Illumina Inc v. Molecular Loop Biosciences Inc

1. Case Identification

• Case #: IPR2024-01419
• Patent #: 11,840,730
• Filed: September 30, 2024
• Petitioner(s): Illumina, Inc.
• Patent Owner(s): Molecular Loop Biosciences, Inc.
• Challenged Claims: 1-9

2. Patent Overview

• Title: Method for Correcting Errors in Nucleic Acid Analysis
• Brief Description: The ’730 patent discloses methods for correcting errors and bias introduced during nucleic acid sequencing workflows. The claimed invention involves attaching unique molecular identifiers, termed "differentiator tags," to individual nucleic acid molecules in a sample, amplifying the tagged molecules, and then using the tags to computationally correct for amplification and sequencing artifacts.

3. Grounds for Unpatentability

Ground 1: Claims 1-4 and 9 are anticipated by Chee

• Prior Art Relied Upon: Chee (Patent 9,085,798).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Chee, filed before the ’730 patent’s priority date, discloses every element of the challenged claims. Chee teaches a method for correcting bias and sequencing errors by creating a "construct" for each nucleic acid molecule that includes a "unique identifier." Chee explicitly states that following amplification, these unique identifiers are used to identify copies originating from the same initial molecule, which allows for correction of amplification bias by counting each unique construct only once. This, Petitioner asserted, directly corresponds to the ’730 patent's limitation of "collapsing target:differentiator tag combinations observed more than once into a single count." Chee also teaches using multiple reads of constructs with the same unique identifier to generate a "consensus sequence," thereby correcting for sequencing errors, which maps to the limitations of dependent claim 2.
  • Key Aspects: Petitioner contended that Chee teaches the very feature—tagging individual molecules with unique identifiers to correct for workflow errors—that the Patent Owner argued was the "distinguishing feature" of its claims during prosecution.

Ground 2: Claims 1, 4-6, and 9 are obvious over Bignell in view of McCloskey

• Prior Art Relied Upon: Bignell (Patent 8,053,192) and McCloskey (Application # US2007/0020640).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner asserted that Bignell teaches methods for preparing and sequencing DNA samples using next-generation sequencing, including the use of tags to identify samples for multiplexing. McCloskey teaches a solution to the well-known problem of amplification bias and PCR errors by adding a unique molecular "barcode" to each nucleic acid fragment in a sample prior to amplification. Petitioner argued the combination discloses adding McCloskey’s unique barcodes to Bignell's standard sequencing workflow. This combined method would correct for bias by "counting only distinctly tagged sequences" to quantify molecules, which meets the "collapsing" limitation of claim 1.
  • Motivation to Combine: A person of ordinary skill in the art (POSITA) would have been motivated to combine these references to solve a known problem. A POSITA implementing Bignell’s next-generation sequencing workflow would have recognized the inherent problem of amplification bias and would have looked to known solutions like that taught by McCloskey. McCloskey’s method of using unique barcodes was a known technique to improve the accuracy of quantification in sequencing.
  • Expectation of Success: A POSITA would have had a reasonable expectation of success, as the combination involved applying a known error-correction technique (McCloskey's unique barcodes) to a conventional sequencing workflow (Bignell). The technologies were compatible, both involved tagging nucleic acid fragments, and the simultaneous invention by Chee and the ’730 patent’s inventors demonstrated that this solution was within the skill of the art.

Ground 3: Claims 5-6 and 8 are obvious over Chee in view of Gahan

• Prior Art Relied Upon: Chee (Patent 9,085,798) and Gahan (a 2008 scientific article on circulating nucleic acids).

• Core Argument for this Ground:

  • Prior Art Mapping: This ground built upon the teachings of Chee for the base method of claims 1 and 9. Petitioner argued that dependent claims 5, 6, and 8, which specify particular sources of nucleic acids (bacterial/viral, circulating tumor, or fetal/placental), recite nothing more than conventional and well-known sample types. Gahan, a review article, was cited to show it was common knowledge that circulating nucleic acids in blood could be sourced from tumors ("cancer-related DNA"), a fetus, or viruses, and that analyzing these molecules was useful for diagnostic purposes.
  • Motivation to Combine: A POSITA would have been motivated to apply Chee’s error-correction method to these specific, diagnostically important sample types described in Gahan. Since the accuracy of diagnostic tests is paramount, a POSITA would find it obvious to use Chee’s method to reduce bias and errors when analyzing nucleic acids from tumors or fetal cells to improve diagnostic reliability.

• Additional Grounds: Petitioner asserted additional obviousness challenges, including that claims 2-3 are obvious over Bignell, McCloskey, and Bentley (a 2006 article on consensus sequencing), and that claim 7 is obvious over Bignell, McCloskey, and Chiang (a 2009 article on copy number variation analysis). These grounds relied on adding further prior art to the Bignell/McCloskey combination to teach specific, well-known downstream analysis techniques.

4. Key Claim Construction Positions

• "Set of [Unique] Differentiator Tags": Petitioner argued this term means a set of tags where each tag has a sequence that is unique compared to the other tags in the set, for the purpose of uniquely identifying each individual nucleic acid molecule. Petitioner supported this construction by citing the ’730 patent’s specification and the Patent Owner’s own arguments during prosecution, where it repeatedly distinguished prior art by stating that its invention required "a different tag on every single molecule."
• "Locus of Origin" Terms: Petitioner contended this term means the location in a genome from which a nucleic acid molecule originated. This construction was argued to clarify that multiple distinct molecules from the same genetic locus would each be associated with a different unique tag.

5. Arguments Regarding Discretionary Denial

• Petitioner argued that the Board should not deny institution under §325(d) because the petition raises new arguments and relies on prior art that is materially different from what the Examiner considered. Specifically, Petitioner emphasized that Chee was never cited during prosecution and that it discloses the exact "unique tagging" feature the applicant relied on to overcome prior art rejections. Further, although McCloskey was cited in an Information Disclosure Statement, it was never substantively discussed by the Examiner, who therefore erred by not considering its highly relevant teachings.
• Petitioner also argued against discretionary denial under Fintiv, stating that the co-pending district court litigation was in its infancy, with no trial date set, and that the average time to trial in that district is significantly longer than the statutory deadline for a Final Written Decision in an IPR.

6. Relief Requested

• Petitioner requested the institution of an inter partes review and the cancellation of claims 1-9 of the ’730 patent as unpatentable.