33 results about "Toxin Conjugates" patented technology

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.

The invention discloses a polyethylene glycol-rTRAIL mutant tripolymer-aplysiatoxin conjugate as well as a preparation method and an application thereof. In the polyethylene glycol-rTRAIL mutant tripolymer-aplysiatoxin conjugate, the amino acid sequence of an rTRAIL mutant is shown in SEQ ID No.1; an rTRAIL mutant tripolymer is coupled with methoxy polyethylene glycol maleimide and aplysiatoxin which is provided with a connecting arm. The conjugate disclosed by the invention has higher tumor cell killing capability than an rTRAIL mutant tripolymer-aplysiatoxin conjugate and longer half-life period than an rTRAIL mutant-monomethyl polyethylene glycol maleimide conjugate; in the conjugate disclosed by the invention, the methoxy polyethylene glycol maleimide, the rTRAIL mutant tripolymer and the aplysiatoxin do not play effects independently but play a relatively high synergistic effect.

According to the invention, light-chain 205-locus valine (V) of a target antibody is modified into cysteine (C); free sulfhydryl group (-SH) of the modified cysteine is subjected to fixed-point conjugation with mc-vc-PAB-OH connexon conjugated with small-molecular high-activity cytotoxin (Payload), such that the cysteine-modified antibody drug conjugate with excellent homogeneity is formed. The drug-antibody ratio (DAR) of the conjugate is 1.6-2.0. The antibody drug conjugate has a general formula 2C1-LC-V205C-mc-vc-PAB-payload. Also, the invention discloses a preparation method and a purification method of the TDC drug, and the application of the drug in treatments of EGFRvIII-expressing and EGFRwt-overexpressing tumors.

The 235-position serine (S) of the heavy chain of the target antibody is transformed into cysteine ​​(C), and the free sulfhydryl group (‑SH) of the transformed cysteine ​​is coupled with a small molecule highly active cytotoxin ( Payload) mc‑vc‑PAB‑OH linker for site-directed coupling to form a homogeneous cysteine ​​engineered antibody‑toxin conjugate with a toxin-to-antibody ratio (DAR) of 1.6‑2.0. The toxin conjugate has a general formula: 2C2-HC-S235C-mc-vc-PAB-payload. At the same time, the present invention also discloses the preparation and purification method of this TDC drug, which is used in the treatment of tumors expressing EGFRvIII and overexpressing EGFRwt application.

The invention discloses an antibody antigen-binding fragment-aplysiatoxin conjugate and a preparation method and application thereof. The preparation method includes steps: (1) providing an antigen-binding fragment of an anti-CD20 monoclonal antibody with an LPXTG sequence at a C-terminal and aplysiatoxin or derivatives thereof with oligonucleotide linkers; (2) under Sortase A enzyme catalysis, the LPXTG sequence and the oligonucleotide linkers have peptide transferase reaction to enable coupling of the antigen-binding fragment with the aplysiatoxin or derivatives thereof with the oligonucleotide linkers; (3) after reaction is completed, separating and purifying to obtain the antigen-binding fragment-aplysiatoxin conjugate. The antigen-binding fragment-aplysiatoxin conjugate has advantagesthat specificity, affinity and CD20 positive tumor cell killing effects of whole antigen-aplysiatoxin conjugates are retained, and high tumor penetrating rate and high tumor position clustering quantity are realized.