41 results about "Immunoglobulin domain" patented technology

The invention discloses a fusion protein taking peptide-N-glycosidase as an active component as well as a preparation method and application of the fusion protein, and belongs to the technical field of biological medicines. The fusion protein comprises: (a) peptide-N-glycosidase or a catalytically active fragment thereof; (b) an immunoglobulin Fc domain, or a combination of a tumor or immune cell antigen binding domain and an immunoglobulin Fc domain; (c) a linker peptide; wherein the form of the tumor or immune cell antigen binding domain is Fab, scFv or VHH; the peptide-N-glycosidase or the catalytic activity fragment of the peptide-N-glycosidase is connected with the Fc structural domain of the immunoglobulin through the connecting peptide; the immunoglobulin Fc domain mediates the fusion protein to form a homodimer or a heterodimer. According to the invention, the synergistic function of targeted binding and local deglycosylation of the target molecule is realized, so that the immunosuppressive activity of the target molecule is interfered, and the anti-tumor immune response is enhanced.

Provided are anti-TIGIT antibodies that bind to “T cell immunoreceptor with Ig and ITIM domains (TIGIT)”, including multispecific anti-TIGIT antibodies with binding specificity for TIGIT and one or more additional antigen, and methods of using the same. In certain embodiments, the anti-TIGIT antibodies comprises a single domain antibody that binds to TIGIT. In certain embodiments, the one or more additional antigen comprises Programmed cell death ligand 1 (PDL1).

Aspects of the disclosure relate to PD-1 binding proteins comprising immunoglobulin domains which bind specifically to PD-1 and comprise at least three or six specific complementarity determining regions (CDRs) and which comprise a specific feature in a variable domain framework region(s), e.g., heavy variable domain framework 1, heavy domain framework 4, and / or light chain variable domain framework 3 region(s). In some embodiments, the PD-1 protein comprises the substitution(s) L 108G and / or THOR of the heavy chain reference sequence and / or 158R relative to the light chain reference sequence(s). The PD-1 binding proteins are useful, e.g., as immunologic adjuvants, for detecting and quantifying PD-1, monitoring patient responses to therapies, diagnosing PD-1 related conditions, and treating or preventing disorders involving PD-1 expressing cells, such as, e.g., cancers and autoimmune diseases. Also provided herein are antigen binding proteins comprising amino acid substitutions in the heavy chain framework 4 region for improved stability and solubility.

Provided is a fusion protein, the fusion protein containing a GLP-1 polypeptide and an immunoglobulin Fc domain, wherein the GLP-1 polypeptide is covalently linked to the immunoglobulin Fc domain, the GLP-1 polypeptide is selected from human GLP-1(9-37) and human GLP-1(9-36) amides, and the GLP-1 polypeptide contains G22E and / or R36G substitutions relative to a natural human GLP-1 polypeptide. The human GLP-1(9-37) and human GLP-1(9-36) amides are products respectively resulting from losing two amino acids at the N-terminus of natural human GLP-1(7-37) and human GLP-1(7-36, by means of DPP4 enzyme degradation, and were previously considered as biologically inactive fragments. Provided are a polynucleotide encoding the fusion protein, a vector and cell containing the polynucleotide, and the use thereof, for example, in the preparation of drugs for treating metabolic diseases related to lipid metabolism disorders, complications of metabolic diseases, neurodegenerative diseases and other related diseases.

The present invention relates to a T cell activation inhibiting factor (VISTA) protein or mRNA containing a V-type immunoglobulin domain, as a diagnostic marker selected for treatment of a patient with an autoimmune disorder, and as a means for monitoring the success of treatment of an autoimmune disorder. The present invention relates to methods for patient selection and treatment monitoring, to combined diagnostic and therapeutic applications for determining VISTA protein and / or mRNA in a patient sample, and to diagnostic kits suitable for use in the methods of the invention.

Aspects of the disclosure relate to PD-1 binding proteins comprising immunoglobulin domains which bind specifically to PD-1 and comprise at least three or six specific complementarity determining regions (CDRs) and which comprise a specific feature in a variable domain framework region(s), e.g., heavy variable domain framework 1, heavy domain framework 4, and / or light chain variable domain framework 3 region(s). In some embodiments, the PD-1 protein comprises the substitution(s) L108G and / or T110R of the heavy chain reference sequence and / or I58R relative to the light chain reference sequence(s). The PD-1 binding proteins are useful, e.g., as immunologic adjuvants, for detecting and quantifying PD-1, monitoring patient responses to therapies, diagnosing PD-1 related conditions, and treating or preventing disorders involving PD-1 expressing cells, such as, e.g., cancers and autoimmune diseases. Also provided herein are antigen binding proteins comprising amino acid substitutions in the heavy chain framework 4 region for improved stability and solubility.

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 invention discloses a kit for rapidly detecting sST2. The kit 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 a second monoclonal antibody which is labeled by fluorescent microspheres and is combined with a 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 a first monoclonal antibody combined with a third immunoglobulin structural domain of sST2, and the quality control strip is coated with a second antibody for resisting a second monoclonal antibody; according to the kit, rapid detection of sST2 can be completed within 6 minutes, cross reaction between isomers (such as soluble ST2 and transmembrane type ST2) is effectively eliminated, the detection accuracy and sensitivity are improved, the kit can directly use a whole blood sample for detection, centrifugation is not needed, and the detection time is saved; and the method is suitable for a full-automatic fluorescence immunoassay analyzer, and can realize automatic, convenient and rapid interpretation.

The present invention relates to V-type immunoglobulin domain-containing inhibitor of T-cell activation (VISTA) protein or mRNA as a diagnostic marker for selecting patients suffering from autoimmune disorders for treatment and as a means for monitoring the success of treatment of autoimmune disorders. The present invention relates to methods for patient selection and treatment monitoring, combined diagnostic and therapeutic applications, which involve the determination of VISTA protein and / or mRNA in patient samples, and diagnostic kits suitable for use in the methods of the invention.

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.

Provided herein are antibodies and antigen binding fragments thereof that have specificity for 2 (VSIG2) containing a V-set immunoglobulin domain. Also provided herein are cells, nucleic acids, vectors, compositions, and methods involving antibodies, or antigen binding domains thereof, specific for VSIG2.

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.

A method of capturing human immunoglobulin Fc domains in a biofluid sample is provided. The method includes providing an affinity capture device. The affinity capture device includes a surface having an aptamer that is at least 80% identical to SEQ ID NO 1 immobilized onto the surface of the affinity capture device. The biofluid sample is diluted with a binding buffer. The binding buffer includes (A) tris(hydroxymethyl)aminomethane (Tris), trimethylamine (TES), 2-ethanesulfonic acid (MES), or 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES); (B) a magnesium cation at a concentration between about 10 μM to about 20 mM; and (C) a total monovalent cation concentration from 0 to no greater than 100 mM. The human immunoglobulin Fc domains in the biofluid sample are adsorbed to the aptamer with the binding buffer.

Herein is reported a polypeptide comprising a first polypeptide and a second polypeptide each comprising in N-terminal to C-terminal direction at least a portion of an immunoglobulin hinge region, which comprises one or more cysteine residues, an immunoglobulin CH2-domain and an immunoglobulin CH3-domain, wherein the first, the second, or the first and the second polypeptide comprise the mutation Y436A (numbering according to the EU index).

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 herein are soluble interleukin-6 receptor (sIL-6R) and CTGF binding proteins, multispecific binding proteins thereof, conjugates thereof, pharmaceutical compositions thereof, and methods of use thereof. The specific binding proteins can be single heavy chain antibodies (VHH), and the multispecific binding protein can include two variable heavy chain (VHH) immunoglobulin domains targeting sIL-6R and CTGF. The conjugates can include a binding protein or multispecific binding protein, conjugated with an anti-transferrin receptor antibody. The pharmaceutical compositions can include one or more binding proteins and / or multispecific binding proteins. The methods of use include the administration of binding proteins and / or multispecific binding protein for the treatment of neurological diseases.

To provide immunomodulatory proteins that provide therapeutic utility for a variety of immunological and oncological conditions.SOLUTION: There are provided immunomodulatory proteins that exhibit altered binding affinities to binding partners that are immune protein ligands involved in immunological responses, comprising at least one affinity modified non-immunoglobulin IgSF domain comprising one or more amino acid substitution(s) in a wild-type immunoglobulin superfamily (IgSF) domain.SELECTED DRAWING: Figure 1A

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.

Provided herein are antibodies and antigen-binding fragments thereof specific for V-set immunoglobulin domain containing 2 (VSIG2). Also provided herein are cells, nucleic acids, vectors, compositions, and methods directed to the VSIG2-specific antibodies or antigen-binding domains thereof.