Janssen Vaccines & Prevention B.v.

Crucell Holland B.v.

Robert Heinz Edward Friesen

Ronald Vogels

Joost Alexander Kolkman

Boerries Brandenburg

Theodorus Hendrikus Jacobus Kwaks

Mark Throsby

Katarina Radosevic

David Adrianus Theodorus Maria Zuijdgeest

Antonietta Impagliazzo

Jaroslaw Juraszek

Mandy Antonia Catharina Jongeneelen

Davide Branduardi

Jan Wilem Meijberg

Philippe Alard

Stefan Loverix

David ATM Zuijdgeest

Mark Kwakkenbos

Adrianus Quirinus Bakker

Tim Beaumont

Hergen Spits

A method of designing a D-polypeptide that binds with an L-target protein can include: identifying a polypeptide target having L-chirality; determining hotspot amino acids of a polypeptide ligand having L-chirality that have binding interactions with the L-target protein; determining transformations of side chains of the hotspot amino acids that retain the binding interactions with the target; generating inversed hotspot amino acids with chirality opposite to the one of the target; identifying a polypeptide having inverse chirality from the target protein, on which a combination of inversed hotspot amino-acid can be grafted without significantly changing their interactions with the target. The designed ligands can be processed and converted to D-ligands that bind with the L-target protein.

Structure based design of d-protein ligands

Multimeric binding molecules that are capable of specifically binding to hemagglutinin (HA) of at least two influenza A virus strains, said strains comprising HA of two different HA subtypes from phylogenetic group 2; or capable of specifically binding to hemagglutinin (HA) of at least one influenza A virus strain from phylogenetic group 1 and at least one influenza A virus strain from phylogenetic group 2; or capable of specifically binding to hemagglutinin (HA) of at least one influenza B virus strain are provided. The binding molecules preferably are also capable of neutralizing at least two influenza A virus strains from phylogenetic group 2; or capable of neutralizing at least one influenza A virus strain from phylogenetic group 1 and at least one influenza A virus strain from phylogenetic group 2; or capable of specifically neutralizing at least one influenza B virus strain.

Binding molecules directed against influenza hemagglutinin and uses thereof

Monomeric and multimeric binding molecules that are capable of specifically binding to hemagglutinin (HA) of at least two influenza A virus strains, said strains including HA of two different HA subtypes from phylogenetic group 2; or capable of specifically binding to hemagglutinin (HA) of at least one influenza A virus strain from phylogenetic group 1 and at least one influenza A virus strain from phylogenetic group 2; or capable of specifically binding to hemagglutinin (HA) of at least one influenza B virus strain are provided. The binding molecules preferably are also capable of neutralizing at least two influenza A virus strains from phylogenetic group 2; or capable of neutralizing at least one influenza A virus strain from phylogenetic group 1 and at least one influenza A virus strain from phylogenetic group 2; or capable of specifically neutralizing at least one influenza B virus strain.

The present disclosure relates to binding molecules, such as human monoclonal antibodies, that bind to an epitope in the stem region of hemagglutinin of influenza A viruses of phylogenetic group 1 and group 2, as well as influenza B viruses, and have a broad neutralizing activity against such influenza viruses. The disclosure provides nucleic acid molecules encoding the binding molecules, their sequences and compositions comprising the binding molecules. The binding molecules can be used in the diagnosis, prophylaxis and/or treatment of influenza A viruses of phylogenetic groups 1 and 2, as well as influenza B viruses.

Human binding molecules capable of neutralizing influenza A viruses of phylogenetic group 1 and phylogenetic group 2 and influenza B viruses

Binding molecules, such as human monoclonal antibodies, that bind to influenza virus comprising HA of the H3 subtype, such as H3N2, and have a broad neutralizing activity against such influenza virus. Provided are nucleic acid molecules encoding the antibodies, their sequences and compositions comprising the antibodies and methods of identifying or producing the antibodies. The antibodies can be used in the diagnosis, prophylaxis and/or treatment of an influenza virus H3N2 infection. The antibodies may provide cross-subtype protection, such that infections with H3, H7, and/or H10-based influenza subtypes can be prevented and/or treated.

Human binding molecules capable of neutralizing influenza virus H3N2 and uses thereof

Growing community of inventors

Wassenaar, Netherlands

Robert Heinz Edward Friesen