New patent suits address groundbreaking techniques.

In IBO's last article that described the state of things litiginous in the instrument business, patent infringement suits among life science companies were the center of attention (see IBO 9/15/05). This year is no different.

It's little surprise that DNA microarrays are at the center of a new suit, and that Affymetrix is involved. Agilent is appealing the June 28, 2006 decision of the US Patent and Trademark Office's (USPTO) Board of Patent Appeals and Interferences (BPAI). In its ruling on the interference--an instance in patent law when two patents claim the same invention--the BPAI found in favor of Affymetrix and nullified two claims (regarding the mechanism by which a fluid between two substrates is mixed) from the patent, which had been exclusively licensed to Agilent. Among Agilent's claims are that the language of the application for the patent, which is exclusively licensed to Affymetrix, "literally cop[ies] the claims" of Agilent's patent, that Affymetrix failed to provide an "adequate written description" of its particular application and that the BPAI erroneously determined that Affymetrix's claims are patentable.

Although Bio-Rad Laboratories settled suits with Applied Biosystems earlier this year (see IBO 2/15/06), it continues to defend itself in other patent cases, both new and old. Last year's legal article discussed Invitrogen's case against Bio-Rad involving patent infringement in the area of gel electrophoresis. The Markman hearing for the case will be held on January 8, 2007.

This is not, however, the only case between the two companies. Invitrogen has recently filed another suit against Bio-Rad for patent infringement. Infringing products include Bio-Rad's kits that optimize PCR assays, such as the iQ Multiplex Powermix, the iTaq Supermix with ROX and the iTaq SYBR Green Supermix with ROX. Bio-Rad is also a defendant, through its purchase of MJ Research (see IBO 8/31/ 04), in a patent infringement suit brought by Stratagene. Stratagene alleges that the companies infringed two thermal cycler patents by selling products such as the iCycler and the DNA Engine, as well as two patents for irradiating biological specimens by selling the GS Gene Linker UV chamber, among other products. Finally, DuPont has accused Bio-Rad of patent infringement, claiming that Bio-Rad's DNA Engine Opticon 2 Real-Time PCR Detection System and MiniOpticon Real-Time PCR Detection System infringe a patent for measuring fluorescence.

Invitrogen is also involved in patent suits with other companies, including an extended conflict with Clontech over Clontech's SuperScript and PowerScript products. On December 31, 1996, Invitrogen sued Clontech, alleging that Clontech had infringed its US Patent No. 5,244,797 ("Cloned Genes Encoding Reverse Transcriptase Lacking RNase H Activity"). US Patent Nos. 5,668,005 (granted in 1997) and 6,063,608 (granted in 2000), both with the same description, were added to the suit as it continued. The legal battle has continued for almost 10 years, but an end is in sight:, a three-week trial is scheduled for May 1, 2007.

Invitrogen is also on the other side of the courtroom. Genetic Applications has filed a claim of patent infringement against Invitrogen. The claim centers on the PLUS Reagent for enhancing transfection, initially produced and distributed by Life Technologies, which was purchased by Invitrogen in 2000 (see IBO 7/15/00). Genetic Applications is located in San Diego, California, and produces transfection reagents, kits for evaluating cellular transfection and cell proliferation assays.

DNA sequencing patents are once again under dispute (see IBO 2/29/04). Enzo Biochem filed a suit against Applera in 2004, claiming the infringement of six patents: US Patent No. 5,328,824 ("Methods of Using Labeled Nucleotides"), US Patent No. 5,449,767 ("Modified Polynucleotides and Methods of Preparing Same"), US Patent No. 5,476,928 ("Modified Nucleotides and Polynucleotides and Complexes Formed Therefrom"), US Patent No. 4,711,955 ("Modified Nucleotides and Methods of Preparing and Using Same"), US Patent No. 5,082,830 ("End Labeled Nudeotide Probe") and US Patent No. 4,994,373 ("Method and Structures Employing Chemically-Labeled Polynucleotide Probes"). The products in question are Applied Biosystems' DNA sequencing products and systems that use labeled nucleotides, such as its Selective Amplification Primers. Enzo announced that on October 12, the Federal Judge overseeing the case delivered a Markman ruling that supported Enzo's position on several patent claim terms.

More recently, in a separate case, the USPTO has declared a patent interference between Enzo Life Sciences' DNA sequencing patent application and a patent held by the California Institute of Technology, exclusively licensed to Applied Biosystems. Enzo has been declared the senior party in the interference because its application was filed earlier. Caltech, as the junior party in the interference, is required to prove that its invention of the technology predates Enzo's invention. According to The New York Times, patent law was reformulated in the 1990s to do away with "submarine patents," patents that are published and granted long after they have been applied for. However, Enzo's patent application dates back to 1982, allegedly a few months before researchers at Caltech arrived at their invention, and is not subject to the reformulated law. Caltech's patent was granted in 1998 as US Patent No. 5,821,058 ("Automated DNA sequencing technique").

The last case is a departure from the legal landscape of the life sciences segment. It was brought by Apogee Scientific against Thermo Electron. Apogee claims that Thermo's Mercury Freedom system, designed for the monitoring of mercury in gas stacks, infringes its existing patent. Apogee, based in Englewood, Colorado, produces mercury detection systems and leak detection systems.

Selected US Patent Infringement Cases Among Instrument Companies

Plaintiff            Defendant                   Patent No.

Agilent              Affymetrix                  US Patent No.
                                                 6,513,968

Apogee Scientific    Thermo Electron             US Patent No.
                                                 6,736,883

DuPont               Bio-Rad Laboratories        US Patent No.
                                                 6,852,986

Genetic              Invitrogen                  US Patent No.
Applications                                     5,670,347

Invitrogen           Bio-Rad Laboratories        US Patent No.
                                                 5,945,313

Stratagene           Bio-Rad Laboratories,       US Patent No.
                     MJ Geneworks, MJ            6,054,263
                     Research                    US Patent No.
                                                 5,779,981

                                                 US Patent No.
                                                 5,288,647

                                                 US Patent No.
                                                 5,395,591

Plaintiff            Patent Tide                 Case Filed

Agilent              Apparatus and Method        9/26/2006
                     for Mixing a Film of
                     Fluid

Apogee Scientific    Particulate Separation      11/13/2006
                     System for Mercury
                     Analysis

DuPont               Fluorometer with Low        5/12/2006
                     Heat-Generating Light
                     Source

Genetic              Peptide-Mediated            10/12/2006
Applications         Gene Transfer

Invitrogen           Process for Controlling     11/6/2006
                     Contamination of
                     Nucleic Acid
                     Amplification Reactions

Stratagene           Thermal Cycler              11/20/2006
                     Including a
                     Temperature Gradient
                     Block

                     Method of Irradiating
                     Biological Specimens

                     Apparatus of Irradiating
                     Biological Specimens