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Anti-hemagglutinin antibodies and methods of use thereof

A hemagglutinin and antibody technology, applied in the direction of antibodies, chemical instruments and methods, antiviral agents, etc., can solve the problems of high cost and low efficiency

Pending Publication Date: 2022-07-15
REGENERON PHARM INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

As a result, new vaccines must be produced each year against the viruses predicted to emerge, a process that is not only costly but also extremely inefficient
While technological advances have increased the ability to generate improved influenza antigens for use in vaccine compositions, there remains a need to provide additional sources of protection against influenza

Method used

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  • Anti-hemagglutinin antibodies and methods of use thereof
  • Anti-hemagglutinin antibodies and methods of use thereof
  • Anti-hemagglutinin antibodies and methods of use thereof

Examples

Experimental program
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Effect test

preparation example Construction

[0176] Preparation of human antibodies

[0177] Methods for producing human antibodies in transgenic mice are known in the art. Any such known method can be used in the context disclosed herein to produce human antibodies that specifically bind to influenza B HA. An immunogen comprising any of the following can be used to generate antibodies against influenza B HA. In certain embodiments, the antibody is derived from a full-length native influenza B HA (see, eg, GenBank Accession Nos. AAA43697.1 or ACA33493.1), or with a live attenuated or inactivated virus, or with an encoded protein or fragment thereof DNA was obtained from immunized mice. Alternatively, influenza B HA protein or fragments thereof can be produced using standard biochemical techniques, modified and used as an immunogen. In some embodiments, the immunogen can be a recombinantly produced influenza B HA protein or a fragment thereof. In certain embodiments, the immunogen can be an influenza virus vaccine. I...

Embodiment 1

[0261] Example 1: Generation of Human Antibodies to Influenza B Hemagglutinin (HA)

[0262] exist Human antibodies to influenza hemagglutinin, which contain DNA encoding the variable regions of human immunoglobulin heavy and kappa light chains, are raised in mice. Mice were immunized with a combination of vectors expressing influenza A and B hemagglutinin, then infected and recovered with influenza A and B strains, followed by administration of a booster containing a cocktail of recombinant hemagglutinin proteins. Antibody immune responses were monitored by an influenza HA specific immunoassay. Anti-influenza B HA antibodies were isolated directly from antigen-positive mouse B cells that were not fused to myeloma cells as described in US Patent 7,582,298, which is specifically incorporated herein by reference in its entirety. Using this method, fully human anti-influenza HA antibodies (ie, antibodies with human variable domains and human constant domains) were obtained.

...

Embodiment 2

[0264] Example 2: Heavy and Light Chain Variable Region Amino Acid and Nucleotide Sequences

[0265] Table 1 lists the heavy and light chain variable regions and CDRs and amino acid sequence identifiers for the heavy and light chain sequences of exemplary anti-influenza B HA antibodies. The corresponding nucleic acid sequence identifiers are listed in Table 2.

[0266] Table 1: Amino Acid Sequence Identifiers

[0267]

[0268] Table 2: Nucleic acid sequence identifiers

[0269]

[0270] The antibodies disclosed herein have fully human variable regions, but may have mouse constant regions (eg, mouse IgG1 Fc or mouse IgG2 Fc (a or b isotype)) or human constant regions (eg, human IgG1 Fc or human IgG4 Fc). As understood by one of ordinary skill in the art, an antibody with a particular Fc isotype can be converted into an antibody with a different Fc isotype (eg, an antibody with mouse IgGl Fc can be converted into an antibody with human IgG4, etc. ), but in any case the...

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Abstract

Provided herein are monoclonal antibodies, or antigen-binding fragments thereof, that bind to the influenza B hemagglutinin (HA) protein, pharmaceutical compositions comprising the antibodies, and methods of use. The antibodies can be used to inhibit or neutralize the activity of influenza B virus, thereby providing a method of treating or preventing influenza infection in humans. The use of one or more antibodies that bind to the influenza B HA for preventing viral adsorption and / or entry into host cells is also provided. The antibodies can be used prophylactically or therapeutically and can be used alone or in combination with one or more other antiviral agents or vaccines.

Description

[0001] government permission [0002] This invention was made with government support under approval HHSO100201700020C awarded by the U.S. Department of Health and Human Services. The government has certain rights in the invention. [0003] sequence listing [0004] An official copy of the Sequence Listing is submitted electronically via EFS-Web in ASCII format at the same time as the Sequence Listing and the specification, the file name is "10625WO01_SEQ_LIST_ST25.txt", the date of creation is October 28, 2020, and the size is approximately 36KB. The Sequence Listing contained in this ASCII formatted file is part of the specification and is incorporated herein by reference in its entirety. Background technique [0005] Influenza is a highly contagious disease with a long history characterized by waves of pandemics, epidemics, relapses and outbreaks. Despite annual vaccination efforts, influenza infection can cause significant morbidity and mortality. [0006] There are fo...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/10A61K39/42A61K39/395A61P31/16
CPCC07K16/1018C07K2317/21C07K2317/33A61K39/42A61K39/395A61P31/16A61K45/06C07K2317/92A61K2039/505
Inventor A·鲍姆C·基拉索斯
Owner REGENERON PHARM INC
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