Milne, A(lan) A(lexander)

(born Jan. 18, 1882, London, Eng.—died Jan. 31, 1956, Hartfield, Sussex) English writer. He joined the staff of Punch in 1906 and produced successful light comedies and a memorable detective novel, The Red House Mystery (1922), before verses written for his son Christopher Robin grew into the collections When We Were Very Young (1924) and Now We Are Six (1927), which became beloved classics. Stories about the adventures of Christopher Robin and the toy animals Pooh, Piglet, Kanga, Roo, Tigger, Rabbit, Owl, and Eeyore are told in the immensely popular Winnie-the-Pooh (1926) and The House at Pooh Corner (1928).

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(born Oct. 5, 1829, North Fairfield, Vt., U.S.—died Nov. 18, 1886, New York, N.Y) 21st president of the U.S. (1881–85). He practiced law in New York City from 1854, later becoming a close associate of Sen. Roscoe Conkling, the Republican boss of New York. With Conkling's backing, he was appointed customs collector for the port of New York (1871–78), an office long known for its use of the spoils system. He conducted the business of the office with integrity but continued to pad its payroll with Conkling loyalists. At the Republican national convention in 1880, Arthur was the compromise choice for vice president on a ticket with James Garfield; he became president on Garfield's assassination. As president, Arthur displayed unexpected independence by vetoing measures that rewarded political patronage. He also signed the Pendleton Civil Service Act, which created a civil-service system based on merit. He and his navy secretary recommended appropriations that later helped transform the U.S. Navy into one of the world's great fleets. He failed to win his party's nomination for a second term.

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Élan Corporation plc is a major drugs firm based in Athlone, County Westmeath, Ireland which has major interests in the United States. In the late 1990's its value on the Irish Stock Exchange reached over €20bn. It has secondary listings on the London Stock Exchange and the New York Stock Exchange. It was one of Ireland's major business success stories. However in the early years of 2000's an accounting scandal and investor reactions to the global slump, caused a major devaluation resulting in a share price slump of over 90%. Since then the company has regained its growth path under the reign of a new American CEO Kelly Martin. Élan employs over 2,000 people worldwide. It is listed on the New York Stock Exchange as ELN, the Irish Stock Exchange as ELN.I, and the London Stock Exchange as ELN.L. Reformulations for client-based projects has contributed to more than $9 billion in in-market sales for these clients. Currently more than 2.5 million patients take Élan's products worldwide.

Products in development

In neurology, Élan is focused on building upon its breakthrough research and extensive experience in the area of neuropathology-related disorders such as Alzheimer’s disease, where the company’s efforts include programs focused on small molecule inhibitors of beta secretase and gamma secretase, enzymes whose actions are thought to affect the accumulation of the amyloid plaques found in the brains of patients with Alzheimer’s disease. Élan is also studying other neurodegenerative diseases, such as Parkinson's disease. Élan, in collaboration with Wyeth, initiated a Phase II clinical trial for an experimental humanized monoclonal antibody with a targeted indication of immunotherapeutic treatment of mild to moderate Alzheimer’s disease. The humanized monoclonal antibody is designed and engineered to clear the neurotoxic beta-amyloid peptide that accumulates in the brains of patients with Alzheimer’s disease. Élan is hopeful that its drug "aab-001" (now known as bapineuzumab) is doing well in trials as the first results are due in 2006.

In autoimmune diseases, Élan’s primary emphasis is studying cell trafficking to discover ways to provide disease-modifying therapies for autoimmune diseases such as rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease. Research efforts are also focused on physiological and neuropathic pain.

Natalizumab/Tysabri

''See main article: Natalizumab/Tysabri

Previously named Antegren, Natalizumab is a drug co-marketed by Biogen Idec and Élan as "Tysabri". Tysabri is a monoclonal antibody that inhibits immune cells from crossing blood vessel walls to reach various tissues, including the brain. It has proven efficacy in the treatment of two serious autoimmune disorders: multiple sclerosis, and Crohn's disease. In multiple sclerosis, Tysabri was shown to reduce relapses by 67% vs. a placebo in double-blind studies. It slowed the progression of disability by 42%. While it is impossible to compare results across different clinical trials, the older generation drugs, i.e. interferons and Copaxone, are generally acknowledged as demonstrating about a 30-35% decrease in relapse rate vs. placebo; and only two drugs have been shown to decrease the progression of disability, but again only by around 20-40%.

Drug delivery

Elan has developed novel drug delivery systems including its nanocyrstal technology and oral controlled release formulations of drug delivery.

NanoCrystal Technology

For poorly water soluble compounds, Élan's proprietary NanoCrystal technology can enable formulation and improve compound activity and final product characteristics. The NanoCrystal technology can be incorporated into all dosage forms both parenteral and oral, including solid, liquid, fast-melt, pulsed release and controlled release dosage forms.

Drugs

Products and drugs that Élan has developed include:

• Avinza – once-daily, novel dual release morphine sulphate
• Emend – oral table form of aprepitant, a poorly water soluble compound
• Focalin XR – once-daily dexmethylphenidate marketed in US and other territories
• Herbesser R – once-daily, high-potency, sustained release diltiazem for Japanese and other Asian markets
• Megace ES – concentrated oral suspension utilizing NanoCrystal Technology, marketed in the U.S.
• NaprÉlan - once-daily, sustained-release naproxen sodium
• Rapamune - oral tablet form of poorly water soluble compound
• Ritalin LA – once-daily, pulsatile release of methylphenidate
• Theo-Dur - twice-daily, sustained-release theophylline
• TriCor - new formulation of Abbott’s fenofibrate, which can be taken without regard to food, launched in the U.S.
• VerÉlan - once-daily, sustained-release verapamil
• VerÉlan PM – modified release, chronotherapeutic verapamil

References

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External links

• Élan's homepage