275 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 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.

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 DUX4. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

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 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 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 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 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.

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.

A drug delivery platform providing flexible fine tune of cell therapy is disclosed herein. Particularly, an engineered fusion protein is coupled with a high affinity ligand carrying at least one payload of drug to be internalized by the transplanted cell to observe or regulate transplanted cell therapy effects.

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.

Disclosed are fusion proteins (and homodimers and heterodimers thereof). Fusion proteins can bind to a protein of interest and to an internalizing receptor (transferrin receptor) on a cell surface. Once bound, the protein of interest can be internalized and / or degraded inside a cell.

The invention provides an anti-CDH17 antibody or an antigen binding fragment thereof, a CDH17-targeted antibody drug conjugate (ADC) and application thereof. The anti-CDH17 antibody provided by the invention can be specifically combined with CDH17 protein, and has a relatively strong CDH17 expression tumor cell killing effect, so that the anti-CDH17 antibody has high-specificity treatment application potential of CDH17 expression tumor. Furthermore, the anti-CDH17 antibody provided by the invention can be effectively internalized on CDH17 expression tumor cells, ADC formed by coupling the anti-CDH17 antibody with a small-molecule toxic compound keeps high internalization activity and strong binding capacity to target protein CDH17, and shows high killing activity to the CDH17 expression tumor cells.

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.

Provided herein are isolated anti-CEACAM5 antibodies, antigen binding portions thereof, bispecific antibodies, and conjugates (e.g., antibody-drug conjugates), which specifically bind to CEACAM5 and are internalized by CEACAM5 expressing cells. Also provided are nucleic acids encoding the anti-CEACAM5 antibodies and antigen binding portions, methods for treating cancer comprising administration of CEACAM5-targeted antibodies, antigen binding portions thereof, bispecific antibodies, and conjugates and / or associated therapies, as well as methods of diagnosis, and kits.

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.

Provided herein are conjugates comprising a promoter peptide conjugated to an agent, such as an antibody or antigen-binding fragment thereof. The promoter peptides promote internalization of an agent (e.g., an antibody or antigen binding fragment thereof). The promoter peptides may also promote internalization of a target protein into a cell when coupled to an agent that binds to the target protein (e.g., a receptor). Also provided are methods of using the conjugates provided herein, for example, for promoting uptake of an antibody or antigen-binding fragment thereof into a cell, for promoting uptake of a target protein into a cell.

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.

Disclosed are fusion proteins (homodimers and heterodimers thereof). Fusion proteins that can bind to a protein of interest that is a G Protein-Coupled Receptor (GPCR) and to an internalizing receptor on a cell surface (transferrin receptor). Once bound, the protein of interest can be internalized and / or degraded inside a cell.

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.

The invention relates to the field of natural medicinal chemistry, in particular to application of mirabilis himalaica to preparation of a product with whitening and anti-oxidation effects, and innovatively adopts mirabilis himalaica to research the whitening and anti-oxidation effects. The mirabilis himalaica-derived extracellular vesicle-like nanoparticles are found to be capable of reducing the content of melanin in melanoma cells at the cellular level and inhibiting the activity of tyrosinase. In addition, the mirabilis himalaica source extracellular vesicle-like nanoparticles can also scavenge free radical ions, inhibit the generation of active oxygen in cells and promote the improvement of cell viability. The mirabilis himalaica-derived extracellular vesicle-like nanoparticles disclosed by the invention can be sufficiently internalized and absorbed by melanoma cells, the melanin content in the melanoma cells is remarkably reduced, melanin pigmentation on the epidermis of a mouse is remarkably reduced, and the mirabilis himalaica-derived extracellular vesicle-like nanoparticles also have excellent oxidation resistance. The method has potential for preparing products with whitening and antioxidant effects.

The present invention provides a method for suppressing a target gene involved in the Wnt / β-catenin signaling pathway in target cells expressing a receptor capable of binding an extracellular Wnt ligand and an intracellular Wnt effector. The method comprises providing nanocarriers and binding the nanocarriers to the target cells and / or internalizing of the nanocarriers into the target cells, whereby the target gene is suppressed in the target cells. In each nanocarrier, an antibody specific for the receptor, a siRNA specific for the effector, or a combination thereof may be attached to a nanoparticle. The target cells may be in a subject. The method may further comprise reducing disease burden and / or inducing stabilization of a disease in the subject. Also provided are methods for synthesizing the nanocarriers.

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.