Exploiting light chains for the scalable generation and platform purification of native human bispecific IgG

Nicolas Fischer (), Greg Elson, Giovanni Magistrelli, Elie Dheilly, Nicolas Fouque, Amélie Laurendon, Franck Gueneau, Ulla Ravn, Jean-François Depoisier, Valery Moine, Sylvain Raimondi, Pauline Malinge, Laura Di Grazia, François Rousseau, Yves Poitevin, Sébastien Calloud, Pierre-Alexis Cayatte, Mathias Alcoz, Guillemette Pontini, Séverine Fagète, Lucile Broyer, Marie Corbier, Delphine Schrag, Gérard Didelot, Nicolas Bosson, Nessie Costes, Laura Cons, Vanessa Buatois, Zoe Johnson, Walter Ferlin, Krzysztof Masternak and Marie Kosco-Vilbois
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Nicolas Fischer: Novimmune SA
Greg Elson: Novimmune SA
Giovanni Magistrelli: Novimmune SA
Elie Dheilly: Novimmune SA
Nicolas Fouque: Novimmune SA
Amélie Laurendon: Novimmune SA
Franck Gueneau: Novimmune SA
Ulla Ravn: Novimmune SA
Jean-François Depoisier: Novimmune SA
Valery Moine: Novimmune SA
Sylvain Raimondi: Novimmune SA
Pauline Malinge: Novimmune SA
Laura Di Grazia: Novimmune SA
François Rousseau: Novimmune SA
Yves Poitevin: Novimmune SA
Sébastien Calloud: Novimmune SA
Pierre-Alexis Cayatte: Novimmune SA
Mathias Alcoz: Novimmune SA
Guillemette Pontini: Novimmune SA
Séverine Fagète: Novimmune SA
Lucile Broyer: Novimmune SA
Marie Corbier: Novimmune SA
Delphine Schrag: Novimmune SA
Gérard Didelot: Novimmune SA
Nicolas Bosson: Novimmune SA
Nessie Costes: Novimmune SA
Laura Cons: Novimmune SA
Vanessa Buatois: Novimmune SA
Zoe Johnson: Novimmune SA
Walter Ferlin: Novimmune SA
Krzysztof Masternak: Novimmune SA
Marie Kosco-Vilbois: Novimmune SA

Nature Communications, 2015, vol. 6, issue 1, 1-12

Abstract: Abstract Bispecific antibodies enable unique therapeutic approaches but it remains a challenge to produce them at the industrial scale, and the modifications introduced to achieve bispecificity often have an impact on stability and risk of immunogenicity. Here we describe a fully human bispecific IgG devoid of any modification, which can be produced at the industrial scale, using a platform process. This format, referred to as a κλ-body, is assembled by co-expressing one heavy chain and two different light chains, one κ and one λ. Using ten different targets, we demonstrate that light chains can play a dominant role in mediating specificity and high affinity. The κλ-bodies support multiple modes of action, and their stability and pharmacokinetic properties are indistinguishable from therapeutic antibodies. Thus, the κλ-body represents a unique, fully human format that exploits light-chain variable domains for antigen binding and light-chain constant domains for robust downstream processing, to realize the potential of bispecific antibodies.

Date: 2015
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7113

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DOI: 10.1038/ncomms7113

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