Illumina and Molecular Loop Patent dispute over UMIs
Illumina has had a sketchy history when it comes to protecting their IP or claiming IP over techniques that many would assume are public domain.
One of these areas of dispute is in Non-Invasive Prenatal Testing (NIPT), where Illumina pooled their patents with a company that is now a shell of itself, and then went out and sued everyone involved in NGS for NIPT.
Illumina and Molecular Loop are now suing each other over IP relating to unique barcoding (UMIs) used in sequencing library preparation.
Unique Molecular Identifiers (UMIs) can be a crucial component in Next-Generation Sequencing (NGS) for distinguishing between truly unique DNA fragments and duplicates created during PCR amplification.
In NGS, short-read sequencing can often produce multiple copies of the same DNA sequence. This makes it challenging to determine whether after sequencing, these events represent multiple instances of the fragment in the original sample or are merely duplicates resulting from the amplification process.
Using UMIs addresses this issue by attaching a unique barcode to each individual DNA molecule before any amplification takes place. These barcodes are short sequences of DNA that are unique to each molecule. The process typically involves the following steps:
Tagging: Each DNA molecule is tagged with a UMI, a unique sequence that serves as a molecular barcode.
Amplification: The DNA fragments are then amplified via PCR, which may create multiple copies of the fragments.
Sequencing: The amplified DNA fragments are sequenced using NGS technology.
UMI Analysis: finding the unique barcode attached to the original molecules determines which fragments were unique and which were duplicates from the PCR amplification.
UMI technologies are specially relevant for applications where the amount of starting DNA may be small, such as those coming from cancer samples or NIPT. In cancer tests, one can find out which SNVs are at which frequency by correcting the number of times are seen using UMIs.
Molecular Loop holds patents to technology developed in George Church's lab and Illumina is now suing them in the US District Court for the District of Delaware alleging infringement of five of these patents, including US Patent Nos. 11,041,852, "Methods for Maintaining the Integrity and Identification of a Nucleic Acid Template in a Multiplex Sequencing Reaction" and 11,840,730, "Methods and Compositions for Evaluating Genetic Markers."
On the other hand, Molecular Loop alleges that Illumina subsidiary Verinata Health's Verifi and VeriSeq tests, and Illumina's TruSight Oncology 500, infringe the patents-in-suit. Molecular Loop asked for a judgment of willful infringement, damages and fees, a permanent injunction or licensing fee, and a jury trial.
In attempts to avoid disruption to their operations, Illumina asked the US District Court for the District of Massachusetts to declare noninfringement of the five patents. Illumina also asked the court to declare unenforceability of the '730 patent, including for inequitable conduct before the US Patent and Trademark Office by Molecular Loop CEO and Cofounder Greg Porreca, an inventor on the patents.
George Church, whose lab has developed numerous sequencing technologies, is a coinventor on at least two of the patents held by Molecular Loop. According to Molecular Loop's suit, Porreca did his doctorate under Church at Harvard.
Since January, Molecular Loop has sent letters to several Illumina customers advising them that their products are using certain kits containing UMIs and/or unique dual indices purchased from Illumina which could become a problem: these include Ambry Genetics, ARUP Laboratories, Fulgent Genetics, NeoGenomics Laboratories, Helix, Tempus Labs, and Personalis.
So in a twist of events, now Illumina’s record of suing everyone under the Sun in NIPT has come back to bite them, and Molecular Loop is challenging Illumina’s cancer test products for UMI patent infringement. This is a big deal for Illumina, given the fact that these are products with a high churn, so any disruption would cause Illumina’s clients to look elsewhere for alternatives.
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Illumina should tread carefully when it comes to fighting IP battles: the company has been mired in controversy with regulators in the US, the UK and the EU in the last few years, and their business plan has been affected by these. Any moves that make Illumina look like they want to control a monopolistic position in NGS will be noted down by the regulators, and it could influence their decisions when it comes to important antitrust investigations in the future.