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"Anti-influenza medicine" Tamiflu (oseltamivir)

Just as Apple’s inspiration for Newton’s inspiration, Duffy’s research and development stems from an academic conference poster.

1. A poster gives scientists inspiration

Just as Apple’s inspiration for Newton’s inspiration, Duffy’s research and development stems from an academic conference poster.


On October 14, 1992, at the annual meeting of a society in Los Angeles, a scientist at Gilead Science was attracted to a poster by Dr. Norbert Bischofberger.


This poster showing the drug development results is a compound code GG167 that inhibits the replication of influenza virus in mice.


The research was carried out by Biota, a biotech company in Australia, and was authorized to be marketed by Glaxo Pharmaceuticals, which was later approved by the FDA in 1999. It is also a fight against the flu virus. Kind of drug, this is a follow-up.


After seeing this, Bischberger had his own different ideas.


Prior to this, the fight against influenza virus can only rely on two major "King Kong" - amantadine and rimantadine, more adverse reactions, hallucinations, mental disorders, and easy to resist, GG167 this drug does have a unique role The target is clear, and it is an enzyme that directly targets the influenza virus, neuraminidase.


By inhibiting the activity of this enzyme, the new virus and the old cells are cut off, and the virus can not infect new cells, which inhibits the reproduction of the virus.


However, due to the chemical structure of GG167, it can not be absorbed by the intestines, so it can not be made orally. It can only be made into a powder spray, which is inconvenient by inhaling into the lungs.


Bilf Berger saw this flaw and decided to invest in the study of oral anti-influenza drugs.


2. The development process is full of twists and turns


Bilf Berger asked Gilead to set up a research and development team with its own team, including organic chemists, biologists, computer experts, etc., to open the way of dreams.


The reality is not as smooth as expected. More than the computer experts of Wolfberger designed the molecular structure model of drugs, organic chemists began to chemically synthesize according to the model, and finally do animal experiments.


This process has been repeated many times, after three years, that is, by the end of 1995, the compound GS4071, which met the initial requirements, was obtained.


However, it is disappointing that this compound was not absorbed into the blood after being administered by the mice, that is, the GG167 of sputum and geranin had the same defect!


Fortunately, the R&D team did not lose heart and continued to adjust. Finally, a new compound, GS4104, was designed. The mice can be absorbed into the bloodstream and then converted into GS4071 to produce an antiviral effect.


3. Animal experiment is only the first step


Friends who are familiar with drug development know that the success of mice cannot be declared successful in drug development, because they have to undergo successive experiments on large animals and human bodies to be truly successful.


Then Gilead's research team carried out experiments on rats, monkeys and ferrets, and the results were very satisfactory!


If the human body experiment is successful, then it is very effective, but we have encountered difficulties here. We know that human trials are clinical trials, which are very complicated. Our current clinical trials are generally divided into I, II, III and IV. Phase clinical trials.


The clinical trial, which cost hundreds of millions of dollars, was an astronomical figure for Gilead at the time, and it was necessary to find a partner.