C - Chemistry – Metallurgy – 12 – N
Patent
C - Chemistry, Metallurgy
12
N
C12N 15/62 (2006.01) A61K 38/45 (2006.01) A61K 48/00 (2006.01) A61P 31/00 (2006.01) A61P 33/00 (2006.01) A61P 35/00 (2006.01) C07K 19/00 (2006.01) C12N 5/10 (2006.01) C12N 9/12 (2006.01) C12N 9/52 (2006.01) C12N 15/38 (2006.01) C12N 15/54 (2006.01) C12N 15/86 (2006.01) C12Q 1/48 (2006.01) G01N 33/58 (2006.01)
Patent
CA 2306443
The present invention provides isolated nucleic acid molecules encoding a Herpesviridae thymidine kinase enzyme comprising one or more mutations, at least one of the mutations encoding an amino acid substitution located toward the N-terminus from a DRH nucleoside binding site which increases a biological activity of the thymidine kinase, as compared to unmutated thymidine kinase. Such mutations include amino acid substitutions within a Q substrate binding domain which increases a biological activity of the thymidine kinase, as compared to unmutated thymidine kinase. Within a further aspect, fusion proteins are provided which have both guanylate kinase and thymidine kinase biological properties. Also provided are vectors suitable for expressing such DNA molecules, as well as methods for utilizing such vectors.
La présente invention concerne des molécules d'acide nucléique isolées codant une enzyme thymidine kinase Herpesviridae renfermant une ou plusieurs mutations, au moins une de ces mutations codant une substitution d'acide aminé située à proximité de la partie N-terminale du site de liaison d'un nucléoside DRH, cette substitution favorisant l'activité biologique de la thymidine kinase par rapport à une thymidine kinase non mutée. Ces mutations renferment des substitutions d'acide aminé à l'intérieur du domaine de liaison d'un substrat Q, ce domaine favorisant l'activité biologique de ladite thymidine kinase par rapport à une thymidine kinase non mutée. Dans un autre aspect de cette invention, des protéines de fusion présentent des propriétés biologiques de guanylate kinase et de thymidine kinase. L'invention concerne enfin des vecteurs permettant d'exprimer de telles molécules d'ADN, ainsi que des procédés d'utilisation de ces vecteurs.
Darwin Molecular Corporation
Gowling Lafleur Henderson Llp
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