On March 17, 2026, the U.S. Patent and Trademark Office issued US12577611B2 to Singular Genomics Systems, Inc., a granted patent titled “Methods for in situ transcriptomics and proteomics.” The plain-language version: it covers techniques for reading molecules — both the RNA a cell is expressing and the proteins it carries — directly inside a tissue sample, rather than grinding the tissue up first. That preserves where each signal came from, which is the central promise of spatial biology. A granted claim, unlike a published application, is enforceable coverage, so this is a position the company can now assert.

The same day carried two more Singular Genomics grants tied to its core chemistry: US12577271B2, “modified nucleotides and uses thereof,” and US12577544B2, a “modified PH129 polymerase” patent. Three grants to one assignee on a single issue date is itself a data point about filing throughput.

What the estate covers

The patent record puts Singular Genomics at 111 issued records, with issuance concentrated in recent years — 34 grants indexed in the 2023 window and 31 in 2024. The classification facets show where the weight sits: the most common CPC tags across the estate are C12Q 1/6869 (40 grants) and C12Q 1/6874 (36 grants), both nucleic-acid sequencing classes, followed by C12Q 1/6841 (21 grants), a tissue and in situ detection class. The portfolio is built on sequencing chemistry, with a growing spatial-biology overlay.

That spatial cluster is visible by number. Beyond the March 17 in situ grant, US12529093B2 covers “detecting tumor infiltrating cells,” US12486532B2 covers “detecting molecules in tissues,” and US12442729B2 covers “devices useful for sample manipulation” for transferring tissue sections. These four grants describe a coherent capability: get a tissue section onto the instrument, then read RNA, protein, and specific cell populations in place.

The chemistry backbone underneath is equally documented. The modified-nucleotide and engineered-polymerase grants from March 17 join earlier records such as US12573039B2, an imaging-systems-and-methods patent for identifying features in patterned structures — the optical read step. The estate spans the full stack a sequencing-tools company needs: the labeled nucleotides, the enzymes that incorporate them, the imaging that detects them, and now the tissue context that turns a sequence into a spatial map.

The enzyme work is its own documented thread. Beyond the March 17 PH129 polymerase grant, the record includes earlier polymerase patents such as the modified Archaeal family B polymerases described in US12630808B2, which claims enzymes “that exhibit improved incorporation of nucleotide analogues utilized in DNA sequencing.” The CPC class C12N 9/1252 — covering the relevant polymerase enzymes — appears on 15 of the company's grants, a count that puts engineered enzymes among the densest sub-clusters in the estate. For a sequencing-by-synthesis platform, the enzyme that reads the template and the labeled nucleotide it incorporates are the two halves of the core chemistry, and the record shows issued claims on both.

The high-density-sequencing filings round out the throughput story. US12600962B2 covers “high density sequencing and multiplexed priming,” describing methods for sequencing overlapping amplification clusters and multiple polynucleotide populations on a single solid support. Methods that raise how much can be read per run are the kind of engineering that drives the cost-per-sample economics of an instrument platform — a fact about where the company has been investing, stated through the record rather than inferred from a press release.

Disclosed herein, inter alia, are compositions and methods of use thereof for interrogating a cell.— Methods for in situ transcriptomics and proteomics, US12577611B2

The business edge in the record

For a company selling sequencing instruments and consumables, granted claims on the in situ read step extend its enforceable footprint from the bench-top sequencing market into spatial biology — a field where multiple tools makers are racing to commercialize tissue-resolved RNA and protein readouts. The March 17 grant, sitting on top of the tumor-infiltrating-cell and molecule-in-tissue grants, gives Singular Genomics issued coverage across the specific step of interrogating intact tissue, not just purified nucleic acid.

The week's broader record gives the comparison. Among the in-situ-and-proteomics grants issued the week of March 17, Singular Genomics was joined by other tools and reagent makers — Nautilus Subsidiary, Inc. logged a grant on affinity reagents with enhanced binding and detection characteristics (US12577608B2) the same week — alongside grants from academic and pharmaceutical assignees touching diagnostics and detection. The tissue-interrogation and proteomics space is being built out by multiple filers at once; Singular Genomics putting three grants on the board on a single March day is one data point in that wider activity, and the kind of throughput a reader can weigh against the rest of the week's record.

The CPC distribution frames the moat the way the data support it: a base of sequencing-chemistry claims (the C12Q 1/6869 and 1/6874 classes) with a deepening layer of in situ detection claims (the C12Q 1/6841 class) on top. The volume trend — grants issued steadily across 2023, 2024, and into the current window, three of them on a single March day — indicates the company is continuing to file rather than coasting on an existing position. There is also a distinction worth keeping straight for any reader parsing the record: the March 17 records discussed here are issued grants, identified by the B2 kind code and enforceable as of their issue date, not published applications. That matters because a grant defines a boundary the holder can act on, whereas an application only signals direction. Every record cited here carries that B2 designation, which is why the framing throughout is about coverage locked in rather than intentions disclosed. What that means for the freedom-to-operate pressure on spatial-biology rivals, and for the durability of the estate, is the reader's call. The record shows a tools company that just locked in another spatial-omics grant inside a 111-patent estate anchored on sequencing chemistry.