Oxirane Ring Is One Of The Cyclos In The Polycyclo Ring System (e.g., Maytansinol, Etc.) Patents (Class 540/462)
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Patent number: 6913748Abstract: Disclosed is a method of making conjugates of cell binding agents and small molecule drugs comprising reacting a cell binding agent with a bifunctional cross-linking moiety to thereby provide the cell binding agent with a reactive disulfide group and then reacting the modified cell binding agent with a small molecule drug comprising a free thiol group. Bifunctional cross-linking moieties are also disclosed.Type: GrantFiled: August 5, 2003Date of Patent: July 5, 2005Assignee: Immunogen, Inc.Inventor: Wayne Charles Widdison
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Publication number: 20040241174Abstract: 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.Type: ApplicationFiled: May 14, 2004Publication date: December 2, 2004Applicant: ImmunoGen, Inc.Inventors: Godfrey Amphlett, Wei Zhang, Michael Fleming, Hung-Wei Chih
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Publication number: 20040235840Abstract: New thiol and disulfide-containing maytansinoids bearing a mono or di-alkyl substitution on the &agr;-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.Type: ApplicationFiled: May 20, 2004Publication date: November 25, 2004Applicant: IMMUNOGEN, INC.Inventors: Ravi V.J. Chari, Wayne C. Widdison
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Patent number: 6790954Abstract: 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.Type: GrantFiled: January 29, 2002Date of Patent: September 14, 2004Assignees: Immunogen, Inc., Genentech, Inc.Inventors: Johnson Chung, Graham S. Byng
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Patent number: 6716821Abstract: Cytotoxic agents bearing a polyethylene glycol (PEG) linking group having a terminal active ester, cytotoxic conjugates comprising one or more cytotoxic agents linked to a cell-binding agent via PEG linking groups, and methods for producing both are disclosed. A therapeutic composition comprising a therapeutically-effective amount of one of the cytotoxic conjugates of the present invention, and a method of killing selected cell populations comprising contacting target cells, or tissue containing target cells, with an effective amount of one of the cytotoxic conjugates, are also disclosed.Type: GrantFiled: December 21, 2001Date of Patent: April 6, 2004Assignee: Immunogen Inc.Inventors: Robert Yongxin Zhao, Michael Louis Miller, Wayne Charles Widdison, Ravi V. J. Chari
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Patent number: 6689802Abstract: 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.Type: GrantFiled: August 9, 2001Date of Patent: February 10, 2004Assignee: Bristol-Myers Squibb CompanyInventors: John D. DiMarco, Jack Z. Gougoutas, Imre M. Vitez, Martha Davidovich, Michael A. Galella, Timothy M. Malloy, Zhenrong Guo, Denis Favreau
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Patent number: 6656711Abstract: The invention relates to a new process for concentrating epothilones in culture media, a new process for the production of epothilones, a new process for separating epothilones A and B and a new strain obtained by mutagenesis for the production of epothilones, as well as aspects related thereto. New crystal forms of epothilone B are also described.Type: GrantFiled: January 29, 2002Date of Patent: December 2, 2003Assignee: Novartis AGInventors: Hans Hofmann, Marion Mahnke, Klaus Memmert, Frank Petersen, Thomas Schupp, Ernst Küsters, Michael Mutz
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Patent number: 6605599Abstract: 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.Type: GrantFiled: May 26, 1998Date of Patent: August 12, 2003Assignee: Bristol-Myers Squibb CompanyInventors: Gregory D. Vite, Soong-Hoon Kim, Robert M. Borzilleri, James A. Johnson
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Publication number: 20030109682Abstract: Cytotoxin-targeting molecule conjugates comprising cytotoxin and an antibody, growth factor, or polysaccharide together with a pH-sensitive or redox potential-sensitive linker. Novel ansamitocins and recombinant genes and organisms that produce them. The use of the described conjugates in the treatment of cancer and other hyperproliferation diseases.Type: ApplicationFiled: September 3, 2002Publication date: June 12, 2003Inventors: Daniel Santi, David C. Myles, Brian Metcalf, C. Richard Hutchinson, Gary Ashley
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Publication number: 20030055226Abstract: 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.Type: ApplicationFiled: June 5, 2002Publication date: March 20, 2003Applicant: IMMUNOGEN, INC.Inventors: Ravi V. J. Chari, Wayne C. Widdison
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Publication number: 20030045711Abstract: This invention relates to compounds of formula (I) 1Type: ApplicationFiled: April 2, 2002Publication date: March 6, 2003Inventors: Gary Ashley, Robert L. Arslanian, John Carney, Brian Metcalf, Li Tang
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Patent number: 6518421Abstract: 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.Type: GrantFiled: February 1, 2001Date of Patent: February 11, 2003Assignee: Bristol-Myers Squibb CompanyInventors: Wen Sen Li, John E. Thornton, Zhenrong Guo, Shankar Swaminathan
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Publication number: 20020188014Abstract: 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 1Type: ApplicationFiled: August 9, 2001Publication date: December 12, 2002Inventors: John D. DiMarco, Jack Z. Gougoutas, Imre M. Vitez, Martha Davidovich, Michael A. Galella, Timothy M. Malloy, Zhenrong Guo, Denis Favreau
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Patent number: 6489314Abstract: The present invention relates to 16-membered macrocyclic compounds. In one aspect of the present invention, compounds of the formula are provided wherein: R1, R2, R3, and R5 are each independently hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, aryl or alkylaryl; R4 is hydrogen, halogen, C1-C10 alkyl, C1-C10 hydroxyalkyl, C1-C10 haloalkyl, aryl, —C(═O)R6, —C(═O)OR6, —NR6R7 where R6 and R7 are each independently hydrogen, C1-C10 aliphatic, aryl or alkylaryl; W is O, NR8 where R8 is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, aryl or alkylaryl; X is O, CH2 or a carbon-carbon double bond; Y is absent or a C1-C10 alkyl, C2-C10 alkenyl, or C2-C10 alkynyl; and Ar is aryl; provided that 10,11-dehydroepothilone C is excluded.Type: GrantFiled: April 3, 2001Date of Patent: December 3, 2002Assignee: Kosan Biosciences, Inc.Inventors: Gary Ashley, Brian Metcalf
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Publication number: 20020156274Abstract: Processes for preparing maytansinol from mixtures of unreduced and over-reduced maytansinoids. The maytansinol is useful for preparing cell-binding/maytansinoid agent complexes.Type: ApplicationFiled: March 11, 2002Publication date: October 24, 2002Inventor: Gerald J. Terfloth
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Patent number: 6441163Abstract: 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.Type: GrantFiled: May 31, 2001Date of Patent: August 27, 2002Assignee: Immunogen, Inc.Inventors: Ravi V. J. Chari, Wayne C. Widdison
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Patent number: 5416064Abstract: A cytotoxic agent comprising one or more maytansinoids linked to a cell binding agent. A therapeutic agent for killing selected cell populations comprising: (a) a cytotoxic amount of one or more maytansinoids linked to a cell binding agent, and (b) a pharmaceutically acceptable carrier, diluent or excipient. A method for killing selected cell populations comprising contacting a cell population or tissue suspected of containing cells from said selected cell population with a cytotoxic amount of a cytotoxic agent comprising one or more maytansinoids linked to a cell binding agent. An N-methyl-alanine-containing ester of maytansinol or an analogue of maytansinol, said N-methyl-alanine-containing ester comprising a linking group capable of linking an N-methyl-alanine-containing maytansinoid ester to a chemical moiety. N-methyl-cysteine-containing ester of maytansinol or an analogue of maytansinol.Type: GrantFiled: December 7, 1992Date of Patent: May 16, 1995Assignee: ImmunoGen, Inc.Inventors: Ravi J. Chari, Victor S. Goldmacher, John M. Lambert, Walter A. Blattler
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Patent number: 5300495Abstract: Sulpinine C, secopenitrem B and 10-oxo-11,33-dihydropenitrem B indole compounds have been isolated from the sclerotia of the fungi Aspergillus sulphureus. Aflatrem B has been isolated from the sclerotia of the fungi Aspergillus flavus, and 14-hydroxypaspalinine and 14-(N,N-dimethylvalyloxy)paspalinine have been isolated from the sclerotia of the fungi Aspergillus nomius. The indole compounds are effective for controlling Coleopteran and Lepidopteran insects.Type: GrantFiled: January 22, 1993Date of Patent: April 5, 1994Assignees: The United States of America, as represented by the Secretary of Agriculture, University of Iowa Research Foundation, Biotechnology Research & Development CorporationInventors: Jodi A. Laakso, Patrick F. Dowd, James B. Gloer, Donald T. Wicklow
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Patent number: 5227396Abstract: Sulpinine C, secopenitrem B and 10-oxo-11,33-dihydropenitrem B indole compounds have been isolated from the sclerotia of the fungi Aspergillus sulphureus. Aflatrem B has been isolated from the sclerotia of the fungi Aspergillus flavus, and 14-hydroxypaspalinine and 14-(N,N-dimethylvalyloxy)paspalinine have been isolated from the sclerotia of the fungi Aspergillus nomius. The indole compounds are effective for controlling Coleopteran and Lepidopteran insects.Type: GrantFiled: April 29, 1992Date of Patent: July 13, 1993Assignees: The United States of America as represented by the Secretary of Agriculture, University of Iowa Research Foundation, Biotechnology Research & Development CorporationInventors: Jodi A. Laakso, Mark R. TePaske, Patrick F. Dowd, James B. Gloer, Donald T. Wicklow, Gail M. Staub
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Patent number: 5208020Abstract: A cytotoxic agent comprising one or more maytansinoids linked to a cell binding agent. A therapeutic agent for killing selected cell populations comprising: (a) a cytotoxic amount of one or more maytansinoids linked to a cell binding agent, and (b) a pharmaceutically acceptable carrier diluent or excipient. A method for killing selected cell populations comprising contacting a cell population or tissue suspected of containing cells from said selected cell population with a cytotoxic amount of a cytotoxic agent comprising one or more maytansinoids linked to a cell binding agent. An N-methyl-alanine-containing ester of maytansinol or an analogue of maytansinol, said N-methyl-alanine-containing ester comprising a linking group capable of linking an N-methyl-alanine-containing maytansinoid ester to a chemical moiety. N-methyl-cysteine-containing ester of maytansinol or an analogue of maytansinol.Type: GrantFiled: July 13, 1992Date of Patent: May 4, 1993Assignee: ImmunoGen Inc.Inventors: Ravi J. Chari, Victor S. Goldmacher, John M. Lambert, Walter A. Blattler
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Patent number: 5130326Abstract: Indole compounds named "sulphinine" and "secopenitrem" have been isolated from the sclerotia of from fungi Aspergillus sulphureus. An indole compound named "aflatrem B" has been isolated from the sclerotia of the fungi Aspergillus flavus. The compounds are effective for controlling Coleopteran and Lepidopteran insects.Type: GrantFiled: July 19, 1991Date of Patent: July 14, 1992Assignees: The United States of America as represented by the Secretary of Agriculture, University of Iowa Research Foundation, Biotechnology Research & Development CorporationInventors: Jodi A. Laakso, Mark R. TePaske, Patrick F. Dowd, James B. Gloer, Donald T. Wicklow
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Patent number: 5059618Abstract: A novel lactam discodermide has been isolated from a marine sponge. This compound, and its derivatives, are useful as antifungal and antitumor agents.Type: GrantFiled: July 6, 1990Date of Patent: October 22, 1991Assignee: Harbor Branch Oceanographic Institution, Inc.Inventors: Sarath P. Gunasekera, Malika Gunasekera, Peter J. McCarthy