61 results about "Receptor complex" patented technology

Novel multispecific antigen-binding molecules maintaining excellent cellular cytotoxicity and high stability, which comprise a domain that contains an antibody variable region having glypican 3-binding activity and a domain that contains an antibody variable region having T-cell receptor complex-binding activity, were discovered. Since the molecules of the present invention show a strong cytotoxicity against cells and tissues expressing glypican 3, it is possible to produce novel pharmaceutical compositions for treating or preventing various cancers.

The present invention relates to a novel compound useful in the treatment of central nervous system diseases and disorders which are responsive to modulation of the GABAA receptor complex.

The present invention relates to an isoindol-sulfilimine compound and its preparation and its use as a sigma-2 receptor inhibitor. Compared with the prior art, the isoindol-sulfilimine compound prepared by the present invention can effectively inhibit the sigma-2 receptor activity by binding to the sigma-2 receptor and deformationally regulating the sigma-2 receptor complex, which will lead to the instability of the binding of adjacent Aβ oligomers to the receptor on the synapse, thus leading to the removal of AB oligomers from the synapse. It can be further used for the preparation of new therapeutic drugs for tumor and neurodegenerative diseases.

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.

To provide improved CLL-1 targeting polypeptides and compositions for adoptive T cell therapies for treating, preventing, or ameliorating at least one symptom of a cancer, infectious disease, autoimmune disease, inflammatory disease, and immunodeficiency, or condition associated therewith.SOLUTION: Provided are VHH-based dimerizing agent regulated immunoreceptor complexes (DARICs) and VHH-based chimeric antigen receptors (CARs) directed against CLL-1, polynucleotides encoding the same, compositions thereof, and methods of making and using the same to treat cancer.SELECTED DRAWING: Figure 1A

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

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 invention relates to a pharmaceutical composition, which consists of two ligand substances of Na / K-ATPase, namely an agonist substance and an antagonist substance of a receptor Na / K-ATPase / Src compound respectively. The combined use of an agonist and an antagonist can regulate the physiological functions of ion transport, in-vivo signal transduction and the like participated by Na / K-ATPase, and the safety threshold is expanded, so that the compound can be developed to diagnose or treat tumors, cardiovascular diseases and other diseases.

The invention provides a de novo drug design method and device based on a light quantum computer. The method comprises the following steps: acquiring a ligand receptor complex structure needing to be optimized; extracting a ligand molecule and an acceptor structure from the ligand-acceptor complex structure, marking an optimizable part in the ligand molecule, and presetting a fragment library for replacement; determining an attribute needing to be optimized according to the marked optimizable part; according to the to-be-optimized attribute and the fragment library, calculating to obtain a corresponding monomial coefficient and a corresponding quadratic coefficient, and according to the calculated monomial coefficient and the calculated quadratic coefficient, constructing a corresponding mathematical model; and converting the constructed mathematical model into a corresponding Isin model, inputting the Isin model into a light quantum computer for solving, and calculating to obtain an optimized structure and ligand information. According to the invention, rapid and accurate de novo drug design can be realized.

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 invention provides a strategy of a carborane electron donor-acceptor (EDA) compound, cross coupling of nested carborane and amino acid or oligopeptide is induced through near-infrared light, then a product is further modified, and a novel boron carrying agent with a fluorescence imaging tracing function is successfully designed and synthesized. The invention not only develops a new method for inducing nested carborane functionalization by near-infrared light and expands the chemical synthesis strategy of boron clusters, but also opens up a new way for developing novel drug molecules and cell dyes based on carborane.

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.