Formulations of antibody molecules to influenza virus
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Publication Number
US-12202885-B2
Publication Date
2025-01-21
Expiration Date
Abstract
This disclosure relates to formulations of peptide agents, e.g., antibodies and antigen-binding fragments thereof, that bind hemagglutinin protein of influenza viruses, and methods of their use.
Core Innovation
The invention provides a pharmaceutical formulation of an anti-hemagglutinin (HA) antibody molecule. The formulation comprises 100 mg/mL of the anti-HA antibody molecule, amino acids consisting of histidine and arginine in defined percentage ranges, 0.02% polysorbate 80, and a pH of 6, and the antibody molecule is a human IgG1 antibody molecule with specified immunoglobulin variable region segments.
The antibody molecule includes heavy chain immunoglobulin variable region segments with defined complementarity-determining regions (CDRs). The HC CDR1 comprises the sequence S-Y-A-M-H (SEQ ID NO: 68), the HC CDR2 comprises the sequence V-V-S-Y-D-G-N-Y-K-Y-Y-A-D-S-V-Q-G (SEQ ID NO: 69), and the HC CDR3 comprises the sequence D-S-R-L-R-S-L-L-Y-F-E-W-L-S-Q-G-Y-F-N-P (SEQ ID NO: 70).
The light chain immunoglobulin variable region segments include defined LC CDR1, LC CDR2, and LC CDR3 sequences. LC CDR1 comprises Q-S-I-T-F-D-Y-K-N-Y-L-A (SEQ ID NO: 145), LC CDR2 comprises W-G-S-Y-L-E-S (SEQ ID NO: 72), and LC CDR3 comprises Q-Q-H-Y-R-T-P-P-S (SEQ ID NO: 73). The antibody molecule is further defined by a minimum purity of at least 90% as determined by reduced or non-reduced CE-SDS.
Claims Coverage
The claims cover one central inventive combination: a human IgG1 anti-HA antibody formulation with specific HC and LC CDR sequences, defined formulation composition, and a purity requirement measured by CE-SDS. The claim set includes 6 inventive features, with dependent claims narrowing the HC and/or LC framework region definitions by SEQ ID NOs and limited amino-acid differences.
Defined anti-HA human IgG1 antibody composition with specified HC and LC CDR sequences
An anti-hemagglutinin (HA) antibody molecule that is a human IgG1 antibody molecule comprising a heavy chain immunoglobulin variable region segment with HC CDR1 SEQ ID NO: 68, HC CDR2 SEQ ID NO: 69, and HC CDR3 SEQ ID NO: 70, and a light chain immunoglobulin variable region segment with LC CDR1 SEQ ID NO: 145, LC CDR2 SEQ ID NO: 72, and LC CDR3 SEQ ID NO: 73.
Pharmaceutical formulation with defined antibody concentration, amino acid excipient ranges, polysorbate 80, and pH
A pharmaceutical formulation having 100 mg/mL of the anti-HA antibody molecule, amino acids consisting of 0.2% to 5% histidine and 0.5% to 5% arginine, 0.02% polysorbate 80, and a pH of 6.
Purity requirement of at least 90% determined by reduced or non-reduced CE-SDS
A formulation wherein the purity of the antibody molecule in the formulation is at least 90% as determined by reduced or non-reduced CE-SDS.
HC framework/variable region definition using SEQ ID NO: 25 with limited amino-acid differences
A formulation wherein the antibody molecule comprises a heavy chain immunoglobulin variable region segment comprising SEQ ID NO: 25 or an amino-acid sequence differing by no more than 1-5 amino acids in that framework region.
LC framework/variable region definition using SEQ ID NO: 52 with limited amino-acid differences
A formulation wherein the antibody molecule comprises a light chain immunoglobulin variable region segment having SEQ ID NO: 52 or a framework region variant differing by no more than 1-5 amino acids from SEQ ID NO: 52.
Human IgG1 anti-hemagglutinin antibody molecule
A human IgG1 anti-hemagglutinin (HA) antibody molecule formulated as a pharmaceutical formulation with defined variable region segments.
The claim set primarily covers a specific anti-HA human IgG1 antibody formulation defined by exact HC and LC CDR sequences, a defined formulation composition including antibody concentration, histidine/arginine ranges, 0.02% polysorbate 80, and pH 6, and a purity threshold of at least 90% by reduced or non-reduced CE-SDS. Dependent claims narrow the scope by specifying HC and/or LC framework/variable region segments using SEQ ID NO: 25 and SEQ ID NO: 52, including allowable differences of no more than 1-5 amino acids for the respective framework region variants.
Stated Advantages
Fewer escape mutants are observed versus reference anti-HA antibodies.
Stable formulations are identified with maintained CE-SDS and SEC profiles under stress conditions.
Documented Applications
Treatment of influenza HA-related disease.
Prevention of influenza HA-related disease.
Diagnostic binding.
Use in a human H1N1 challenge model.
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