Abstract: The invention relates to novel cell-binding agent-cytotoxic agent conjugates, wherein the cell-binding agent (CBA) is covalently linked to the cytotoxic agent through an aldehyde group obtained from oxidation of a 2-hydroxyethylamine moiety on the CBA. The invention also provides methods of preparing the conjugates of the present invention. The invention further provides composition and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the conjugates of the invention.
Type:
Grant
Filed:
September 2, 2015
Date of Patent:
April 27, 2021
Assignee:
IMMUNOGEN, INC.
Inventors:
Nathan Elliott Fishkin, Daniel Tavares, Lingyun Rui, Luke B. Harris, Manami Shizuka, Michael Louis Miller, Ravi V. J. Chari
Abstract: The invention relates to novel methods of preparing cell-binding agent-cytotoxic agent conjugates, wherein the cytotoxic agent is an imine-containing cytotoxic agent bearing a maleimide group. In some embodiments, the cell-binding agent (CBA) is covalently linked to the cytotoxic agent through an engineered Cys, such as an engineered Cys in the heavy chain CH3 domain, at a position corresponds to the EU/OU numbering position 442 (or C442) on an antibody CBA. The invention also provides conjugates prepared by the methods of the present invention, compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the conjugates of the invention.
Type:
Application
Filed:
September 17, 2020
Publication date:
April 8, 2021
Applicants:
IMMUNOGEN, INC., IMMUNOGEN, INC.
Inventors:
Scott A. Hilderbrand, Benjamin M. Hutchins
Abstract: The invention provides novel methods for preparing indolinobenzodiazepine monomer compounds of formula (I) below and their synthetic precursors:
Type:
Grant
Filed:
September 4, 2019
Date of Patent:
April 6, 2021
Assignee:
IMMUNOGEN, INC.
Inventors:
Baudouin Gérard, Richard A. Silva, Michael Louis Miller, Manami Shizuka
Abstract: The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepines of formula (I) and (II), in which the diazepine ring (B) is fused with a heterocyclic ring (CD), wherein the heterocyclic ring is bicyclic or a compound of formula (III), in which the diazepine ring (B) is fused with a heterocyclic ring (C), wherein the heterocyclic ring is monocyclic. The invention provides cytotoxic dimers of these compounds. The invention also provides conjugates of the monomers and the dimers. 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. The invention further relates to methods of using the compounds or conjugates for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.
Type:
Grant
Filed:
December 21, 2018
Date of Patent:
March 16, 2021
Assignee:
IMMUNOGEN, INC.
Inventors:
Wei Li, Nathan Elliott Fishkin, Robert Yongxin Zhao, Michael Louis Miller, Ravi V. J. Chari
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 invention generally relates to antibodies, antigen-binding fragments thereof, polypeptides, and immunoconjugates that bind to CD123 antigen (the ? chain of the interleukine 3 receptor, or IL-3R?). The present invention also relates to methods of using such CD123-binding molecules for diagnosing and treating diseases, such as B-cell malignancies.
Type:
Grant
Filed:
August 3, 2017
Date of Patent:
February 16, 2021
Assignee:
IMMUNOGEN, INC.
Inventors:
Yelena Kovtun, Daniel J. Tavares, Lingyun Rui, Thomas Chittenden
Abstract: Compositions and methods for minimizing antibody disulfide bond reduction are described. In one aspect, a composition is provided for culturing mammalian host cells to express an antibody including an anti-reduction agent that minimizes reduction of a disulfide bond in the antibody or fragment thereof. In some other aspects, methods for minimizing disulfide bond reduction; increasing production of an antibody or fragment thereof with intact native disulfide bonds; increasing a ratio of non-reduced to reduced antibody or fragment thereof; producing a therapeutic antibody or fragment thereof by adding a sufficient amount of an anti-reduction agent to a cell culture media, pre-harvest cell culture fluid, or harvest cell culture fluid are described. In another aspect, minimizing disulfide bond reduction in an antibody or fragment thereof culturing the host cell in a concentration of at least about 20% O2 is described.
Abstract: Novel anti-cancer agents, including, but not limited to, antibodies and immunoconjugates, that bind to human folate receptor 1 are provided. Methods of using the agents, antibodies, or immunoconjugates, such as methods of inhibiting tumor growth are further provided.
Type:
Application
Filed:
July 21, 2020
Publication date:
February 4, 2021
Applicant:
ImmunoGen, Inc.
Inventors:
Olga AB, Daniel Tavares, Lingyun Rui, Gillian Payne, Viktor S. Goldmakher
Abstract: The invention relates to novel cell-binding agent-cytotoxic agent conjugates, wherein the cell-binding agent (CBA) is covalently linked to the cytotoxic agent through an engineered Cys, such as an engineered Cys in the heavy chain CH3 domain, at a position corresponds to the EU/OU numbering position 442 (or C442) on an antibody CBA. The invention also provides methods of preparing the conjugates of the present invention. The invention further provides composition and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the conjugates of the invention.
Type:
Grant
Filed:
June 28, 2016
Date of Patent:
January 26, 2021
Assignee:
IMMUNOGEN, INC.
Inventors:
Nicholas C. Yoder, Chen Bai, Michael Louis Miller
Abstract: The present invention generally relates to antibodies, antigen-binding fragments thereof, polypeptides, and immunoconjugates that bind to CD123 antigen (the ? chain of the interleukine 3 receptor, or IL-3R?). The present invention also relates to methods of using such CD123-binding molecules for diagnosing and treating diseases, such as B-cell malignancies.
Type:
Grant
Filed:
January 31, 2020
Date of Patent:
December 29, 2020
Assignee:
IMMUNOGEN, INC.
Inventors:
Yelena Kovtun, Daniel J. Tavares, Lingyun Rui, Thomas Chittenden
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 invention relates to novel methods of preparing cell-binding agent-cytotoxic agent conjugates, wherein the cytotoxic agent is an imine-containing cytotoxic agent bearing a maleimide group. In some embodiments, the cell-binding agent (CBA) is covalently linked to the cytotoxic agent through an engineered Cys, such as an engineered Cys in the heavy chain CH3 domain, at a position corresponds to the EU/OU numbering position 442 (or C442) on an antibody CBA. The invention also provides conjugates prepared by the methods of the present invention, compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the conjugates of the invention.
Type:
Grant
Filed:
October 30, 2019
Date of Patent:
November 3, 2020
Assignee:
IMMUNOGEN, INC.
Inventors:
Scott A. Hilderbrand, Benjamin M. Hutchins
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.
Type:
Grant
Filed:
February 1, 2019
Date of Patent:
October 27, 2020
Assignee:
IMMUNOGEN, INC.
Inventors:
Brenda A. Kellogg, Rajeeva Singh, Ravi V. Chari
Abstract: The invention relates to novel cell-binding agent-maytansinoid conjugate having a self-immolative peptide linker and more specifically to conjugates of formula (I). The invention also provides novel maytansinoid compounds of formula (II), (III), (IV) or (V). 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: Novel anti-cancer agents, including, but not limited to, antibodies and immunoconjugates, that bind to human folate receptor 1 are provided. Methods of using the agents, antibodies, or immunoconjugates, such as methods of inhibiting tumor growth are further provided.
Type:
Grant
Filed:
April 15, 2019
Date of Patent:
August 25, 2020
Assignee:
ImmunoGen, Inc.
Inventors:
Olga Ab, Daniel Tavares, Lingyun Rui, Gillian Payne, Viktor S. Goldmakher