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Scale Biosciences Joins Single-Cell Sequencing Scene With Instrument-Free Kits, Patent Challenges


This story has been updated to include additional information about Scale Biosciences' patent infringement lawsuit against Parse Biosciences.

NEW YORK – Scale Biosciences, a spinout from Jay Shendure's lab at the University of Washington, has made its debut on the single-cell sequencing scene over the last year, marking its arrival with several assays and a legal challenge to its most similar rival.

Scale's ambitions are right in its name. The firm believes that its kits, based on combinatorial indexing technology developed by Shendure in collaboration with other researchers, can provide the capacity to generate single-cell transcriptomes at a greater scale than ever before. Moreover, without the need for a separate, costly instrument, Scale is hoping its kit could be run faster and in more types of labs than competing single-cell technology, especially labs that are more cost-sensitive.

The single-cell transcriptomics assay launched by Scale in December 2022 offers the ability to analyze between 125,000 and 500,000 cells for as little as $.04 per cell, according to the firm. Additionally, a new single-cell DNA methylation assay, based on a method developed by Andrew Adey's lab at Oregon Health and Science University, is a differentiated way to attract customers. The firm also offers a single-cell CRISPR perturbation assay.

Operating out of public view from its founding in 2019 until late 2022, Scale is one of the most recent entrants in a market dominated by 10x Genomics and its Chromium droplet isolation-based single-cell assays. It is also one of several companies offering kits that don't rely on a special instrument. Simply put, Scale is late to the party.

"Maybe we're just fashionably late," countered Giovanna Prout, Scale's new CEO, who was appointed earlier this summer. "With our new products and capabilities, you'll start to see us not replicate what's already on the market but take a separate approach of putting out differentiated products."

Already, the company is making noise. It has sued fellow UW spinout Parse Biosciences, which likewise offers an instrument-free approach to single-cell transcriptomics. In December 2022, Scale sued Parse for patent infringement in the US District Court for the District of Delaware. As part of the proceedings, Scale sued Roche Sequencing Solutions, from which it has licensed certain patents covering barcoding, to make it join the suit as a plaintiff. In May, the parties agreed to realign Roche Sequencing Solutions as a plaintiff.

Parse has denied wrongdoing and has filed a countersuit, alleging that Scale's technology infringes patents licensed by Parse. Parse also alleged that Scale defamed it by making "false and misleading statements" about Parse's intellectual property rights, including in emails to prospective customers.

Already, the firm has grown to approximately 50 employees, mostly split across two sites in the US, a headquarters in San Diego and a facility in San Carlos, California. The firm also has a global team of field applications scientists, working as far away as Sweden.

Scale sells directly in several European countries, including the UK, Germany, and Switzerland, Prout said, and has distributors in Australia, Japan, India, the Middle East, Israel, and numerous European regions.

Prout declined to comment on specific sales figures but noted that while academic customers greatly outnumber pharma customers, "from a dollars perspective, it's probably equally weighted between [the] academic and pharma [markets]."

The core indexing technology uses Tn5 transposase to barcode molecules in order to identify them after sequencing. In Scale's hands, the assay entails three rounds of barcoding on 384- and 96- well plates, resulting in approximately 3.5 million combinations. The workflow takes about eight hours, including library preparation, Prout said.

Optimizing the barcodes is one way the company has improved the method. It has also tweaked the enzymes and the fixation chemistry and adopted certain plastics to make pipetting easier.

The base RNA sequencing kit costs $8,500, which can run anything between 125,000 cells from one sample and 1,300 cells from 96 samples. The higher throughput kit costs $17,500 for up to half a million cells.

"What separates Scale from the rest is the ability to do 100,000 cells," or more, said Allen Yen, a graduate student in Joseph Dougherty's lab at Washington University in St. Louis who has used the kits, along with products from 10x and Parse, in his single-nucleus sequencing-based studies of neurological development. Being able to freeze or fix cells and run them all at once was another benefit, he said, although not unique to Scale's method.

Yen also praised Scale's field application scientists, who offer on-site training. "We really appreciated that in the beginning," he said. "Doing it with you and explaining every step really boosts your chance for success."

Scale's single-cell methylation kit also leverages combinatorial indexing and can assay more than 18,000 cells.

Adey, whose method Scale has licensed to create this product, said the kits are "working really well." Recent advances that his lab made to the method required special oligos, such as fully methylated adapters, that were hard and expensive to obtain. The kit makes the cost of those reagents "more palatable," he said. Scale has also made it easier to use rigorously tested safe stopping points, among other optimizations.

"Generally, [the kit] consistently produces better data," Adey said, noting that his lab now uses components of the Scale kit as a "backbone" for further method development.

At $36,500 for more than 18,000 cells, the sample prep cost per cell is around $2, which is less than other academic protocols, he said. For example, a competing single-cell methylation method, developed by Joe Ecker at the Salk Institute for Biological Studies, costs about $6 per cell in Adey's lab, he said, which they used prior to the development of their own method, called sciMET. The Scale assay also comes in a smaller kit, priced at $9,950 for around 4,600 cells.

According to Prout, the single-cell methylation assay is just the first of a number of new products the firm hopes will invigorate the single-cell field. She declined to offer more details on other kits in development although the Sci family of assays developed by Shendure, Adey, and Scale cofounder Cole Trapnell, also of the University of Washington, offers many to choose from. She noted that the company is working on targeted methylation panels that would decrease the amount of sequencing necessary or enable deeper sequencing of particular methylated regions. Scale's lawsuit against Parse notes that Scale's license agreement with Roche Sequencing Solutions covers diagnostics as well as research.

"A question I get asked a lot is, 'Why now?'" Prout said, especially with spatial technologies on the rise. "How we look at it is that what was done with single-cell omics over the past five years was foundational, but it hasn't gone to applications that need enormous scale." Analyzing larger cohorts, with more disease-affected tissues, in translational studies in fields like neurology or cardiology is a possible use of Scale's products, she said. The products could also be used to minimize batch effects, she added.

"We've made it to base camp," she said. "But there's still a large climb to get to all these other applications."