It's actually kind of wild how a protein from a slow-growing bacterium became the center of a massive legal and scientific tug-of-war. If you've been following the world of genomics, you’ve likely heard the term "nanopore sequencing." But the real star behind the scenes isn't always the big corporate names you see on the boxes. It’s a tiny, funnel-shaped protein called MspA (Mycobacterium smegmatis porin A).
The buzz around the MspA nanopore US patent application—and the subsequent granted patents—is basically the story of how we learned to read DNA like a ticker tape.
Most people think nanopore sequencing just "happened" at Oxford Nanopore. In reality, the intellectual property (IP) landscape is a messy web involving the University of Washington, the UAB Research Foundation, and giants like Illumina. Honestly, the drama is as thick as the science.
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Why MspA Changed the Game
Before MspA showed up, everyone was obsessed with alpha-hemolysin ($\alpha$-HL). It was the "OG" nanopore. But $\alpha$-HL had a big problem: its sensing region was too long. It was like trying to read a single letter on a page through a tube that showed ten lines at once. Everything was blurry.
MspA changed that because it’s shaped like a goblet with a very short, narrow neck. The constriction is only about $0.6 \text{ nm}$ long. Because it’s so short, only one or two DNA bases contribute to the electrical signal at a time. This gives it a "signal-to-noise" ratio that makes other pores look like static on an old TV.
- Better Resolution: It can actually tell the difference between A, T, C, and G with high precision.
- Speed Control: Scientists had to engineer "mutant" versions (like M1-MspA) to stop the DNA from flying through too fast to read.
- Durability: Being from a Mycobacterium, this thing is built like a tank. It stays stable in conditions that would make other proteins shred.
The Patent Rabbit Hole
The core of the MspA nanopore US patent application history traces back to inventors like Jens Gundlach and Michael Niederweis. If you look at the filings (like US Patent 8,673,550 or the more recent 2024 and 2025 applications from the UAB Research Foundation), you’ll see they aren't just about the protein itself. They cover the modifications.
You see, wild-type MspA is negatively charged. DNA is also negatively charged. In nature, they repel each other. To make it work for sequencing, the inventors had to swap out specific amino acids—specifically replacing negatively charged aspartic acids with neutral asparagines. This "neutralized" the pore so DNA would actually want to go through it.
The patent applications cover these specific mutations and the "single-chain" versions of the pore. Instead of eight separate pieces coming together, they engineered a way for the protein to be produced as one long string that folds into the pore shape. It’s more stable and easier to manufacture.
The Illumina vs. Oxford Nanopore Conflict
You can't talk about the MspA patent without mentioning the 2016 lawsuit. Illumina, which had licensed the MspA patents from the University of Washington and UAB, sued Oxford Nanopore. They claimed Oxford’s "CsgG" and other pores were infringing or that Oxford was essentially using the MspA tech they had spent years refining.
They eventually settled, but it highlighted a crucial point: whoever owns the rights to the most efficient pore owns the future of medicine.
What’s Happening in 2025 and 2026?
We are seeing a new wave of filings. The latest MspA nanopore US patent application trends are moving toward "hybrid" sensors. These combine the biological MspA pore with solid-state membranes (like silicon nitride).
Why? Because biological membranes are fragile. If you want a sequencer that works in the middle of a jungle or on the Space Station, it needs to be rugged. Recent applications focus on "tethering" the pore into these synthetic holes to get the best of both worlds: the biological precision of MspA and the industrial strength of a chip.
Real-World Impact
This isn't just "science for the sake of science." The MspA technology is what allowed researchers to:
- Sequence the Ebola virus in real-time during outbreaks.
- Identify "ultra-long" reads of DNA—think 100,000+ bases in one go—which is impossible with older tech.
- Detect "epigenetic" marks (like methylation) directly, without having to do extra chemical treatments.
How to Track These Patents Yourself
If you're a total geek for this (like me) and want to dig into the USPTO database, don't just search for "MspA." You’ll miss half the stuff.
Look for the "assignees" first. The UAB Research Foundation and the University of Washington are the big ones. You should also keep an eye on Pacific Biosciences and Roche, as they’ve been quietly snapping up or filing "continuation" applications to keep their foot in the door.
Common patent numbers to start your search include:
- US 8,673,550 (The big foundation patent)
- US 10,870,883 (Refinements on mutant pores)
- US 2024/0124928 (Recent updates on Msp methods)
Misconceptions to Clear Up
One big mistake people make is thinking that one patent covers "all nanopores." It doesn't. The MspA patents are very specific to the Mycobacterium protein structure. Oxford Nanopore, for instance, shifted much of its focus to the CsgG pore (from E. coli) specifically to navigate around some of the MspA IP landmines.
Also, a "patent application" isn't a "patent." A lot of the "MspA nanopore US patent application" listings you see online are just the published versions of what someone hopes to own. Many get rejected or narrowed down so much they become useless.
Actionable Insights for 2026
If you are an investor, researcher, or just a curious mind, here is what you actually need to do with this info:
- Monitor the "Status Date": In the USPTO File Wrapper, check for "Notice of Allowance." That’s the signal that a patent is about to go live and could potentially shut down competitors.
- Look for "Single-Chain" Tech: This is the current frontier. Patents focusing on the "stoichiometry" (the math of how the protein pieces fit together) are the ones that will define how cheap these sensors become.
- Check the "Expirations": The earliest MspA patents will start hitting their 20-year limits in the early 2030s. When that happens, expect a flood of "generic" nanopore sequencers to hit the market.
- Diversify Your Search: Use keywords like "porin," "stochastic sensing," and "analyte translocation" alongside MspA to find the applications that are trying to hide in plain sight.
The MspA pore isn't just a protein; it's the foundation of a multi-billion dollar shift in how we understand life itself. Keeping an eye on who owns the rights to that "goblet" is the only way to know where the industry is headed next.