C - Chemistry – Metallurgy – 12 – Q
Patent
C - Chemistry, Metallurgy
12
Q
C12Q 1/68 (2006.01)
Patent
CA 2630838
The present invention relates to an in vitro method of diagnosing a drug- associated angioedema or a predisposition thereto in a subject being suspected of having developed or of having a predisposition to develop a drug-associated angioedema or in a subject being suspected of being a carrier for a drug- associated angioedema or in a subject being intended to be treated with a drug associated with the development of angioedema, the method comprising determining in a biological sample from said subject the presence or absence of a disease-associated mutation in a nucleic acid molecule regulating the expression of or encoding coagulation factor XII; wherein the presence of such a mutation is indicative of a drug- associated angioedema or a predisposition thereto. The present invention also relates to a method of diagnosing a drug- associated angioedema or a predisposition thereto in a subject being suspected of having developed or of having a predisposition to develop a drug-associated angioedema or in a subject being suspected of being a carrier for a drug- associated angioedema or in a subject being intended to be treated with a drug associated with the development of angioedema, the method comprising assessing the presence, amount and/or activity of coagulation factor XII in said subject and including the steps of: (a) determining from a biological sample of said subject in vitro, the presence, amount and/or activity of: (i) a (poly)peptide encoded by the coagulation factor XII gene; (ii) a substrate of the (poly)peptide of (i); or (iii) a (poly)peptide processed by the substrate mentioned in (ii); (b) comparing said presence, amount and/or activity with that determined from a reference sample; and (c) diagnosing, based on the difference between the samples compared in step (b), the pathological condition of a drug-associated angioedema or a predisposition thereto. The present invention also relates to a method of identifying a compound modulating coagulation factor XII activity which is suitable as a medicament or a lead compound for a medicament for the treatment and/or prevention of drug-associated angioedema, the method comprising the steps of: (a) in vitro contacting a coagulation factor XII (poly)peptide or a functionally related (poly)peptide with the potential modulator; and (b) testing for modulation of coagulation factor XII activity, wherein modulation of coagulation factor XII activity is indicative of a compound's suitability as a medicament or a lead compound for a medicament for the treatment and/or prevention of drug- associated angioedema. Furthermore, the present invention relates to gene therapy methods and to a kit for diagnosing drug-associated angioedema.
La présente invention concerne un procédé in vitro de diagnostic d~un AEdème de Quincke associé à un médicament ou d~une prédisposition à celui-ci chez un sujet soupçonné d~avoir développé ou d~avoir une prédisposition à développer un AEdème de Quincke associé à un médicament ou chez un sujet soupçonné d~être le porteur d~un AEdème de Quincke associé à un médicament ou chez un sujet que l~on a l~intention de traiter avec un médicament associé au développement d~un AEdème de Quincke, le procédé permettant d~établir, dans un prélèvement biologique dudit sujet, la présence ou l~absence d~une mutation associée à une maladie dans une molécule d~acide nucléique qui régularise l~expression d~un facteur XII de coagulation ou qui l~encode ; la présence d~une telle mutation étant indicatrice d~un AEdème de Quincke associé à un médicament ou d~une prédisposition à celui-ci. La présente invention concerne également un procédé de diagnostic d~un AEdème de Quincke associé à un médicament ou d~une prédisposition à celui-ci chez un sujet soupçonné d~avoir développé ou d~avoir une prédisposition à développer un AEdème de Quincke associé à un médicament ou chez un sujet soupçonné d~être le porteur d~un AEdème de Quincke associé à un médicament ou chez un sujet que l~on a l~intention de traiter avec un médicament associé au développement d~un AEdème de Quincke, le procédé permettant d~évaluer la présence, la quantité et/ou l~activité du facteur XII de coagulation chez ledit sujet et comprenant les étapes de : (a) l~évaluation in vitro, dans un prélèvement biologique dudit sujet, de la présence, de la quantité et/ou de l~activité : (i) d~un (poly)peptide codé par le gène du facteur XII de coagulation ; (ii) d~un substrat du (poly)peptide de (i) ; ou (iii) d~un (poly)peptide traité par le substrat mentionné en (ii) ; (b) la comparaison de ladite présence, quantité et/ou activité avec celle évaluée sur un échantillon témoin ; et (c) le diagnostic, basé sur la différence entre les échantillons comparés à l~étape (b), de l~état pathologique de l~AEdème de Quincke associé à un médicament ou d~une prédisposition à celui-ci.
Dewald Georg
Torys Llp
LandOfFree
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