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33 results about "Toxin Conjugates" patented technology

Therapeutic nucleic acid-3' -conjugates

Methods are described for improvement of the serum half life of therapeutic nucleic acids by 3′ conjugation to useful target proteins, or other large molecules with useful function. In one embodiment, a 3′ A, C or G overhang is added to ds-DNA and the primary amines conjugated using biocompatible bifunctional linkers to proteins. The resulting nucleic acid-3′-conjugates are serum nuclease-resistant and retained in vivo for long periods without rapid kidney clearance. Further, the choice of conjugate imparts additional functionality to the nucleic acid-3-conjugate. For example, if the protein in the DNA-protein conjugate is the first component of the complement cascade (Clq or Clqrs) and the DNA aptamer has been developed against surface components of a target cell, it can be used to treat bacterial or parasitic infections and cancers. If the protein is serum albumin or another common (nonimmunogenic) blood protein and the aptamer is directed against a toxin or venom, the aptamer-protein conjugate can be used as an antidote that binds and neutralizes the toxin or venom. Similar DNA (aptamer)-nanotube, -enzyme, and -toxin conjugates could also be used to target and selectively kill bacteria, parasites, and cancer cells in vivo. If the protein is an Fc antibody fragment or C3b protein from the complement system and the aptamer is developed against a bacterial cell capsular material, other cell surface component or viral cell surface component, then the aptamer-3′-protein conjugate can aid in opsonization of the target cells or viruses by phagocytic leukocytes.
Owner:OTC BIOTECH

Therapeutic nucleic acid-3' -conjugates

Methods are described for improvement of the serum half life of therapeutic nucleic acids by 3′ conjugation to useful target proteins, or other large molecules with useful function. In one embodiment, a 3′ A, C or G overhang is added to ds-DNA and the primary amines conjugated using biocompatible bifunctional linkers to proteins. The resulting nucleic acid-3′-conjugates are serum nuclease-resistant and retained in vivo for long periods without rapid kidney clearance. Further, the choice of conjugate imparts additional functionality to the nucleic acid-3-conjugate.For example, if the protein in the DNA-protein conjugate is the first component of the complement cascade (Clq or Clqrs) and the DNA aptamer has been developed against surface components of a target cell, it can be used to treat bacterial or parasitic infections and cancers. If the protein is serum albumin or another common (nonimmunogenic) blood protein and the aptamer is directed against a toxin or venom, the aptamer-protein conjugate can be used as an antidote that binds and neutralizes the toxin or venom. Similar DNA (aptamer)-nanotube, -enzyme, and -toxin conjugates could also be used to target and selectively kill bacteria, parasites, and cancer cells in vivo. If the protein is an Fc antibody fragment or C3b protein from the complement system and the aptamer is developed against a bacterial cell capsular material, other cell surface component or viral cell surface component, then the aptamer-3′-protein conjugate can aid in opsonization of the target cells or viruses by phagocytic leukocytes.
Owner:OTC BIOTECH

An antibody-dolastatin conjugate and its preparation method and application

The invention discloses a preparation method for an antibody-monomethyl auristatin E (MMAE) conjugate. The method comprises the following steps: (1) a monoclonal antibody with an LPXTG sequence at each C terminus of an anti-MART-1 protein presentation peptide EAAGIGILTV / HLA-A2 composite, and monomethyl auristatin E or a monomethyl auristatin E derivative with an oligo-glycine joint are provided; (2) under the catalysis of a Sortase A enzyme, the LPXTG sequences and the oligo-glycine joint are subjected to a transpeptidation reaction, and the monoclonal antibody is coupled with and the monomethyl auristatin E or the monomethyl auristatin E derivative with the oligo-glycine joint; and (3) after the reaction is completed, separation purification is performed, and therefore the antibody-monomethyl auristatin E conjugate is obtained. Through site-direct coupling, the method provided by the invention makes per molecule of the antibody have four molecules of the MMAE, has good uniformity, andexhibits good tumor killing capacity in vivo experiments; and compared with current target spots of ADCs (antibody-drug conjugates), CLA12-vcMMAE ADCs expand the selection areas of the current targetspots of the ADCs, demonstrate the view that an intracellular protein can also be taken as the target spot of the ADCs through presentation of MHC (major histocompatibility complex) I molecules.
Owner:ZHEJIANG UNIV
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