In the early 1980s, Phillips Petroleum had contracted with the Salk Institute Biotechnology / Industrial Associate INC. (SIBIA) to develop Pichia pastoris (found also under the Komagataella pastoris designation).

As a heterologous gene expression system, researchers at SIBIA isolated the AOX1 gene and its promoter and developed vectors, strains and methods for molecular genetic manipulation of P. pastoris.

According to USPTO (United States Patent and Trademark Office), Phillips Petroleum Company filed more that 4975 patents and 61 of them are dealing with P. pastoris. In 1993, Phillips Petroleum sold all these patents on P. pastoris expression system to Research Corporation Technologies (RCT), the current patent holder. In addition, Phillips Petroleum licensed Invitrogen to sell components of the system to researchers world wide, and this arrangement continues under RCT. Thus, the last Phillips Petroleum Company patent was filed more that 20 years ago meaning that the P. pastoris expression system as it was developed by Phillips Petroleum Company is now in public domain.

However, RCT and VTU Technology (now Validogen) continues to develop and patent the P. pastoris expression system. Thus according to USPTO, Research Corporation Technologies filed more that 345 patents and 16 of them are dealing with Pichia pastoris.

Our “freedom to operate” studies were focused on the pPICK9K vector and the Pichia pastoris GS115 and KM71 strains. From our research, it appears that none of the elements of the pPIC9K vector are individually protected alone or in combination with a patent or patent application in force, at least in Europe. Regarding the strains, the coast is clear as all patents have expired and are now in public domain.

However, as previously observed for T7 promoter system, the situation is more complex than we might initially have thought. You may read on the Life Technologies site: « You may not use the Expression Vectors for any commercial purpose without a license for such purpose from Research Corporation Technologies, Inc., Tucson, Arizona.  ».

So once again, we are facing an issue connected to a contractual aspect but that can be easily circumvented with some relatively minor investments (in our opinion). Have a look, but we are pretty sure that the production strains GS115 and KM71 are available from public microbiology collections. Regarding the expression vector, a pPICK9K like vector should be synthesized easily de novo from sequences available. There is a solution for every problem!

We will be very pleased to get your opinion on the subject. So feel free to react!