The PTAB recently handed down two consequential inter partes review decisions that emphasize the importance of the stated function for an agent specified in the claims. In particular, the PTAB held that glucose, which is a component of an anticoagulant used in the prior art, is not “an agent that inhibits cells lysis” simply because it can maintain isotonicity and provide a nutrient source to cells.

Illumina (“Petitioner”) filed two petitions to institute inter partes review[1] of claims of U.S. Patent Nos. 7,332,277 (’277 patent) and 7,727,720 (’720 patent) granted to Ravgen Inc. (“Patent Owner”). The ’277 patent is directed to, e.g., noninvasive methods for sampling cell-free fetal DNA (cffDNA) and detecting genetic disorders in a fetus. The disputed claims relate to analyzing cffDNA, which is present in maternal plasma and serum together with maternal DNA, through the use of cell lysis inhibitors in the isolation procedure. According to the patents, maternal blood contains vastly more maternal cells than fetal cells, and by reducing the lysis of maternal cells, there is a relative increase in the percentage of cffDNA relative to maternal DNA in the sample. Independent claim 55 of the ’277 patent is illustrative:

55. A method comprising determining the sequence of a locus of interest on free fetal DNA isolated from a sample obtained from a pregnant female, wherein said sample comprises free fetal DNA and an agent that inhibits lysis of cells, if cells are present, wherein said agent is selected from the group consisting of membrane stabilizer, cross-linker, and cell lysis inhibitor.

Petitioner asserted that the claims reciting an agent that inhibits lysis of cells were unpatentable as anticipated by the Landes reference.[2] According to Petitioner, Landes discloses collecting maternal blood in tubes containing acid citrate dextrose (ACD), which necessarily exposes the blood to dextrose (aka glucose), an agent that inhibits cell lysis. Patent Owner responded, arguing that Landes uses ACD only as an anticoagulant and that the reference does not disclose the functionality of the glucose.

Based on the ’277 and ’720 patents and their prosecution history, the PTAB construed the term “an agent that inhibits lysis of cells” to exclude anticoagulant chelators such as ACD. However, the Board noted that ACD also includes a pH buffer (citric acid), glucose (for isotonicity) and a chelator (sodium citrate). Thus, the issues presented to the PTAB were 1) whether the exclusion of anticoagulant chelators from the meaning of an “agent that inhibits lysis of cells” operates to exclude the glucose introduced through ACD and 2) whether Petitioner established, by a preponderance of the evidence, that the glucose in ACD actually inhibits lysis of cells in Landes’ method.

Regarding the first issue, the PTAB stated that “it would seem incongruous that a blood sample to which is added a substance listed as an ‘agent’ in the Specification would be excluded from meeting the claims simply because that substance (glucose) was introduced to the sample as one component of a solution also comprising an anticoagulant chelator (sodium citrate).”[3] For this reason, the PTAB found that Patent Owner’s disavowal of the anticoagulant component of ACD as an agent that inhibits cell lysis did not extend to the glucose component of ACD.

Regarding the second issue, while the PTAB found that the glucose component in ACD can maintain isotonicity within cells – which can inhibit cell lysis – failure to maintain isotonicity does not necessarily result in lysis. Thus, the PTAB found that “Petitioner has shown, at best, that it is possible for glucose to help inhibit cell lysis by reason of isotonicity and providing a nutrient source. But such possibilities are not enough for Petitioner to prevail on its challenge to the claims as anticipated by Landes.”[4] As a result, the PTAB found that Petitioner did not meet its burden to show that the glucose component of ACD in the Landes method is “an agent that inhibits cell lysis,” and thus, the Petitioner could not establish that the claims were anticipated by Landes.

An agent within a biological or chemical mixture may be capable of exerting multiple, albeit secondary, effects. However, these PTAB decisions make clear that the mere possibility that an agent could have a particular effect as a corollary will not necessarily be conclusive in a determination of whether such an agent would have actually produced the stated effect. When evaluating a prior art reference’s disclosure, applicants should evaluate the effects that a disclosed agent will necessarily bring about when determining whether an agent will be deemed to produce a stated effect.

[1] Illumina, Inc. v. Ravgen, Inc., IPR2021-01272 (Jan. 25, 2023); Illumina, Inc. v. Ravgen, Inc., IPR2021-01271 (Jan. 25, 2023).

[2] WO2003062441.

[3] Illumina, Inc. v. Ravgen, Inc., IPR2021-01272, 35 (Jan. 25, 2023).

[4] Id. at 45.

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