40 results about "Receptor subunit" patented technology

The present application discloses an IL-2 derivative, by introducing at least one cysteine residue on the basis of wild type IL-2, partially or completely closing the binding plane of the IL-2 derivative with the alpha receptor subunit, while basically retaining the affinity to the beta and gamma receptor subunit complex.

The invention belongs to the technical field of in-vitro diagnosis and anesthesia monitoring. The invention discloses a serum protein marker combination for evaluating anesthesia depth and application of the serum protein marker combination. The composition is composed of orexin, S100 calcium binding protein B, C reactive protein and gamma-aminobutyric acid A type receptor alpha1 subunit, and can synergistically reflect the anesthesia sedation state from multiple dimensions. The invention also provides a detection kit containing the marker and application of the detection kit in evaluation of anesthesia depth. The combination has the advantages of being high in accuracy, objective, stable and easy to detect, can serve as an effective supplementary tool of an existing nerve electrophysiology monitoring technology, and provides a new reference means for intraoperative sedation depth monitoring and precise anesthesia management.

Provided are antibodies and antigen binding fragments thereof that bind to human interleukin-11 receptor subunit α (IL-11Rα) and related compositions, which may be used in any of a variety of therapeutic or diagnostic methods, including the treatment or diagnosis of cancers, inflammatory diseases, autoimmune diseases, and others.

Disclosed is a polypeptide dimeric protein containing two monomers, each of which contains an extracellular domain (FcεRIa-ECD) of an alpha subunit of an IgE Fc receptor. The dimeric protein has advantages that an excellent binding ability to IgE is exhibited as compared with a conventional therapeutic agent containing an anti-IgE antibody, and less other side effects are exhibited due to lack of ADCC and CDC functions. Thus, the dimeric protein can be applied to a medical product for treating or preventing an IgE-mediated allergic disease.

The present invention provides compounds of formula (I) and / or salts thereof and / or biologically active metabolites thereof and / or prodrugs thereof and / or solvates thereof and / or hydrates thereof and / or polymorphs thereof having affinity and selectivity for the gamma-aminobutyric acid A receptor subunit alpha 5 and act as GABAA α5 positive allosteric modulators, thereby useful in the treatment or prevention of diseases related to the GABAA α5 receptor, process for the preparation and intermediates of the preparation process thereof, pharmaceutical compositions comprising them alone or in combination with one or more other active ingredients and their use as medicaments.

The present invention provides compounds of formula (I) and / or salt thereof and / or biologically active metabolite thereof and / or prodrug thereof and / or solvate thereof and / or hydrate thereof and / or polymorph thereof having affinity and selectivity for the gamma-aminobutyric acid A receptor subunit alpha 5 and act as GABAA α5 negative allosteric modulators, thereby useful in the treatment or prevention of diseases related to the GABAA α5 receptor, process for the preparation and intermediates of the preparation process thereof, pharmaceutical compositions comprising them alone or in combination with one or more other active ingredients and their use as medicaments.

Provided are binding molecules with at least one interleukin-31 (IL-31) receptor subunit alpha-antigen-binding domain (IL-31RA-antigen-bindingdomain)capable of inhibiting IL-31activity,compositions of such binding molecules for treating IL-31-mediated disorders, uses of such binding molecules as medicaments for treating IL-31-mediated disorders, and methods of treating IL-31-mediated disorders using such binding molecules.Also provided herein are binding molecules with an IL-31RA-antigen-binding domain capable of inhibiting IL-31 activity and an IL-13-antigen binding domain capable of inhibiting IL-13activity, compositions of such binding molecules for treating IL-31-mediated disorders and / or IL-13-mediated disorders,uses of such binding molecules as medicaments for treating IL-31-mediated disorders and / or IL-13-mediateddisorders, and methods of treating IL-31-mediated disorders and / or IL-13-mediated disorders using such binding molecules.

The present application relates to the technical fields of biological medicine and cellular immunotherapy, and particularly relates to a signal conversion receptor targeting IL-10, an engineered macrophage and application thereof. The signal conversion receptor is composed of an extracellular domain and a transmembrane domain and an intracellular domain derived from TLR9, and the extracellular domain sequentially comprises a signal peptide, a HA tag and a specific binding domain of an IL-10 receptor alpha subunit from N-terminal to C-terminal. The present application further prepares an engineered macrophage SR CAR-M capable of specifically recognizing IL-10 and converting it into a TLR9 activation signal, which can induce macrophages to polarize to M1 type and has excellent phagocytosis and killing capacity for bladder cancer, breast cancer, lung cancer and melanoma cells, and can be used for preparing related tumor treatment drugs, overcoming the common problems of existing cell therapy, such as easy exhaustion, difficult infiltration and easy inhibition in solid tumors, and having significant clinical transformation potential.

The present disclosure provides a population of genetically modified immune cells and uses thereof, the modified immune cells comprising (i) a chimeric antigen receptor (CAR) targeting a target protein on a target cell; (ii) a first immunomodulatory fusion protein comprising an ectodomain derived from a protein of tumor necrosis factor (TNF) superfamily, and an endodomain derived from a costimulatory molecule of a TNF receptor superfamily protein; (iii) a second immunomodulatory fusion protein comprising an ectodomain derived from a protein of TNF receptor superfamily, and an endodomain derived from a common g-chain cytokine receptor; and (iv) a third immunomodulatory fusion protein comprising an ectodomain derived from the same TNF receptor superfamily protein as in the second immunomodulatory fusion protein, and an endodomain derived from an a or b receptor subunit of the common g-chain cytokine receptor family.

A series of subunit selective allosteric modulators of NMDA receptor function according to Formula (I) is provided herein. Also provided is a method of treating neurological disorders such as Alzheimer's disease Parkinson's disease, schizophrenia, depression, stroke, psychosis and the like using compounds of Formula (I), optionally in combination with one or more further active agent. Pharmaceutical compositions containing a compound of Formula (I) and optionally one or more active agent for treating such disorders may be provided in the form of a tablet, capsule, pill, gel, granules, aerosol, aqueous buffer or a nanoparticle formulation, emulsion, liposome, etc.

Provided are antibodies and antigen binding fragments thereof that bind to human interleukin-11 receptor subunit α (IL-11Rα) and related compositions, which may be used in any of a variety of therapeutic or diagnostic methods, including the treatment or diagnosis of cancers, inflammatory diseases, autoimmune diseases, and others.

Methods for treating thyroid eye disease (TED) are provided by administering an antibody or antigen-binding fragment thereof that binds to human interleukin-11 receptor subunit alpha (IL-11Rα).

Provided are binding molecules comprising at least one interleukin-31 (IL-31) receptor subunit alpha-antigen-binding domain (IL-31RA-antigen-binding domain) capable of inhibiting IL-31 activity and uses of such binding molecules as medicaments for treating IL-31-mediated disorders. Also provided herein are binding molecules with an IL-31RA-antigen-binding domain capable of inhibiting IL-31 activity, and an IL-31RA-antigen-binding domain capable of inhibiting IL-13 activity, as well as uses of such binding molecules as medicaments for treating IL-31-mediated disorders and / or IL-13-mediated disorders.

The application belongs to the field of biomedical technology, and aims to solve the problems of lack of metabolic typing characteristics in the current ESCC molecular typing method, lack of esophageal squamous cell carcinoma molecular typing method based on proteomics and metabolomics, and provides an esophageal squamous carcinoma ESCC molecular typing marker based on DIA proteomics and non-targeted metabolomics and its application. The marker is a combination of 4 proteins and 2 metabolites, the 4 proteins are: hexokinase 3 (HK3), Sec1 family domain protein 1 (SCFD1), septin 5 (SEPTIN5), and signal sequence receptor alpha subunit (SSR1); the 2 metabolites are creatine and 2-deoxy-D-glucose (2'DG). The application fills the gap of the molecular typing method based on proteomics and metabolomics in the field of esophageal squamous carcinoma research, and the proposed molecular typing model can be used as a method for diagnosis, treatment and prognosis evaluation of esophageal squamous carcinoma patients.

Engineered synthetic signal transduction molecules, referred to herein as "trikines," are provided. A trikine is a trispecific ligand of genetically engineered cell surface receptors, wherein the trikine specifically binds with high affinity to the extracellular domains of three different cell surface receptor polypeptides. In some embodiments, receptor multimerization resulting from binding to a trikine leads to intracellular transphosphorylation of the receptor subunits. In some embodiments, a trikine modulates STAT signal transduction resulting from receptor binding and multimerization.

Provided herein is a method of treating a subject for a glioblastoma, the method comprising: administering to the subject an immune cell genetically modified with: (a) a nucleic acid sequence encoding a binding triggered transcriptional switch (BTTS) that binds to a priming antigen that is tissue-specifically expressed in the central nervous system; (b) a nucleic acid sequence encoding a tandem chimeric antigen receptor (CAR) or T cell receptor (TCR) that has a first binding domain that recognizes Ephrin type-A receptor 2 (EphA2) and a second binding domain that recognizes Interleukin-13 receptor subunit alpha-2 (IL13RA2); and (c) a regulatory sequence operably linked to (b) that is responsive to the BTTS, wherein binding of the BTTS to the priming antigen activates expression of the tandem CAR or TCR, which binds EphA2 and / or IL13RA2 in the glioblastoma and induces killing of glioblastoma cells.

The present invention relates to a synthetic cytokine from the IL-6 family. The synthetic cytokine is a polypeptide comprising two binding sites from the same cytokine of the IL-6 family and a third binding site from an additional cytokine of the IL-6 family, wherein the additional cytokine does not require a cytokine-specific non-signaling alpha receptor subunit as part of the receptor complex to trigger signal transduction. All three binding sites of the polypeptide of the present invention must bind to their specific partners to trigger signal transduction. The present invention further relates to a polypeptide for use in medical applications, preferably for the prevention and / or treatment of conditions selected from the group consisting of lymphopenia, muscle atrophy, osteoporosis, thrombocytopenia, obesity-related metabolic disorders such as type II diabetes, obesity, insulin resistance, impaired glucose tolerance, dyslipidemia, hypertension, stroke, or cardiovascular disease, neurological disorders such as paraplegia, Alzheimer's disease, and Parkinson's disease.

The disclosure provides, in various embodiments, polypeptides (e.g., antibodies and antigen binding fragments thereof) that bind to IL-4 receptor subunit alpha (IL-4Rα). The disclosure also provides, in various embodiments, fusion proteins comprising one or more of polypeptides, polynucleotides encoding polypeptides, vectors and host cells suitable for expressing polypeptides, and methods for treating inflammatory conditions (e.g., atopic dermatitis).

The invention relates to the technical field of biology, in particular to an IL-2 mutant and a construction method and application thereof, and the IL-2 mutant comprises a mutation site for enhancing IL-2R alpha binding and a mutation site for weakening IL-2R beta / gamma binding. The mutation site for enhancing IL-2R alpha binding comprises 1, 2, 3, 4, 5, 6, 7, 8 or 9 mutation sites selected from the group consisting of T37R, V69Y, E68Q, N71W, Y107D, M104F, L66G, E60H and L63W; the mutation site for weakening IL-2R beta / gamma binding comprises 1, 2, 3, 4 or 5 mutation sites selected from the group consisting of H16D, N88L, Q126V, L18E and Q126L. According to the application, the IL-2 antagonist is designed, the binding affinity of the IL-2 antagonist to IL-2R alpha is enhanced, and meanwhile, the binding affinity to IL-2R beta and IL-2R gamma is reduced, so that the proliferation of Tregs is inhibited, the anti-tumor immune response is enhanced, and the systemic toxicity and immunogenicity are reduced. According to the application, a molecular dynamics simulation and calculation method is also utilized to accurately identify and regulate the binding affinity of IL-2 and different receptor subunits, an IL-2 antagonist with multi-target specific binding is designed, and accurate regulation of an IL-2 signal channel is realized.

Provided herein are proteins that include a Vascular Endothelial Growth Factor A (VEGF-A) protein binding domain; proteins that include an Epstein-Barr Virus BCL-2 homolog (BHRF1) protein binding domain; proteins that include a Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) RBD protein binding domain; proteins that include an Interleukin-7 receptor subunit alpha (IL7R-α) protein binding domain; proteins that include a Programmed death-ligand 1 (PD-L1) protein binding domain; proteins that include a Tropomyosin-receptor kinase A (Trk-A) protein binding domain; and proteins that include an Interleukin-17 (IL-17A) protein binding domain.

Provided are genetically modified non-human animals that are immunodeficient and optionally comprise xenotransplanted hepatocytes such as human hepatocytes, wherein the genetically modified non-human animal and / or the transplanted hepatocytes are modified to restore, activate, or increase interleukin-6 (IL-6) / interleukin-6 receptor (IL-6R) signaling pathway activity or interleukin-6 receptor subunit beta (GP130) signaling pathway activity and to restore, activate, or increase hepatocyte growth factor (HGF) / hepatocyte growth factor receptor (MET) signaling pathway activity in the transplanted hepatocytes. Also provided are methods of measuring or assessing the activity of human-liver-targeting reagents in such non-human animals and methods of making animals with a humanized liver (e.g., with reduced steatosis). Also provided are genetically modified, immunodeficient, non-human animals comprising a humanized HGF gene and optionally a humanized IL6 gene and methods of using and making such animals. Also provided are methods of increasing or accelerating engraftment of xenotransplanted hepatocytes in non-human animals.

The present invention describes a mutein of IL-15 that can bind to its receptor subunit IL-15Rβ only at acidic pH. The mutant, called Switch-15β, has 8 amino acid changes at the interface with the receptor. The binding of Switch-15β to IL-15Rβ is disrupted at neutral pH but retained at low pH. The present claims are directed towards Interleukin-15 (IL-15) 's innovative use and pH-biased. The IL-15 mutein of the present invention is thus tailored to become more active or stable within the acidic conditions of the tumor microenvironment. This pH-switchable characteristic ensures that the therapeutic activity of IL-15 is maximized where it is most needed, enhancing its ability to stimulate immune cells such as natural killer (NK) cells and CD8+ T cells specifically within the tumor site. Such precision not only improves the efficacy of the treatment but also potentially reduces systemic side effects of IL-15 by limiting the activation of the immune system to the targeted area.

Provided are methods of treating idiopathic pulmonary fibrosis (IPF) comprising administering an antibody that binds to human interleukin-11 receptor subunit α (IL-11Rα) and related compositions.

The disclosure provides, in various embodiments, polypeptides (e.g., antibodies and antigen binding fragments thereof) that bind to IL-4 receptor subunit alpha (IL-4Rα). The disclosure also provides, in various embodiments, fusion proteins comprising one or more of polypeptides, polynucleotides encoding polypeptides, vectors and host cells suitable for expressing polypeptides, and methods for treating inflammatory conditions (e.g., atopic dermatitis).

The present disclosure relates to an application of a peptide in preparing drugs for treating and / or preventing cognitive impairment, belonging to the technical field of drugs for cognitive impairment. The present disclosure discloses an application of an artificially synthesized small molecule peptide in preparing drugs for treating and / or preventing cognitive impairment. When the peptide in the present disclosure is applied to cognitive impairment models, it may effectively play its biological role in blocking the binding between Synapsin IIb (Syn2b) and AMPA receptor subunit (GluA2), enabling the increase of GluA2 membrane expression, increase of AMPA current, enhancement of neuronal excitability and synaptic transmission, thereby alleviating learning and memory impairment in cognitive impairment model mice to some extent.

The present invention describes a mutein of IL-15 that exhibits PH-dependent binding characteristics for its receptor subunit IL-15Rα only at acidic pH. The mutant, called Switch- 15α, has 10 amino acid changes at the interface with the receptor. The binding of Switch-15a to IL-15Rα is substantially reduced or undetectable at physiological pH (7.5) but exhibits detectable binding at acidic pH (5.0), albeit at reduced levels compared to wild-type IL-15. The IL-15 mutein of the present invention is thus tailored to become more active or stable within the acidic conditions of the tumor microenvironment. This pH-switchable characteristic ensures that the therapeutic activity of IL-15 is maximized where it is most needed, enhancing its ability to stimulate immune cells such as natural killer (NK) cells and CD8+ T cells specifically within the tumor site. Such precision not only improves the efficacy of the treatment but also potentially reduces systemic side effects of IL-15 by limiting the activation of the immune system to the targeted area.

The present invention is in the field of immunology and relates to proteins and polypeptides comprising an immunoglobulin single variable domain (ISVD) fused to a cytokine. In particular, the present invention provides a chimeric protein comprising an immunoglobulin single variable domain (ISVD) fused to a cytokine, wherein the internal fusion site of the ISVD is linked to the cytokine, wherein the internal fusion site is located in a loop or turn between two secondary structure elements. The fusion of the cytokine to the ISVD allows for the modulation of cytokine receptor activity and / or downstream signaling upon binding to a cytokine receptor or receptor subunit.

Provided are methods of treating thyroid eye disease (TED) comprising administering an antibody that binds to human interleukin-11 receptor subunit α (IL-11Rα) and related compositions.