Coumarin-based crosslinking reagents

Inventors

Hong, Rui • Lefever, Mark • May, Eric

Assignees

Ventana Medical Systems Inc

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Publication Number

US-12693297-B2

Patent

Publication Date

2026-07-28

Expiration Date


Abstract

Disclosed herein are novel coumarin-based reagents, e.g. linkers, and conjugates including one or more of the disclosed coumarin-based reagents. In some embodiments, the presence of a coumarin moiety within the coumarin-based reagents enables detection of labels which are typically difficult to detect, e.g. certain haptens.

Core Innovation

The disclosure relates to coumarin-based crosslinking reagents, coumarin-based reagents, and coumarin-based conjugates that include a coumarin moiety linked via linkers to functional groups, including reactive groups, detectable labels, enzyme-reactive moieties, haptens, and binding entities. The coumarin-containing reagents are described through structural formulae and variants in which the coumarin structure is coupled to different reactive and detectable elements.

The disclosure further relates to enzyme-reactive reporter conjugate scaffolds and labeled coumarin-containing compounds in which the coumarin moiety is combined with an enzyme reactive moiety and a hapten or reactive group, with linkers and spacer bonds defining the scaffold. The enzyme reactive moiety is defined using tyramine and derivatives and quinone methide precursors, and click-chemistry handles such as DBCO and azide pairs are included in some embodiments.

The document also describes detection conjugate and complex compositions that include a specific binding entity or biomolecule, including antibodies, nucleic acids, peptides, proteins, saccharides, drugs, lipids, and nanoparticles. It describes detection formats using coumarin-bearing reagents in biological samples, including direct or indirect detection, primary and secondary antibodies, labeled nucleic acid probes, and enzyme-mediated detection via peroxidase or phosphatase.

Claims Coverage

The provided material contains three independent claims, but the claim text is truncated and does not provide the actual group contents or identifiable inventive limitations. Across the provided claims, the only identifiable coverage concept is that the claimed subject matter is a compound selected from a group consisting of unspecified compounds.

Selected compound from a group consisting of compounds

The claim recites a compound selected from a group consisting of unspecified compounds; the specific members of the group are not provided in the supplied claim text.

Based on the incomplete claim text provided, claim coverage cannot be mapped to specific coumarin-linker conjugates, detectable labels, or other structurally defined features because the groups and members are not included in the supplied claim excerpts.

Stated Advantages

Improved detection of difficult-to-detect haptens, including benzofuran haptens and thiazolesulfonamide haptens such as NP, TS, DCC, and BF.

High extinction coefficients, including at least 10,000 to at least 25,000 M−1cm−1.

Absorbance bands around 340–500 nm.

Multiplex detection using different detectable labels.

Documented Applications

Detection workflows in immunohistochemistry (IHC) using the coumarin-bearing crosslinking reagents and conjugates.

Detection workflows in in situ hybridization (ISH) using the coumarin-bearing crosslinking reagents and conjugates.

Detection of biological samples using direct or indirect detection, including primary and secondary antibodies and labeled nucleic acid probes.

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