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

1. Case Identification

• Case #: IPR2012-00006
• Patent #: 7,713,698
• Filed: September 16, 2012
• Petitioner(s): Illumina, Inc.
• Patent Owner(s): The Trustees of Columbia University in the City of New York
• Challenged Claims: 1-7, 11-12, 14-15, and 17

2. Patent Overview

• Title: Massive Parallel Method for Decoding DNA and RNA
• Brief Description: The ’698 patent describes a "sequencing by synthesis" method for determining the sequence of a nucleic acid template. The method uses nucleotide analogues that have both a unique label for identification and a removable chemical moiety capping the 3'-OH group, which allows for the controlled, single-base-at-a-time extension of a primer strand.

3. Grounds for Unpatentability

Ground 1: Anticipation over Tsien - Claims 1-7, 11-12, 14-15, and 17 are anticipated under 35 U.S.C. §102(b) by Tsien.

• Prior Art Relied Upon: Tsien (WO 91/06678) and Prober I (Science 238 (1987)), which is incorporated by reference into Tsien.
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Tsien taught every element of the challenged claims. Tsien disclosed a sequencing by synthesis method where a template DNA is immobilized on a solid support, a primer is hybridized, and a polymerase adds 3'-OH blocked and fluorescently labeled nucleotides one at a time. After a nucleotide is added, its unique fluorescent label is detected to identify the base, and then a "deblocking solution" removes the 3'-OH blocking group to allow the next cycle. For the key limitation requiring a "deaza-substituted" nucleotide analogue, Petitioner asserted that Tsien expressly incorporated the disclosure of Prober I for its teaching on attaching fluorescent tags to the nucleotide base moiety. Prober I explicitly disclosed attaching fluorescent labels to the 7-position of 7-deazapurines. Therefore, Petitioner contended that the complete claimed invention, including the deaza-substituted element, was disclosed in a single prior art reference through incorporation.

Ground 2: Obviousness over Dower and Prober I - Claims 1-7, 11-12, 14-15, and 17 are obvious over Dower in view of Prober I.

• Prior Art Relied Upon: Dower (Patent 5,547,839) and Prober I (Science 238 (1987)).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Dower disclosed a nucleic acid sequencing by synthesis method using chain-terminating nucleotide analogues with both a removable fluorescent label attached to the base and a removable blocking group at the 3'-OH position. Dower taught immobilizing a plurality of templates on a solid surface and elongating primers one nucleotide at a time, followed by detection and removal of the label and blocking group. Prober I disclosed fluorescence-tagged, chain-terminating reagents where a linker attaches a label to the 7-position of 7-deazapurines.
  • Motivation to Combine: Petitioner asserted that Dower expressly taught combining its method with fluorescent chain terminators as described in references like Prober I. A person of ordinary skill in the art (POSITA) reading Dower’s disclosure on using labeled nucleotides would be directly motivated to use the specific deaza-substituted labeled nucleotides from Prober I. The combination was argued to be a predictable implementation of known components, as Prober I showed that this modification was compatible with polymerase enzymes and provided a stable linker attachment point.
  • Expectation of Success: A POSITA would have a high expectation of success because both Dower and Prober I used similar polymerase-based sequencing systems, and Prober I demonstrated successful enzymatic incorporation of its deaza-substituted nucleotides.

Ground 3: Obviousness over Stemple II and Anazawa - Claims 1-7, 11-12, 14-15, and 17 are obvious over Stemple II in view of Anazawa.

• Prior Art Relied Upon: Stemple II (WO 00/53805) and Anazawa (WO 98/33939).

• Core Argument for this Ground:

  • Prior Art Mapping: Stemple II disclosed a sequencing by synthesis method using nucleotides having a detachable labeling group and a detachable 3'-OH blocking group. The method involved cycles of incorporation, detection, and unblocking to sequence a template attached to a solid support. For attaching the label to the base of the nucleotide, Stemple II expressly directed a POSITA to the method described in Anazawa. Anazawa, in turn, disclosed the attachment of fluorescent labels to the 7-position of the 7-deaza-guanine base.
  • Motivation to Combine: The motivation was explicit, as Stemple II directly cited and incorporated Anazawa for the specific purpose of providing a method to attach a label to the nucleotide base. A POSITA following the teachings of Stemple II would be led directly to Anazawa's method, which involved using deaza-substituted nucleotides.
  • Expectation of Success: A POSITA would expect success because Stemple II provided an express instruction to use Anazawa’s method in its own sequencing system, indicating compatibility and a clear path for implementation.

• Additional Grounds: Petitioner asserted numerous additional challenges, primarily obviousness grounds under 35 U.S.C. §103. These grounds relied on similar theories, combining a primary reference disclosing a sequencing by synthesis method (e.g., Tsien, Dower, Stemple II, or Stemple III) with a secondary reference teaching the use and advantages of deaza-substituted nucleotides (e.g., Prober I, Prober II, Seela I, or Hobbs).

4. Key Technical Contentions (Beyond Claim Construction)

• Deaza-Substituted Nucleotides Were Well-Known and Obvious to Use: A central contention spanning multiple grounds was that the use of "deaza-substituted" nucleotide analogues was not an inventive step but a well-known, obvious design choice in the field of nucleic acid sequencing. Petitioner argued that the patentee only added this limitation during prosecution to overcome rejections. However, prior art like Prober I, Seela I, and Hobbs taught that substituting the nitrogen at the 7-position of a purine with carbon (creating a "deazapurine") provided a more stable attachment point for linker arms and labels without interfering with polymerase activity. Therefore, a POSITA seeking to create labeled nucleotides for any sequencing by synthesis method would have found it obvious to use this known and advantageous modification.

5. Relief Requested

• Petitioner requested institution of an inter partes review and cancellation of claims 1-7, 11-12, 14-15, and 17 of the ’698 patent as unpatentable.