Anti-c-Met Antibody Drug Conjugates Aiming a Topoisomerase Inhibitor at a Lung Cancer Target

This application covers antibody-drug conjugates directed at c-Met, together with the drug linkers and novel topoisomerase inhibitor payloads used to build them, and methods of making and using them. The applicant is AbbVie Manufacturing Management Unlimited Company, part of the pharmaceutical group AbbVie.

The Problem

c-Met is a receptor tyrosine kinase found on the surface of epithelial and endothelial cells. Its only known activating partner is hepatocyte growth factor, and when the two meet, the resulting signal drives cell proliferation, blood vessel formation, cell survival and cell movement. Those are useful processes in normal tissue and dangerous ones in a tumour.

Non-small-cell lung cancer accounts for about 85 per cent of all lung cancers, and lung cancer remains the leading cause of cancer death worldwide. Deregulated c-Met signalling turns up frequently in this disease, and it can arise through several different mechanisms, including gene amplification, mutation and overexpression of the receptor. That makes c-Met an attractive target, but a difficult one, because the receptor is also present on healthy epithelial tissue. A drug that simply blocks c-Met everywhere risks toxicity, and a cytotoxic drug given systemically risks the same problem in a different form.

What This Invention Does

An antibody-drug conjugate solves the targeting problem by bolting the cytotoxic drug onto an antibody. The antibody finds cells displaying the target on their surface, the conjugate is internalised, and the drug is released inside the cell where it does its work. Healthy tissue that does not display the target in the same way sees far less of the drug.

This application claims that architecture applied to c-Met, and it claims the components as well as the assembled product. The specification describes novel topoisomerase inhibitor drugs, the drug linkers that attach them to the antibody, the anti-c-Met conjugates themselves, and the methods of making them. Topoisomerase inhibitors interfere with the enzymes cells use to unwind and manage DNA during replication, which is lethal to rapidly dividing cells and has become a favoured payload class in recent conjugate development.

The linker matters as much as the payload. It has to hold the drug securely while the conjugate circulates in the bloodstream, then release it reliably once inside the target cell. Get that balance wrong in one direction and the drug leaks into circulation, reproducing the toxicity the design was meant to avoid. Get it wrong in the other and the payload never becomes active.

Key Features

• c-Met targeting. The conjugates are directed at c-Met, a receptor tyrosine kinase implicated in non-small-cell lung cancer.
• Topoisomerase inhibitor payload. Novel topoisomerase inhibitor drugs are described as the cytotoxic component.
• Drug linkers. The chemistry connecting payload to antibody is claimed alongside the conjugate.
• Compositions. Pharmaceutical compositions containing the conjugates fall within the disclosure.
• Methods of use. Methods of using the conjugates, including in cancer treatment, are covered.
• Methods of manufacture. Methods of making the drugs, linkers and conjugates are also disclosed.

Who Is Behind It

The applicant is AbbVie Manufacturing Management Unlimited Company, an entity within AbbVie, the research-based biopharmaceutical company spun out of Abbott Laboratories in 2013 and headquartered in North Chicago, Illinois. The named inventors are Andrew C. Phillips, Regina M. Reilly, George A. Doherty, Cheng Ji, Milan Bruncko, Erwin R. Boghaert and Mark Anderson. The application is a divisional of Australian application 2022267394, which entered the national phase from international application PCT/US2022/072008, with priority running back to a United States provisional filed in April 2021.

Why It Matters

Antibody-drug conjugates have moved from a promising idea to one of the more productive areas of oncology drug development, with a series of approvals across breast, lung, bladder and blood cancers over the past decade. Much of the recent progress has come from improvements to the payload and linker rather than the antibody, and topoisomerase inhibitor payloads in particular have driven several of the successful newer products.

c-Met is a target AbbVie has pursued before, and it has proved a demanding one, since earlier c-Met conjugate programs have run into questions about which patients benefit and how to select them. A new payload class and new linker chemistry directed at the same target reflects that iterative reality: the target biology stays constant while the delivery chemistry is reworked to widen the gap between effect on the tumour and effect on healthy tissue. This application has already been accepted by IP Australia, which means it has passed examination and, absent a successful opposition, is on the path to grant.

Related Concepts

• Antibody-drug conjugate – the drug architecture at the centre of this application.
• c-Met – the receptor tyrosine kinase being targeted.
• Topoisomerase inhibitor – the payload class described in the specification.
• Non-small-cell lung carcinoma – the disease the target is most associated with.
• Hepatocyte growth factor – the only known ligand that activates c-Met.
• Monoclonal antibody therapy – the wider treatment approach conjugates build on.

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AU 2026202052 was published in the Australian Official Journal of Patents on 9 April 2026 and is open for public inspection. Patent applications represent inventions that are sought to be protected and do not necessarily reflect commercially available products.