Abstract: The present application relates to a chimeric antigen receptor (CAR) which comprises a target-dependent on-switch CAR. The CAR of the invention may reduce cytotoxicity towards normal cells and improve CAR-T safety. CAR molecules were designed using the transmembrane and juxtamembrane motifs of the IL2 receptor ? chain (IL2R? or IL2Rb), the L ow-Density Lipoprotein Receptor (LDLR), the Seizure 6-like Protein 2 (SEZ6L2), and degradation sequence (PSKFFSQL) of IL2R?, which resulted in greatly reduced CAR expression at the cell surface in the absence of target antigen, while retaining downstream activation ability in response to antigen-expressing target cells. In the absence of target antigen, CAR surface expression is undetectable. The present application has shown that primary T cells expressing these surface-unstable CAR variants are able to elicit antigen-dependent target cell killing. By limiting CAR activity in this way, the present application can reduce therapeutic toxicity and T cell exhaustion.

Abstract: The present invention relates to pharmaceutical formulations for heterodimeric Fc-fused proteins which are advantageous for achieving higher titers of the proteins during production, higher stability during storage, and improved efficacy when used as a therapeutic. Also provided are dosage regimens for such heterodimeric Fc-fused proteins and pharmaceutical formulations for use in treating cancer, such as locally advanced or metastatic solid tumor.

Abstract: Recombinant NK cells, and especially recombinant NK-92 cells express a chimeric antigen receptor (CAR) having an intracellular domain of Fc?RI?. Notably, CAR constructs with an intracellular domain of Fc?RI? had a substantially prolonged duration of expression and significantly extended cytotoxicity over time. The CAR may be expressed from RNA and DNA, preferably as a tricistronic construct that further encodes CD16 and a cytokine to confer autocrine growth support. Advantageously, such constructs also enable high levels of transfection and expression of the recombinant proteins and provide a convenient selection marker to facilitate rapid production of recombinant NK/NK-92 cells.

Abstract: The present invention provides for the intratumoral delivery of immunomodulators. hi particular, it provides delivery of co-stimulatory molecules using intratumoral electroporation. The present invention provides a method for the treatment of malignancies, wherein the administration of a plasmid encoding for a therapeutic costimulatory protein, in combination with electroporation has a therapeutic effect on primmy tumors as well as distant tumors and metastases.

Abstract: The present disclosure pertains to compositions comprising anti-VEGF proteins.

Abstract: The present invention provides a fusion protein comprising interleukin-1 receptor antagonist (IL-1Ra) and an extracellular matrix (ECM) binding peptide which specifically binds to one or more or all extracellular matrix proteins selected from the group consisting of fibrinogen, fibronectin, vitronectin, tenascin C and heparan sulfate and use of the fusion protein to treat conditions in which administration of IL-1Ra is beneficial or in which IL-1R1 signalling needs to be dampened, to enhance tissue regeneration, particularly bone regeneration and/or wound repair or for treating wounds, burns and muscle, cartilage, tendon and bone disorders, to enhance the regenerative activity of growth factor administration or to reduce inflammation or desensitisation of a cell to growth factor stimulation.

Abstract: The present invention falls within the field of genetic engineering. More particularly, disclosed is a gene for expressing a fusion protein of human collagen and human fibronectin, which is expressed and purified in vitro by means of a genetic engineering method. By means of using Pichia pastoris as an expression host cell, a new-type, highly active recombinant fusion protein can be provided.

Abstract: The present disclosure provides transferring receptor binding polypeptides of the general formula H1-H2-E1-H3-E2-E3-H-4, herein H1, H2, H3, and H4 each independently comprise an alpha, helical domain of between 11-20 amino acids in length; E1, E2, and E3 each independently comprise a beta sheet of 5 amino acids in length; and optional amino acid linkers between domains.

Abstract: The invention relates to antigen binding sites, antibodies and fragments thereof, as well as compositions, kits and uses thereof for the treatment, attenuation and/or prevention of human immunodeficiency virus type 1 (HIV-1).

Abstract: Provided herein are binding proteins recognizing HPV16 E7 antigen and uses thereof.

Abstract: The present invention relates to novel proteins that specifically bind to the spike protein or domains thereof of the severe acute respiratory syndrome corona vims 2 (SARS-Cov-2) or variants of SARS-Cov-2. The proteins of the present invention represent advanced and powerful tools, for example for the purification of the virus or a vaccine for the virus, by virtue of said binding affinity for spike protein or domains of the spike protein of SARS-Cov-2 or variants thereof. Thus, the novel proteins of the present invention are particularly advantageous because they allow precise capturing of proteins or particles comprising spike proteins, S1 domain, and/or RBD in affinity chromatography. Further, the novel proteins of the present invention can be used in medical applications caused by or related to SARS-Cov-2 or variants thereof.

Abstract: This disclosure provides antibodies and antigen-binding fragments that can be administered to an individual that is infected or suspected of being infected with a virus. Antibodies and antigen-binding fragments herein can be capable of treating or curing the virus, and which may provide protection against the virus for up to several weeks. Antibodies and antigen-binding fragments herein can be used to diagnose a SARS-CoV-2 infection.

Abstract: The invention relates inter alia to a nucleic acid composition for the expression of at least two antibodies, preferably a mixture of assembled antibodies in a cell or subject, wherein at least one coding sequence of the nucleic acid composition encodes at least one antibody chain assembly promoter. Further, the invention relates to a nucleic acid sequence set for expression of at least one assembled antibody and to a combination of different nucleic acid sequence sets. Additionally, first and second medical uses, methods of treating or preventing diseases, disorders or conditions, and methods for the production of antibody mixtures are provided.

Abstract: Provided herein are compositions and combinations for the therapeutic and diagnostic use in treating and preventing biofilms and associated disorders using a high mobility group box protein (HMGB) polypeptide, mutant and/or fragment thereof and an anti-DNABII antibody, fragment or variant thereof. The polypeptide and antibody can be administered in the same or separate compositions.

Abstract: Anti-mutant calreticulin (mutCALR) antibodies are disclosed. Also disclosed are related nucleic acids, vectors, cells, kits, and pharmaceutical compositions. Methods of treating or diagnosing myeloproliferative neoplasms with the anti-mutCALR antibodies are also disclosed.

Abstract: Provided herein are anti-LAP antibodies (e.g., recombinant humanized, chimeric, and human anti-LAP antibodies) or antigen binding fragments thereof which have therapeutically beneficial properties, such as binding specifically to LAP-TGF?1 on cells but not to LAP-TGF?1 in extracellular matrix, as well as compositions including the same. Also provided are uses of these antibodies or antigen binding fragments in therapeutic applications, such as in the treatment of cancer, and diagnostic applications.

Abstract: The present invention relates to mouse antibodies that bind to angiopoietin-2 (Ang2), humanized anti-Ang2 antibodies derived therefrom, and the use thereof. The anti-Ang2 antibodies have a dual function of activating the Tie2 receptor together with neutralizing Ang2. The anti-Ang2 antibodies show the property of normalizing abnormal and pathological blood vessels, and thus exhibits therapeutic efficacy against various diseases and disorders associated with abnormal blood vessels. The present invention further provides an angiogenesis inhibitor and a composition for treatment of diseases associated with abnormal Ang2 expression and Tie2 dysregulation, which comprise the antibody as an active ingredient, and a composition for diagnosing diseases associated with Ang2 inhibition and Tie2 activation, which comprises the antibody.

Abstract: A method of preventing or treating an acute kidney injury-induced acute lung injury (AKI-ALI) in a subject in need by administration of a therapeutically effective amount of an osteopontin inhibitor is disclosed.

Abstract: The present invention relates to antibody molecules and functional fragments thereof, capable of binding to tumor necrosis factor alpha (TNF?), to processes for their production, and to their therapeutic uses.

Abstract: Compositions of TNF family of cytokines in covalently linked trimeric forms are disclosed. The resulting fusion proteins are secreted as disulfide bond—linked homotrimers, which are more stable in structure and therapeutically more efficacious than their native counterparts.

Abstract: Provided are methods, systems, and kits for selecting a patient for treatment with a therapeutic agent based on a presence of a genotype associated with a positive therapeutic response to the therapeutic agent. The therapeutic agent, in some embodiments, is an inhibitor of TL1A activity or expression, such as for example, an anti-TL1A antibody.

Abstract: The present disclosure provides methods of identifying subjects having a lung disease or at risk of developing a lung disease that will respond favorably to treatment with a therapeutic agent that treats or inhibits a lung disease, such as dupilumab, an inhaled corticosteroid (ICS), or a long-acting beta agonist (LABA), and methods of treating a subject having a lung disease with a therapeutic agent that treats or inhibits a lung disease, such as dupilumab, an ICS, or a LABA, and determining or having determined the subject's FEV1 polygenic score (FEV1-PS).

Abstract: Antibodies that specifically bind to the human tight junction molecule CLDN18.2 and have functional properties that make them suitable for use in antibody-based immunotherapies of a disease associated with aberrant expression of CLDN18.2 are disclosed.

Abstract: A monoclonal antibody or a derivative thereof that binds to a human TIGIT antigen with high-affinity and antagonistically inhibits the binding of TIGIT to a ligand thereof such as CD155 is provided. Amino acid sequences of antigen complementarity-determining regions CDR-L1, CDR-L2 and CDR-L3 of an antibody light chain variable region, and amino acid sequences of antigen complementarity-determining regions CDR-H1, CDR-H2 and CDR-H3 of an antibody heavy chain variable region are specified. Further, a humanization preparation method for the antibody and amino acid sequences of the heavy chain variable region and light chain variable region of the humanized antibody are provided. The antibody or the derivative thereof can serve as an ingredient of a pharmaceutical composition or can be prepared into an appropriate drug preparation, and administered alone or in combination with other medications, such as an anti-PD-1 monoclonal antibody, or treatment means, for treating diseases such as tumors.

Abstract: Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits expression or activity of DUX4. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

Abstract: The present invention relates to a targeting module comprising a chemically synthesized peptide binding moiety specific for a human cell surface protein or protein complex, a kit comprising the targeting module and a vector or a cell comprising a nucleic acid encoding a universal chimeric antigen receptor and the use for the treatment of cancer, infections and autoimmune disorders.

Abstract: The present invention relates to anti-TIGIT antibodies and antigen-binding fragments thereof that bind to both human TIGIT and mouse TIGIT. The present application also provides are nucleotides encoding the antibodies or fragments thereof, compositions or combinations comprising the antibodies or fragments thereof, and uses of the antibodies or fragments thereof in treatment of immune-related disease such as cancers and viral infection.

Abstract: The present application relates to modular chimeric receptors, such as chimeric antigen receptors (CARs) comprising chimeric receptor and signaling modules with synthetic transmembrane domains that favor electrostatic interactions between the synthetic transmembrane domains in the cell membrane while eliminating or minimizing electrostatic interactions with the native transmembrane domains of immune receptors and signaling proteins. The modular chimeric receptors, which mimic the structure and signaling of native immune receptors, enable the distribution of the signaling domains across different cytoplasmic chains, display suitable surface expression as well as improved kinetics and sensitivities relative to current standard-of-care (SOC) CAR-based therapies.

Abstract: The present invention discloses a nucleic acid molecule for encoding a chimeric antigen receptor targeting CD22 and CD19. The chimeric antigen receptor of the present invention can be used for treatment of CD19+ and CD22+ B-cell hematological tumors, as well as combined treatment with CD19 CAR-T cells or CD22 CAR-T cells.

Abstract: The present disclosure relates to antibody-drug conjugates (ADCs) wherein one or more active agents are conjugated to an anti-CD19 antibody through a linker. The linker may comprise a unit that covalently links active agents to the antibody. The disclosure further relates to monoclonal antibodies and antigen binding fragments, variants, multimeric versions, or bispecifics thereof that specifically bind CD19, as well as methods of making and using these anti-CD19 antibodies and antigen-binding fragments thereof in a variety of therapeutic, diagnostic and prophylactic indications.

Abstract: Described herein are nucleotide and polypeptide sequences of alternative immunoglobulin domains, engineered to create non-native N?- and C?-termini in the loop regions of the three-dimensional ?-sheet structure of the domain, for use as fusion partners with additional polypeptide sequences. Such polypeptides can be used as reagents, research tools, or therapeutics.

Abstract: Embodiments provided herein, provide for polypeptides, pharmaceutical compositions, and methods that can be used to target at least two types of cells to modulate the activity of the same to treat disorders, such as autoimmune disorders or cancers.

Abstract: The present invention provides antibodies for the treatment of chronic lymphocytic leukemia (CLL). These antibodies target the B-cell receptor (BCR) of CLL cells characterised by R110-mutated immunoglobulin lambda variable 3-21 (IGLV3-21R110). The invention also provides nucleic acid sequences encoding the forgoing antibodies, vectors containing the same, pharmaceutical compositions and kits with instructions for use.

Abstract: The disclosure provides antibody molecules that bind to TCR V? regions and multispecific molecules comprising said antibody molecules. Additionally, disclosed are nucleic acids encoding the same, methods of producing the aforesaid molecules, pharmaceutical compositions comprising aforesaid molecules, and methods of treating a cancer using the aforesaid molecules.

Abstract: The present invention relates to human CD3 antigen-binding polypeptides and their preparation and use in the treatment and/or diagnosis of various diseases, and also relates to bispecific antibody molecules capable of activating immune effector cells and their use in diagnosis and/or treatment of various diseases.

Abstract: Provided herein are compositions, methods and uses involving antibodies that specifically bind to Programmed Death-1 (PD-1) and modulate the expression and/or activity of PD-1.

Abstract: A novel therapeutic strategy for the anti-PD-1 antibody therapy is provided. A pharmaceutical composition which comprises at least one substance selected from the group consisting of the following (i) to (iii) and is administered before, after or simultaneously with the administration of a PD-1 signal inhibitor: (i) ROS generators and substances that regulate downstream signaling pathways thereof, (ii) substances exhibiting an uncoupling effect and substances that regulate downstream signaling pathways thereof, and (iii) amino acids.

Abstract: The present invention provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds human CD28, and a second antigen-binding molecule that specifically binds human PSMA. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of tumors expressing PSMA, such as prostate tumors. The antibodies and bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an up-regulated or induced targeted immune response is desired and/or therapeutically beneficial.

Abstract: The present invention provides isolated monoclonal antibodies, particularly human monoclonal antibodies, that specifically bind to PD-1 with high affinity. Nucleic acid molecules encoding the antibodies of the invention, expression vectors, host cells and methods for expressing the antibodies of the invention are also provided. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. The invention also provides methods for detecting PD-1, as well as methods for treating various diseases, including cancer and infectious diseases, using anti-PD-1 antibodies. The present invention further provides methods for using a combination immunotherapy, such as the combination of anti-CTLA-4 and anti-PD-1 antibodies, to treat hyperproliferative disease, such as cancer. The invention also provides methods for altering adverse events related to treatment with such antibodies individually.

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

Abstract: Provided herein, in some embodiments, are fusion proteins comprising recombinantly engineered variant of stefin polypeptide (an AFFIMER® polypeptide) that binds to PD-L1 and a polypeptide that binds to human serum albumin (HSA). Also provided herein, in some embodiments, are compositions containing the fusion proteins, methods of using the fusion proteins, and methods of producing the fusion proteins.

Abstract: Provided herein are antibody molecules that bind specifically to VISTA and antigen-binding portions thereof and related compositions, nucleic acid molecules, vectors and host cells. Also provided herein are medical uses of such antibody molecules.

Abstract: The present invention relates to combination therapies useful for the treatment of cancer. In particular, the invention relates to a therapeutic combination which comprises an anti-PD-L antibody and a DNA-PK inhibitor, optionally together with one or more additional chemotherapeutic agents or radiotherapy. The therapeutic combination is particularly intended for use in treating a subject having a cancer that tests positive for PD-L1 expression.

Abstract: The present invention is directed to novel B7-H3-binding molecules capable of binding to human and non-human B7-H3, and in particular to such molecules that are cross-reactive with B7-H3 of a non-human primate (e.g., a cynomolgus monkey). The invention additionally pertains to B7-H3-binding molecules that comprise Variable Light Chain and/or Variable Heavy Chain (VH) Domains that have been humanized and/or deimmunized so as to exhibit a reduced immunogenicity upon administration to recipient subjects. The invention particularly pertains to bispecific, trispecific or multispecific B7-H3-binding molecules, including bispecific diabodies, BiTEs, bispecific antibodies, trivalent binding molecules, etc. that comprise: (i) such B7-H3-binding Variable Domains and (ii) a domain capable of binding to an epitope of a molecule present on the surface of an effector cell.

Abstract: The present invention provides methods for treating, preventing or reducing the severity of eosinophilic esophagitis. The methods of the present invention comprise administering to a subject in need thereof a therapeutic composition comprising an interleukin-4 receptor (IL-4R?) inhibitor such as an anti-IL-4R? antibody.

Abstract: Provided is an ST2 antigen binding protein, such as a mouse, human, chimeric or humanized antibody or antigen binding fragment thereof that specifically binds to ST2. Also provided are nucleic acid molecules encoding the above-mentioned antibodies and antigen binding fragments thereof, and an expression vector and host cell for expressing the antibodies or antigen binding fragments thereof. Further provided are methods for preparing and using the antibodies and antigen binding fragments thereof. The methods comprise treating and preventing IL33/ST2-mediated related diseases or conditions.

Abstract: The present disclosure relates to methods of treating or preventing acute respiratory distress syndrome (ARDS) using compounds that inhibit G-CSF signaling. The present disclosure also relates to compounds for use in the treatment or prevention of ARDS, as well as the use of such compounds in the manufacture of medicaments for the treatment or prevention of ARDS.

Abstract: Provided herein are IFNGR binding molecules that bind to IFNGR1 and IFNGR2 and comprise an anti-IFNGR2 sdAb and an anti-IFNGR2 VHH antibody.

Abstract: The present disclosure relates to biologically active molecules comprising a single domain antibody (sdAb) that specifically binds to the extracellular domain of human IL2Rg, compositions comprising such antibodies, and methods of use thereof.

Abstract: The present disclosure relates to biologically active molecules comprising a single domain antibody (sdAb) that specifically binds to the extracellular domain of IL2Rb, compositions comprising such antibodies, and methods of use thereof.