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

1. Case Identification

• Case #: IPR2018-00318
• Patent #: 9,719,139
• Filed: December 15, 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: Thymine Deoxyribonucleotide Analogue
• Brief Description: The ’139 patent is directed to a specific thymine deoxyribonucleotide analogue for use in DNA sequencing-by-synthesis. The analogue features a small, chemically cleavable 3'-O-capping group and a detectable fluorescent tag attached to the 5-position of the thymine base via a chemically cleavable linker.

3. Grounds for Unpatentability

Ground 1: Obviousness over Tsien - Claim 1 is obvious over Tsien.

• Prior Art Relied Upon: Tsien (WO 91/06678).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Claim 1 is merely a pictorial representation of a nucleotide analogue previously found unpatentable over Tsien in related inter partes review (IPR) proceedings (IPR2012-00007). Tsien allegedly disclosed all elements of the claimed analogue for use in DNA sequencing. Specifically, Tsien taught nucleotide analogues having a 3'-OH blocking group and a fluorescent label. The claimed capping group "R" was met by Tsien's disclosure of a 3'-O-allyl group, which Petitioner asserted was known to be small, chemically cleavable, stable during polymerase reactions, and free of ketone, methoxy, or ester groups. The claimed linker "Y" and tag "Tag" were met by Tsien's disclosure of attaching a fluorescent label to the 5-position of a thymine base via a cleavable linker. All functional requirements of the analogue—such as polymerase recognition, incorporation, and subsequent cleavage to produce a free 3'-OH group—were described in Tsien's sequencing method.
  • Motivation to Combine: Petitioner contended that a person of ordinary skill in the art (POSITA) would be motivated to combine the teachings within Tsien itself. Tsien described the 3'-O-allyl group as an advantageous capping group and separately described the advantages of labeling thymine at the 5-position, such as providing flexibility for the linker. A POSITA would have been motivated to combine these disclosed advantageous features to create an optimized nucleotide for Tsien's sequencing method.
  • Expectation of Success: Petitioner asserted that the Board and the Federal Circuit had previously affirmed that a POSITA would have had a reasonable expectation of success in creating 3'-capped nucleotide analogues with a cleavably linked label based on Tsien's teachings. The synthetic steps required were considered to be within the level of ordinary skill at the time.

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 238:336-41, 1987), and Metzker (Nucleic Acids Research 22:4259-67, 1994).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued this combination of references taught all elements of the claimed nucleotide analogue. Dower provided the foundational teaching of DNA sequencing using nucleotide analogues with a small, removable 3'-OH blocking group and a removable fluorescent label attached to the base. To implement Dower’s method, a POSITA would have looked to Prober, which Dower cited repeatedly, for specific labeling techniques. Prober taught the well-known and advantageous method of attaching a label via a linker to the 5-position of thymine. To select a specific small capping group, a POSITA would have been motivated to use the 3'-O-allyl group taught by Metzker, which demonstrated successful incorporation by polymerase and was known to be chemically cleavable. Metzker’s 3'-O-allyl group also met the claim’s negative limitations, as it does not contain a ketone, methoxy, or ester group.
  • Motivation to Combine: A POSITA would combine these references to optimize the sequencing method disclosed by Dower. Dower’s repeated citations to Prober provided a strong motivation to use Prober’s established 5-position labeling strategy. A POSITA would have been further motivated to replace Dower’s generic “small blocking group” with a specific, proven group from the art. Metzker provided an ideal candidate with the 3'-O-allyl group, which was shown to be compatible with polymerase and chemically cleavable with high yield. The combination represented a straightforward implementation of known, advantageous components to achieve a predictable result.
  • Expectation of Success: Petitioner contended there was a high expectation of success, as the chemical steps for creating the claimed analogue were all well-established. The patent’s specification acknowledged that similar nucleotides could be made using "well-established" procedures taught by references like Prober. Combining Dower’s sequencing framework with Prober’s labeling position and Metzker’s capping group involved routine techniques that were well within the capabilities of a POSITA.

4. Arguments Regarding Discretionary Denial

• Petitioner argued that discretionary denial under 35 U.S.C. §325(d) would be improper. It asserted that the Patent Owner engaged in improper prosecution tactics by re-litigating patentability before an Examiner after the Board had already found parent claims unpatentable over the same primary reference (Tsien).
• The petition contended that it presented the prior art in a new light, particularly through the expert testimony of its declarant, which was not available to the Examiner. This new evidence and argument addressed a significant oversight during prosecution, where the Patent Owner allegedly avoided addressing the key teachings of Tsien concerning the 3'-O-allyl capping group.

5. Relief Requested

• Petitioner requests the institution of an inter partes review and the cancellation of Claim 1 of Patent 9,719,139 as unpatentable under 35 U.S.C. §103.