PTAB

IPR2013-00390

Sequenom Inc v. Sequenom Inc

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Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Digital Quantification of DNA
  • Brief Description: The ’415 patent discloses methods for non-invasively detecting fetal chromosomal abnormalities, such as aneuploidy, by analyzing a mixed sample of maternal and fetal DNA from a pregnant subject. The method involves shotgun sequencing of DNA fragments, mapping the resulting sequence tags to a reference genome, and enumerating the tags per chromosome to detect abnormal distributions.

3. Grounds for Unpatentability

Ground 1: Anticipation - Claims 1-6 and 8-12 are anticipated by Lo II

  • Prior Art Relied Upon: Lo II (Application # 2009/0029377).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Lo II discloses every limitation of independent claim 1 and its dependents. Lo II teaches a method for determining nucleic acid sequence imbalances (e.g., fetal aneuploidy) from a biological sample from a pregnant female containing fetal and maternal DNA. The method involves randomly sequencing DNA fragments, assigning the sequence tags to chromosomes by comparison to a reference genome, and determining a differential between chromosomes to identify an abnormal distribution. Petitioner contended that Lo II’s disclosure of using “chromosomal regions” to determine aneuploidy is equivalent to the ’415 patent’s use of “windows of defined length,” thereby anticipating this key limitation. The dependent claims were also argued to be disclosed, covering aspects like massively parallel sequencing, specific aneuploidies (chromosomes 13, 18, 21), and tag length, all of which are exemplified in Lo II.

Ground 2: Obviousness over Lo II and Wang - Claims 13 and 16 are obvious over Lo II in view of Wang

  • Prior Art Relied Upon: Lo II (Application # 2009/0029377) and Wang (a 2002 article on digital karyotyping).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that independent claim 13, which recites determining an abnormal chromosomal distribution using "sliding windows," is obvious over the combination. Lo II was asserted to teach the foundational method of sequencing a mixed DNA sample and mapping tags to chromosomes. Wang was presented as teaching the use of sliding windows to analyze tag densities along each chromosome for quantitative analysis of DNA copy number. Petitioner argued Wang's method was a well-known technique for improving the resolution of karyotyping analyses like the one disclosed in Lo II.
    • Motivation to Combine: A Person of Ordinary Skill in the Art (POSITA) would combine Wang's sliding window analysis with the method of Lo II to improve the precision and statistical power of the aneuploidy detection. Wang explicitly demonstrates that this technique successfully identifies chromosomal amplifications and deletions, providing a clear path to apply it to the similar problem addressed by Lo II.
    • Expectation of Success: A POSITA would have a reasonable expectation of success because applying a known data analysis technique (Wang's sliding windows) to a sequencing dataset (from Lo II's method) to detect chromosomal copy number variations was a predictable application of established principles.

Ground 3: Contingent Obviousness over Lo I and Shimkets - Claims 1-6 and 8-12 are obvious over Lo I in view of Shimkets

  • Prior Art Relied Upon: Lo I (U.S. Provisional Application No. 60/951,438) and Shimkets (Application # 2005/0221341).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground was presented as an alternative in case Lo II was found not to be prior art. Petitioner argued Lo I, the provisional application for Lo II, discloses the core method of detecting fetal aneuploidy by random sequencing of DNA from maternal plasma. However, Lo I does not explicitly detail assigning sequences via a reference genome or using windows for analysis. Shimkets was argued to supply these missing elements, as it discloses a sequence-based karyotyping method that explicitly teaches generating sequence tags, mapping them to a reference genomic scaffold, and normalizing the data using windows of defined length to detect chromosomal abnormalities.
    • Motivation to Combine: A POSITA would combine the methods because both Lo I and Shimkets address the same technical problem of detecting chromosomal abnormalities via random sequencing. A POSITA reading Lo I would have naturally turned to known techniques, such as those in Shimkets, to implement the necessary steps of mapping sequences to a reference genome and analyzing the data using windows, which were standard in the field.
    • Expectation of Success: Success would be expected because the combination merely involves applying Shimkets's specific, well-defined data processing and analysis steps to the raw sequence data generated by the method disclosed in Lo I.
  • Additional Grounds: Petitioner asserted numerous additional obviousness challenges for all 17 claims based on various combinations of Lo II (or Lo I) with references teaching specific, well-known techniques. These included combinations with Hillier and/or Smith (for allowing one mismatch during sequence mapping), Shimkets and/or Dohm (for correcting GC content bias), and Quake (for using t-statistics in data analysis).

4. Key Claim Construction Positions

  • "Window" and "Sliding Window": Petitioner argued that based on the patent’s specification, "window" should be construed as "a predefined subsection of a chromosome." This construction was central to the argument that the concept was already broadly known in the art. For "sliding window," Petitioner argued for a broad construction meaning "contiguous, overlapping or non-overlapping, predefined subsections of a chromosome." This was critical to map prior art like Wang, which used sliding windows, to the claims and to counter the Patent Owner's arguments during prosecution that distinguished the invention based on the use of windows.
  • "Chromosome Portion": Petitioner proposed construing this term according to its explicit definition in the specification as "either an entire chromosome or a significant fragment of a chromosome."

5. Relief Requested

  • Petitioner requested the institution of an inter partes review and the cancellation of claims 1-17 of the ’415 patent as unpatentable.