Monoclonal antibodies and cocktails for treatment of ebola infections
Inventors
Bornholdt, Zachary A. • Zeitlin, Larry • Chandran, Kartik • Wec, Anna • Walker, Laura
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Assignees
Albert Einstein College of Medicine • Adimab LLC • Mapp Biopharmaceutical Inc
Member
Mapp Biopharmaceutical, Inc.Mapp Biopharmaceutical, Inc. is a US-based biotechnology company focused on developing monoclonal antibody therapeutics for the prevention and treatment of infectious diseases with an emphasis on addressing unmet needs in global health and biodefense. Founded in 2003 by Drs. Kevin Whaley and Larry Zeitlin, the company pursues treatments for high-priority pathogens, including ebolaviruses, Marburg virus, Nipah virus, and other threats such as hantavirus and ricin. Mapp advances candidates through preclinical and clinical evaluation, often in partnership with government and academic entities.
Mapp Biopharmaceutical, Inc. is a US-based biotechnology company focused on developing monoclonal antibody therapeutics for the prevention and treatment of infectious diseases with an emphasis on addressing unmet needs in global health and biodefense. Founded in 2003 by Drs. Kevin Whaley and Larry Zeitlin, the company pursues treatments for high-priority pathogens, including ebolaviruses, Marburg virus, Nipah virus, and other threats such as hantavirus and ricin. Mapp advances candidates through preclinical and clinical evaluation, often in partnership with government and academic entities.
Publication Number
US-10836810-B2
Publication Date
2020-11-17
Expiration Date
Abstract
Described herein are compositions and methods for the prevention and treatment of ebolavirus infection certain embodiments of the present invention, monoclonal antibodies substantially similar to those described herein, as well as affinity matured variants thereof, alone or in combination, provide therapeutic efficacy in a patient against multiple species of ebolavirus.
Core Innovation
The disclosed invention provides cross-reactive, pan-ebolavirus neutralizing human monoclonal antibodies and their affinity-matured variants. The antibodies are defined by specific heavy chain variable region and light chain variable region amino acid sequence identity thresholds to SEQ ID NO: 12 and SEQ ID NO: 14, respectively, and include defined heavy chain CDR1/CDR2/CDR3 and light chain CDR1/CDR2/CDR3 sequences mapped to SEQ ID NOs: 53-58. The antigen targeted by the antigen binding portion is Ebola glycoprotein.
The invention further includes glycoengineered variants comprising predominantly single-glycoform antibodies with specified glycoform types such as GnGn, G1/G2, and NaNa. The glycoengineered antibodies are characterized by reduced or absent fucose and/or xylose, and are presented as functional pan-ebolavirus neutralizers with cross-reactivity across multiple ebolavirus species including EBOV, SUDV, and BDBV. The disclosure also references functional targeting related to endosomal cleaved GP (GP_CL) and NPC1-associated steps.
The disclosed compositions include therapeutically effective combinations and antibody cocktails. One example described is MBP134 combining PE-87 and PE-47 for post-exposure treatment across ebolavirus species. The disclosure reports cross-reactivity and neutralization data using ELISA and neutralization assays, and it describes in vivo protection outcomes and escape-mutant behavior in multiple animal models, including mouse, guinea pig, ferret, and non-human primate models.
Claims Coverage
The partial claims provided include two independent claims. The first independent claim recites a treatment composition defined by a therapeutically effective combination of a first Ebola glycoprotein-binding monoclonal antibody or antigen-binding fragment with specified variable-region identity and defined CDR sequences, together with a pharmaceutically acceptable excipient or carrier. The second independent claim recites a monoclonal antibody or antigen-binding fragment effective to treat Ebola with the same variable-region identity and CDR constraints, further requiring a predominantly single glycoform that binds at least two species of Ebola glycoprotein.
Therapeutically effective combination for treating Ebola with specified variable regions, CDR sequences, and Ebola glycoprotein binding
A first monoclonal antibody or antigen binding fragment comprising a heavy chain variable region at least 90% identical to SEQ ID NO: 12 and a light chain variable region at least 90% identical to SEQ ID NO: 14, with heavy chain CDR1, CDR2, CDR3 comprising SEQ ID NOs: 53, 54, 55 and light chain CDR1, CDR2, CDR3 comprising SEQ ID NOs: 56, 57, 58, wherein the antigen to which the antigen binding fragment binds comprises Ebola glycoprotein, together with a pharmaceutically acceptable excipient or carrier.
Monoclonal antibody effective to treat Ebola with defined variable regions, CDR sequences, and predominantly single glycoform binding at least two species
A monoclonal antibody or antigen binding fragment effective to treat Ebola comprising a heavy chain variable region at least 90% identical to SEQ ID NO: 12 and a light chain variable region at least 90% identical to SEQ ID NO: 14, with heavy chain CDR1, CDR2, CDR3 comprising SEQ ID NOs: 53, 54, 55 and light chain CDR1, CDR2, CDR3 comprising SEQ ID NOs: 56, 57, 58, wherein the monoclonal antibody or antigen binding fragment comprises predominantly a single glycoform and binds at least two species of Ebola glycoprotein.
Across the independent claims, the core inventive coverage is centered on antibodies or antigen-binding fragments with specified heavy and light variable-region identity to SEQ ID NO: 12 and SEQ ID NO: 14, specified heavy and light CDR sequences (SEQ ID NOs: 53-58), binding to Ebola glycoprotein, and, in the antibody claim, binding at least two Ebola glycoprotein species with a predominantly single glycoform.
Stated Advantages
Documented Applications
No documented applications found
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