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:
September 8, 2023
Publication date:
April 25, 2024
Applicant:
ImmunoGen, Inc.
Inventors:
Olga AB, Daniel TAVARES, Lingyun RUI, Gillian PAYNE, Viktor S. GOLDMAKER
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: The invention generally relates to antibodies that bind to human folate receptor and diagnostic assays for folate receptor 1-based therapies. Methods of using the antibodies to monitor therapy are further provided.
Type:
Grant
Filed:
November 10, 2021
Date of Patent:
March 19, 2024
Assignee:
ImmunoGen, Inc.
Inventors:
Olga Ab, Daniel Tavares, Julianto Setiady, Sharron Ladd, Christina N. Carrigan, Lingyun Rui
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:
April 1, 2022
Date of Patent:
February 13, 2024
Assignee:
IMMUNOGEN, INC.
Inventors:
Yelena Kovtun, Daniel J. Tavares, Lingyun Rui, Thomas Chittenden
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:
December 30, 2022
Publication date:
December 7, 2023
Applicant:
IMMUNOGEN, INC.
Inventors:
Scott A. Hilderbrand, Benjamin M. Hutchins
Abstract: The present invention provides methods of preparing a cell-binding agent-cytotoxic agent conjugate comprising a cell-binding agent (CysCBA) having one or more unpaired cysteine residues covalently linked to a cytotoxic agent. Also provided are conjugates prepared by the methods described herein and pharmaceutical composition and methods of use thereof.
Abstract: The present disclosure provides biparatopic antibodies comprising polypeptides that bind to folate receptor alpha (FR?) compositions comprising such biparatopic antibodies. In a specific aspect, the biparatopic antibodies bind to FR? and modulate FR? activity. The present disclosure also provides methods for treating disorders, such as cancer, by administering a biparatopic antibody that specifically binds to FR? and modulates FR? activity.
Type:
Grant
Filed:
June 10, 2022
Date of Patent:
December 5, 2023
Assignee:
ImmunoGen, Inc.
Inventors:
Olga Ab, Neeraj Kohli, Thomas Chittenden, Julianto Setiady
Abstract: The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepine compounds of formulae (I), (II) and (III). 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:
December 27, 2018
Date of Patent:
October 24, 2023
Assignee:
IMMUNOGEN, INC.
Inventors:
Michael Louis Miller, Manami Shizuka, Ravi V. J. Chari
Abstract: 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.
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:
February 12, 2021
Date of Patent:
August 22, 2023
Assignee:
IMMUNOGEN, INC.
Inventors:
Nathan Elliott Fishkin, Daniel J. Tavares, Lingyun Rui, Luke B. Harris, Manami Shizuka, Michael Louis Miller, Ravi V. J. Chari
Abstract: Therapeutic combinations of immunoconjugates that bind to CD123 (e.g., IMGN632) with BCL-2 inhibitors (e.g., venetoclax), and/or a hypomethylating agent (e.g., azacitidine or decitabine) are provided. Methods of administering the combinations to treat hematological malignancies with clinical efficacy and/or decreased toxicity are also provided. Methods of treating hematological malignances present as minimal residual disease using immunoconjugates that bind to CD123 (e.g., IMGN632) are also provided.
Type:
Grant
Filed:
April 29, 2020
Date of Patent:
July 18, 2023
Assignee:
ImmunoGen, Inc.
Inventors:
Sharlene Adams, Callum M. Sloss, Patrick Zweidler-McKay
Abstract: The present disclosure demonstrates that the amount of soluble folate receptor alpha (FR?) present in a cancer patient is a strong predictor of the efficacy of FR?-targeting therapies. Surprisingly, increased levels of soluble FR? are associated with improved outcomes. Accordingly, the present disclosure provides methods for treating cancer in patients with soluble FR? and methods for identifying a cancer as likely to respond to an anti-FR? therapy based on soluble FR? levels.
Type:
Application
Filed:
June 2, 2022
Publication date:
April 13, 2023
Applicant:
ImmunoGen, Inc.
Inventors:
Eric WESTIN, Jiuzhou WANG, Callum SLOSS
Abstract: The invention relates to benzodiazepine derivatives with antiproliferative activity and more specifically to benzodiazepine compounds of formulae (I), (II), (TI) and (T2). The invention also provides conjugates of the benzodiazepine compounds linked to a cell-binding agent. The invention further provides compositions and methods for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention.
Type:
Application
Filed:
March 27, 2020
Publication date:
March 30, 2023
Applicant:
IMMUNOGEN, INC.
Inventors:
Ravi V.J. Chari, Michael Louis Miller, Manami Shizuka, Katie Elizabeth Archer, Emily Elizabeth Reid
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:
September 17, 2020
Date of Patent:
February 7, 2023
Assignee:
IMMUNOGEN, INC.
Inventors:
Scott A. Hilderbrand, Benjamin M. Hutchins
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:
May 10, 2021
Date of Patent:
April 16, 2024
Assignee:
IMMUNOGEN, INC.
Inventors:
Wei Li, Michael Louis Miller, Nathan Elliott Fishkin, Ravi V. J. Chari