PTAB

IPR2013-00276

Ariosa Diagnostics v. Verinata Health Inc

Key Events

Petition

petition

Title: Sample Multiplexing Method for Aneuploidy Detection
Brief Description: The ’430 patent discloses a method for detecting fetal aneuploidies from multiple maternal blood samples simultaneously. The method involves counting DNA fragments from a chromosome suspected of being aneuploid and comparing that count to the number of fragments from a normal reference chromosome, using indexing techniques to distinguish results from different samples.

Prior Art Relied Upon: Dhallan (Patent 7,332,277) and Binladen (a 2007 PLoS One journal article).
Core Argument for this Ground:
- Prior Art Mapping: Petitioner argued that Dhallan taught the core method of detecting fetal aneuploidy from maternal blood by amplifying specific loci on a test chromosome and a reference chromosome and comparing their ratios. However, Dhallan did not explicitly teach multiplexing samples. Petitioner asserted that Binladen taught a now-conventional technique for multiplexing, where initial PCR primers are tagged with short, unique nucleotide sequences (indexes or tags) to identify the source of each DNA template in a pooled sample for high-throughput sequencing. Combining these teachings rendered all claim limitations obvious.
- Motivation to Combine: A person of ordinary skill in the art (POSITA) would combine the aneuploidy detection method of Dhallan with the multiplexing and indexing method of Binladen to achieve enhanced productivity and increased throughput of sample analysis, which were well-known goals in the field.
- Expectation of Success: Petitioner contended that combining a known detection method with a standard indexing technique for high-throughput sequencing was a routine and predictable application of existing technologies, leading to a high expectation of success.

Prior Art Relied Upon: Quake (Application # 2007/0202525) and Craig (a 2008 Nature Methods journal article).
Core Argument for this Ground:
- Prior Art Mapping: Petitioner argued that Quake disclosed detecting fetal aneuploidy from maternal blood by quantifying DNA sequences from a test chromosome and a control chromosome using techniques like digital PCR. Craig disclosed a specific, successful method for the simultaneous, or multiplexed, sequencing of targeted regions from a large number of individuals. This was achieved by bar-coding (indexing) the DNA from each individual with a short, identifying oligonucleotide before pooling and sequencing.
- Motivation to Combine: A POSITA would have been motivated to apply the indexing approach described in Craig to the aneuploidy detection process of Quake. The motivation was to improve productivity and cost-effectiveness by analyzing multiple samples in a single sequencing run, a clear and recognized advantage in the field of genetic analysis.
- Expectation of Success: The combination involved applying a known indexing method to a known genetic analysis technique to achieve a predictable increase in efficiency. As such, a POSITA would have had a reasonable expectation of successfully implementing the claimed method.

Prior Art Relied Upon: Shoemaker (Application # 2008/0090239), Dhallan (Patent 7,332,277), and Binladen (a 2007 PLoS One journal article).
Core Argument for this Ground:
- Prior Art Mapping: This ground built upon the combination in Ground 1. Petitioner argued that Shoemaker disclosed systems and methods for detecting abnormalities in rare analytes, such as fetal cells in maternal blood, and specifically taught using allele abundance to determine aneuploidy for chromosomes 13, 18, and 21. Petitioner contended that a POSITA would have readily understood that Shoemaker’s methods could be carried out using the cell-free DNA described in Dhallan and implemented using the multiplexed, indexed sequencing techniques taught by Binladen.
- Motivation to Combine: A POSITA would combine these references to apply Shoemaker's methods for determining fetal abnormalities using the efficient, high-throughput platform created by combining Dhallan's cell-free DNA approach with Binladen's multiplexing technique. This would allow for the robust and efficient analysis of multiple samples for the conditions described in Shoemaker.
- Expectation of Success: The combination represented the application of a well-understood multiplexing technology (Binladen) to established methods of analyzing cell-free fetal DNA (Dhallan) to detect specific fetal abnormalities (Shoemaker), a straightforward and predictable convergence of known techniques.

"Selectively enriching": Petitioner argued this term should be construed as increasing the concentration of a selected subset of nucleic acids relative to other nucleic acids in the sample. The petition asserted that in the context of the ’430 patent, this is achieved by amplification methods like Polymerase Chain Reaction (PCR), as described in the specification.
"Sequence reads corresponding to enriched and indexed fetal and maternal non-random polynucleotide sequences": Petitioner proposed this phrase should be construed as the informational result of determining the order of nucleotides from polynucleotides that have been both selectively enriched and indexed. This construction distinguishes the informational "sequence read" from the physical DNA molecule.
"Reference chromosome": Petitioner argued this term should be construed as a chromosome that is not being tested for aneuploidy and is presumed to be diploid prior to testing. This construction is necessary for the claimed comparison to be meaningful for aneuploidy detection.

Petitioner requested the institution of an inter partes review and the cancellation of claims 1-18 of Patent 8,318,430 as unpatentable under 35 U.S.C. §103.