Abstract: The present invention is directed to methods of preparing a conjugate of a cell-binding agent and a drug (such as a cytotoxic compound). The methods comprise the use of an imine reactive compound to enable efficient conjugations of cytotoxic compounds with cell binding agents.
Type:
Grant
Filed:
August 15, 2017
Date of Patent:
July 30, 2019
Assignee:
IMMUNOGEN, INC.
Inventors:
Nathan Elliott Fishkin, Michael Louis Miller, Wei Li, Rajeeva Singh
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:
May 1, 2017
Date of Patent:
May 28, 2019
Assignee:
ImmunoGen, Inc.
Inventors:
Olga Ab, Daniel Tavares, Lingyun Rui, Gillian Payne, Viktor S. Goldmakher
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:
November 22, 2017
Date of Patent:
May 14, 2019
Assignee:
IMMUNOGEN, INC.
Inventors:
Scott A. Hilderbrand, Benjamin M. Hutchins
Abstract: Disclosed is a method and composition for treating a disease associated with target cells expressing CD138 in a multiple dose regimen. An immunoconjugate comprising an engineered targeting antibody targeting CD138 expressing cells and an effector molecule is administered in a multiple dose regimen. The multiple dose regimen comprises at least two doses and the aggregate dose administered within an active treatment cycle is an aggregate maximum tolerable dose (AMTD) or a fraction of the AMTD. The AMTD and/or said fraction exceeds the dose resulting in dose limiting toxicity (DLT) and/or exceeds the maximum tolerable dose (MTD) when the immunoconjugate is administered as a single dose, including as part of a multiple single dose regimen within said active treatment cycle.
Type:
Application
Filed:
September 24, 2018
Publication date:
April 25, 2019
Applicants:
Biotest AG, ImmunoGen, Inc.
Inventors:
Gregor Schulz, Frank Osterroth, Thomas Haeder, Christoph Bruecher, Gabriele Niemann, Andre Engling, Christoph Uherek, Benjamin Daelken, Andrea Wartenberg-Demand, Chantal Zuber, Marcus Gutscher, Katrin Bernoester, Martin Koenig
Abstract: The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepine compounds of formula (I)-(VI). The invention also provides conjugates of the benzodiazepine compounds linked to a cell-binding agent. 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.
Type:
Grant
Filed:
April 28, 2017
Date of Patent:
March 26, 2019
Assignee:
IMMUNOGEN, INC.
Inventors:
Ravi V. J. Chari, Michael Louis Miller, Manami Shizuka
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:
September 1, 2017
Date of Patent:
March 19, 2019
Assignee:
IMMUNOGEN, INC.
Inventors:
Brenda A. Kellogg, Rajeeva Singh, Ravi V. J. Chari
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:
May 8, 2018
Date of Patent:
February 19, 2019
Assignee:
IMMUNOGEN, INC.
Inventors:
Wei Li, Nathan Elliott Fishkin, Robert Yongxin Zhao, Michael Louis Miller, Ravi V. J. Chari
Abstract: This invention relates to antibody-drug conjugates capable of delivering cytotoxic compounds to cancers expressing the guanylyl cyclase C (GCC) transmembrane cell surface receptor.
Type:
Application
Filed:
February 3, 2017
Publication date:
February 7, 2019
Applicants:
MILLENNIUM PHARMACEUTICALS, INC., IMMUNOGEN, INC.
Inventors:
Ole Petter VEIBY, Ravi V. J. CHARI, John M. LAMBERT, Katharine C. LAI, Robert W. HERBST, Scott A. HILDERBRAND
Abstract: The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepine compounds of formula (I)-(VII). The invention also provides conjugates of the benzodiazepine compounds linked to a cell-binding agent. 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.
Type:
Grant
Filed:
July 10, 2017
Date of Patent:
January 15, 2019
Assignee:
IMMUNOGEN, INC.
Inventors:
Wei Li, Michael Louis Miller, Nathan Elliott Fishkin, Ravi V. J. Chari
Abstract: The invention generally relates to antibodies that bind to human folate receptor 1 and diagnostic assays for folate receptor 1-based therapies. Methods of using the antibodies to monitor therapy are further provided.
Type:
Grant
Filed:
June 12, 2017
Date of Patent:
January 15, 2019
Assignee:
ImmunoGen, inc.
Inventors:
Christina N. Carrigan, Olga Ab, Daniel Tavares, Beni B. Wolf
Abstract: 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:
Application
Filed:
April 2, 2018
Publication date:
January 10, 2019
Applicant:
ImmunoGen, Inc.
Inventors:
Godfrey AMPHLETT, Wei ZHANG, Michael FLEMING, Hung-Wei CHIH
Abstract: Therapeutic combinations of immunoconjugates that bind to FOLR1 (e.g., IMGN853) with anti-VEGF agents (e.g., bevacizumab), a platinum-based agent, and/or doxorubicin are provided. Methods of administering the combinations to treat cancers, e.g., ovarian cancers, with greater clinical efficacy and/or decreased toxicity are also provided.
Type:
Grant
Filed:
September 16, 2016
Date of Patent:
January 8, 2019
Assignee:
ImmunoGen, inc.
Inventors:
Jose Ponte, Jan Pinkas, Rodrigo R. Ruiz-Soto
Abstract: Therapeutic combinations of immunoconjugates that bind to FOLR1 (e.g., IMGN853) with anti-PD-1 antibodies or antigen-binding fragments thereof (e.g., pembrolizumab) are provided. Methods of administering the combinations to treat cancers, e.g., ovarian, peritoneal, or fallopian tube cancers, with greater clinical efficacy and/or decreased toxicity are also provided.
Abstract: Disclosed is a method and composition for treating a disease associated with target cells expressing CD138 in a multiple dose regimen. An immunoconjugate comprising an engineered targeting antibody targeting CD138 expressing cells and an effector molecule is administered in a multiple dose regimen. The multiple dose regimen comprises at least two doses and the aggregate dose administered within an active treatment cycle is an aggregate maximum tolerable dose (AMTD) or a fraction of the AMTD. The AMTD and/or said fraction exceeds the dose resulting in dose limiting toxicity (DLT) and/or exceeds the maximum tolerable dose (MTD) when the immunoconjugate is administered as a single dose, including as part of a multiple single dose regimen within said active treatment cycle.
Type:
Grant
Filed:
December 7, 2012
Date of Patent:
November 6, 2018
Assignees:
BIOTEST AG, IMMUNOGEN INC.
Inventors:
Gregor Schulz, Frank Osterroth, Thomas Haeder, Christoph Bruecher, Gabriele Niemann, Andre Engling, Christoph Uherek, Benjamin Daelken, Andrea Wartenberg-Demand, Chantal Zuber, Marcus Gutscher, Katrin Bernoester, Martin Koenig
Abstract: Processes for the preparation of charged crosslinkers bearing a sulfonic acid moiety are disclosed. These procedures also optionally include methods to convert the resulting products to substantially a single salt form.
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:
June 28, 2016
Date of Patent:
September 18, 2018
Assignee:
IMMUNOGEN, INC.
Inventors:
Yelena Kovtun, Daniel Tavares, Lingyun Rui, Thomas Chittenden
Abstract: Conjugates and compounds for making conjugates which are PBD molecules linked via the N10 position are disclosed, along with the use of the conjugates for treating proliferative diseases, including cancer.