BA401 Eli Lilly and Company

Eli Lilly and Company

History

Eli Lilly and Company has been in business more than 132 years. The global, research-based company was founded in May 1876 by Colonel Eli Lilly in Indianapolis, Ind., in the Midwestern section of the United States. A 38-year-old pharmaceutical chemist and a veteran of the U.S. Civil War, Colonel Lilly was frustrated by the poorly prepared, often ineffective medicines of his day. Consequently, he made these commitments to himself and to society: - He would found a company that manufactured pharmaceutical products of the highest possible quality. - His company would develop only medicines that would be dispensed at the suggestion of physicians rather than by eloquent sideshow hucksters. - Lilly pharmaceuticals would be based on the best science of the day.

Eli Lilly and Company Major Product

Prozac®, the first major introduction in a new class of drugs for treatment of clinical depression.

Zyprexa®, now the world's top-selling antipsychotic for the treatment of schizophrenia

Humulin® insulin identical to that produced by the human body.

Ceclor®, a member of the cephalosporin family, was eventually became the world's top-selling oral antibiotic.

Innovation in the new drug development process

19th century, Synthetic chemistry

1980s, genetic engineering and rational drug discovery

Late 1980s, Combinatorial chemistry

Combinatorial chemistry

Combinatorial chemistry is one of the important new methodologies developed by researchers in the pharmaceutical industry to reduce the time and costs associated with producing effective and competitive new drugs.By accelerating the process of chemical synthesis, this method is having a profound effect on all branches of chemistry, but especially on drug discovery. Through the rapidly evolving technology of combi-chemistry, it is now possible to produce compound libraries to screen for novel bioactivities. This powerful new technology has begun to help pharmaceutical companies to find new drug candidates quickly, save significant money in preclinical development costs and ultimately change their fundamental approach to drug discovery.

Combinatorial chemistry at Lilly

In September 1994, Lilly acquired a financially strapped biotechnology firm named Sphinx Pharmaceuticals which had leading expertise in combinatorial chemistry and high-throughput screening.

Drug discovery for central nervous system (cns) diseases

In the mid-1990s, roughly one billion people, or one-fifth of the world’s people, suffered from a neurological or psychiatric disorder at one point in their lifetime such as clinical depression, severe insomnia, and migraine that might predispose people to suicide.

Drug discovery for central nervous system (CNS) diseases

Many CNS diseases were thought to result from imbalances of neurotransmitters. Different neurotransmitters were known to activate different receptors just as different keys might open up different doorways.

Drug discovery for central nervous system (CNS) diseases

Various classes of neurotransmitters, such as dopamine, norepinephrine, and serotonin, were associated with differing diseases. For example, Serotonin was associated with a variety of conditions ranging from depression to insomnia to aggression to migraine.

Drug discovery for central nervous system (CNS) diseases

-Lilly’s first billion dollar blockbuster antidepressant drug, Prozac® very selectively boosted levels of serotonin to exert its therapeutic effects.

-Prozac® had undesirable side-effects such as sedation, anxiety, and dry mouth.

-Prozac® would come off patent in 2003

Lilly’s migraine project

1994:March/April

-“Hot” lead compound found from the screen with good fit at the serotonin 1f receptor.

-Kaldor gives combinatorial chemistry seminar to an in-house audience at Lilly that includes Schaus. This serves as catalyst for Kaldor-Schaus collaboration.

Lilly’s migraine project

1994:March/June

-Improvements upon this lead made using traditional chemistry. Screening proceeds using an improved assay, which now tests 50 compounds per week

Lilly’s migraine project

1994:September

-Sphinx acquired. Will take almost another year to integrate Sphinx’s leading-edge technology in combichem and high-throughput screening.

1994:December

-Schaus presents seminar on his research to other CNS research group leaders. Able to demonstrate that combichem can lead to pure, quantifiable results.

Lilly’s migraine project

1995:February

-PTAC (project approval committee) meets to discuss strategic choices in migraine project.