Does Cellomics Deserve Honors for HCS Patent Primacy, or Did Jeff Price Beat It to the Punch?

These days, few will dispute that Fisher subsidiary Cellomics maintains the strongest intellectual property position in high-content screening, and most will agree that it was the first company to market the concept of high-content automated microscopy for the purpose of drug discovery.

Yet some industry insiders believe that the HCS patent estate on which Cellomics' business is built may not be as cut and dried as previously thought. In fact, some believe that microscopy innovator Jeff Price, who developed an automated image cytometer in the early 1990s that eventually became the flagship of startup biotech Q3DM, may have been the first to patent many of the concepts that underlie modern HCS.

Because of this, it may only be a matter of time before someone questions the validity of Cellomics' estate — an inquiry that could have significant implications for most HCS tool vendors and users, as Cellomics currently licenses its core patent portfolio to several vendors.

These issues may now be especially important since Q3DM's portfolio is again up for sale again after Beckman Coulter, which acquired the core assets in late 2003, discontinued the product line late last year.

"The IP that goes along with [high-content screening] — there are some IP battles that might pop up one of these days," said one cell biologist familiar with both companies' technologies, but who asked to remain anonymous because of his business relationships with Cellomics and Q3DM. "Who has the first IP? Is it Cellomics and [Cellomics founder] Lans Taylor? Was it Jeff Price at Q3DM, and what overlaps? I don't know."

It appears that Cellomics essentially patented the concept of HCS when it was awarded US Patent No. 5,989,835, "System for cell-based screening," in November 1999. It subsequently won additional patents over the next several years, many of which were extensions of the original IP. Currently, there are 17 patents in the US Patent Database on which Cellomics is the assignee.

These patents comprise Cellomics core HCS patent portfolio, although it is unclear whether the company has additional patents in that portfolio licensed from individual inventors. Cellomics' Taylor is not listed as inventor on any other HCS-related patents prior to the ''835 patent.

In August 1996, Jeff Price was awarded US Patent No. 5,548,661, "Operator-independent image cytometer." This patent essentially describes a system and method for making quantitative measurements from live cells. In fact, Cellomics references this IP in its '835 patent.

Price — either alone, through his startup Q3DM, or through the University of California, San Diego, where he is a professor — went on to win several additional related patents, a few of which were also awarded before Cellomics won its '835 patent (see accompanying table for complete patent information).

"Q3DM's patent portfolio probably hasn't been marketed very well, but if you look at the number of sort of fundamental patents — that is, ones that are different from each other, rather than continuations of previous patents — then I think we have the largest and most diverse set of patents on fundamental image cytometry and screening methods," Price told CBA News this week.

The question remains, however, about whether specific claims in Cellomics' patents overlap at all with specific claims in Price's. At first glance, it appears that Price's patents are more technology- and methods-focused, while Cellomics' patents may be more application-focused. Therefore, even if Price was the first to describe the underlying technology and methods, it may be that Cellomics was the first to be awarded patents describing particular drug-screening applications of automated microscopy, or what it dubbed high-content screening.

"My early work was directed at general-purpose image cytometry, which, at its most fundamental level, is just measurement of cells from images," Price said. "The first patent … didn't talk much about the market that it would go into, but I envisioned it going into all markets — much the way flow cytometry [did]. Flow cytometry is a fundamental platform that's used in clinical applications, drug-discovery applications, and academic basic research applications.

"Probably my first motivation was drug-screening applications," he added. "I wanted to develop a system that would allow you to do drug-sensitivity assays on tumor biopsies, basically. So the idea of putting something in a plate and looking at a response of a drug was one of the early motivators for doing this."

The fact that Cellomics referenced Price's '661 patent in its '835 patent is an important point to note, according to Jonathan Fritz, a patent attorney specializing in biotechnology with law firm Whyte Hirschboeck Dudek.

"This is pertinent information, because there is a presumption in patent law that if a reference is cited on the face of a patent, then that patent examiner viewed that in detail and, in their professional judgment, believed that it did not cause a problem for patentability of that later technology," Fritz said.

In addition, Fritz said that "the claims really are the most important part of the patent. They identify what is protectable and what you can exclude others from practicing. It is also important to note that the patent holder or the inventor is considered to be their own lexicographer, which means they can give specific definitions to terms.

"The important thing to realize, though, is that the patent does not give you an exclusive right to practice the invention, but it allows you to assert it against another party and prevent them from using or selling what is explained in the patent," he added.

Marketing Savvy

One thing is not in question: Cellomics was certainly the first to market the concept of HCS, which may have gone a long way toward at least strengthening its IP position.

"It's a fact that the HCS phrase was coined by Lans Taylor," Price said. "I believe that they entered the field and marketed the idea of automated imaging for high-content screening, and did an excellent job of that. Perhaps they were the first to do that.

"But the idea of screening for drugs and doing things like that was well understood by others before they entered the market; it's just that they got there and marketed it first," Price added. "Sorting out the details of the patents is a lot of work. I don't know that anybody has sat down and looked at all the patents and developed a matrix and figured out who owns what. It's not an easy thing to do."

Cellomics has also certainly convinced lawyers from competing high-content screening vendors that it has the strongest IP position. GE Healthcare (see CBA News, 6/29/2004), BD Biosciences (11/16/2004), and Evotec Technologies (2/3/2006) have all licensed Cellomics' core patent portfolio in the last few years to ensure that their customers can freely practice HCS methods on their instrumentation platforms.

In addition, these patent issues may now be especially important in light of the fact that Q3DM's patent portfolio is now up for sale again. Companies considering purchasing the Q3DM portfolio may want to examine it closely and consider what it includes.

"I would think that all the instrument manufacturers would potentially be interested in both the IP and the instrument," Price said. "Because [Cellomics has] … a very strong patent position, it offers the opportunity to counter the perception, whether or not it's true, that Cellomics kind of owns the IP that gives them the right to practice HCS."

Some experts, including the cell biologist mentioned earlier in this article, feel that Cellomics is actually a prime candidate to license the technology from Q3DM, if not temporarily take over the service contract from Beckman Coulter. "I thought Cellomics would probably gobble it up just to have both IP portfolios. That way no one will ever have a fight," the cell biologist said.

Cellomics and parent company Fisher Biosciences did not respond to requests for comment in time for this publication.

"It's almost impossible to say whether a patent should or should not have been awarded," Price said. "Only a judge and a court can decide that in the end," he added. "Maybe Cellomics will go there some day, but I don't think Cellomics or anyone else wants to. They just want to understand how best to practice the business and make HCS take off."

— Ben Butkus ([email protected])