32 results about "Receptor complex" patented technology

The present disclosure provides compositions and methods for the treatment of coronavirus infections, such as SAR-CoV, SARS-CoV-2, and MERS-CoV. The compositions include antibodies targeting the IL-6 receptor complex, antibodies targeting CD3, dactinomycin, and combinations thereof. The methods of treatment include administration of antibodies and combination therapies to reduce or eliminate symptoms associated with coronavirus infection or pulmonary inflammatory disease.

The invention relates to variants of the alpha subunit of interleukin-2 receptor (IL2R) and interleukin-2 (IL2). In one embodiment, the IL2 variants described herein have amino acid substitutions at the region of IL2 that contacts the alpha (α) subunit of the heterotrimeric IL2 receptor complex, IL2Rαβγ, reducing its ability to bind and activate the heterotrimeric receptor complex. Conversely, the corresponding IL2Rα variants described herein have amino acid substitutions compensating for such reduced ability of IL2 variants to bind to and activate IL2Rαβγ, preferably at amino acid residues contacted by IL2 amino acid residues that are substituted in the IL2 variants described herein.

The application relates to cytokine receptor agonists comprising: i) a first PD-1 binding domain capable of binding a first epitope on PD-1, ii) a second PD-1 binding domain capable of binding a second epitope on PD-1, iii) an IL2Rγ binding domain, iv) an IL2Rβ binding domain, and v) an Fc region, and wherein the first and second PD-1 binding domains do not compete for binding on PD-1. The PD1-binding domains simultaneously bind the PD-1 and the IL-2 receptor-binding domains bind subunits of an IL-2 receptor complex. Biparatopic assembly of the IL-2 receptor-binding domains in the presence of PD-1 allows to selectively activate IL-2 receptors and effectively mimic cytokine activity in a targeted manner.

The application provides an application of a hair follicle immune homeostasis regulation strategy in treating alopecia diseases. A group of pathological LAMP3 + CCR7 + IL4I1 + DC3 dendritic cell subpopulation. A DC3 dendritic cell subpopulation marker gene Il4i1 Drive conditionally knockout one of the CGRP receptor complexes Calcrl The constructed spontaneous alopecia areata animal model can well simulate the progressive and active hair loss of alopecia areata patients, form stable hair loss patches, and combine with pathological changes such as hair follicle immune cell infiltration, which indicates that the dendritic cell CGRP signal loss is an important inducement for mediating systemic alopecia areata. The application also discloses a pharmaceutical composition or kit for preparing a drug for relieving / treating hair loss, improving hair follicle homeostasis, or enhancing hair growth / black coloration (reducing white hair), which comprises: (a) a JAK kinase inhibitor, and (b) a neuropeptide CGRP or a receptor agonist thereof.

A modified immune cell that does not express a T-cell receptor (TCR) and comprises a CD3 antibody receptor complex. Also relates to a pharmaceutical composition comprising said modified immune cell and a bispecific antibody, and the use of said pharmaceutical composition in the preparation of a medicament.

Disclosed herein are methods of and compositions for identifying components of a molecular pathway, wherein the molecular pathway comprises a cell surface receptor. The method comprises use of ligand-coated nanoparticles and cells that internalize the ligand-coated nanoparticles. The methods allow analysis of a wide range of ligand- receptor complexes.

The present disclosure provides methods and compositions for using a novel class of glycan conjugates for modulating cell surface proteins and receptor complexes that can be used to engage signaling pathways within desired cell types. Such defined cell-targeting bioactive glycoligands are directed to cell engagement and activation in therapeutic applications.

A multifunctional antibody acquired via a genetic engineering technique, targeting PD-1 and, at the same time, providing biological effects of an IL-15 / IL-15Rα complex, a nucleic acid molecule encoding the antibody, a recombinant vector comprising the nucleic acid molecule, a recombinant cell comprising the recombinant vector, a preparation method for the multifunctional antibody, and medicinal uses thereof. The multifunctional antibody effectively solves drug resistance against a single target antibody medicament and relapse, also reduces the effective dose, kills tumor cells more effectively, and extends the survival period of in situ tumor model animals; and, compared with an IL-15 or IL-15 / IL-15 receptor complex, extends the serum half-life, increases tumor targeting, and reduces toxic and side effects.

A protein complex includes a first protein and a second protein. The first protein includes an IL- 15 domain operably linked to both a first functional domain and a second functional domain. The second protein includes an IL-15Rα domain operably linked to at least one functional domain. In one or more embodiments, at least one of the functional domains is a targeting domain. In one or more embodiments, at least one functional domain includes albumin. In one or more embodiments, the IL15Rα domain is operably linked to two or more functional domains.

The application discloses a dual-specific antibody with functions of inflammation microenvironment regulation and simultaneous inhibition of choroidal neovascularization, and a preparation method and application thereof. The dual-specific antibody is a single-chain antibody, comprises an IL1R, an IL-1 receptor complex auxiliary subunit IL-1RAcP fragment, and extracellular domains D2 (VEGFR2D2) and D3 (VEGFR2D3) of a tyrosine kinase transmembrane receptor VEGFR2, can simultaneously bind to IL-1 and VEGF, has functions of regulating an inflammation microenvironment and inhibiting choroidal neovascularization, and can more accurately treat fundus-related diseases represented by age-related macular degeneration.

The application discloses interleukin 2 mutants and application thereof, and the application introduces at least one amino acid mutation to change the binding of IL-2 to different receptors by structural analysis of IL-2 and its three receptors, computer-aided design technology, modeling and molecular docking. In the construction of the designed different IL-2 mutants, expression, purification and function analysis are carried out to confirm that the mutants do not bind to IL-2R alpha receptor, but basically do not affect the binding to IL-2R beta / gamma receptor complex. The mutants provided by the application can better activate Teff cells and NK cells, instead of preferentially activating Treg cells with inhibitory function like wild-type IL-2, and the mutants of IL-2 can better play an anti-tumor role in vivo.

The present invention relates to one or more target-binding molecules, each comprising a binding domain [S1] and a binding domain [S2] that are each capable of binding to a scaffold protein, a binding domain [R1] that is capable of binding to a first receptor protein, and a binding domain [R2] that is capable of binding to a second receptor protein. The target-binding molecule is capable of inducing receptor signaling of a receptor complex, conditioned upon binding to a scaffold protein.

The present disclosure relates to combinations of tumor-targeted IL2 receptor agonists and multispecific T-cell engagers, e.g., for use in stimulating T-cells against cancer cells or treatment of cancer. The tumor-targeted IL2 receptor agonists comprise a tumor-associated antigen targeting moiety and an IL2 moiety. The multispecific T-cell engagers comprise a tumor-associated antigen targeting moiety and a T-cell receptor complex targeting moiety.

The present disclosure provides multispecific binding molecules that specifically bind to BCMA, a component of a human T-cell receptor complex and either CD2 or a tumor associated antigen, conjugates comprising the multispecific binding molecules, and pharmaceutical compositions comprising the multispecific binding molecules and the conjugates. The disclosure further provides methods of using the multispecific binding molecules to treat disease and disorders associated with expression of BCMA. The disclosure yet further provides recombinant host cells engineered to express the multispecific binding molecules and methods of producing the multispecific binding molecules by culturing the host cells under conditions in which the multispecific binding molecules are expressed.

The present disclosure relates to monoclonal antibodies that specifically bind to thymic stromal lymphopoietin (TSLP) and methods for treating atopic dermatitis. The antibodies block TSLP interaction with its receptor complex, preventing downstream inflammatory signaling. Administration involves weekly loading doses followed by biweekly maintenance doses, achieving superior clinical efficacy with >90% reduction in disease severity. The antibodies demonstrate favorable pharmacokinetics with a 25-day half-life, low immunogenicity, and a well-tolerated safety profile. This disclosure also covers methods for evaluating treatment efficacy and safety in moderate to severe atopic dermatitis patients.

The invention relates to variants of interleukin-2 (IL2). In particular, the invention relates to a polypeptide comprising a mutein of human IL2 or of a functional variant of human IL2, wherein the human IL2 or functional variant thereof is substituted such that affinity for the βγ IL2 receptor complex (IL2Rβγ) is enhanced. In one embodiment, the human IL2 or functional variant thereof is further substituted such that affinity for the αβγ IL2 receptor complex (IL2αβγ) is reduced. In one embodiment, the polypeptide activates effector T cells over regulatory T cells. The invention also relates to polynucleotides coding for the polypeptides of the invention, host cells comprising the polynucleotides, pharmaceutical compositions comprising the polypeptides, polynucleotides or host cells, therapeutic or prophylactic methods of treatment using the polypeptides, polynucleotides, host cells or pharmaceutical compositions and medical preparations comprising the polypeptides, polynucleotides, host cells or pharmaceutical compositions.

Systems and methods for t-cell receptor complex optimization using quantum variational autoencoders. Mixed-state t-cell receptor (TCR) embeddings and mixedstate major histocompatibility complex peptide (pMHC) embeddings can be generated (110) by embedding input TCR sequences and input pMHC sequences, respectively, using a quantum variational autoencoder (QVAE). A combinatorial optimization of the mixed-state TCR embeddings while fixing the mixed-state pMHC embeddings can be performed (120) using a machine learning-based predictor. TCR sequences from the mixed-state TCR embeddings and the mixed-state pMHC embeddings, after the combinatorial optimization, can be decoded (130) using the QVAE to generate an optimized TCR sequence. The optimized TCR sequence can be synthesized (140) as a synthetic compound for downstream tasks.

This disclosure relates to a fusion protein (e.g., a reverse cytokine receptor) comprising the extracellular domain of an immunosuppressive cytokine receptor (e.g., IL-4R) and the intracellular domain of an immunostimulatory receptor (e.g., an IL-23 receptor complex). This fusion protein (e.g., a reverse cytokine receptor) binds to inhibitory / suppressive cytokines and converts their intracellular signals into immunostimulatory / activating signals. This disclosure further relates to polynucleotides encoding such fusion proteins, modified cells expressing such fusion proteins, therapeutic uses of such fusion proteins, and pharmaceutical compositions comprising such fusion proteins.

This invention provides methods of subcutaneous administration of anti-CD3 monoclonal antibodies (mAbs) either alone or in combination with monoclonal antibodies, that recognize the Interleukin-6 (IL-6) and IL-6 receptor (IL-6R) complex for the treatment, prevention or alleviating a symptom of a disease.

Several embodiments disclosed herein relate to the treatment of a tumor using immunotherapy. Several embodiments relate to the treatment of a liver tumor, such as hepatocellular carcinoma or a metastasis from another tumor location. Additional embodiments relate to combination therapies that employ Natural Killer (NK) cells engineered to express cytotoxic receptor complexes and additional anti-cancer agents to treat tumors.

This document provides methods and compositions relating to mice that express human or humanized Fcα receptors (FcαR) from the FcαR locus located in the mouse leukocyte receptor complex (LRC). In some embodiments, such mice can be used for in vivo testing of therapeutic agents containing human IgA Fc (e.g., testing of the pharmacokinetic and / or pharmacodynamic properties and dosing regimens of such therapeutic agents). This document also provides methods for using such mice, cells derived from such mice, methods for preparing such mice, and ES cells containing the same genetic modifications as such mice.

Recombinant antibodies that specifically bind to IL-15 as well as a complex of IL-15 and the IL-15 Receptor-alpha are provided. The antibodies inhibit immune cell proliferation, and are capable of use in the treatment of any autoimmune or inflammatory disease or condition where IL-15 is dysregulated, including Celiac disease.

The invention discloses a trispecific antibody which comprises a first antigen binding region, a second antigen binding region, a compound of IL-15 and a receptor thereof, and an Fc fragment, the first antigen binding region has CD16 binding activity; the second antigen binding region has HLAG binding activity; the compounds of the first antigen binding region and the second antigen binding region IL-15 and the receptors thereof are directly or indirectly connected with the Fc fragment respectively. The trispecific antibody can be combined with HLAG on tumor cells and CD16 and IL-15 receptors on NK cells at the same time, cell synapse is promoted to be formed between the two cells, then the NK cells are activated to kill HLAG positive tumor cells, and NK cell proliferation can be promoted. Therefore, the trispecific antibody provided by the invention can kill HLAG positive tumor cells, and can effectively treat HLAG-mediated related diseases (such as cancers).

The present invention provides a nucleic acid molecule having an intracellular signaling domain and a transmembrane domain of NKp30, and a chimeric antigen receptor containing the same. The nucleic acid molecule includes a nucleic acid sequence of a fragment comprising (a) an extracellular antigen-binding domain, (b) a hinge domain, (c) a transmembrane domain of NKp30, (d) a cytoplasmic domain of NKp30, and (e) an intracellular signaling domain. By transduction of the nucleic acid sequences of the intracellular signaling domain, the transmembrane domain of NKp30, and the cytoplasmic domain of NKp30 into T cells, the T cells acquire an NKp30 receptor complex and become heavy chain CAR-T cells, which can form stable immune synapses with cancer cells and have excellent cancer cell-toxic activity.

Variants of interleukin-2 (IL2) are provided.SOLUTION: The present invention relates to a polypeptide comprising a mutein of human IL2 or a functional variant of human IL2, wherein the human IL2 or the functional variant thereof is substituted such that the affinity to β γ IL2 receptor complexes (IL2R β γ) is enhanced. In one embodiment, the human IL2 or functional variant thereof is further substituted to have reduced affinity for α β γ IL2 receptor complexes (IL2R α β γ). In one embodiment, the polypeptide activates effector T cells more than regulatory T cells. The invention also relates to a polynucleotide encoding a polypeptide of the invention, a host cell comprising said polynucleotide, a pharmaceutical composition comprising said polypeptide, polynucleotide or host cell.SELECTED DRAWING: None

The invention discloses a method and related device for solving a molecular docking problem, and the method comprises the steps: constructing a topological graph of pharmacophore pairs, the vertex of the topological graph being used for representing the pharmacophore pair formed by docking a ligand pharmacophore and a receptor pharmacophore, and the edge of the topological graph being used for representing the combination between the pharmacophore pairs; the topological graph is represented as a quadratic unconstrained binary optimization problem, vertexes of the topological graph form single items of Hamiltonian of the quadratic unconstrained binary optimization problem, and edges of the topological graph form double items of Hamiltonian of the quadratic unconstrained binary optimization problem; a QAOA quantum circuit is constructed according to the Hamiltonian value of the secondary unconstrained binary optimization problem, and the QAOA quantum circuit is operated based on a quantum chip of a real quantum computer to solve the molecular docking problem; according to the method, a punishment mechanism is introduced for the molecular docking problem, the universality of the molecular docking model is improved, the molecular docking model is made to be suitable for more diversified ligand and receptor compounds, and then the optimal molecular docking configuration is solved.

The invention relates to a phycobiliprotein source xanthine oxidase inhibitory peptide as well as a preparation method and application thereof, and belongs to the technical field of bioactive peptides and functional foods. The phycobiliprotein source xanthine oxidase inhibitory peptide has an amino acid sequence of Ile-Gly-Tyr-Tyr-Leu-Arg or Lu-Asp-Tyr-Tyr-Leu-Arg, and the amino acid sequence table of the phycobiliprotein source xanthine oxidase inhibitory peptide is as shown in SEQ ID NO. 1 or SEQ ID NO. 2. The phycobiliprotein source xanthine oxidase inhibitory peptide provided by the invention is an important protein resource in spirulina and a high-quality source of bioactive peptide, and can be widely applied; the phycobiliprotein source xanthine oxidase inhibitory peptide is low in molecular weight, and compared with a chemically synthesized preparation, food-borne peptides are safer, more efficient, free of toxic and side effects and easy to digest and absorb; the phycobiliprotein source xanthine oxidase inhibitory peptide has high binding affinity with xanthine oxidase, can form a very stable ligand receptor complex, and has excellent inhibition performance on xanthine oxidase.

The present disclosure relates to methods of treating and / or preventing neurodegenerative diseases by modulating interactions between the heparan sulfate-Triggering Receptor Expressed on Myeloid Cell-2 (HS-TREM2) complex and preventing accumulation of amyloid-β (Aβ).

Described herein are methods of using fusion proteins consisting of elements such as one or more proteins / polypeptides capable of translocation into the endoplasmic reticulum (ER) and fragments or variants of interleukin 18 (IL-18) or IL-18. Proteins / polypeptides capable of translocation into the ER include, but are not limited to, immunoglobulins such as Fc regions, VHH antibodies and scFvs, and globular proteins such as serum albumin. IL-18 can be a precursor IL-18 similar to a native procytokine, wherein IL-18 is fused to the C-terminus of its propeptide or propeptide variant. These fusion proteins are useful in methods of treating cancer or fibrosis by activating IL-18 receptor complex (RC) signaling on a cell, releasing or exposing mature IL-18 in or adjacent to a tumor, and / or increasing memory CD8-T cell proliferation.