316 results about "Drug conjugation" patented technology

This invention discloses compositions of chloroquine-coupled active agents such as therapeutic antibodies or insulin, including methods for their preparation. The prior art has shown that chloroquines given as free drug in high enough concentration, enhances the release of various agents from cellular endosomes into the cytoplasm. The purpose of these compositions is to provide a controlled amount of chloroquine at the same site where the drug is delivered, thereby reducing the overall dosage needed. The compositions comprise a chloroquine substance coupled to a drug directly or through a variety of pharmaceutical carrier substances. The carrier substances include polysaccharides, synthetic polymers, proteins, micelles and other substances for carrying and releasing the chloroquine compositions in the body for therapeutic effect. The compositions can also include a biocleavable linkage for carrying and releasing the drug for therapeutic or other medical uses. The invention also discloses carrier compositions that are coupled to targeting molecules for targeting the delivery of chloroquine substances and antibody or insulin to their site of action.

Chimeric and humanized anti-5T4 antibodies and antibody/drug conjugates and methods for preparing and using the same.

Ligand Drug conjugate compounds comprising a β-glucuronide-based linker and methods of using such compounds are provided.

A drug conjugate is provided herein. The conjugate comprises a protein based recognition-molecule (PBRM) and a polymeric carrier substituted with one or more -L^D-D, the protein based recognition-molecule being connected to the polymeric carrier by L^P. Each occurrence of D is independently a therapeutic agent having a molecular weight ≦5 kDa. L^D and L^P are linkers connecting the therapeutic agent and PBRM to the polymeric carrier respectively. Also disclosed are polymeric scaffolds useful for conjugating with a PBRM to form a polymer-drug-PBRM conjugate described herein, compositions comprising the conjugates, methods of their preparation, and methods of treating various disorders with the conjugates or their compositions.

The present invention provides Ligand-Drug Conjugates comprising a PEG Unit in a parallel orientation to the Drug Unit. The invention provides inter alia, Ligand-Drug Conjugates (LDCs), methods of preparing and using them, and intermediates thereof. The Ligand-Drug Conjugates are stable in circulation, yet capable of inflicting cell death on targeted cells or inhibiting proliferation of targeted cells once its drug cargo is released in the vicinity or within targeted cells. In principle embodiments, an LDC of the present invention is represented by the structure of Formula I.

The invention relates to conjugates that bind to targets, methods of using conjugates that bind to targets and methods of treating undesirable or aberrant cell proliferation or hyperproliferative disorders, such as tumors, cancers, neoplasia and malignancies that express a target.

The present invention is directed to antibodies, and antigen-binding portions thereof, engineered to introduce amino acids for site-specific conjugation. The invention relates to engineered antibody constant region (Fc, Cγ, Cκ, and Cλ) polypeptides, and portions thereof, and antibodies comprising the polypeptides. Further, the invention relates to Fc fusion proteins comprising an engineered Fc region. The invention also relates to methods and uses of the engineered antibodies and portions for, among other things, production of antibody-drug conjugate therapeutics.

The present invention provides folate receptor binding ligand‐drug delivery conjugates having the formula (F) nL1L2D. The conjugates have high affinity to folate receptor‐positive tumor cells and low toxicity for normal cells. The present invention also relates to preparation methods for such conjugates, pharmaceutical compositions comprising such conjugates, and use of such conjugates for preparing anti‐tumor medicaments.

Antibody-cytotoxin antibody-drug conjugates and related compounds, such as linker-cytotoxin conjugates and the linkers used to make them, tubulysin analogs, and intermediates in their synthesis; compositions; and methods, including methods of treating cancers.

Among other aspects, provided herein is a mixed-acid salt of a water-soluble polymer-drug conjugate, along with related methods of making and using the same. The mixed-salt acid salt is stably formed, and appears to be more resistant to hydrolytic degradation than the corresponding predominantly pure acid salt or free base forms of the polymer-drug conjugate. The mixed acid salt is reproducibly prepared and recovered, and provides surprising advantages over non-mixed acid salt forms of the water-soluble polymer drug conjugate.

The invention relates to a biological nanometer magnetic target anti-cancer drug, which is formed by coupled biological nanometer magnetic smalls and anti-cancer chemical drug. Wherein, the biological nanometer magnetic small is nanometer magnetic particle formed in magnetic bacterial cell, at 35-120nm diameter, while its main component is Fe3O4 or Fe3S4; single magnetic particle is packed by film; and the coupled anti-cancer chemical drug comprises chemotherapy drug, nucleic acid drug, radioactive nuclide or antibody drug. The invention also provides relative production that using physical adsorption couple or based on the active function group contained by smalls and anti-cancer drug, to select right coupler via chemical reaction to couple them. And the smalls has better bioavailability, less side effect, therefore, the anti-cancer drug can be accurately transmitted to ill part via external magnetic field, to reduce the contact between drug and normal organism., to realize target positioning treatment.

The present invention concerns compositions and methods of use of a humanized Class III anti-CEA antibody, comprising the heavy and light amino acid sequences SEQ ID NO:1 and SEQ ID NO:2. The antibody is effective to treat CEACAM5-expressing tumors, either alone or in combination with one or more therapeutic agents. Drug conjugated Class III anti-CEA antibodies, such as SN-38 or P2PDox immunoconjugates, are particularly efficacious. Surprisingly, the antibody-drug conjugates (ADCs) exhibit high anti-cancer efficacy, while exhibiting low levels of systemic toxicity that are readily treated with standard amelioration techniques. Antibodies and/or immunoconjugates comprising the amino acid sequences SEQ ID NO:1 and SEQ ID NO:2 are surprisingly efficacious for therapy of solid tumors, even when the tumor has proven resistant to standard anti-cancer therapies.

The invention discloses a poloxamer-carboxylic acid drug conjugate and a preparation method and application thereof. The conjugate is formed by directly linking the carboxyl of the carboxylic acid drug with the carboxyl of the poloxamer by the ester bond in the presence of a catalyst. The conjugate is the compound in the general formula (i) or (ii). Compared with the original carboxylic acid drugs, the conjugate has greatly improved drug solubility, enhanced pharmacological effects, reduced adverse reaction and higher safety. By utilizing the hydrophobic carboxylic acid drug, the conjugate can enhance the hydrophobicity of the poloxamer and greatly improve the amphipathy of the poloxamer, thus being capable of forming stable micellar structure under waterborne environment. As the drug carrier, the conjugate can complete further encapsulation of the drugs and can meet different release requirements by controlling the chemical grafted amount and the physical encapsulation amount or realize combined therapy of the drugs by physically embedding other pharmaceutically active drugs. The invention has simple preparation method, mature process and high yield and is suitable for industrialproduction.

Sulfonamide-containing linkage systems for release of payload compounds from an attached targeting moiety in drug conjugates. The conjugates have the formula of [(P)-(L)]m-(T), wherein (P) is a payload compound, (L) is a linker, (T) is a targeting moiety and m is an integer from 1- to 10. Also provided are pharmaceutical compositions comprising such conjugates and there use in treating cancer.

The present invention describes small molecule ligand-drug conjugates and methods of using the small molecule ligand-drug conjugates for targeted treatment of cancer in a patient in need thereof. Further described are methods of sterilizing circulating tumor cells and determining drug concentration in cancer tissue.

The present invention discloses an antibody drug conjugate of a CLDN 18.2-resistant antibody. The structure of the antibody drug conjugate (ADC) is shown as Ab-[(L2)n-L1-D]y in a formula I, wherein Dis a small-molecule cytotoxic drug, L1 and L2 are connected to the drug and the antibody separately, and n is 0 or 1; y represents the average number of D which is coupled to Ab, 0 < y <= 10, and Ab is an antibody which can be specifically bound to human CLDN 18.2, and includes a light-chain variable region (VL) and/or a heavy-chain variable region (VH); and the CLDN 18.2-resistant antibody correspondingly contains at least one specific complementary determining region (CDR) sequence or a mutant sequence of the specific complementary determining region (CDR) sequence in the light-chain variable region (VL) and/or a heavy-chain variable region (VH), and binding of the antibody to CLDN 18.2 is maintained or improved through the mutation. The invention also discloses a ADC-containing pharmaceutical composition and a preparation method and application of ADC. The antibody drug conjugate of the antibody has a large security window and low toxic and side effects, and provides more specific,more effective and better treatment option for tumor patients.

According to the invention, one or more cysteine residues or cysteine derivative residues are used as a drug connection carrier; one or more drugs are coupled to limited connecting sites of the antibody at the same time, so that drugs with higher drug loading capacity are prepared or drugs with lower toxicity can be selected to prepare ADC products, and ADC products with larger treatment windows are obtained. Furthermore, since a plurality of drug molecules can be coupled at one connection site, the ADC product obtained by the method provided by the invention has better uniformity under the condition of preparing antibody drug conjugates with the same DAR value. The use amount of the antibody required in production can be greatly reduced, so that the production cost is effectively reduced.Compared with the antibody drug conjugate of which the same site can only be connected with one drug molecule, the antibody drug conjugate prepared by adopting the method disclosed by the invention still has the same inhibiting or killing effect on tumor cells under the condition that the total amount of the coupled drug molecules is greatly reduced.

As an antitumor drug which is excellent in terms of antitumor effect and safety and has an excellent therapeutic effect, there is provided an antibody-drug conjugate in which an antitumor compound represented by the following formula is conjugated to an anti-HER2 antibody via a linker having a structure represented by the formula: L¹-L²-L^P-NH—(CH₂)n¹-L^a-L^b-L^c or -L¹-L²-L^P- wherein the anti-HER2 antibody is connected to the terminal L¹, and the antitumor compound is connected to the terminal L^c or L^P with the nitrogen atom of the amino group at position 1 as the connecting position.

The present invention relates to compositions and methods using an isolated chimeric molecule, wherein the isolated chimeric molecule comprises an antibody, one or more albumin motifs, optional peptide linkers, and two or more antibiotics or cytotoxic drug molecules conjugated to the unpaired cysteine residues, optionally through linkers. In one embodiment, each of the said albumin motifs in the isolated chimeric molecule contains 2 or more unpaired cysteine residues. In another embodiment, the said antibody in the isolated chimeric molecule targets antigens on cancer cells or drug-resistant bacteria. In another embodiment, the cancer cells have upregulated macropinocytosis. In another embodiment, the cancer cells contain one or more mutations in their RAS family genes. The compositions of the invention are used to treat drug-resistant bacterial infections and cancers, preferably the ones with upregulated macropinocytosis, and the ones containing one or more mutations in their RAS family genes.