure have low critical micelle concentrations (CMC) as well as superior ability to lower the surface tension of a liquid.

Abstract: Provided is a novel antibody and a method for treating breast cancer. More specifically, the present disclosure relates to a bispecific antibody targeting CD3 and a tumor antigen target such as HER2, a preparation method, and uses thereof. The present disclosure also relates to a composition containing said antibody and a method for treating cancer by using the antibody.

Abstract: The present disclosure provides pharmaceutical compositions for monoclonal antibodies, antibody-related products, therapeutic proteins, peptides and other biopharmaceuticals. The compositions provide initial and long term stability of the biopharmaceutical agent, rendering them suitable for parenteral, pulmonary, transdermal, topical, intradermal, intrascleral, intracorneal, ocular and other forms of delivery. The compositions and methods lead to higher yields in dilute solutions and reduce unwanted aggregation of the biopharmaceutical agent. The compositions and methods also allow for disaggregation of previously aggregated proteins and protection from aggregation upon dilution. Additionally, provided are non-aggregating antibody reagents for analytical immunoassays including ELISA methods. The invention provides compositions and methods for topical, enteral, parenteral, pulmonary and other forms of delivery of biologically active substances.

Abstract: The present invention relates to anti-OPG antibodies, and to methods of treatment, uses and pharmaceutical compositions comprising such antibodies, for example in the treatment and prevention of PAH.

Abstract: Provided are Shp2- and Spleen tyrosine kinase (Syk)-integrated sensing and actuating protein (iSNAP) (Shp2- and Syk-iSNAP) chimeric proteins comprising: a bi-phosphorylatable peptide, optionally a bisphosphoryl tyrosine-based activation (BTAM) motif; a Fluorescent Protein (FP) Förster Resonance Energy Transfer (FRET) (or FP FRET) pair or pair of motifs; a truncated Shp2 domain comprising an N-Src Homology 2(N-SH2) domain and a C-Src Homology 2(C-SH2) domain; and, a phosphatase (PTP) domain or a kinase domain. Provided are engineered cells and methods for cancer cell or tumor eradication, or for the treatment or amelioration of a cancer, tumor or dysfunctional cell, or for promoting an anti-cancer, anti-tumor or anti-dysfunctional cell inflammatory response, including enhancing macrophage-, monocyte-, microglia-, osteoclast-, Kupffer cell- or dendritic cell-mediated antibody- or monoclonal antibody (mAb)-guided cancer or dysfunctional cell or tumor eradication, amelioration, or treatment.

Abstract: The application discloses method of treatment of cancer utilizing a linear or substantially linear epitope on netrin-1 that likely corresponds to the specific binding region of netrin-1 to receptor, in particular of the UNC5 class, especially UNC5B and UNC5A, or alternatively corresponds to a region nearby the specific binding region of netrin-1 to receptor that when bound to an antibody prevents netrin-1/receptor interaction. This determination of a linear epitope allows for the production of antibodies binding to netrin-1 and interfering with netrin-1/receptor interaction, thereby inducing apoptosis or cell death of tumour cells expressing or overexpressing netrin-1 and at least one netrin-1 receptor, owing the fact that this interaction inhibits netrin-1 binding to a receptor and the multimerization of the receptor. The application also discloses a murine monoclonal antibody directed against this epitope and various humanized forms thereof.

Abstract: The present invention relates to compositions and methods for the prevention or the treatment of prostate cancer, wherein said compositions comprise an antibody binding to progastrin and said methods comprise the use of an antibody binding to progastrin.

Abstract: A bioinformatics method for determining a risk score that indicates a risk that a subject will experience a negative clinical event within a certain period of time. The risk score is based on a combination of activities of two or more cellular signaling pathways in a subject, such as a human, wherein the specific cellular signaling pathways are the PI3K pathway and one or more of a Wnt pathway, an ER pathway, and an HH pathway. The invention also includes an apparatus with a digital processor configured to perform such a method, to a non-transitory storage medium storing instructions that are executable by a digital processing device to perform such a method, and to a computer program comprising program code means for causing a digital processing device to perform such a method. The invention achieves advanced prognosis of negative clinical events, for example, disease progression, recurrence, development of metastasis, or even death.

Abstract: The invention relates to a method for a computer device, for detecting an optimal candidate compound based on a plurality of samples comprising a cell line and one or more biomarkers, and a plate map configuration, wherein the plate map configuration is providing locations of samples comprising cell lines exposed to one or more biomarkers and different concentrations of a candidate compound forming at least one concentration gradient, the candidate compound being comprised in a plurality of candidate compounds, said method comprising generating (310) phenotypic profiles of each concentration gradient of each of the plurality of candidate compounds at a plurality of successive points in time to form a plurality of compound profiles, wherein generating phenotypic profiles comprises the steps obtaining (312) image data depicting each sample comprised in the concentration gradient, generating (314) a class-label and a class for each cell of the samples based on the image data, detecting (320) the optimal candidat

Abstract: The present invention relates to a method for quantifying an anti-TNF antibody in a sample of a human individual comprising a step of adding to a test sample which may contain therapeutic anti-TNF antibodies a known amount of two or more labeled forms of said anti-TNF antibodies.

Abstract: A method for treating or preventing idiopathic polypoidal choroidal vasculopathy is provided comprising intravitreal injections of Zimura™ (or another anti-C5 agent) and Eylea® (or another VEGF antagonist).

Abstract: The present invention relates to engineered extra-cellular vesicle internalizing receptors that have the ability to enhance uptake, processing, and presentation to T-cells of tumor-associated antigens by an antigen-presenting cell. It further relates to vectors or antigen presenting cells expressing said receptors, composition and uses thereof for the prevention and/or treatment of a cancer.

Abstract: The present invention relates to artificial antigen presenting cell (aAPC) scaffolds to provide cells with specific functional stimulation to obtain phenotypic and functional properties ideal to mediate tumor regression or viral clearance. In particular, the scaffolds of the present invention comprise antigens, such as peptide-MHC (pMHC) class I molecules, and specific combinations of cytokines and co-stimulatory molecules to allow effective expansion and functional stimulation of specific T cells.

Abstract: The present invention is concerned with a protein oligomer comprising (i) at least two NC-monomers of collagen 18 or (ii) at least two endostatin domains of collagen 18 or (iii) at least two N-terminal peptides of the collagen 18 endostatin domain, for use in treating, ameliorating or preventing fibrosis or a fibrosis-associated disease, a vascular endothelial growth factor (VEGF)-related disease or a matrix metalloproteinase (MMP)-related disease. The invention further relates to the mentioned protein oligomer for use for detecting and/or diagnosing fibrosis or a fibrosis-associated disease, a vascular endothelial growth factor (VEGF)-related disease or a matrix metalloproteinase (MMP)-related disease.

Abstract: The present invention is directed to the field of immunotherapy. Specifically, the invention provides compositions and methods for improved T cell modulation ex vivo and in vivo and for the treatment of cancer and other pathologies. More specifically, embodiments of the invention are directed to the use of soluble NTB-A polypeptides or agonists thereof for the treatment of cancer patients, for preventing and treating cytopenia in susceptible patients, and for the ex vivo preparation of improved cell compositions.

Abstract: The present invention provides a nucleic acid construct comprising the following structure: A-X-B in which A and B are nucleic acid sequences encoding a first and a second polypeptide of interest (POI); and X is a nucleic acid sequence which encodes a cleavage site, wherein either the first or second POI is a transmembrane protein which comprises an intracellular retention signal.

Abstract: The invention provides antagonistic and agonistic anti-human VISTA antibodies and antibody fragments. These antagonist antibodies and antibody fragments may be used to inhibit or block VISTA's suppressive effects on T cell immunity and thereby promote T cell immunity. 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 antagonist antibodies and antibody fragments are especially useful in the treatment of cancer and infectious conditions. 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 anti-BTC antibodies, methods of producing said antibodies, pharmaceutical compositions comprising said antibodies, and methods of using said antibodies. The present disclosure also provides multi-specific binding molecules, e.g., bispecific antibodies, comprising a BTC binding moiety and an anti-VEGF binding moiety.

Abstract: Genetically modified non-human animals comprising a humanized interleukin-15 (IL-15) gene. Cells, embryos, and non-human animals comprising a human IL-15 gene. Rodents that express humanized or human IL-15 protein.

Abstract: The present disclosure presents a general approach to engineering existing protein-protein interactions through domain addition and evolution. The disclosure teaches the creation of novel fusion proteins that include knottin peptides where a portion of the knottin peptide is replaced with a sequence that has been created for binding to a particular target. Such fusion proteins can also be bispecific or multi specific in that they can bind to and/or inhibit two or more receptors or receptor ligands. Knottins may be fused with an existing ligand (or receptor) as a general platform tor increasing the affinity of a ligand-receptor interaction or for creating a multi specific protein. In addition, the fusion proteins may comprise a knottin peptide fused to another protein where the other protein facilitates proper expression and folding of the knottin.

Abstract: The disclosure provides, in part, follistatin polypeptides that are suitable for use in local administration and methods for use.

Abstract: The present disclosure provides a heterodimeric, conditionally active chimeric antigen receptor (CAR), and a nucleic acid comprising a nucleotide sequence encoding the CAR. The present disclosure provides cells genetically modified to produce the CAR. A CAR of the present disclosure can be used in various methods, which are also provided.

Abstract: Provided herein are methods for the treatment in a subject of anemia, anemia requiring RBC transfusion, low or intermediate-1-risk myelodysplastic syndromes (MDS), and/or non-proliferative chronic myelomonocytic leukemia (CMML) in any mammals wherein the methods comprise administration of Activin-ActRII signaling inhibitors to a subject in need of the treatment.

Abstract: Provided herein are agents that hind to binding domain I of LRP1 and mimic the activity of prosaposin in stimulating Tsp-1. Further provided herein are agents that inhibit the function (e.g., the ability to repress Tsp-1) of Protease, Serine 2 (PRSS2) by inhibiting the binding of PRSS2 to LRP1. Methods of using these agents in treating cancer are also provided.

Abstract: Antibody derivatives that have diminished effector function in the initial state owing to the presence of one or more disabling moieties that substantially prevent engagement of the antibody regions responsible for interaction with humoral and cellular immune system effector molecules, and methods of use thereof.

Abstract: The present invention relates to an isolated cellular targeted delivery system comprising a CD45+ leukocyte cell comprising within said cell a complex of one or more iron binding proteins and an active ingredient as well as methods for producing such isolated cellular targeted delivery system and uses of such system for therapy, in particular for therapy of cancer.

Abstract: Compositions and methods for treating cancer in humans are provided using CARs. The invention includes engineered CARs (chimeric receptor antigens) and genetically modified immune cells that express such a CAR with a high affinity for VEGFR. More specifically, the cells are CAR-T cells recognizing VEGFR-2 on solid tumors, uses thereof, compositions thereof and methods of making. The invention includes therapeutic methods to treat VEGFR-2 dependent cancers targeting tumor angiogenesis. A chimeric antigen receptor (CAR) that binds to VEGFR-2, an epitope or fragment thereof, or a variant thereof.

Abstract: The present invention is directed in part to pharmaceutical compositions for storage and administration comprising a) a HER2/neu antibody (“margetuximab”), b) buffering agents, and c) stabilizers, wherein said margetuximab is stable. The invention in part provides, containers and kits comprising such pharmaceutical compositions. The invention is directed in part to the use of such pharmaceutical compositions, containers, and kits containing margetuximab in the treatment of HER2/neu-positive cancer (i.e., a cancer that expresses HER2), including breast cancer or gastric cancer or GEJ cancer.