Erasmus University Medical Center

Erasmus University Medical Center Rotterdam

Craig, Roger Kingdon

Ernie De Boer

Roger Kingdon Craig

Franklin Gerardus Grosveld

Richard Wilhelm Janssens

Dubravka Drabek

Tao Chen

Marinus Johannes Van Haperen

A transgenic non-human mammal containing a heterologous lambda light chain gene locus, and/or a heterologous kappa light chain gene locus, and/or a heterologous heavy chain gene locus, each of which can re-arrange so that immunoglobulin heavy and light chain genes are formed and expressed in B-cells following antigen challenge.

Antibody production

The present invention provides a high affinity, antigen-specific, soluble heavy chain-only antibody which: lacks hallmark camelid-related amino acid substitutions and has FR2 substitutions which are not found in antibodies which comprise heavy and light chain; shows increased net hydrophobicity within CDR1 and an increased number of charged amino acids present in CDR3; and comprises one or more amino acid substitutions within the framework &#x3b2;-pleated sheet leading to increased net hydrophobicity within FR1 and increased number of charged amino acids present in FR3. Also provided are VH domains having the same properties, gene segments for their production, methods for their production, transgenic animals and uses of the antibody of the VH domains in therapy.

Soluble heavy-chain only antibodies

Soluble 'heavy-chain only' antibodies

Growing community of inventors

Rotterdam, Netherlands

Ernie De Boer