Antibodies useful in passive influenza immunization, and compositions, combinations and methods for use thereof
Inventors
Estelles, Angeles • Kauvar, Lawrence M. • VIGIL, Adam • Wittekind, Michael
Assignees
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Publication Number
US-11246928-B2
Publication Date
2022-02-15
Expiration Date
Abstract
Antibodies, compositions and methods are provided for treatment and prophylaxis of influenza virus. Antibodies and antigen-binding fragments are provided that hind near the HA0 maturation cleavage site consensus sequence of influenza hemagglutinin A. Antibody compositions, combinations and methods for effective passive immunization across influenza A and B strains are also provided.
Core Innovation
The invention relates to isolated human antibodies and antigen-binding fragments that bind to one or more strains of each of influenza B Yamagata and influenza B Victoria clades. The antibodies are defined by specific heavy chain variable regions and light chain variable regions with complementarity determining regions provided as amino acid sequences identified by SEQ ID NOs. The binding coverage is structured to include Yamagata and Victoria clade strains in a single antibody formulation.
A further aspect is directed to pharmaceutical compositions that combine multiple influenza-targeting antibodies or antigen-binding fragments. The composition includes a first antibody and a second antibody that bind to and/or inhibit influenza virus, each defined by its own heavy and light chain complementarity determining region sequences, and a third antibody or antigen-binding fragment that binds to one or more strains of each of influenza B Yamagata and influenza B Victoria clades. The third antibody is defined by alternative heavy and light chain CDR sequence sets or heavy/light variable sequence pairs.
The disclosed compositions include embodiments where stability-related characterization and composition constraints are specified. The composition identifies representative antibodies such as TRL053/Mab53 and TRL579/Mab579, and includes melting temperature in phosphate buffered saline and, in some embodiments, an isoelectric point range as constraints for pharmaceutical composition embodiments.
Claims Coverage
The provided content identifies three independent claims. Across these claims, the inventive subject matter is organized around clade-spanning influenza B binding antibodies defined by specific CDR sequence sets or by enumerated heavy-variable and light-variable sequence pair selections, and pharmaceutical compositions that combine multiple influenza-targeting antibodies, including a clade-spanning influenza B antibody.
Influenza B clade-binding isolated human antibody defined by enumerated heavy/light CDRs
An isolated human antibody, or antigen-binding fragment thereof, that binds to one or more strains of each of influenza B Yamagata and influenza B Victoria clades, comprising specified heavy chain complementarity determining regions (HCDR1/HCDR2/HCDR3) and specified light chain complementarity determining regions (LCDR1/LCDR2/LCDR3) defined by enumerated SEQ ID NOs across multiple alternative CDR sets.
Influenza B clade-binding isolated human antibody defined by heavy/light variable sequence pairs
An isolated human antibody or antigen-binding fragment thereof that binds to one or more strains of each of influenza B Yamagata and influenza B Victoria clades, comprising a heavy chain variable region and a light chain variable sequence pair selected from enumerated SEQ ID NO pair options.
Pharmaceutical composition with first, second, and third influenza-targeting antibodies including Yamagata/Victoria-binding influenza B antibody
A pharmaceutical composition comprising a first antibody that binds to and/or inhibits influenza virus, a second antibody that binds to and/or inhibits influenza virus, and a third antibody that binds to one or more strains of each of influenza B Yamagata and influenza B Victoria clades, where the third antibody is defined by selectable heavy-chain and light-chain CDR sequence sets.
The claim coverage centers on antibodies that span influenza B Yamagata and Victoria clades, defined either by explicit CDR amino acid sequences or by enumerated heavy/light variable sequence pair selections, and on a pharmaceutical composition that combines two influenza-inhibiting antibodies with a third clade-spanning influenza B antibody.
Stated Advantages
Broad coverage across influenza B Yamagata and influenza B Victoria clades through antibodies that bind one or more strains of each clade.
Intranasal or inhalation delivery of neutralizing antibodies increases in vivo efficacy compared with systemic intraperitoneal or intravenous delivery.
Compatibility among co-formulated antibodies is asserted, based on similar isoelectric point and thermal stability, and reduced aggregation or competition.
Documented Applications
Passive immunization against influenza using antibodies or antigen-binding fragments.
Pulmonary administration of a low-dose influenza antibody cocktail effective against influenza A and influenza B without needing strain diagnosis, including embodiments that combine intranasal with systemic intraperitoneal and/or intravenous dosing.
Use of intranasal or inhalation delivery of neutralizing antibodies as compared with systemic routes.
Prophylaxis using administration timing windows.
Pharmaceutical compositions for treating and/or preventing influenza A and B, including multi-antibody combinations.
Formulation and delivery use cases for nasal sprays, nebulizers, and dry-powder inhalers, including stable dry-powder or propellant formulations produced via supercritical fluid processes.
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