C - Chemistry – Metallurgy – 12 – N
Patent
C - Chemistry, Metallurgy
12
N
C12N 15/13 (2006.01) A61K 47/48 (2006.01) A61P 35/00 (2006.01) C07K 16/28 (2006.01) C07K 19/00 (2006.01) C12N 15/62 (2006.01)
Patent
CA 2400868
The invention provides antibodies for a mutant form of the epidermal growth factor receptor known as EGFRvIII. This mutant is found only or primarily on the surface of glioblastoma cells, and on cells of breast, ovarian and non- small cell lung carcinomas. The antibodies provided by the invention have higher affinity for EGFRvIII, and form immunotoxins with higher cytotoxicity and yield, than prior art antibodies, including the scFv designated MR1. In particular, the invention provides an antibody, designated MR1-1, which mutates MR1 in the CDR3 of the VH and VL chains to provide an antibody with especially good cytotoxicity. The invention provides additional antibodies in which MR1 is mutated in the CDR1 and 2 of VH or VL, or both, with better binding to EGFRvIII than that of the parental MR1 antibody.
L'invention concerne des anticorps destinés à une forme de mutant du récepteur du facteur de croissance épidermale connu en tant que EGFRvIII. On trouve ce mutant seulement ou principalement sur la surface des cellules du glioblastome et sur les cellules de la poitrine, des carcinomes ovariens et des carcinomes non à petites cellules du poumon. Les anticorps selon l'invention présentent une affinité plus élevée pour les EGFRvIII et créent des immunotoxines possédant une cytotoxicité et d'un rendement plus élevés que les anticorps actuellement disponibles, notamment les MR1 désignés scFv. L'invention concerne en particulier un anticorps, désigné MR1-1 qui mute MR1 dans la CDR3 des chaînes VH et VL en vue de produire un anticorps possédant une toxicité spécialement bonne. L'invention concerne des anticorps supplémentaires dans lesquels MR1 est muté dans la CDR1 et 2 de la VH ou VL ou les deux, avec une meilleure liaison au EGFRvIII que l'anticorps MR1 parental.
Beers Richard
Bigner Darell
Chowdhury Partha S.
Pastan Ira
Duke University
Sim & Mcburney
The Government Of The United States Of America As Represented By The Se Cretary Of The Department Of Health And
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