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69 results about "Maytansinoid" patented technology
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A maytansinoid is a chemical derivative of maytansine. Some are being investigated as the cytotoxic component of antibody-drug conjugates. Anticancer properties of maytansinoids have been attributed to their ability to disrupt microtubule function.
Cytotoxic agents comprising new maytansinoids
ActiveUS7276497B2Improve anti-tumor activityImprove biological activityOrganic active ingredientsOrganic chemistryAnimal tumorEfficacy
New thiol and disulfide-containing maytansinoids bearing a mono or di-alkyl substitution on the α-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.
Owner:IMMUNOGEN INC
Method of targeting specific cell populations using cell-binding agent maytansinoid conjugates linked via a non-cleavable linker, said conjugates, and methods of making said conjugates
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.
Owner:IMMUNOGEN INC
Methods for preparation of cytotoxic conjugates of maytansinoids and cell binding agents
InactiveUS7368565B2Increase productionMinimizes time processing timeAntibacterial agentsOrganic active ingredientsCell bindingCytotoxicity
The present invention discloses a one-step process for the production of cytotoxic conjugates of maytansinoids and cell binding agents. Maytansinoids having a disulfide linker that bears a reactive moiety are linked to cell binding agents, such as antibodies, without prior modification of the cell binding agent. These conjugates are useful as therapeutic agents which are delivered specifically to target cells and are cytotoxic.
Owner:IMMUNOGEN INC
Methods of treatment using anti-ErbB antibody-maytansinoid conjugates
ActiveUS7097840B2Superior clinical activityBetter objective response rateOrganic active ingredientsPharmaceutical delivery mechanismMedicineCancer therapy
The application concerns methods of treatment using anti-ErbB receptor antibody-maytansinoid conjugates, and articles of manufacture suitable for use in such methods. In particular, the invention concerns ErbB receptor-directed cancer therapies, using anri-ErbB receptor antibody-maytansinoid conjugates.
Alaninyl maytansinol antibody conjugates
InactiveUS20120121615A1Immunoglobulins against cell receptors/antigens/surface-determinantsAntibody ingredientsAntibody conjugateMaytansinoid
Owner:GENENTECH INC
Drug conjugate composition
ActiveUS7374762B2Snake antigen ingredientsAntibody ingredientsDrug conjugationAntiendomysial antibodies
The invention provides a liquid composition and a lyophilized composition comprising a therapeutically effective amount of a conjugate comprising an antibody chemically coupled to a maytansinoid. The invention further provides a method for killing a cell in a human comprising administering to the human either of the compositions such that the antibody binds to the surface of the cell and the cytotoxicity of the maytansinoid is activated, whereby the cell is killed.
Owner:IMMUNOGEN INC
Process for the preparation and purification of thiol-containing maytansinoids
InactiveUSRE39151E1Reduce process complexityAllows scalabilityOrganic active ingredientsOrganic chemistryLithiumThiol
The present invention provides a process for the preparation and purification of thiol-containing maytansinoids comprising the steps of: (1) reductive hydrolysis of a maytansinoid C-3 ester with a reducing agent selected from the group consisting lithium trimethoxyaluminum hydride (LiAl (OMe)3H), lithium triethoxyaluminum hydride (LiAl(OEt)3H), lithium tripropoxyaluminum hydride (LiAl (OPr)3H), sodium trimethoxyaluminum hydride (NaAl (OMe)3H), sodium triethoxyaluminum hydride (NaAl(OEt)3H) and sodium tripropoxyaluminum hydride (NaAl(OPr)3H) to yield a maytansinol; (2) purifying the maytansinol to remove side products when present; (3) esterifying the purified maytansinol with a carboxylic acid to yield a mixture of an L- and a D-aminoacyl ester of maytansinol; (4) separating the L-aminoacyl ester of maytansinol from the reaction mixture in (3); (5) reducing the L-aminoacyl ester of maytansinol to yield a thiol-containing maytansinoid; and (5) purifying the thiol-containing maytansinoid.
Owner:IMMUNOGEN INC
Methods of treatment using Anti-erbb antibody-maytansinoid conjugates
InactiveUS20080226659A1High activityIncrease ratingsOrganic active ingredientsPharmaceutical delivery mechanismMedicineTreatment use
The application concerns methods of treatment using anti-ErbB receptor antibody-maytansinoid conjugates, and articles of manufacture suitable for use in such methods. In particular, the invention concerns ErbB receptor-directed cancer therapies, using anri-ErbB receptor antibody-maytansinoid conjugates.
Owner:IMMUNOGEN INC
Method for the preparation of maytansinoid esters
Owner:IMMUNOGEN INC
Method of acylating maytansinol with chiral amino acids
This invention provides a method for making maytansinoids having a chiral amino acid side chain, such as DM1 and DM4 that are used to treat cancer. According to this method, the side chain may be added with little epimerization of the amino acid chiral center.
Owner:IMMUNOGEN INC
Method for the preparation of maytansinoid esters
Improved processes for the preparation and purification of maytansinoid esters, especially thiol and disulfide-containing maytansinoids are described. In one aspect the process comprises a process of making a maytansinoid ester comprising forming an anion of maytansinol or a maytansinoid bearing a free C-3 hydroxyl moiety and reacting the anion with an activated carboxyl compound to thereby produce the maytansinoid ester.
Owner:IMMUNOGEN INC
Methods for the identification of polypeptide antigens associated with disorders involving aberrant cell proliferation and compositions useful for the treatment of such disorders
Methods and compositions for the development of effective cancer therapies using mitotic inhibitors which have limited general toxicity to normal, non-cancerous cells and tissues are provided. The methods and compositions utilize cytotoxic compounds comprised of a cell-binding agent (e.g., antibodies) conjugated to an anti-mitotic compound (e.g., maytansinoids). The invention further provides antibodies which are substantially incapable of inducing antibody-dependent cell-mediated cytotoxicity (ADCC) and / or complement dependent cytotoxicity (CDC), thereby ensuring that the therapeutic effect is mediated primarily by the anti-mitotic component of the cytotoxic compound, rather than by indirect cell killing via ADCC and / or CDC. The antibodies of the invention further are capable of differentiating between polypeptide antigens which are more highly expressed on proliferating cancer cells as compared to proliferating non-cancer cells.
Owner:GENENTECH INC
Method of targeting specific cell populations using cell-binding agent maytansinoid conjugates linked via a non-cleavable linker, said conjugates and methods of making said conjugates
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.
Owner:IMMUNOGEN INC
Drug conjugate composition
InactiveUS7494649B2Snake antigen ingredientsAntibody ingredientsAntiendomysial antibodiesPharmaceutical drug
The invention provides a liquid composition and a lyophilized composition comprising a therapeutically effective amount of a conjugate comprising an antibody chemically coupled to a maytansinoid. The invention further provides a method for killing a cell in a human comprising administering to the human either of the compositions such that the antibody binds to the surface of the cell and the cytotoxicity of the maytansinoid is activated, whereby the cell is killed.
Owner:IMMUNOGEN INC
Compositions and methods for treating cancer using cytotoxic CD44 antibody immunoconjugates and chemotherapeutic agents
InactiveUS20050244413A1Organic active ingredientsHybrid immunoglobulinsCompound (substance)Maytansinoid
The invention relates to the combined use of conjugates of CD44 specific antibodies with cytotoxic compounds and chemotherapeutic agents in cancer therapy, pharmaceutical compositions comprising such compounds and / or chemotherapeutic agents, and methods of cancer treatment. Preferred conjugates contain maytansinoids as cytotoxic compounds, and preferred chemotherapeutic agents are taxanes, epothilones, and vinca alcaloids.
Owner:ADOLF GUENTHER +2
Method of acylating maytansinol with chiral amino acids
This invention provides a method for making maytansinoids having a chiral amino acid side chain, such as DM1 and DM4 that are used to treat cancer. According to this method, the side chain may be added with little epimerization of the amino acid chiral center.
Owner:IMMUNOGEN INC
Method of targeting specific cell populations using cell-binding agent maytansinoid conjugates linked via a non-cleavable linker, said conjugates, and methods of making said conjugates
The invention discloses a method for targeting maytansinoids to a selected cell population, the method comprising: contacting a cell population suspected of containing the selected cell population with a cell-binding agent maytansinoid conjugate or tissue, wherein one or more maytansinoids are covalently linked to the cell-binding agent through a non-cleavable linker, and the cell-binding agent binds cells in a selected cell population.
Owner:IMMUNOGEN INC
Process for preparing stable antibody maytansinoid conjugates
InactiveUS20150306242A1Organic active ingredientsImmunoglobulins against cell receptors/antigens/surface-determinantsCell bindingCytotoxicity
The invention provides processes for manufacturing cell-binding agent-cytotoxic agent conjugates of improved stability comprising performing the modification reaction at a high pH. The inventive processes comprise contacting a cell-binding agent with a bifunctional crosslinking reagent in a solution having a pH of 7.1 to 9 to covalently attach a linker to the cell-binding agent and thereby prepare a mixture comprising cell-binding agents having linkers bound thereto.
Owner:IMMUNOGEN INC
Preparation of maytansinoid antibody conjugates by a one-step process
ActiveUS8795673B2High purityImprove stabilityAntibody ingredientsPeptide preparation methodsAntibody conjugateCrosslinking reagent
The invention provides a one-step process for preparing a cell-binding agent cytotoxic agent conjugate comprising contacting a cell-binding agent with a cytotoxic agent to form a first mixture comprising the cell-binding agent and the cytotoxic agent and contacting the first mixture comprising the cell-binding agent and the cytotoxic agent with a bifunctional crosslinking reagent, which provides a linker, in a solution having a pH of about 4 to about 9 to provide a second mixture comprising the cell-binding agent cytotoxic agent conjugate, wherein the cell-binding agent is chemically coupled through the linker to the cytotoxic agent, free cytotoxic agent, and reaction by-products. The second mixture is then optionally subjected to purification to provide a purified cell-binding agent cytotoxic agent conjugate.
Owner:IMMUNOGEN INC
Preparation of maytansinoid antibody conjugates by a one-step process
ActiveUS20140309406A1High purityImprove stabilityPeptide preparation methodsImmunoglobulinsAntiendomysial antibodiesAntibody conjugate
Owner:IMMUNOGEN INC
Potent cell-binding agent drug conjugates
InactiveUS20100092495A1Immunoglobulins against cell receptors/antigens/surface-determinantsAntibody ingredientsCell bindingMedicine
Owner:IMMUNOGEN INC
Potent conjugates and hydrophilic linkers
InactiveUS20120226026A1Improve drug activitySimple wayAntiviralsImmunoglobulins against cell receptors/antigens/surface-determinantsBound drugAntigen
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.
Owner:IMMUNOGEN INC
Process for preapring maytansinol
Processes for preparing maytansinol from disulfide-containing maytansinoid esters by reduction with LiAlH4. The maytansinol is useful for preparing cell-binding agent / maytansinoid complexes.
Owner:FOCKE & CO (GMBH & CO KG)
Cytotoxic agents comprising new maytansinoids
ActiveUS20070264266A1Improve anti-tumor activityImprove biological activityOrganic active ingredientsBiocideCytotoxicityAlkaloid
New thiol and disulfide-containing maytansinoids bearing a mono or di-alkyl substitution on the α-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.
Owner:IMMUNOGEN INC
Potent conjugates and hydrophilic linkers
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.
Owner:IMMUNOGEN INC
Process for preparing maytansinol
Processes for preparing maytansinol from mixtures of unreduced and over-reduced maytansinoids. The maytansinol is useful for preparing cell-binding / maytansinoid agent complexes.
Owner:SMITHKLINE BECKMAN CORP
Potent conjugates and hydrophilic linkers
InactiveUS9150649B2Improve drug activitySimple wayPeptide/protein ingredientsImmunoglobulins against cell receptors/antigens/surface-determinantsAntigenBound drug
Owner:IMMUNOGEN INC
Methods for the identification of polypeptide antigens associated with disorders involving aberrant cell proliferation and compositions useful for the treatment of such disorders
Methods and compositions for the development of effective cancer therapies using mitotic inhibitors which have limited general toxicity to normal, non-cancerous cells and tissues are provided. The methods and compositions utilize cytotoxic compounds comprised of a cell-binding agent (e.g., antibodies) conjugated to an anti-mitotic compound (e.g., maytansinoids). The invention further provides antibodies which are substantially incapable of inducing antibody-dependent cell-mediated cytotoxicity (ADCC) and / or complement dependent cytotoxicity (CDC), thereby ensuring that the therapeutic effect is mediated primarily by the anti-mitotic component of the cytotoxic compound, rather than by indirect cell killing via ADCC and / or CDC. The antibodies of the invention further are capable of differentiating between polypeptide antigens which are more highly expressed on proliferating cancer cells as compared to proliferating non-cancer cells.
Owner:LEVINSON ARTHUR D
Maytansinoid derivatives
ActiveUS8877706B2Prevent relapseUndesirable side-effectOrganic active ingredientsPeptide/protein ingredientsDiseaseMedicine
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.
Owner:BIO THERA SOLUTIONS LTD
Improved cytotoxic agents comprising new maytansinoids
New thiol and disulfide-containing maytansinoids bearing a mono or di-alkyl substitution on the alpha-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.
Owner:IMMUNOGEN INC
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