Yl-based insulin-like growth factors exhibiting high...

Details Yl-based insulin-like growth factors exhibiting high... Yl-based insulin-like growth factors exhibiting high...

C - Chemistry, Metallurgy

07

K

C07K 14/65 (2006.01) A61K 38/17 (2006.01) A61K 38/30 (2006.01) A61P 3/10 (2006.01)

Patent

CA 2747720

Insulin-like growth factor analogs are disclosed wherein substitution of the IGF native amino acids, at positions corresponding to positions B 16 and B 17 of native insulin, with tyrosine and leucine, respectively, increases potency of the result-ing analog at the insulin receptor by tenfold. Also disclosed are prodrug and depot formulations of the IGF analogs, wherein the IGF analog has been modified by the linkage of a dipeptide to the analog through an amide bond linkage. The prodrug and depot formulations disclosed herein have extended half lives of at least 2 hours, 10 hours, and more typically greater than 20 hours, and are converted to the active form at physiological conditions through a non- enzymatic reaction driven by chemical instability.

L'invention concerne des analogues de facteurs de croissance semblables à l'insuline dans lesquels la substitution des acides aminés natifs de l'IGF, à des positions qui correspondent aux positions B 16 et B 17 de l'insuline native, avec la tyrosine et la leucine, respectivement, augmente par dix la puissance de l'analogue résultant au récepteur de l'insuline. L'invention concerne aussi des formulations de promédicament et retard des analogues de l'IGF, dans lesquelles l'analogue de l'IGF a été modifié par liaison d'un dipeptide à l'analogue grâce à une liaison amide. Les formulations en question ont des demi-vies prolongées d'au moins 2 heures, 10 heures, et plus généralement supérieures à 20 heures, puis sont converties en forme active dans des conditions physiologiques par réaction non enzymatique menée par instabilité chimique.

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