Jing xu dds1/17/2024 ![]() ![]() Advised a public Canadian company in connection with internal investigations initiated by the Canadian Competition Bureau for alleged infringements under the Competition Act.Advised various US private equity firms on foreign investment approvals in connection with their Canadian investments.Advised an international telecommunications company on foreign investment filings and approvals in connection with their establishment of a new business in Canada.Acted as Canadian counsel to Allergan Plc., regarding all competition matters and filings in connection with its acquisition by AbbVie Inc., for USD 63 billion.Advised Northland Properties Corporation on competition matters and filings in connection with its acquisition of the Grouse Mountain Resort.Advised Hexo Corp on competition matters and filings in connection with its acquisition of Redecan.Advised Tervita Corporation on all competition matters and filings in connection with its contested merger with SECURE energy services.Provide ongoing advice to major food manufacturers regarding their food regulatory and marketing requirements.Advised Sika AG on competition and foreign investment review aspects of its EUR 5.3 billion acquisition of the MBCC Group, and the divestment of MBCC's admixtures business in the United States, Canada, the UK, the European Union, Australia and New Zealand to Cinven. ![]() These studies support the interpretation of toxicology studies, help characterize the disposition of givosiran in humans, and support the clinical use of givosiran for the treatment of acute hepatic porphyria.Ĭopyright © 2021 by The American Society for Pharmacology and Experimental Therapeutics. Subcutaneous administration results in adequate exposure of givosiran to the target organ (liver). Givosiran shows similar pharmacokinetics and ADME properties across rats and monkeys in vivo and across human and animal matrices in vitro. SIGNIFICANCE STATEMENT: Nonclinical pharmacokinetics and absorption, distribution, metabolism, and excretion (ADME) properties of givosiran were characterized. Thus, givosiran has a low potential of mediating drug-drug interactions involving P450 isozymes and drug transporters. Givosiran is not a substrate, inhibitor, or inducer of P450 isozymes, and it is not a substrate or inhibitor of uptake and most efflux transporters. Renal and fecal excretion were minor routes of elimination of givosiran as approximately 10% and 16% of the dose was recovered intact in excreta of rats and monkeys, respectively. Givosiran metabolized to form one primary active metabolite with the loss of one nucleotide from the 3' end of antisense strand, AS(N-1)3' givosiran, which was equipotent to givosiran. Givosiran was metabolized by nucleases, not cytochrome P450 (P450) isozymes, across species with no human unique metabolites. Givosiran predominantly distributed to the liver by asialoglycoprotein receptor-mediated uptake, and the t 1/2 in the liver was significantly longer (∼1 week). Plasma protein binding was concentration dependent across all species tested and was around 90% at clinically relevant concentration in human. Plasma exposure increased approximately dose proportionally with no accumulation after repeat doses. Givosiran was completely absorbed after subcutaneous administration with relatively short plasma elimination half-life (t 1/2 less than 4 hours). ![]() Herein, nonclinical pharmacokinetics and absorption, distribution, metabolism, and excretion properties of givosiran were characterized. Givosiran is an N-acetylgalactosamine-conjugated RNA interference therapeutic that targets 5'-aminolevulinate synthase 1 mRNA in the liver and is currently marketed for the treatment of acute hepatic porphyria. ![]()
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