Questions.

The tyramide amplification system (for showing peroxidase activity at sites of antibody binding or in situ nucleic acid hybridization) is sold commercially in patented kits. The principal reagent (tyramine coupled to biotin or various fluorescent compounds) can be synthesized in the laboratory, following quite simple techniques published in the Journal of Histochemistry and Cytochemistry, and elsewhere. Is there a risk of being sued by the firm that sells the kits, for following a published method to make a reagent in one's own lab?

Answer.

[There was some rather heated discussion on the HistoNet listserver in August 1998, involving various individuals and one of the patent holders. It centered around the unavailability of individual reagents and a claim that a company might even sue individuals for daring to encourage others to carry out the published syntheses. ]

Linda Margraf relayed this to HistoNet. It was from Mark Bobrow. He is an author of some of the published procedures and also one of patent holders.

[Beginning of M. Bobrow's message]

The patent system goes back over five hundred years when, in Britain, one could obtain a patent granted by the King. In the U.S., the first patent commission was headed by George Washington, who personally signed every patent granted during his tenure.

A patent is a right granted by the government. Article I, Section 8 of the United States Constitution states, "The Congress shall have the power to promote the progress of science and useful arts, by securing for limited times to authors and inventors the exclusive right to their respective writings and discoveries."

It is often misunderstood that the purpose of the patent system is, as stated in the Constitution, *to promote the progress of science and useful arts.* The concept is that by disclosing (and not keeping a secret) an invention, technological innovation will continue. In the process of obtaining a patent, the inventor must disclose the invention and the best mode of practising it (in other words, they can't hold anything back, or the patent will not be valid).

In return for disclosing the invention, the government grants the patent holder the right to exclude others from making, using, or selling the invention. Currently, these rights extend for 20 years from the filing date. After the term expires, everyone is free to make, use or sell the product or method which was disclosed in the patent.

The right to exclude others from practising the invention applies to everyone, including academic investigators. In terms of being able to use what is in the published literature, U.S. patents are published after they issue; in Europe the applications are published 18 months after filing. So, even though patented products and methods are in the published literature, using them without proper authorization from the patent holder is not legal.

There have been some questions as to the extent of coverage of the tyramide amplification patents. In the spirit of simplification, four basic concepts are claimed. They are the enzyme substrates (e.g., tyramides), the product of the enzyme-substrate reaction, the method of catalyzed reporter deposition (e.g., detecting an analyte with a reporter enzyme using the deposition of a reporter), and assays using the method of catalyzed reporter deposition. If you wish, you may look it up yourselves. One of the patents is U.S. Patent 5,731,158, Catalyzed Reporter Deposition. As an added note, the readers should be reminded that patents are written in a style that is a hybrid of law and science (perhaps a suspension is more descriptive).

Patent information is available on the internet.  Here is a list of some sites:

http://www.uspto.gov/    This is the US Patent Office site.  You can search for patents here, and get some information about patents in general.  Later this year, or early next year, the full text and images of patents will be available.

http://patent.womplex.ibm.com/searchhelp.html   This is an IBM site where one can search for patents and view the entire document (it tends to be slow though).

http://www-sul.stanford.edu/depts/swain/patent/patgeninf.html General patent information.

[End of reported communication from M. Bobrow]