806 results about "Drug conjugation" patented technology

Provided is an antibody-drug conjugate for use in the treatment of cancer in which one or more KRAS mutants, particularly a KRAS G12V mutant, a KRAS G12D mutant, and a KRAS G12C mutant, are expressed. Also provided are a drug and a drug-linker conjugate for use in the antibody-drug conjugate.　The present inventors have produced an antibody-drug conjugate with which a heterocyclic compound represented by formula (II) and having an activity of inducing the decomposition of KRAS mutant proteins can be delivered to cancer in which EGFRs are expressed, the production being achieved by linking the compound to an anti-EGFR antibody. The present inventors have also discovered a drug-linker conjugate for use in the antibody-drug conjugate or a salt thereof. In cancer in which EGFRs are expressed, the antibody-drug conjugate induces the decomposition of one or more KRAS mutants, particularly a KRAS G12V mutant protein, a KRAS G12D mutant protein, and a KRAS G12C mutant protein, thereby inhibiting the KRAS mutants and exhibiting an anti-tumor effect.

Provided are an antibody-drug conjugate, a preparation method therefor, and use thereof. The antibody-drug conjugate has a structure represented by the formula Ab-[M-L-E-D]x, has a superior drug-to-antibody ratio, and has an excellent targeted killing effect on various cancers or tumors.

Provided are a ligand-drug conjugate represented by general formula Pc-(L-D)n or a pharmaceutically acceptable salt thereof, and further provided is a linker for conjugation represented by formula (L). The linker can efficiently and highly selectively perform chemical conjugation with a thiol group on cysteine, and the antibody-drug conjugate formed has good stability.

Linkers for linking a therapeutic agent to other moieties, such as an Fc region of an antibody. A linker having two or more maleimide functional groups, which may be subjected to a nucleophilic conjugate addition reaction. A method for increasing the duration of action of a therapeutic agent by linking a novel linker to the Fc region of an antibody. Antibody drug conjugates having a longer duration of action than the drug alone.

The present disclosure provides antibodies specifically targeting CD142, antibody drug conjugates, preparation and uses thereof. An antibody, or antigen-binding fragment thereof, that binds to CD142 is covalently linked to a cytotoxic payload via a linker. Antibodies, or antigen-binding fragments thereof, and antibody drug conjugates that bind to CD142 exhibit a cytotoxic effect on tumor cells.

The present invention discloses a method for preparing a linker-drug conjugate and its intermediates. Specifically, a method for preparing compound LE14 is provided, which comprises subjecting an intermediate compound of formula II to an amide condensation reaction with a compound of formula III or its mesylate in the presence of a condensing agent, a base, and a solvent to obtain a compound of formula I. This method can produce a high-purity intermediate II, which is directly condensed with isotecan mesylate to obtain compound I, and then subjected to subsequent reactions to obtain the final product LE14. The preparation method of the present invention has one or more of the following advantages: using intermediate II as the starting material for the production process reduces process steps, facilitates product quality control, significantly reduces impurities in the final product, and improves purity. Furthermore, using the more economical isotecan for the condensation reaction significantly reduces production costs, making it more suitable for industrial production.

Disclosed in the present invention are a monoclonal antibody against an interleukin-6 protein and the use thereof. The present invention provides a nucleic acid molecule, a vector, a cell, a composition, a product, a bispecific antibody, a CAR, an antibody-drug conjugate and a pharmaceutical composition comprising an anti-IL-6 monoclonal antibody or an antigen-binding fragment thereof; and further provides the use of the monoclonal antibody or the antigen-binding fragment thereof, the nucleic acid molecule, the vector, the cell, the composition and the product in the detection of IL-6 or a nucleic acid fragment encoding same, in the preparation of a product for detecting IL-6, in a pharmaceutical composition for preventing or treating diseases related to abnormal IL-6 expression, and in the preparation of a pharmaceutical composition for regulating the expression level or activity of IL-6.

Methods and apparatus for protein and drug design using multicapitate (“two or more headed”) neural networks, wherein one head, a sequence head, is trained to generate the sequence of a protein, and another head, a structure head, is trained to generate the structure of the protein; and wherein the neural network is configured to accept a representation of a specified condition as input, and output a representation of a protein's sequence and structure. The structure head and sequence head each have their own loss functions, and the weights of the neural network body are shared, and jointly updated during training. Non-limiting examples of specified input conditions include representations of associated proteins and / or sets of properties of the desired output protein. Some embodiments of the invention include for the design and synthesis of effective peptide drug ligands, synthetic biologic antibody drugs, antibody drug conjugates, and monoclonal antibody (mAb) drugs.

The invention discloses a triggering probiotic-drug conjugate and a preparation method and application thereof, and belongs to the technical field of oral drug delivery systems, the triggering probiotic-drug conjugate comprises probiotics, an adhesive inner layer formed by coordination of tannic acid and Fe < 3 + >, and an outer layer formed by pterostilbene-phospholipid bridged by ROS-responsive thioether bonds and cholesterol; the inner layer coats the surfaces of the probiotics through coordination, and the outer layer coats the outer part of the inner layer through self-assembly. An outer lipid layer is decomposed under high-concentration ROS in an inflammation colon area, and probiotics coated with pterostilbene and a tannic acid layer are released. Pterostilbene relieves inflammation and rebuilds a pathological microenvironment, and catechol groups in a tannic acid layer and the surface of the intestinal tract generate multiple interactions to promote planting of probiotics. In UC mouse models, the conjugates exhibit enhanced therapeutic effects by inhibiting inflammation, restoring intestinal barrier function, and improving intestinal microbiota homeostasis. The invention has important transformation potential in clinical application of gastrointestinal diseases.

The present invention relates to antibodies and antibody-drug conjugates, and more particularly to antibodies and antibody-drug conjugates (ADCs) targeting TROP2 and / or NECTIN4 as well as compositions containing said antibodies or ADCs and therapeutic applications thereof.

The present disclosure relates to a ligand-drug conjugate of a novel structure or a pharmaceutically acceptable salt thereof. Specifically, the present disclosure provides a ligand-drug conjugate having a structural general formula represented by Pc-(L-D)n or a pharmaceutically acceptable salt thereof, a method for preparing same, a pharmaceutical composition comprising the conjugate, and use thereof in treating a tumor.

The invention relates to an antibody or an antibody fragment targeting TROP2, an antibody drug conjugate containing the antibody or the antibody fragment, and a preparation method and application of the antibody or the antibody fragment.

The invention relates to an antibody drug conjugate which is shown in a formula (I) and contains two or more bioactive molecules with different action mechanisms, a preparation method of the antibody drug conjugate, and application of the antibody drug conjugate in prevention and / or treatment of diseases related to abnormal cell activity, including but not limited to prevention and / or treatment of tumor diseases. # imgabs0 #

Provided are an antibody specifically binding to hEGFR or an antigen-binding fragment thereof, and a bispecific antibody, antibody-drug conjugate and pharmaceutical composition comprising the antibody. Further provided is the use of the antibody or the antigen-binding fragment thereof or the bispecific antibody.

The present disclosure relates to antibody-drug conjugates, and more particularly to antibody-drug conjugates (ADCs) loaded with inhibitors of Ras mutations as well as compositions containing the ADC molecules and therapeutic applications thereof.

Disclosed are drug conjugates comprising a targeting moiety conjugated to a drug molecule, wherein the targeting moiety binds to a cell adhesion moiety and / or receptor expressed on a Schwann cell to mediate targeted delivery of the drug conjugate to the Schwann cell, and wherein the drug molecule modifies expression or activity of a disease-associated molecule, and / or confers a cytotoxic effect, in the Schwann cell. Further disclosed herein are methods of targeted delivery of a drug to the Schwann cells.

Provided are an antibody-drug conjugate, a method for preparing same, and use thereof. The antibody-drug conjugate has a structure represented by formula Ab-[M-L-E-D] x, a superior drug-to-antibody ratio, and an excellent targeted killing effect on various cancers or tumors.

The present invention relates to an antibody or an antigen-binding fragment thereof binding to CLDN18.2, an antibody-drug conjugate comprising same, and a use of the antibody and the antibody-drug conjugate. An anti-CLDN18.2 monoclonal antibody according to the present invention comprises a fully human antibody sequence, thereby having low in vivo immunogenicity, and exhibits excellent antigen affinity and binding ability specific to a low expression to a high expression level of the CLDN18.2 protein. Thus, the antibody is expected to exhibit high specificity and safety as an antibody-based therapeutic agent such as in the form of a monoclonal antibody and / or an antigen-binding fragment (scFv), an antibody-drug conjugate (ADC), an immune cell engager, a chimeric antigen receptor (CAR), a multispecific antibody, and the like. In addition, the antibody according to the present invention may undergo cellular internalization, enables an anti-CLDN18.2 antibody-drug conjugate comprising said antibodies to be conveniently prepared, and has excellent yield and quality and thus is expected to be highly likely to be developed as a drug. A drug conjugate comprising the anti-CLDN18.2 antibody according to the present invention has excellent in vivo anticancer efficacy and has an expanded therapeutic index (TI) and thus is expected to be usefully employable for the treatment and / or prevention of cancer diseases expressing CLDN18.2 and related diseases.

The present invention relates to polypeptides which are covalently bound to molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold. In particular, the invention describes peptides which are high affinity binders of membrane type 1 metalloprotease (MT1-MMP). The invention also describes drug conjugates comprising said peptides, conjugated to one or more effector and / or functional groups which have utility in imaging and targeted cancer therapy.

Provided herein are methods for treating or preventing progression of cancer in an individual, comprising administering to the individual an effective amount of an anti-PD-1 antibody, e.g., toripalimab, and an anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugate that comprises an anti-HER2 antibody and a cytotoxic molecule. Compositions, uses, and kits related thereto are also provided.

Provided are an anti-Cadherin6 antibody, a drug conjugate thereof, and a preparation method therefor. The anti-Cadherin6 antibody and the antibody-drug conjugate thereof can be used for treating diseases or disorders, such as cancers.

The invention relates to combined application of an antibody drug conjugate and an immune checkpoint inhibitor, in particular to application of single drug or combined use of the antibody drug conjugate in preparation of drugs for preventing and / or treating cancers. Specifically, the invention provides an application of the antibody drug conjugate or pharmaceutically acceptable salt, metabolite or solvate single drug thereof or a combined immune checkpoint inhibitor in preparation of drugs for preventing and / or treating cancers.

The invention discloses a bispecific antibody which comprises a first protein functional region targeting CD30 and a second protein functional region targeting CD16a, the first protein functional region comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3. The invention also discloses nucleic acid for coding the antibody, a recombinant expression vector, a transformant, a preparation method of the antibody, an antibody drug conjugate, a pharmaceutical composition or a kit containing the antibody drug conjugate, and applications of the nucleic acid, the recombinant expression vector and the transformant in preparation of drugs for preventing and / or treating tumors. The bispecific antibody provided by the invention can effectively activate the NK cells and can effectively target human tumor cell related antigen CD30 protein, mediate the killing activity of the NK cells to target cells, and induce and further enhance the tumor inhibition effect of the NK cells to tumor cells.

A linker-payload compound for targeting molecule-drug conjugate, and the corresponding conjugate, the preparation and use thereof are provided.

The present invention relates to self immolative compounds, and compositions comprising the self immolative compounds and uses thereof. Specifically, the invention relates to enzyme cleavable self immolative compounds and compositions comprising enzyme cleavable self immolative compounds. Also described herein are specific binding molecule – drug conjugates comprising the cleavable self immolative compounds disclosed herein.

The present invention relates to the use of a PD-L1 binding molecule in improving the stability of a protein-drug conjugate formulation. The present invention also relates to a pharmaceutical composition consisting of the PD-L1 binding molecule and the protein-drug conjugate, and discloses an anti-tumor use thereof.

Described are RNAi agents, compositions that include RNAi agents, and methods for inhibition of a microtubule associated protein tau (MAPT) gene. The MAPT RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of a MAPT gene. The MAPT RNAi agents are conjugated to an antigen binding protein that may enable subcutaneous delivery of the RNAi agents by facilitating crossing of the blood brain barrier (BBB). Pharmaceutical compositions that include one or more MAPT RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described MAPT RNAi agents to central nervous system (CNS) tissue, in vivo, provides for inhibition of MAPT gene expression and a reduction in MAPT activity, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including Alzheimer's disease, Frontotemporal lobar degeneration dementia (FTLD), Progressive supranuclear palsy, and other tauopathies.

The present invention relates to an antibody-drug conjugate containing two or more functional small molecules for enhancement of targeted treatment of cancers and refractory diseases. The invention also relates to preparation of such conjugate, pharmaceutical compositions, and methods in treatment of cancers and refractory diseases.

Provided herein is a preparation of a stable drug conjugate containing one or two opened ring structures of thiosuccinimides linked to an antibody or an antibody-like protein for enhancement of targeted treatment of cancers and refractory diseases. In particular, provided herein are preparation of such conjugate homogenously, and its pharmaceutical compositions, as well methods in treatment of refractory diseases.

Method, system and computer-accessible medium can be provided for generating one or more drug conjugates of one or more small molecules. For example, with such exemplary method, system and computer-accessible medium, a multimodal discriminative model can be trained to predict at least one peptide-ligand binding for one or more DNA ligands, a generative nucleotide model can be trained to generate a plurality of compounds. Further, a feedback can be provided from the multimodal discriminative model to fine-tune the generative nucleotide model so as to facilitate the generation of the drug conjugate(s).