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

1. Case Identification

• Case #: IPR2018-00385
• Patent #: 9,725,480
• Filed: December 22, 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 ’480 patent discloses a specific guanine deoxyribonucleotide analogue for use in sequencing-by-synthesis methods. The claimed analogue features a removable 3'-OH capping group and a detectable fluorescent tag attached to the 7-position of a deaza-guanine base via a chemically cleavable linker.

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 (Science, 238:336-341 (1987)).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Tsien disclosed the core elements of the claimed invention: a nucleotide analogue for DNA sequencing with a removable 3'-OH blocking group and a tag attached to the nucleobase via a cleavable linker. Specifically, Tsien taught a 3'-O-allyl group, which Petitioner asserted meets the claim’s requirement for a “small, chemically cleavable” capping group. For the base-labeling component, Tsien expressly cited Prober, which disclosed attaching a fluorescent label via a linker to the 7-position of a deaza-guanine base—the exact structure depicted in claim 1.
  • Motivation to Combine: Petitioner contended that Tsien’s explicit and repeated citation to Prober provided a clear motivation for a Person of Ordinary Skill in the Art (POSA) to combine the references. A POSA seeking to implement Tsien’s sequencing method would have been directly guided to use Prober's proven method of attaching fluorescent labels to a deaza-guanine base, as it was a well-known and advantageous technique at the time.
  • Expectation of Success: A POSA would have had a reasonable expectation of success in making the proposed combination. Petitioner noted that the Board and Federal Circuit had previously found substantially similar claims in Columbia’s parent patent (’869 patent) to be obvious over the same Tsien and Prober combination. The synthetic steps required were considered within the ordinary skill in the art.
  • Key Aspects: Petitioner emphasized that the structure depicted in claim 1 is merely a repackaged, pictorial representation of the same deaza-guanine nucleotide that was previously held unpatentable in IPR2012-00007.

Ground 2: Obviousness over Dower, 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 (Science, 238:336-341 (1987)), and Metzker (Nucleic Acids Research, 22:4259-67 (1994)).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner asserted that Dower taught a sequencing method using nucleotide analogues with a "small" removable 3'-OH blocking group and a cleavably linked fluorescent label on the base. Like Tsien, Dower repeatedly cited Prober for its teachings on labeled nucleotide analogues, including the 7-deaza-guanine base disclosed by Prober. To identify a specific, suitable capping group, Petitioner turned to Metzker. Metzker disclosed that a 3'-O-allyl ether group was compatible with DNA polymerase and chemically cleavable, thereby meeting the functional requirements of the claim, including the negative limitation that the capping group is not a methoxy or ester group.
  • Motivation to Combine: A POSA would combine Dower with Prober because Dower’s express citations provided a strong reason to incorporate Prober's well-established base-labeling techniques, which were known to be beneficial for stability and polymerase interaction. The POSA would have been motivated to consult Metzker to find a specific "small" capping group for Dower's system, as Metzker demonstrated that the 3'-O-allyl group was both effective and compatible with polymerase, addressing a key challenge in the field.
  • Expectation of Success: Petitioner argued that a POSA would have reasonably expected success in this combination. The required steps involved applying known components to a known sequencing framework to achieve predictable benefits. The patent itself acknowledged that the claimed nucleotides could be made using "well-established" procedures taught by references like Prober.

4. Arguments Regarding Discretionary Denial

• Petitioner argued that discretionary denial under 35 U.S.C. §325(d) would be improper. It contended that the Patent Owner avoided the Board’s prior unpatentability decisions on a parent patent by re-litigating previously rejected arguments before an Examiner during prosecution of the ’480 patent. Petitioner asserted that this petition rectifies oversights from prosecution by presenting the prior art in a new light, supported by expert testimony from Dr. Romesberg, which was not available to the Examiner.

5. Relief Requested

• Petitioner requests institution of an inter partes review and cancellation of claim 1 of Patent 9,725,480 as unpatentable.