33 results about "Calicheamicin" patented technology

This invention describes processes for the convergent synthesis of calicheamicin derivatives, and similar analogs using bifunctional and trifunctional linker intermediates.

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

A method is disclosed for preparing hydrazides from hydrazine and an acyl chloride which comprises the steps of (a) preparing a stirred substantially uniform slurry comprising hydrazine and an inert solvent at low temperature; and (b) adding an acyl chloride continuously to said slurry. The method avoids or limits production of undesired bis-hydrazide by-products. The method is used to prepare 3-methyl-3-mercaptobutanoic acid hydrazide, a molecule used to link calicheamicin to a monoclonal antibody.

The present invention provides methods of treating cancer cells comprising administering to a patient in need thereof a therapeutically effective amount of a non-specific antibody conjugated to a cytotoxin, wherein the cancer cells do not express an antigen to which the non-specific antibody binds. In one embodiment, the non-specific antibody is an anti-CD33 antibody (e.g., hp67.6), an anti-CD22 antibody (e.g., g5 / 44), or an anti-CD20 antibody (e.g., rituximab). In another embodiment, the non-specific antibody does not bind a human antigen. The cancer cells treated can be, e.g., gastric, colon, non-small cell lung (NSCLC), breast, epidermoid, or prostate carcinoma cells. In one embodiment, the cytotoxin is calicheamicin. Calicheamicin can be conjugated to the non-specific antibody using a 4-(4′-acetylphenoxy)butanoic acid (AcBut) or (3-Acetylphenyl)acetic acid (AcPAc) linker. In another embodiment, the antibody to the non-specific antigen conjugated to a cytotoxin is administered in combination with a bioactive agent, e.g., an anti-cancer agent.

The present invention relates to a method of treating patients with solid tumors, leukemias, and other malignancies using a combination of zosuquidar and a calicheamicin-antibody conjugate, such as Mylotarg. The invention is also directed to pharmaceutical formulations comprising zosuquidar and calicheamicin-antibody conjugates. The formulations are particularly effective in treating relapsed Acute Myelogenous Leukemia (AML) and metastatic breast cancer.

Methods for preparing monomeric cytotoxic drug / carrier conjugates with a drug loading significantly higher than in previously reported procedures and with decreased aggregation and low conjugate fraction (LCF) are described. Cytotoxic drug derivative / antibody conjugates, compositions comprising the conjugates and uses of the conjugates are also described. Monomeric calicheamicin derivative / anti-CD22 antibody conjugates, compositions comprising the conjugates and uses of the conjugates are also described.

This invention describes processes for the convergent synthesis of calicheamicin derivatives, and similar analogs using bifunctional and trifunctional linker intermediates.

This invention describes processes for the convergent synthesis of calicheamicin derivatives, and similar analogs using bifunctional and trifunctional linker intermediates.

The present invention concerns antibody-conjugate having general structure (2):AB-[(L6)-{Z-(L1)n-(L2)o-(L3)p-(L4)q-D}xx]yy   (2)wherein AB is an antibody capable of targeting Trop-2-expressing tumours and D is selected from the group consisting of taxanes, anthracyclines, camptothecins, epothilones, mytomycins, combretastatins, vinca alkaloids, maytansinoids, enediynes such as calicheamicins, duocarmycins, tubulysins, amatoxins, bleomycins, dolastatins and auristatins, pyrrolobenzodiazepine dimers, indolinobenzodiazepine dimers, radioisotopes, therapeutic proteins and peptides (or fragments thereof), kinase inhibitors, MEK inhibitors, KSP inhibitors, and analogues or prodrugs thereof. These antibody-conjugates exhibit an improved therapeutic index. The invention further concerns a process for preparing the antibody-conjugate according to the invention, a method for targeting Trop-2-expressing cells, medical uses of the antibody-conjugates according to the invention.

The present invention relates to intermediates of Formula Iand to methods of synthesizing and purifying calicheamicin derivatives.

Provided herein are antibody drug conjugates (ADCs) comprising calicheamicin and methods of using the same to treat proliferative disorders.

The present invention relates to intermediates of Formula Iand to methods of synthesizing and purifying calicheamicin derivatives.

The present invention relates to a method of treating patients with solid tumors, leukemias, and other malignancies using a combination of zosuquidar and a calicheamicin-antibody conjugate, such as Mylotarg. The invention is also directed to pharmaceutical formulations comprising zosuquidar and calicheamicin-antibody conjugates. The formulations are particularly effective in treating relapsed Acute Myelogenous Leukemia (AML) and metastatic breast cancer.

A cancer targeted therapeutic agent includes a drug-linker-AS1411 structure. The drug may be selected from monomethyl auristatin E (MMAE), monomethyl auristatin F (MMAF), cytarabine, gemcitabine, maytansine, DM1, DM4, calicheamicin and a derivative thereof, doxorubicin, duocarmycin and a derivative thereof, pyrrolobenzodiazepine (PBD), SN-38, a-amanitin, or a tubulysin analog.

The present invention concerns antibody-conjugate having general structure (2): AB-[(L 6 )-{Z-(L1) n -(L2 ) o -(L3 ) p-(L4 ) q-D} xx ] yy (2) wherein AB is an antibody capable of targeting Trop-2-expressing tumours and D is selected from the group consisting of taxanes, anthracyclines, camptothecins, epothilones, mytomycins, combretastatins, vinca alkaloids, maytansinoids, enediynes such as calicheamicins, duocarmycins, tubulysins, amatoxins, bleomycins, dolastatins and auristatins, pyrrolobenzodiazepine dimers, indolinobenzodiazepine dimers, radioisotopes, therapeutic proteins and peptides (or fragments thereof), kinase inhibitors, MEK inhibitors, KSP inhibitors, and analogues or prodrugs thereof. These antibody-conjugates exhibit an improved therapeutic index. The invention further concerns a process for preparing the antibody-conjugate according to the invention, a method for targeting Trop-2-expressing cells, medical uses of the antibody-conjugates according to the invention.

The invention provides a fermentation medium for fermentation production of an antibiotic calicheamicin gamma1 I. The fermentation medium comprises one or more organic carbon sources and one or more organic nitrogen sources, wherein based on a total volume of the fermentation medium, the content of the one or more organic carbon sources is in a range of 5 to 130g / L and is preferably in a range of 20 to 110g / L; the content of the one or more organic nitrogen sources is in a range of 2 to 150g / L, is preferably in a range of 4 to 60g / L and is more preferably in a range of 15 to 40g / L; the one or more organic carbon sources are selected from cane sugar, molasses, glycerin and corn starch; and the one or more organic nitrogen sources are selected from fine bean meal and corn steep powder. The invention also provides a fermentation method for fermentation production of an antibiotic calicheamicin gamma1 I by the fermentation medium and a use of the fermentation medium. The fermentation medium greatly provides fermentation titer units of calicheamicin gamma1 I, improves production efficiency, reduces a production cost, and is suitable for large-scale production of calicheamicin gamma1 I.

The invention provides a novel microbial fertilizer special for tobaccos. The fertilizer comprises the following components in parts by weight: 5 to 25 parts of a complex microbial inoculant and 75 to 95 parts of a carrier, wherein the complex microbial inoculant contains 1.6 to 8 hundred million cfu / g of bacillus subtilis, 1.6 to 8 hundred million cfu / g of bacillus licheniformis, 0.4 to 2.0 hundred million cfu / g of trichoderma harzianum and 0.4 to 2.0 hundred million cfu / g of calicheamicin streptomyces hygroscopicus; the carrier is a powdered material which are made by performing microbe fermentation and decomposition on rape seed cakes, bean pulp cakes and sesame-seed cakes, and then performing drying and sieveing. The microbial fertilizer contains bacterial strains for antagonizing fungus pathogenic bacteria, bacterial strains for preventing and curing the breeding of soil pathogenic bacteria, bacterial strains for improving the soil environment and the like. The carrier is fermented three-cake fertilizer. The invention also provides a preparing method for the microbial fertilizer. The microbial fertilizer special for the tobaccos, provided by the invention, is powder, is capable of absorbing the water and preserving the moisture. The fertilizer is mainly used as the base fertilizer when fertilizing, the soil fertility can be improved, the nutrient absorption of crops is improved, the diseases of a plurality of crops can be prevented, and the quality and the yield of tobacco leaves can be effectively improved.

The invention discloses a key exchange domain for controlling the change of the lipid chain length of lipopeptides, wherein the key exchange domain refers to the exchange of the Cs-AL domain of rhizopeptide with the Cs-AL domain of rhizopeptide The latter Cs-AL structural domain, or the Cs-AL structural domain after the Cs-AL structural domain of the chrysanthemum peptide is replaced by the Cs-AL structural domain of the rhizopeptide, or the Cs-AL structural domain of the chrysanthemum peptide The Cs-AL domain after being replaced by the Cs-AL domain of calicheamicin. The invention also discloses mutants obtained by exchanging the key exchange domains and their applications. Experiments show that for rhizopamide, the rzmACsholA mutant can directionally obtain derivatives with C8 lipid chain length, and for rhizopeptides , the holACsrzmA mutant can be directed to obtain derivatives of C2 lipid chain length, while the two mutants of synobactin, glbACsholA and glbACsglpA, can obtain derivatives of C8 and C10 lipid chain lengths, respectively. It is predicted that the present invention has great application value in guiding the transformation of lipopeptides with medicinal prospects and even drugs.

Provided herein are antibody drug conjugates (ADCs) comprising calicheamicin and methods of using the same to treat proliferative disorders.