Illumina, Inc. v. The Trustees of Columbia University in the 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: Adenine Deoxyribonucleotide Analogues for Sequencing
• Brief Description: The ’852 patent relates to specific adenine deoxyribonucleotide analogues used in DNA sequencing-by-synthesis methods. The single claim describes an analogue having a 7-deaza-adenine base, a fluorescent tag attached via a cleavable linker, and a "small," chemically cleavable 3'-O-capping group.

3. Grounds for Unpatentability

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

• Prior Art Relied Upon: Tsien (WO 91/06678) and Prober (a 1987 article in Science).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Claim 1 is merely a pictorial representation of subject matter previously found unpatentable by the Board and the Federal Circuit in IPRs against a parent patent (the ’869 patent). Tsien was argued to disclose all elements of the claimed analogue except for the specific 7-deaza-adenine base. Tsien teaches a sequencing method using nucleotides with a reversible 3'-OH blocking group (specifically, a "small" 3'-O-allyl group) and a fluorescent tag attached to the base via a cleavable linker. Prober, which is explicitly cited by Tsien, was asserted to disclose the missing element: the use of a 7-deaza-adenine base with a fluorescent label attached at the 7-position for sequencing.
  • Motivation to Combine: Petitioner contended that a person of ordinary skill in the art (POSITA) would combine the references because Tsien expressly directs the reader to Prober's method for base labeling. This express reference was argued to provide a clear and explicit motivation to incorporate Prober's well-known 7-deaza-adenine base into the sequencing method taught by Tsien, particularly since this modification was known to improve sequencing results. This motivation was previously affirmed by the Federal Circuit in a related case.
  • Expectation of Success: A POSITA would have had a reasonable expectation of success because the synthesis of the combined nucleotide analogue involved well-established, conventional chemical procedures. Petitioner noted that the ’852 patent specification itself does not provide novel chemistry and acknowledges that such nucleotides could be made using established procedures, confirming that the combination was within the ordinary skill in the art.

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

• Prior Art Relied Upon: Dower (Patent 5,547,839), Prober (a 1987 article in Science), and Metzker (a 1994 article in Nucleic Acids Research).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner asserted this alternative combination also renders Claim 1 obvious. Dower was argued to disclose a sequencing method using nucleotide analogues with a removable label on the base and a "small" removable 3'-OH capping group. Dower repeatedly cites Prober for its disclosure of labeled nucleotide analogues, including 7-substituted deaza-purines. Metzker was asserted to disclose a 3'-O-allyl capping group, which satisfies the claim's requirement for a small, cleavable group that is not a ketone, methoxy, or ester. Metzker also demonstrates that this specific capping group is compatible with DNA polymerase.
  • Motivation to Combine: A POSITA would combine Dower and Prober because Dower expressly and repeatedly cites Prober for base labeling, suggesting Prober's 7-deaza-adenine base would be a beneficial and logical choice for Dower's method. A POSITA would be further motivated to incorporate Metzker's 3'-O-allyl capping group because Dower teaches the desirability of "small" capping groups, and Metzker teaches that the 3'-O-allyl group is not only small and polymerase-compatible but also avoids issues with other known groups (like esters, which were not polymerase substrates).
  • Expectation of Success: Petitioner argued that a POSA would have reasonably expected success in making the proposed combination. The individual components and synthetic steps were all known, and their combination represented a predictable solution to improve DNA sequencing, using established chemical procedures to achieve a desired and expected result.

4. Key Technical Contentions (Beyond Claim Construction)

• Functional Claiming vs. Lead Compound Analysis: Petitioner argued that a "lead compound" analysis, which focuses on structural similarity, is inappropriate here. It contended that Claim 1 is defined by broad functional language (e.g., a "small, chemically cleavable, chemical group") rather than a specific arrangement of atoms for the key R, Y, and Tag groups. Therefore, the obviousness analysis should be based on combining known functional components, not a strict structural modification of a single prior art compound.
• Structural vs. Textual Claim Equivalence: A central contention was that the structural format of Claim 1 does not make it patentably distinct from the text-based claims in the parent ’869 patent, which were previously invalidated over the same Tsien and Prober prior art combination. Petitioner argued this was merely repackaging an unpatentable invention.

5. Arguments Regarding Discretionary Denial

• Petitioner argued that discretionary denial under 35 U.S.C. §325(d) would be inappropriate due to the Patent Owner’s alleged improper prosecution tactics. Petitioner contended that the Patent Owner re-litigated patentability before an examiner after the Board had already found patentably indistinct claims unpatentable in prior IPRs. It was asserted that the Patent Owner misled the examiner by arguing the "smallness" of the capping group was inventive, a concept the Board had already rejected.
• The petition also asserted it presents significant new evidence and arguments not before the examiner, including the expert testimony of Dr. Romesberg and a specific focus on teachings from the prior art that were allegedly overlooked or avoided during prosecution.

6. Relief Requested

• Petitioner requested the institution of an inter partes review and the cancellation of Claim 1 of Patent 9,718,852 as unpatentable under 35 U.S.C. §103.