Abstract: This invention describes a method of conjugating a cell binding agent such as an antibody with an effector group (e.g., a cytotoxic agent) or a reporter group (e.g., a radionuclide), whereby the reporter or effector group is first reacted with a bifunctional linker and the mixture is then used without purification for the conjugation reaction with the cell binding agent. The method described in this invention is advantageous for preparation of stably-linked conjugates of cell binding agents, such as antibodies with effector or reporter groups. This conjugation method provides in high yields conjugates of high purity and homogeneity that are without inter-chain cross-linking and inactivated linker residues.

Abstract: Novel anti-cancer agents, including, but not limited to, antibodies and immunoconjugates, that bind to CD37 are provided. Methods of using the agents, antibodies, or immunoconjugates, such as methods of inhibiting tumor growth are further provided.

Abstract: The present invention relates to a novel process of making ixabepilone, ixabepilone derivatives and analogues, and intermediates thereof.

Abstract: The present invention relates to compounds of the formula in which the variables G, W, Q, X, Y, B1, B2, Z1, Z2, and R1-R7 are as defined herein, methods for the preparation of the derivatives and intermediates thereof.

Abstract: Aspects of the present invention provide compositions comprising a sulfur containing compound and a compound of the formula (I); and also provide methods of their preparation and use.

Abstract: Disclosed herein are anti-EGFR antibodies conjugated with maytansinoid drugs for targeted delivery to disease tissues. Methods related to the preparation and uses of such antibody drug conjugates to treat EGFR positive cells in cancers are provided.

Abstract: Provided are efficient methods for direct coupling of a maytansinoid with a carboxylic acid to prepare a maytansinoid C-3 ester in high yield using a rare earth metal-based or trifluoromethanesulfonate-based Lewis acid catalyst and a base together with a coupling reagent. Also provided are compositions used in such methods.

Abstract: Disclosed herein are maytansinoid drug linker derivatives which can be linked to a antigen binding unit (Abu), and maytansinoid drugs linked with an antigen binding unit (Drug-Linker-Antigen binding Unit: D-L-Abu), for targeted delivery to disease tissues. D-L-Abu, D-L-Abu derivatives, and methods relating to the use of such drug conjugates to treat antigen positive cells in cancers and immunological disorders are provided.

Abstract: Disclosed is a method of preparing an amino acid ester of maytansinol by reacting maytansinol with an N-carboxyanhydride of an amino acid (NCA) in the presence of a drying agent. Also disclosed is an improved method of preparing an amino acid ester of maytansinol in which a nucleophile is added to the reaction mixture after completion of the reaction between maytansinol and an N-carboxyanhydride of an amino acid.

Abstract: The present disclosure provides conjugate structures (e.g., polypeptide conjugates) and hydrazinyl-indole compounds used to produce these conjugates. The disclosure also provides methods of production of such conjugates, as well as methods of using the same.

Abstract: A process for formulating certain epothilone analogs for parenteral administration is disclosed wherein the analog is dissolved in a mixture of at least 50% by volume tertiary-butanol in water, the mixture is lyophilized, the resulting lyophilized product is packaged in one vial with a sufficient amount of solvent comprising anhydrous ethanol and a suitable nonionic surfactant in a second vial. All steps are carried out with protection from light. In use, the contents of the second or diluent vial are added to the lyophilized product and mixed to constitute the epothilone analog and the resulting solution is diluted with a suitable diluent to produce a solution for intravenous injection containing the epothilone analog in a concentration of from about 0.1 mg/mL to about 0.9 mg/mL. A preferred surfactant is polyethoxylated castor oil and a preferred diluent is Lactated Ringer's Injection.

Abstract: The present invention relates to compounds of the formula in which the variables G, W, Q, X, Y, B1, B2, Z1, Z2, and R1-R7 are as defined herein, methods for the preparation of the derivatives and intermediates thereof.

Abstract: New ansamitocin derivatives bearing a linking group are disclosed. Also disclosed are methods for the synthesis of these new ansamitocin derivatives and methods for their linkage to cell-binding agents. The ansamitocin derivative-cell-binding agent conjugates are useful as therapeutic agents, which are delivered specifically to target cells and are cytotoxic. These conjugates display vastly improved therapeutic efficacy in animal tumor models compared to the previously described agents.

Abstract: The invention relates to novel cell-binding agent-cytotoxic agent conjugate having a peptide linkers and more specifically to conjugates of formula (I). The invention also provides novel cytotoxic agents of formula (II), linker compounds represented by formula (III), and drug-linker compounds represented by formula (IV). The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention.

Abstract: The invention relates to a compound of formula (I): wherein: ALK is a (C1-C6)alkylene group; X1 et X2 are each independently one of the following groups: —CH?CH—, —CO—, —CONR—, —NRCO—, —COO—, —OCO—, —OCONR—, —NRCOO—, —NRCONR?—, —NR—, —S(O)n (n=0, 1 or 2) or —O—; R and R? are independently H or a (C1-C6)alkyl group; i is an integer of from 1 to 40, preferably from 1 to 20, and more preferably from 1 to 10; j is an integer corresponding to 1 when X2 is —CH?CH— and 2 when X2 is not —CH?CH—; Zb is a simple bond, —O— or —NH— and Rb is H or a (C1-C6)alkyl, (C3-C7)cycloalkyl, aryl, heteroaryl or (C3-C7)heterocycloalkyl group; or Zb is a single bond and Rb is Hal.

Abstract: Linkers for binding drugs to cell binding agents are modified to hydrophilic linkers by incorporating a polyethylene glycol spacer. The potency or the efficacy of the cell-binding agent-drug conjugates is surprisingly enhanced several folds in a variety of cancer cell types, including those expressing a low number of antigens on the cell surface or cancer cells that are resistant to treatment. A method for preparing maytansinoids bearing a thioether moiety and a reactive group which allows the maytansinoid to be linked to a cell-binding agent in essentially a single step is also provided.

Abstract: Linker-drug intermediates of Formula I are conjugated to antibodies to form antibody-drug conjugates where the drug moiety is an N-methylalaninyl-maytansinoid. L is E is n is 2, 3, 4, 5, or 6; m is 2, 3 or 4; and q is 0 or 1.

Abstract: The present invention is directed to compositions of matter useful for the diagnosis and treatment of tumor in mammals and to methods of using those compositions of matter for the same.

Abstract: The present application describes deuterium-enriched ixabepilone, pharmaceutically acceptable salt forms thereof, and methods of treating using the same.

Abstract: The present invention discloses a method for targeting maytansinoids to a selected cell population, the method comprising contacting a cell population or tissue suspected of containing the selected cell population with a cell-binding agent maytansinoid conjugate, wherein one or more maytansinoids is covalently linked to the cell-binding agent via a non-cleavable linker and the cell-binding agent binds to cells of the selected cell population.

Abstract: New thiol and disulfide-containing maytansinoids bearing a mono or di-alkyl substitution on the ?-carbon atom bearing the sulfur atom are disclosed. Also disclosed are methods for the synthesis of these new maytansinoids and methods for the linkage of these new maytansinoids to cell-binding agents. The maytansinoid-cell-binding agent conjugates are useful as therapeutic agents, which are delivered specifically to target cells and are cytotoxic. These conjugates display vastly improved therapeutic efficacy in animal tumor models compared to the previously described agents.

Abstract: The invention provides a process for preparing a cell-binding agent chemically coupled to a drug. The process comprises covalently attaching a linker to a cell-binding agent, a purification step, conjugating a drug to the cell-binding agent and a subsequent purification step.

Abstract: This invention describes a method of conjugating a cell binding agent such as an antibody with an effector group (e.g., a cytotoxic agent) or a reporter group (e.g., a radionuclide), whereby the reporter or effector group is first reacted with a bifunctional linker and the mixture is then used without purification for the conjugation reaction with the cell binding agent. The method described in this invention is advantageous for preparation of stably-linked conjugates of cell binding agents, such as antibodies with effector or reporter groups.

Abstract: Linkers for binding drugs to cell binding agents are modified to hydrophilic linkers by incorporating a polyethylene glycol spacer. The potency or the efficacy of the cell-binding agent-drug conjugates is surprisingly enhanced several folds in a variety of cancer cell types, including those expressing a low number of antigens on the cell surface or cancer cells that are resistant to treatment. A method for preparing maytansinoids bearing a thioether moiety and a reactive group which allows the maytansinoid to be linked to a cell-binding agent in essentially a single step is also provided.

Abstract: The present invention provides analogs of benzoquinone-containing ansamycins and uses thereof for treating and modulating disorders associated with hyperproliferation, such as cancer. The present invention provides analogs of benzoquinone-containing ansamycins where the benzoquinone is reduced to a hydroquinone and trapped by reaction with a suitable acid, preferably ones that increase the solubility and air stability of the resulting 17-ammonium hydroquinone ansamycin analog.

Abstract: Provided are among other things ansamitocin derivatives, pharmaceutical compositions comprising these novel ansamitocin derivatives, methods for the production of the ansamitocin derivatives and their use for the treatment of cancer.

Abstract: The present application describes deuterium-enriched ixabepilone, pharmaceutically acceptable salt forms thereof, and methods of treating using the same.

Abstract: A process for formulating certain epothilone analogs for parenteral administration is disclosed wherein the analog is dissolved in a mixture of at least 50% by volume tertiary-butanol in water, the mixture is lyophilized, the resulting lyophilized product is packaged in one vial with a sufficient amount of solvent comprising anhydrous ethanol and a suitable nonionic surfactant in a second vial. All steps are carried out with protection from light. In use, the contents of the second or diluent vial are added to the lyophilized product and mixed to constitute the epothilone analog and the resulting solution is diluted with a suitable diluent to produce a solution for intravenous injection containing the epothilone analog in a concentration of from about 0.1 mg/mL to about 0.9 mg/mL. A preferred surfactant is polyethoxylated castor oil and a preferred diluent is Lactated Ringer's Injection.

Abstract: Ansamycin analogs, including maytansinoid analogs, and their use in treating cell proliferative diseases and conditions, and in particular, for use as antitumor agents.

Abstract: A process of the large-scale fermentation of a highly productive ansamitocin-producing strains. A method for isolating crude ansamitocins. A method for purifying ansamitocins.

Abstract: The present invention discloses a method for targeting maytansinoids to a selected cell population, the method comprising contacting a cell population or tissue suspected of containing the selected cell population with a cell-binding agent maytansinoid conjugate, wherein one or more maytansinoids is covalently linked to the cell-binding agent via a non-cleavable linker and the cell-binding agent binds to cells of the selected cell population.

Abstract: The present invention provides analogs of benzoquinone-containing ansamycins and uses thereof for treating and modulating disorders associated with hyperproliferation, such as cancer. The present invention provides analogs of benzoquinone-containing ansamycins where the benzoquinone is reduced to a hydroquinone and trapped by reaction with a suitable acid, preferably ones that increase the solubility and air stability of the resulting 17-ammonium hydroquinone ansamycin analog.

Abstract: The present invention discloses a method for targeting maytansinoids to a selected cell population, the method comprising contacting a cell population or tissue suspected of containing the selected cell population with a cell-binding agent maytansinoid conjugate, wherein one or more maytansinoids is covalently linked to the cell-binding agent via a non-cleavable linker and the cell-binding agent binds to cells of the selected cell population.

Abstract: The present invention provides analogs of benzoquinone-containing ansamycins and uses thereof for treating and modulating disorders associated with hyperproliferation, such as cancer. The present invention provides analogs of benzoquinone-containing ansamycins where the benzoquinone is reduced to a hydroquinone and trapped by reaction with a suitable acid, preferably ones that increase the solubility and air stability of the resulting 17-ammonium hydroquinone ansamycin analog.

Abstract: The present invention relates to C4-demethyl-epothilones or C4-bisnor-epothilones of Formula (I), their pharmaceutical use, pharmaceutical composition containing the same and methods for their preparation.

Abstract: The present invention provides analogs of benzoquinone-containing ansamycins and uses thereof for treating and modulating disorders associated with hyperproliferation, such as cancer. The present invention provides analogs of benzoquinone-containing ansamycins where the benzoquinone is reduced to a hydroquinone and trapped by reaction with a suitable acid, preferably ones that increase the solubility and air stability of the resulting 17-ammonium hydroquinone ansamycin analog.

Abstract: A microbial method for the preparation of an epothilone containing a terminal hydroxyalkyl group, comprising contacting at least one epothilone having a terminal alkyl group with an enzyme or microorganism capable of catalyzing the selective hydroxylation of said alkyl group to a hydroxyalkyl group, and effecting said hydroxylation.

Abstract: The present invention relates to compounds of the formula in which the variables G, W, Q, X, Y, B1, B2, Z1, Z2, and R1–R7 are as defined herein, methods for the preparation of the derivatives and intermediates thereof.

Abstract: A microorganism that is a mutant bacterial strain of the species Actinosynnema pretiosum, designated PF4-4, (ATCC PTA-3921), being capable of producing maytansinoid ansamitocins such as ansamitocin P-3 in improved yield compared to previous known strains, and capable of growth under varied culture conditions, and methods of producing maytansinoid ansamitocins by culturing PF4-4 in a suitable growth medium.

Abstract: This invention relates to compounds of formula (I) and to pharmaceutically acceptable salts and solvates thereof, wherein R1, R2, R3, R4, R5, W, X, Y, and Ar are as defined herein. Compounds of formula (I) are useful in the treatment of diseases or conditions characterized by cellular hyperproliferation. This invention also relates to means for the preparation of compounds of formula (I); formulations containing compounds of formula (I); and methods for the use of said compounds and formulations in the treatment of a disease or condition characterized by cellular hyperproliferation, including cancer.

Abstract: There are provided in accordance with the present invention two crystalline polymorphs, designated Form A and Form B, respectively, as well as mixtures thereof, of an epothilone analog represented by the formula Also provided are methods of forming the novel polymorphs, therapeutic methods utilizing them and pharmaceutical dosage forms containing them.

Abstract: This invention describes the new 6-alkenyl- and 6-alkinyl-epothilone derivatives of general formula I in which R1a, R1b, R2a, R3a, R3b, R4, R5, R6, R7, A, Y, D, E, G, Y and Z are as defined in the specification. The compounds are useful in treating malignant tumours, for example, ovarian, stomach, colon, breast, adeno-, head and neck carcinomas, acute lymphocytic and myelocytic leukemia. In addition, these compounds are suitable for anti-angiogenesis therapy as well as for treatment of chronic inflammatory diseases such as psoriasis and arthritis. Methods of use and preparation of the compounds are also described.

Abstract: There are provided in accordance with the present invention two crystalline polymorphs, designated Form A and Form B, respectively, as well as mixtures thereof, of an epothilone analog represented by the formula Also provided are methods of forming the novel polymorphs, therapeutic methods utilizing them and pharmaceutical dosage forms containing them.

Abstract: A compund of formula I, an epothilone derivative, its method of preparation, and use as a pharmaceutical agent in treating malignant tumors

Abstract: There are provided in accordance with the present invention two crystalline polymorphs, designated Form A and Form B, respectively, as well as mixtures thereof, of an epothilone analog represented by the formula Also provided are methods of forming the novel polymorphs, therapeutic methods utilizing them and pharmaceutical dosage forms containing them.

Abstract: The present invention relates to a process for the preparation of epothilone analogs by initially forming novel ring-opened epothilones and carrying out a macrolactamization reaction thereon. The subject process is amenable to being carried out in a single reaction vessel without isolation of the intermediate compound and provides at least about a three-fold increase in yield over prior processes for preparing the desired epothilone analogs.

Abstract: The present invention relates to epothilone derivatives, having the following formula in which the variables G, W, Q, X, Y, B1, B2, Z1, Z2, and R1-R7 are as defined herein, methods for the preparation of the derivatives and intermediates thereof.

Abstract: The present invention relates to epothilone derivatives, having the following formula in which the variables G, W, Q, X, Y, B1, B2, Z1, Z2, and R1-R7 are as defined herein, methods for the preparation of the derivatives and intermediates thereof.

Abstract: The present invention relates to epothilone derivatives, having the following formula in which the variables G, W, Q, X, Y, B1, B2, Z1, Z2, and R1-R7 are as defined herein, methods for the preparation of the derivatives and intermediates thereof.

Abstract: The present invention relates to compounds of the formula in which the variables G, W, Q, X, Y, B1, B2, Z1, Z2, and R1–R7 are as defined herein, methods for the preparation of the derivatives and intermediates thereof.