46 results about "Receptor complex" patented technology

Systems and methods for particularly t-cell receptor complex optimization with reinforcement learning. Classifiers using variational information bottleneck with attention of experts (AVIB classifiers) can be fine-tuned (110) for different representations of desired t-cell receptor (TCR) sequences for a patient. Proximal policy optimization (PPO) models can be trained (120) with reinforcement learning using the AVIB classifiers as reward functions to achieve higher affinity in generating interaction sequences for the desired TCR sequences through automated decision making. The interaction sequences can be clustered (130) based on k-mer profiles to select the interaction sequences having highest binding scores in each cluster as final sequences. A biological functional potency of the final sequences can be validated (140).

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 invention relates to one or more binding molecules capable of inducing receptor signaling of a receptor complex under conditions of non-competitive and / or two-site binding to a scaffold protein. The invention also relates to the therapeutic use of said one or more binding molecules in cancer and autoimmune diseases.

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 a binding molecule which is at least bispecific comprising a first and a second binding domain, wherein the first binding domain is capable of binding to epitope cluster 3 of BCMA, and the second binding domain is capable of binding to the T cell CD3 receptor complex. Moreover, the invention provides a nucleic acid sequence encoding the binding molecule, a vector comprising said nucleic acid sequence and a host cell transformed or transfected with said vector. Furthermore, the invention provides a process for the production of the binding molecule of the invention, a medical use of said binding molecule and a kit comprising said binding molecule.

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.

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.

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.

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.

The invention relates to the technical field of computer-aided drug design and molecular dynamics simulation, in particular to a ligand dissociation path prediction method and system based on atomic resistance constraint, and the method comprises the steps: screening hindering atoms by calculating the atomic spatial distance of a ligand-receptor compound, and extracting ligand coordinates; a uniform direction vector set is generated based on the mass center of the matching body, and the initial traction direction with the minimum resistance is judged and selected through conical area space obstruction; and finally, generating a fine tuning direction set by disturbing the initial direction, and optimizing by taking the minimization of the average blocked number of ligand atoms as a standard to obtain an optimal dissociation path. According to the method, full-automatic high-precision path prediction is realized, the defect that a non-physical penetration path is easily generated in a traditional geometric simplification method is overcome, meanwhile, the calculation efficiency is remarkably improved, the problem of high time consumption of unbiased molecular dynamics simulation is avoided, and the method is suitable for large-scale virtual screening tasks in a complex receptor environment.

The invention relates to variants of interleukin-2 (IL2). In one embodiment, the IL2 variants activate effector T cells over regulatory T cells. 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 at at least a position having an acidic or basic amino acid residue in wild type human IL2 that contacts the alpha subunit of the αβγ IL2 receptor complex (I12Kαβγ). Alternatively, the mutein of human IL2 or of a functional variant of human IL2 comprises at least (i) one or more amino acid substitutions which reduce the affinity for the alpha subunit of II_2Kαβγ and (ii) one or more amino acid substitutions which enhance the affinity for II_2Kβγ. 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.

The present disclosure relates to protein molecules that specifically bind to CD123, which may have at least one humanized or human CD123-binding domain. Such molecules are useful for the treatment of cancer. The protein molecule binding to CD123 may have a second binding domain that binds to another target. In one embodiment, multi-specific polypeptide molecules bind both CD123-expressing cells and the T-cell receptor complex on T-cells to induce target-dependent T-cell cytotoxicity, activation, and proliferation. The disclosure also provides pharmaceutical compositions comprising the CD123-binding polypeptide molecules, nucleic acid molecules encoding these polypeptides and methods of making these molecules.

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.