Aurinia Pharmaceuticals Inc.
Cyclosporine analogue mixtures and their use as immunomodulating agents

Abstract:

The invention is directed to isomeric mixtures of cyclosporine analogues that are structurally similar to cyclosporine A. The mixtures possess enhanced efficacy and reduced toxicity over the individual isomers and over naturally occurring and other presently known cyclosporines and cyclosporine derivatives. Embodiments of the present invention are directed toward cis and trans-isomers of cyclosporin A analogs referred to as ISA.sub.TX247, and derivatives thereof. Mixtures of ISA.sub.TX247 isomers exhibit a combination of enhanced potency and reduced toxicity over the naturally occurring and presently known cyclosporins. ISA.sub.TX247 isomers and alkylated, arylated, and deuterated derivatives are synthesized by stereoselective pathways where the particular conditions of a reaction determine the degree of stereoselectivity. The ratio of isomers in a mixture comprises from about 70 to about 80 percent by weight of the E-isomer and from about 20 to about 30 percent by weight of the Z-isomer, based on the total weight of the mixture.