213 results about "Internalization" patented technology

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits expression or activity of a DMPK allele comprising a disease-associated-repeat. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

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 invention relates to the technical field of biology, in particular to a ROR1 antibody as well as a preparation method and application thereof. The ROR1 antibody provided by the invention can be highly specifically combined with an antigen, and has rapid and efficient internalization ability. Besides, the anti-ROR1 antibody provided by the invention has high selectivity and high biological activity, not only can be used as an anti-tumor drug or an antibody coupling drug, but also can be used as a diagnostic tool to detect ROR expression in ROR related diseases.

The invention provides a TF and Her2 targeting bispecific antibody coupling drug as well as a preparation method and application thereof, and belongs to the technical field of biological drug preparation. The bispecific antibody provided by the invention can target TF and / or Her2 antigens in tumor cells, and has the advantages of high stability, easiness in expression, purification and coupling and the like. The bispecific antibody can be specifically combined with a tumor surface antigen and internalized into tumor cells, so that the tumor cells can be specifically killed. The bispecific antibody coupling drug prepared on the basis of the bispecific antibody has a good tumor inhibition effect in a cell model and an animal model, is nontoxic and harmless to animals, and has an excellent cancer treatment potential.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits activity of a disease allele associated with muscle disease. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

Disclosed are compositions and methods useful for targeting and internalizing molecules into cells of interest and for penetration by molecules of tissues of interest. The compositions and methods are based on peptide sequences that are selectively internalized by a cell, penetrate tissue, or both. The disclosed internalization and tissue penetration is useful for delivering therapeutic and detectable agents to cells and tissues of interest.

The invention provides an apigenin nanoparticle preparation as well as a preparation method and application thereof. The preparation method comprises the following steps: weighing apigenin, dissolving the apigenin in an acetone solution containing a polylactic acid-glycolic acid copolymer, or dissolving the apigenin in an acetone solution containing the polylactic acid-glycolic acid copolymer and Eudragit S100, and uniformly stirring and mixing at room temperature to obtain a mixed solution; dropwise adding the mixed solution into a polyvinyl alcohol solution, carrying out ultrasonic treatment, and removing the solvent to prepare PANPs or PEANPs. The preparation method is simple, and the prepared PANPs and PEANPs are small in particle size and high in encapsulation efficiency, can effectively penetrate through intestinal epithelial barriers and promote internalization of apigenin into cells, have a good slow release characteristic, can remarkably improve the bioavailability of apigenin, and have a good treatment effect on inflammatory bowel diseases. PANPs has a better treatment effect on ulcerative colitis, and PEANPs has a better treatment effect on diffuse colitis.

The present invention relates to a bispecific antibody that specifically binds to VISTA and MSLN, and uses thereof. The bispecific antibody exhibits significant immuno-oncological activity and ADCC activity compared to a monospecific antibody, degrades target proteins through internalization activity, and possesses tumor-targeting ability, and thus can be advantageously used for the prevention or treatment of various cancers.

The present invention provides an antibody binding a human tumor-associated calcium signal sensor 2 (Trop-2) protein or fragments thereof, and use of the antibody or fragments thereof in preventing or treating diseases. The antibody or fragments thereof of the present invention can effectively bind to the human Trop-2 protein, and have internalization activity, and the internalization activity is enhanced after ADC drug labeling, and the in vivo efficacy and safety of a mouse model are not lower than those of a control antibody.

A perilla leaf-derived nanovesicle and the use thereof in the preparation of a product with anti-inflammatory efficacy. The nanovesicle can be phagocytosed and internalized by HaCaT cells, reduce the levels of ROS and inflammatory factors in HaCaT cells, and exert an anti-inflammatory effect. Meanwhile, the nanovesicle has excellent transdermal properties, and thus can effectively alleviate and treat psoriatic dermatitis symptoms in mice. The nanovesicle can also be added as an active ingredient to different matrices to form compositions.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

Therapeutic compounds for red blood cell-mediated delivery of an active pharmaceutical ingredient to a target cell are described. The therapeutic compounds are configured to bind CD47 on the surface of a red blood cell and to be subsequently transferred to CD47 on the surface of the target cell, the therapeutic compound ultimately being internalized by the target cell via endocytosis. The target cell may be a cancer cell.

The application provides a bispecific antibody conjugate drug targeting TF and Her2, and a preparation method and application thereof, and belongs to the technical field of biological drug preparation. The bispecific antibody provided by the application can target TF and / or Her2 antigens in tumor cells, has high stability, and has the advantages of easy expression, purification and conjugation. The bispecific antibody can specifically bind to tumor surface antigens and be internalized into tumor cells, and can specifically kill tumor cells. The bispecific antibody conjugate drug prepared based on the bispecific antibody has good tumor inhibition effect in a cell model and an animal model, is non-toxic and harmless to animals, and has excellent potential for treating cancer.

Therapeutic compounds for red blood cell-mediated delivery of an active pharmaceutical ingredient to a target cell are described. The therapeutic compounds are configured to bind CD47 on the surface of a red blood cell and to be subsequently transferred to CD47 on the surface of the target cell, the therapeutic compound ultimately being internalized by the target cell via endocytosis. The target cell may be a cancer cell, a virus-infected cell, or a fibrotic cell.

The invention discloses a traditional Chinese medicine composition for treating recurrent urinary tract infection as well as a preparation method and application thereof. The traditional Chinese medicine composition is prepared from 30-90 parts of astragalus membranaceus, 3-9 parts of cordyceps mycelia, 12-36 parts of rhizoma anemarrhenae, 10-30 parts of golden cypress and 6-18 parts of cinnamon. According to the pathogenesis characteristics of recurrent urinary tract infection and the principle of treatment based on syndrome differentiation of traditional Chinese medicine, the optimal raw material composition and dosage part ratio are obtained through screening, simplification and optimization of a large number of experiments, and the traditional Chinese medicine composition can remarkably improve the frequent micturition symptom, bacterial load and bladder pathological injury of rUTI mice. In addition, the drug-containing serum can promote migration of the SV-HUC-1 cells and reduce the level of inflammatory factors secreted by co-culture of the SV-HUC-1 cells and the UTI89 cells; the adhesion and internalization of the UTI89 to the cells are reduced. In addition, according to different bacterial strains and mouse modeling results, it is found that the modeling rate is obviously increased in a mode of enhancing infection every 24 hours, a recurrent urinary tract infection model of UTI89 infected C57BL / 6J is constructed, and a stable model is provided for screening drugs for treating recurrent urinary tract infection.

This patent discloses a dual targeting lipid-based formulation designed for precise drug delivery to the thyroid gland, addressing the complexities of thyroid disorders. The formulation integrates two key technologies: the RGDFK Targeting Motif and Iodine Coupling. The RGDFK motif enhances specific binding to αvβ3 integrin receptors, facilitating internalization of therapeutic agents. Simultaneously, the Iodine Coupling technology leverages the thyroid gland's natural affinity for iodine, ensuring increased accumulation of lipid-based vesicles in thyroid tissue. Applications of this formulation extend to targeted treatment of diverse thyroid disorders, symptom-specific relief, and nutritional supplementation. The formulation serves as a fundamental component in pharmaceutical compositions, adaptable for various administration routes. The manufacturing process emphasizes scalability, reproducibility, and standardized quality. A comprehensive treatment kit has been devised, offering a convenient and tailored approach to thyroid drug delivery. In conclusion, this dual targeting lipid-based formulation signifies a paradigm shift in thyroid disorder therapeutics, promising precision, efficacy, and patient-centric care. As it advances towards clinical applications, it holds the potential to redefine the landscape of thyroid health management for enhanced patient outcomes.

The invention discloses a preparation method of DRP1 engineered mitochondrial derived vesicles and application of the DRP1 engineered mitochondrial derived vesicles in cell aging resistance. The method comprises the following steps: firstly, constructing a lentiviral vector of an overexpressed DRP1 gene, and transfecting cells to obtain a cell strain of the stable overexpressed DRP1 gene; and culturing the cell strain, collecting a culture solution, and separating and extracting the mitochondrial derived vesicles to obtain the DRP1 engineered mitochondrial derived vesicles DRP1-MDVs rich in mtDNA. The DRP1-MDVs is used for treating senescent cells, the DRP1-MDVs is successfully internalized into senescent cells, the ROS level can be effectively reduced, the mitochondrial mtDNA and ATP content can be improved, the mtDNA mutation rate can be reduced, the mitochondrial membrane potential and the mitochondrial network structure can be recovered, and finally the expression of senescence-related proteins P16 and P21 can be reduced. The obvious mitochondrial function repairing potential and the cell aging improving effect are shown.

The invention provides a mouse monoclonal antibody specifically combined with PRLR and application of the mouse monoclonal antibody. Specifically, the invention provides a PRLR-targeted antibody or an antigen binding fragment thereof, and the antibody or the antigen binding fragment thereof comprises a heavy chain variable region and a light chain variable region. The antibody provided by the invention can specifically recognize and bind to PRLR protein, can mediate internalization after binding to the PRLR protein expressed on the cell surface, and can bind to human and monkey PRLR antigens and inhibit the growth and / or proliferation of tumors or tumor cells.

Problem The purpose of the present invention is to provide a novel method for prevention and / or treatment of opioid tolerance or opioid dependence. Specifically, the purpose of the present invention is to develop peptide-based blockers to block MOR-DOR and KOR-DOR heterodimerization. In addition, the purpose of the present invention is to develop homodimer blockers for MOR, DOR, and KOR which modulate their downstream signaling without affecting their internalization. Solution The present invention is a prophylactic and / or therapeutic agent for the prevention and / or treatment of opioid tolerance or opioid dependence comprising the peptide which inhibits the dimer formation of the opioid receptor, wherein the above opioid receptor dimer is a heterodimer or a homodimer formed from one or two opioid receptors selected from the group consisting of the μ type (MOR), the κ type (KOR), and the δ type (DOR).

The present invention relates to the technical field of immune engineering, and in particular to a CD155-targeting antibody or antigen-binding fragment and a use thereof. The antibody comprises a heavy chain variable region having at least 70% identity to a sequence shown in SEQ ID NO: 23 and a light chain variable region having at least 70% identity to a sequence shown in SEQ ID NO: 24, or a heavy chain variable region having at least 70% identity to a sequence shown in SEQ ID NO: 25 and a light chain variable region having at least 70% identity to a sequence shown in SEQ ID NO: 26. The antibody has an excellent binding capability with CD155, and CAR-T cells constructed on the basis of the antibody have a significant killing capability against tumor cells expressing CD155, as well as an obvious cellular internalization effect, the capability of promoting the cytotoxic effect of NK cells, and the capability of promoting the phagocytosis effect of macrophages, thereby exhibiting an excellent anti-tumor effect.

The invention provides a preparation method and application of lipid nanoparticles based on lipoic acid derivatives. The lipoic acid derivative provided by the invention depends on a cyclopentane structure and a disulfide bond of lipoic acid, so that a lipid compound is more easily internalized by cells, and the effectiveness of nucleic acid delivery is improved. The lipid nanoparticles have excellent spleen targeting performance, and drugs are preferentially delivered to the spleen.

Provided are a BCMA binding protein, a bispecific antibody, a preparation method, and a use. The BCMA binding protein comprises a heavy chain variable region and a light chain variable region. The light chain variable region comprises LCDR1, LCDR2, and LCDR3; and the heavy chain variable region comprises HCDR1, HCDR2, and HCDR3. The BCMA binding protein of the present invention has good specific affinity, binds better to a tumor cell line than a control antibody, and has an internalization effect better than that of the control. The bispecific antibody effectively targets both human BCMA and human CD3.

Relates to anti-5T4 antibodies, in particular humanized antibodies. The invention also relates to pharmaceutical compositions comprising these antibodies and pharmaceutical uses thereof. The antibody has relatively high affinity, relatively good cell binding force and relatively high internalization rate, and can be used for treating 5T4 overexpression diseases, such as cancers.

In the present invention, an antibody or antigen-binding fragment thereof that specifically binds to an extracellular region of the CD179b protein expressed on a cell surface and has the ability to be internalized into cells expressing the CD179b protein on the cell surface can be used as an intracellular drug delivery agent for delivering a drug into cells expressing the CD179b protein on the cell surface.

Disclosed are compositions that can bind to a CCR6 G Protein-Coupled Receptor (GPCR) and to a transferrin receptor on a cell surface. Once bound, the protein of interest (CCR6) can be internalized and / or degraded inside a cell.

Provided herein are antibodies or antigen-binding portions thereof that bind to STEAP1 and uses thereof. The antibody provided by the invention can be combined with STEAP1 of human, cynomolgus monkeys or mice, and the antibody provided by the invention has good affinity and internalization effect, and has the potential of preparing anti-tumor ADC drugs.

Provided herein are isolated anti-LRRC15 antibodies, antigen binding portions thereof, bispecific antibodies, and conjugates (e.g., antibody-drug conjugates), which specifically bind to LRRC15 and are internalized by LRRC15 expressing cells. Also provided are nucleic acids encoding the anti-LRRC15 antibodies and antigen binding portions, methods for treating cancer comprising administration of LRRC15-targeted antibodies, antigen binding portions thereof, bispecific antibodies, and conjugates and / or associated therapies, as well as methods of diagnosis, and kits.

The present application provides a PSMA-targeting ligand compound and chelate thereof and use thereof. The structure of the PSMA-targeting ligand compound is shown in formula I, wherein R1, R2 and R4 are each independently selected from H and optionally substituted C1-C5 linear or branched alkyl; R3 is selected from optionally substituted aryl ring group and optionally substituted aromatic heterocyclic group; X is a sulfur or oxygen atom; Y is selected from a chemical bond and -NH-(CH2)m-, wherein m is an integer selected from 0-18; and Z is a radioactive metal ion chelating group. The pharmacokinetic characteristics of the PSMA-targeting ligand compound are obviously improved, which can be more effectively absorbed by the human body, stably exist in the body, and be taken up and internalized by cancer cells, so that the coupling of the radioactive nuclide can obtain cancer treatment drugs and diagnostic reagents with obviously improved therapeutic effect.

The present disclosure relates to anti-SCUBEl antibodies, antigen-binding fragments thereof, and antibody drug conjugates (ADCs), as well as methods of treating and / or preventing SCUBEl-expressing cancers.