19 results about "Immunoglobulin domain" patented technology

The present disclosure provides a novel type of drug for treating subjects suffering from inflammatory and / or autoimmune diseases, particularly rheumatoid arthritis. Specifically, the present disclosure provides a polypeptide comprising at least three immunoglobulin single variable domains (ISVDs), wherein at least one ISVD binds to TNF-α and at least two ISVDs bind to IL-6. The present disclosure also provides nucleic acids, vectors, and compositions.

The invention relates autonomous VH domains (aVH) with cysteines in positions 52a and 71 or in positions 33 and 52 in order to stabilize the autonomous VH domains. Said cysteines are capable of forming a disulfide bond and / or form a disulfide bond under suitable conditions. The invention further relates to aVH libraries.

The application discloses a SARS-CoV-2 epitope type vaccine multi-epitope combination and application, and belongs to the technical field of coronavirus vaccine research and development.The first aspect of the application relates to a fusion protein, which comprises in sequence: (a) a SARS-CoV-2 spike protein receptor binding domain or a functional fragment thereof; (b) a T cell epitope domain, comprising: a CTL epitope cluster, the CTL epitope cluster comprising at least one CD8+ T cell epitope polypeptide selected from SEQ ID NO: 1-15; and (c) an immunoglobulin Fc domain.The application adopts a tandem strategy of immunodominant epitopes + conserved epitopes, predicts high-affinity T cell epitopes by computational biology methods, evaluates the HLA restriction in different populations, introduces a flexible linker peptide for optimization design, evaluates the immune effect difference of different combinations through in vitro and animal models, analyzes the synergistic or competitive relationship between epitopes, and optimizes the vaccine design.Through systematic comparison of the immunological effect difference of different epitope combinations and the adaptability to various vaccine platforms, the application establishes an optimized safe, efficient, broad-spectrum and long-acting multi-epitope vaccine design strategy, and has significant application value and important transformation value.

Provided are bispecific antibodies comprising first and second VIIII binding domains that specifically bind to the extracellular domains of interleukin- 10 receptor (IL-10R) alpha subunit (IL-10Rα) and beta subunit (IL-10Rβ), and that selectively suppress activation of myeloid cells and induce minimal or no direct activation of T cells or B cells.

The present invention provides improved constructs comprising an immunoglobulin-domain. In particular, the present invention provides novel VHH-CH3 fusion antigen-binding forms, as well as improved methods of producing the VHH-CH3 fusions.

To provide a method for reducing drug target interference in an anti-drug antibody (ADA) immunoassay.SOLUTION: The present disclosure provides methods for mitigating drug target interference in an anti-drug antibody (ADA) immunoassay, wherein the ADA immunoassay comprises one or more target blocking reagents under weakly basic pH assay conditions. In one aspect, the agents of the invention are therapeutic proteins used to treat humans, such as therapeutic binding molecules such as monoclonal antibodies (e.g., fully human monoclonal antibodies) or therapeutic fusion proteins such as receptor proteins fused to an immunoglobin Fc domain, e.g., a IgG1Fc domain designed to treat humans. In certain aspects, the drug is a therapeutic human monoclonal antibody.SELECTED DRAWING: None

The application provides a chimeric antigen receptor comprising five domain structures of antigen-specific binding, hinge, transmembrane, costimulation and CD3 zeta signaling; specifically binds to an antigen comprising an immunoglobulin IgE EMPD domain through the antigen-specific binding domain; and provides its long-term therapeutic application for IgE-mediated allergic diseases. Compared with the prior art, the application combines anti-IgE monoclonal antibody technology and CAR technology, changes from targeting the produced IgE protein to targeting the IgE-producing B cells, and the IgE CAR-T has been proved to have a killing effect on mIgE + B cells in vitro and in vivo experiments, solving the problems of short half-life of monoclonal antibody drugs and high drug frequency. In addition, the CAR of the application can effectively avoid the interference of free sIgE, and the therapeutic effect of CAR-T is successfully verified through in vivo experiments by constructing a humanized mouse model.

Genetically modified non-human animals are provided that express an immunoglobulin variable domain that comprises at least one histidine, wherein the at least one histidine is encoded by a substitution of a non-histidine codon in the germline of the animal with a histidine codon, or the insertion of a histidine codon in a germline immunoglobulin nucleic acid sequence. Immunoglobulin genes comprising histidines in one or more CDRs, in an N-terminal region, and / or in a loop 4 region are also provided. Immunoglobulin variable domains comprising one or more histidines (e.g., histidine clusters) substituted for non-antigen-binding non-histidine residues. Non-human animals that are progeny of animals comprising modified heavy chain variable loci (V, D, J segments), modified light chain variable loci (V, J segments), and rearranged germline light chain genes (VJ sequences) are also provided. Non-human animals that make immunoglobulin domains that bind antigens in a pH-sensitive manner are provided.

The present disclosure provides a method for degrading a target protein, comprising: contacting an IL-2Rβγ positive cell with a multispecific binding protein, wherein the multispecific binding protein comprises: a) a first cell surface binding moiety that specifically binds to a CD122 (IL-2Rβ) subunit and / or a CD132 (IL-2Rγ) subunit, on the surface of the IL-2Rβγ positive cell, wherein the first cell surface binding moiety comprises at least one immunoglobulin domain or a fragment thereof; and b) a second binding moiety that is operatively linked to the first cell surface binding moiety and that specifically binds to the target protein, wherein specific binding of the multispecific binding protein to the IL-2Rβ subunit and / or the IL-2Rγ subunit facilitates the internalization of the target protein into the IL-2Rβγ positive cell. The present disclosure also provides multispecific binding proteins and methods of using the multispecific binding proteins to treat disease.

The present invention is based on the finding that administration of a polypeptide comprising at least one immunoglobulin single variable domain against vWF to human TTP patients provides a significantly reduced time to response. The present invention provides a polypeptide comprising at least one immunoglobulin single variable domain (ISVD) directed against von Willebrand factor (vWF) for use in treating vWF-associated diseases in a human in need thereof. The present invention further relates to dosage unit forms, kits, and medical uses for treating TTP.

This technology aims to provide a novel type of drug for treating patients suffering from cancer. [Solution] Specifically, this technology provides a polypeptide comprising at least four immunoglobulin monovariable domains (ISVDs), characterized in that one ISVD binds to the TCR and at least two ISVDs bind to GPC3. This technology also provides nucleic acids, vectors, and compositions.

The present invention relates to a novel immunoglobulin Fc domain variant protein and use thereof, and when expressed in the form of a fusion protein with another biologically active protein, an immunoglobulin Fc domain variant protein according to an embodiment of the present invention can prolong the half-life in vivo of the biologically active protein as well as effectively suppress effector functions such as ADCC or CDC to minimize unexpected side effects.

Genetically modified non-human animals are provided that express an immunoglobulin variable domain that comprises at least one histidine, wherein the at least one histidine is encoded by a substitution of a non-histidine codon in the germline of the animal with a histidine codon, or the insertion of a histidine codon in a germline immunoglobulin nucleic acid sequence. Immunoglobulin genes comprising histidines in one or more CDRs, in an N-terminal region, and / or in a loop 4 region are also provided. Immunoglobulin variable domains comprising one or more histidines (e.g., histidine clusters) substituted for non-antigen-binding non-histidine residues. Non-human animals that are progeny of animals comprising modified heavy chain variable loci (V, D, J segments), modified light chain variable loci (V, J segments), and rearranged germline light chain genes (VJ sequences) are also provided. Non-human animals that make immunoglobulin domains that bind antigens in a pH-sensitive manner are provided.

The present disclosure is directed to methods for preventing or treating helminth (e.g., filarial) diseases in animals. The methods are accomplished by administering to the animal a therapeutically effective amount of an inhibitor of UDP-glucoronosyl transferase (UGT) or immunoglobulin I-set domain containing protein (Igl-DCP, also known as BMA-Lad-2). The inhibitors include those known to inhibit glucuronyltransferase enzyme activity as well as cell adhesion molecule inhibitors and antibodies specific for Igl-DCP and / or UGT.

Provided are an Irisin fusion protein, a polynucleotide encoding the fusion protein, a vector comprising the polynucleotide, a cell and applications thereof. Specifically, provided is a fusion protein comprising an Irisin polypeptide and an immunoglobulin Fc domain, wherein the Irisin polypeptide is covalently linked to the immunoglobulin Fc domain via a linker comprising an enzyme recognition sequence. Also provided are a polynucleotide encoding the fusion protein, a vector comprising the polynucleotide, a cell and a composition thereof, and use of the fusion protein, the polynucleotide, the vector, the cell and the composition in medicine and / or in the preparation of a medicament for treating or preventing metabolic diseases, complications or other related diseases associated with disorders of glucose metabolism and / or lipid metabolism.

Recombinant cell surface capture proteins and detection molecules that are useful for isolating and detecting cells that produce a secreted heterodimeric protein of interest (POI) that has an immunoglobulin CH3 domain and / or substituted CH3 domain are provided. Recombinant cell surface capture proteins and detection molecules that isolate and detect bispecific antibodies are also provided. The invention also provides recombinant antigen-binding proteins that are capable of recognizing and binding to proteins of interest that contain a CH3 domain and / or a modified CH3 domain, such as a CH3 domain with or without amino acid substitutions at H95 and Y96 (IMGT).

The application discloses a kit for rapidly detecting sST2, which comprises a test strip; the test strip comprises a back plate and a water absorption pad, an NC membrane, a fluorescent pad and a sample pad which are sequentially laid on the back plate; the fluorescent pad is coated with fluorescent microsphere labeled second monoclonal antibodies which are combined with the C-terminal unique region of sST2; the NC membrane is provided with a detection strip and a quality control strip, the detection strip is coated with first monoclonal antibodies which are combined with the 3rd immunoglobulin domain of sST2, and the quality control strip is coated with secondary antibodies which are combined with the second monoclonal antibodies; the kit can complete the rapid detection of sST2 within 6 minutes, effectively eliminates the cross reaction between isomers (such as soluble ST2 and transmembrane ST2), improves the detection accuracy and sensitivity, can directly use whole blood samples for detection, does not need to be centrifuged, saves the detection time, and can be applied to a full-automatic fluorescent immunoassay instrument, and automatic, convenient and rapid interpretation can be realized.

The present invention provides a delivery construct comprising: (a) a transport facilitator comprising an immunoglobulin CH2 domain; (b) a transporter comprising a cholix domain Ia; and (c) a therapeutic cargo; wherein the transporter is cleavably coupled to the therapeutic cargo and wherein the transport facilitator is N-terminal to the transporter. Also provided are pharmaceutical compositions comprising the delivery construct.