Like most other high-school students, I struggled with SAT vocabulary.  Let’s face it, even voracious readers rarely encounter “susurration,” “verisimilitude,” or “eleemosynary.”  Apparently, however, no 10th grader could hope to enter college without understanding them.  I therefore cringed to read “conflate” in the Federal Circuit’s decision in Intelligent Bio-Systems v. Illumina Cambridge (decided May 9, 2016).  According to Webster’s (not so) New Collegiate Dictionary (1977), “conflate” can mean “to bring together” or “fuse.”  However, it can also mean “to confuse.”  Yet another meaning is “to combine (as two readings of a text) into a composite whole.”  Confused, I turned to Black’s Law Dictionary, Sixth Edition (1990), but alas, “conflate” appears to have no special meaning in the law.

Illumina owns U.S. Pat. No. 7,566,537, which claims a method of labeling nucleosides in a DNA strand.  The invention relates to the well-known “sequencing by synthesis” or “SBS” method, which relies on stepwise protection and deprotection of a 3’ hydroxyl group of a sugar moiety.  The prior art (WO 91/06698, “Tsien” and U.S. 6,664,079, “Ju”) had taught the importance of using a variety of different protecting groups and the need for an essentially quantitative yield in the deprotection step.  Illumina’s claimed invention differed in using an azido protecting group (e.g., an azidomethyl group) in the SBS method.  Claim 1 of the ‘537 patent, with the court’s emphasis, appears below:

1. A method of labeling a nucleic acid molecule, the method comprising incorporating into the nucleic acid molecule a nucleotide or nucleoside molecule, wherein the nucleotide or nucleoside molecule has a base that is linked to a detectable label via a cleavable linker and the nucleotide or nucleoside molecule has a ribose or deoxyribose sugar moiety, wherein the ribose or deoxyribose sugar moiety comprises a protecting group attached via the 2′ or 3′ oxygen atom, and said protecting group can be modified or removed to expose a 3′ OH group and the protecting group comprisesan azido group.

Intelligent Bio-Systems (“IBS”) challenged claim 1 as obvious under Section 103, and the Board granted a request to institute inter partes review.  IBS argued that the claim was obvious from the combined teachings of Tsien or Ju with Zavgorodny (Tetrahedron Lett. 7593 (1991)), which described the use of the azidomethyl protecting group.  Specifically, IBS separately argued that there was motivation to combine the references (a skilled person would have considered protecting groups other than those used by Tsien or Ju) and that the skilled person would have had a reasonable expectation of success from using the combined teachings.  Illumina countered that Tsien requires “quantitative and rapid removal” of the protecting group, and the skilled person would have expected much lower removal efficiency from Zavgorodny.  Illumina also cited Loubinoux (Tetrahedron 44 (1988) 6055), which reported 60-80% removal efficiency for the azidomethyl protecting group using triphenylphosphine.

Although the Board agreed with IBS that the azidomethyl protecting group is suitable for protecting the 3’ hydroxyl position of nucleosides and is cleavable under specific and mild conditions, it ultimately ruled in Illumina’s favor; according to the Board, IBS had not shown “by a preponderance of the evidence, that an ordinary artisan would have considered it obvious to use Zavgorodny’s azidomethyl group as the 3’ hydroxyl protecting group in Tsien’s process.”  The Board emphasized the requirement of a reasonable expectation of success, and especially the requirement of quantitative removal of the protecting group taught by Tsien.

The Federal Circuit affirmed the Board decision, finding that substantial evidence supported it.  However, the court criticized the Board’s “precise legal underpinnings” as being “difficult to discern.”  Did the Board correctly analyze the facts under the requisite two-pronged approach (motive to combine and reasonable expectation of success)?  “The Board’s opinion conflates these legal issues,” wrote Judge O’Malley, “but its ultimate conclusion is clear.  IBS failed to demonstrate that the challenged claims were obvious under the prior art at issue.”

IBS had argued that the patent claims had no requirement of quantitative deprotection, so the Board erred in imposing such a requirement through the “reasonable expectation of success.”  Judge O’Malley agreed with IBS on this point and wrote (p. 12):

Accordingly, it is of no moment that Zavgorodny’s protecting group would not be removed quantitatively in Tsien or Ju’s sequencing method—removal is simply not required by the claim of the ‘537 patent.  The Board seemed to believe that the “reasonable expectation of success” inquiry looked to whether one would reasonably expect the prior art references to operate as those references intended once combined.  That is not the correct inquiry—one must have a motivation to combine accompanied by a reasonable expectation of achieving what is claimed in the patent-at issue.  The Board’s reliance on the absence of a reasonable expectation of success was, thus, improper.

Never mind the Board’s “conflation” of “two different legal concepts,” the court opined; IBS failed to demonstrate that both prongs of the test were satisfied:  “Despite the loose language employed by the Board, its factual findings support its conclusion that the claims are not invalid” (p. 13).

The court stressed that there could be no motivation to combine the references absent any way to satisfy the requirement of quantitative deblocking from a combination of Tsien (or Ju) with Zavgorodny.  Thus, it was the lack of a proper motivation to combine the teachings rather than the lack of a reasonable expectation of success that doomed IBS’s argument.  “IBS made a clear argument as to why a person of ordinary skill would be motivated to combine the prior art references at issue and Illumina demonstrated the error in that argument, which the Board credited” (p. 15).

That the Board focused on the “reasonable expectation of success” rather than the “motivation to combine” on these facts should surprise most practitioners less than it did this Federal Circuit panel.  In my own experience, most Office actions waste little ink—seldom more than a sentence—asserting the motivation to combine.  Often, the motivation is simply that the references “are in the same field of endeavor,” “both relate to coatings,” or similar language.  Applicant is left to argue or demonstrate otherwise.  A garden variety Office action on these facts might conclude that there was adequate motivation to combine Tsien and Zavgorodny “because both references relate to protection of a 3’ hydroxyl position on a sugar moiety.”  According to this Federal Circuit panel, such a position taken by the Office would be inadequate and subject to challenge.  However, at least within the USPTO, I believe most applicants would lose on such a challenge.  Hereafter, an applicant might cite this opinion to urge that, under her set of facts, the “motivation to combine” is lacking.

The Board’s bottom-line focus on the outcome of combining the teachings may have “conflated” legal issues, but Illumina’s argument that even the combined teachings failed to provide a reasonable expectation of success was sensible and persuaded the Board.  Although the Board treated the motivation to combine as a low hurdle, this is consistent with current USPTO practice if not the law.

I don’t know about you, but this case leaves me dazed and conflated.  And I’m glad SAT days are behind me; I simply don’t remember what “fustigate” or “contumely” means without Googling it.   I just may cite Intelligent Bio-Systems v. Illumina Cambridge to the next examiner that presents the usual short-shrift “motivation to combine” argument.  If you try it, too, let me know how it works for you!

– Jonathan Schuchardt, Ph.D, JD

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