Illumina Inc v. Trustees Of Columbia University In City Of New York

1. Case Identification

• Case #: IPR2018-00291
• Patent #: 9,718,852
• Filed: December 8, 2017
• Petitioner(s): Illumina, Inc.
• Patent Owner(s): The Trustees of Columbia University in the City of New York
• Challenged Claims: 1

2. Patent Overview

• Title: Deoxyribonucleotide Analogues for DNA Sequencing
• Brief Description: The '852 patent discloses and claims a specific adenine deoxyribonucleotide analogue for use in sequencing-by-synthesis methods. The analogue is defined by a chemical structure featuring a 7-deaza-adenine base, a "small, chemically cleavable" 3'-OH capping group (R), and a detectable fluorescent tag attached to the base via a chemically cleavable linker (Y).

3. Grounds for Unpatentability

Ground 1: Obviousness over Tsien in view of Prober - Claim 1 is obvious over Tsien in view of Prober.

• Prior Art Relied Upon: Tsien (WO 91/06678) and Prober (a 1987 journal article in Science).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Claim 1 is merely a structural depiction of a nucleotide previously held unpatentable by the Board and affirmed by the Federal Circuit in a proceeding involving a related patent. Tsien allegedly taught a DNA sequencing method using nucleotide analogues with a 3'-OH blocking group and a fluorescent tag attached to the base via a cleavable linker. Petitioner asserted Tsien’s disclosed 3'-O-allyl group meets all functional requirements for the claimed capping group (R), including being small, chemically cleavable, stable, and lacking a ketone, methoxy, or ester group. Prober was cited for teaching the use of 7-substituted deaza-adenine bases with fluorescent labels attached at the 7-position, which directly corresponds to the claimed nucleobase structure.
  • Motivation to Combine: Petitioner contended that Tsien explicitly referenced Prober’s method for base labeling. This was argued to provide a direct and express motivation for a Person of Ordinary Skill in the Art (POSA) to incorporate Prober's preferred 7-deaza-adenine base into the nucleotide analogues of Tsien's sequencing system.
  • Expectation of Success: The petition noted that both the Board and the Federal Circuit had previously found that a POSA would have had a reasonable expectation of success in making this combination. The synthetic steps required were considered to be well within the level of ordinary skill.

Ground 2: Obviousness over Dower in view of Prober and Metzker - Claim 1 is obvious over Dower in view of Prober and Metzker.

• Prior Art Relied Upon: Dower (Patent 5,547,839), Prober (a 1987 journal article in Science), and Metzker (a 1994 journal article in Nucleic Acids Research).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner asserted this combination teaches all elements of the claimed nucleotide. Dower was alleged to disclose a sequencing method using nucleotide analogues with a "small," removable 3'-OH blocking group and a cleavably linked fluorescent label on the base. Prober, which Dower repeatedly cited, was argued to teach the specific 7-substituted deaza-adenine base recited in the claim. Metzker was cited for disclosing 3'-ether capping groups, specifically the 3'-O-allyl group, which are compatible with polymerase incorporation and chemically cleavable. Petitioner contended Metzker’s group satisfies all functional and negative limitations for the claimed R group (e.g., it is not an ester or methoxy group).
  • Motivation to Combine: A POSA would combine Dower and Prober because Dower expressly directed a skilled artisan to Prober for suitable labeled nucleotides. A POSA would have been motivated to use Metzker’s proven 3'-O-allyl capping group to implement Dower’s requirement for a “small” blocking group that is both compatible with polymerase and chemically removable, as Metzker demonstrated these advantageous properties.
  • Expectation of Success: Petitioner argued a POSA would have reasonably expected success in creating the claimed analogue. The necessary synthetic procedures for each component—the 7-deaza-adenine base from Prober, the 3'-O-allyl capping group from Metzker, and the cleavable linker chemistry—were all well-established in the art at the time.

4. Arguments Regarding Discretionary Denial

• Petitioner argued against discretionary denial under 35 U.S.C. §325(d), asserting that the Patent Owner engaged in improper prosecution tactics. The petition contended that the Patent Owner re-litigated the patentability of subject matter from claims previously found unpatentable by the Board in a related patent ('869 patent). Petitioner alleged the Patent Owner did so by filing a terminal disclaimer over the invalidated parent patent claims without substantively distinguishing the new claim and by misleading the Examiner on the inventiveness of a "small" capping group, a feature the Board had already found to be unpatentable. Petitioner also asserted that the petition presented significant new evidence and arguments not considered by the Examiner, including expert testimony clarifying that Tsien’s disclosed 3’-O-allyl capping group was, in fact, "small."

5. Relief Requested

• Petitioner requests institution of an inter partes review and cancellation of Claim 1 of Patent 9,718,852 as unpatentable.