Advanced Cell Diagnostics, Inc v Molecular Instruments, Inc

For obviousness, the skilled person is identified by the established field in which the patent’s problem arises. In nucleic-acid detection, that field may encompass both in-vitro and in-situ techniques. A claimed prejudice must form part of the common general knowledge and must show more than the need for empirical optimisation.

For claim construction, “non-overlapping” regions need not be completely non-overlapping where the claimed purpose remains achievable through two stable duplexes. A variant may also fall within the scope of protection by equivalence where it achieves substantially the same result in substantially the same way and the patent does not indicate that literal compliance is essential.

Accessory liability requires assistance, a common design, and commission of the tort. Tailored troubleshooting may satisfy that test.

Advanced Cell Diagnostics alleged that Molecular Instruments infringed European Patent (UK) Nos 1 910 572 B1 and 2 500 439 B1, concerning in-situ detection of nucleic acids using capture probes, label probes and optional amplification. Molecular Instruments denied infringement and counterclaimed for revocation.

The principal issues were claim construction, infringement by equivalence, joint tortfeasorship, anticipation, obviousness, insufficiency and added matter. The obviousness case relied principally on Collins, read with Kern, and alternatively on Player. The court also considered whether the use of branched-DNA amplification in situ, and the use of cruciform probes, formed part of the common general knowledge.

1. Skilled person and common general knowledge. The skilled person was involved in nucleic-acid detection generally, including but not limited to in-situ hybridisation. The alleged prejudice against transferring in-vitro techniques to in-situ use was not established. The evidence showed an empirical need for optimisation, but not a lack of reasonable prospects of success. Player established that branched-DNA amplification had successfully been used in situ and formed part of the common general knowledge. Cruciform probes did not.
2. Infringement. The “non-overlapping” requirement concerned whether each L section could form a stable duplex with a non-overlapping region of the label probe. It did not require complete absence of overlap in every possible binding region. Molecular Instruments’ products achieved the relevant benefit of two stable duplexes. The label probe need not be detectable alone or be a terminating molecule. The hairpin arrangement also satisfied the broad definition of “amplifier”.
3. Equivalence. Alternatively, the variant achieved substantially the same result in substantially the same way. Nothing in the specification indicated that strict literal compliance with complete non-overlap or direct attachment was essential.
4. Joint liability. Mere provision of standard instructions would have been insufficient. Tailored troubleshooting, involving advice on the parameters required to make the products work, constituted assistance pursuant to a common design. Molecular Instruments would therefore have been jointly liable for infringing use of EP572 had it been valid. EP439 was not infringed on importation because the imported kits did not contain the required permeabilising reagent.
5. Validity and disposition. Collins and Kern did not clearly and unmistakably anticipate the claims, whether separately or together. However, their combination made the claimed subject matter obvious, particularly because the skilled person had motivation to try it and reasonable, indeed good, prospects of success. The attack over Player failed because cruciform probes were not common general knowledge and Player gave no pointer to them. The patents were invalid for obviousness. The insufficiency and added-matter issues did not require separate determination.