A small privately held Arizona biotechnology firm said it hasdemonstrated a naturally occurring serine protease inhibitor hasantiviral activity and could be used for AIDS, but so far it has beenunable to find a corporate partner to assist in development.

"None of the big drug companies wants to license our patents," saidJohn Lezdey, president of Protease Sciences in Tempe, Ariz. "Theyall want the drug in-house."

Lezdey said Protease Sciences, which has been in business for 12years, has patents for use of alpha 1-protease inhibitor, or alpha 1-antitrypsin (AAT), as an antiviral agent against HIV and hepatitis.

"We were studying protease inhibitors for HIV long before theybecame popular," he noted.

Although AAT is a natural protein, it does not exist in large enoughquantities to be effective as an anti-HIV agent, Lezdey said.Supplementing the body's own AAT with additional protein, headded, may be more effective against HIV than the current small-molecule protease inhibitors, several of which have been approved inthe last eight months by the FDA to battle AIDS.

Two problems with protease inhibitor compounds, Lezdey observed,are they eventually become neutralized by antibodies and HIVmutates quickly to resist them.

A natural serine protease inhibitor would not be subjected to such animmune system response and Protease Sciences' researchers, in testtube studies, have demonstrated the protein counters the virusesmutations.

Lezdey said compounding a lack of corporate interest for developingalpha 1-protease inhibitors as antivirals is another hurdle _ findingan effective method of producing commercial quantities of theprotein other than taking it from limited blood plasma supplies.

Bayer AG, of Leverkusen, Germany, sells plasma-derived alpha 1-protease inhibitor in the U.S. under the brand name Prolastin fortreatment of congenital emphysema caused by a deficiency in alpha1-antitrypsin. The drug was approved in 1987.

In addition to intellectual property protection for alpha 1-proteaseinhibitor as an antiviral agent, Protein Sciences has patents onadministering the protein through inhalation for emphysema andother pulmonary diseases, such as cystic fibrosis and asthma. Thecompany also has patents covering use of other serine proteaseinhibitors as anti-inflammatory drugs.

In the treatment of cystic fibrosis, the alpha 1-protease inhibitorreduces in the lungs excess elastase, which causes several problems,including a buildup of mucus.

To resolve the production problem, Lezdey said he has talked withGenzyme Transgenics Corp., of Framingham, Mass., and PPLTherapeutics plc, of Edinburgh, Scotland _ both of which havedeveloped transgenic animals whose milk can produce humanproteins. Genzyme uses goats and PPL sheep.

Lezdey was to meet with PPL officials in Scotland last week todiscuss a collaboration. PPL has raised a production flock of sheep toproduce alpha 1-antitrypsin and also is targeting the drug fortreatment of cystic fibrosis. Protease Sciences, Lezdey said, alreadyis evaluating the natural protease inhibitor for the disease in Phase IItrials.

"We've been studying protease inhibitors since 1984," Lezdey said."We have 14 patents in the U.S. and Europe on the use of proteaseinhibitors, mostly in the serine protease series." n

-- Charles Craig

(c) 1997 American Health Consultants. All rights reserved.

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