Mcgill University

Elanco US Inc.

Roger K Prichard

Timothy G Geary

Catherine Bourguinat

Ming Xu

Ana Paula Ribeiro

William J Blackhall

Robin N Beech

Marcelo Molento

Hao Yuan Liu

Elias Georges

Jean-Francedillaois Pouliot

Disclosed are nucleic acid molecules from the genome ofspp. nematodes that contain single nucleotide polymorphisms related to reduced responsiveness of the nematodes to macrocyclic lactones. In one example, the species ofis(the agent of heartworm in animals). Also disclosed are methods for determining the responsiveness ofspp. nematodes to macrocyclic lactones, methods for selecting a treatment to treat an animal infected withspp. nematode, and kits for determining the responsiveness ofspp. nematodes to macrocyclic lactones.

Markers to predict macrocyclic lactone drug resistance in, the causative agent of heartworm disease

Disclosed are nucleic acid molecules from the genome ofspp. nematodes that contain single nucleotide polymorphisms related to reduced responsiveness of the nematodes to macrocyclic lactones. In one example, the species ofis(the agent of heartworm in animals). Also disclosed are methods for determining the responsiveness ofspp. nematodes to macrocyclic lactones, methods for selecting a treatment to treat an animal infected with aspp. nematode, and kits for determining the responsiveness ofspp. nematodes to macrocyclic lactones.

Markers to predict macrocyclic lactone drug resistance in dirofilaria immitis, the causative agent of heartworm disease

This invention describes novel purified and isolated nucleic acid molecules or the fragments thereof, extracted from nematode or arthropod pests or recombinant, which encode P-glycoprotein homologs and regulate resistance to the macrocyclic lactone compounds. The invention further relates to the new P-glycoprotein homolog expression product of these nucleic acids. Also described herein are methods for detecting the gene encoding for resistance to the macrocyclic lactone compounds in nematode or arthropod pests which comprise comparing the nucleic acids extracted from a pest specimen to the nucleic acids encoding for resistance and the nucleic acids encoding for susceptibility to the macrocyclic lactone compounds. Lastly, the present invention is also drawn to methods and compositions for increasing the efficacy of the macrocyclic lactone compounds against resistant nematode or resistant arthropod pests which comprise administering to a mammal or applying to crops and the like a pesticidal enhancing effective amount of a multidrug resistance reversing agent.

Methods for detecting and reversing resistance to macrocyclic lactone compounds

This invention describes methods for increasing the toxicity of a cytostatic hydrophobic chemotherapeutic agent against resistant tumor cells in mammals which comprise administering a multidrug resistant reversing agent to the mammal in connection with the administration of the cytostatic hydrophobic chemotherapeutic agent in an amount effective to increase the toxicity of the chemotherapeutic agent, wherein the multidrug resistant reversing agent is a macrocyclic lactone compound. Examples of the macrocyclic lactone compounds useful in the present invention include, but are not limited to, the LL-F28249.alpha.-.lambda. series of compounds, the 23-oxo or 23-imino derivative thereof, the avermectins, the 22,23-dihydro derivatives thereof and the milbemycins. Compositions comprising the macrocyclic lactone compounds and the chemotherapeutic agents are also described herein.

Methods for using macrocyclic lactone compounds as multidrug resistance

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Beaconsfield, Canada

Roger K Prichard