Factor XII, Kallikrein B Plasma 1, and Kininogen 1 iRNA Compositions and Methods of Use Silencing the Genes Behind Hereditary Angioedema

This patent covers RNA interference drugs that switch off specific genes in the blood to treat hereditary angioedema, a rare disease that causes sudden, dangerous swelling. It comes from Alnylam Pharmaceuticals, Inc., a company that pioneered turning gene silencing into approved medicines.

The Problem

Hereditary angioedema causes unpredictable attacks of severe swelling in the skin, gut, and airway, and an airway attack can be life threatening. The swelling is driven by a signalling molecule called bradykinin, which the body overproduces through a chain of blood proteins known as the kallikrein-kinin system, or contact activation pathway. Three proteins sit at the heart of that pathway: Factor XII, plasma kallikrein, and kininogen. Reducing the activity of these proteins can prevent attacks, but blocking them with conventional drugs has limits. A treatment that lowers how much of these proteins the body makes in the first place, rather than just blocking them after they appear, could prevent attacks more durably.

What This Invention Does

The patent provides RNA interference agents, in particular double-stranded RNAi agents, that target the F12 (Factor XII), KLKB1 (plasma kallikrein), or KNG1 (kininogen 1) genes, along with methods of using them. RNA interference is a natural process that cells use to silence genes, and these agents are designed to harness it to reduce production of the chosen protein in the liver, where these clotting and contact-activation proteins are made. By lowering the amount of Factor XII, kallikrein, or kininogen, the treatment dials down the contact activation pathway that generates bradykinin, aiming to prevent the swelling attacks of hereditary angioedema and other disorders linked to that pathway. The filing covers the RNAi compositions and the methods of treating patients with them.

Key Features

• Gene silencing. Double-stranded RNAi agents use the cell’s own machinery to reduce production of a target protein.
• Three targets. The agents can target the F12, KLKB1, or KNG1 genes, all central to the contact activation pathway.
• Disease focus. The methods aim to treat hereditary angioedema and related contact-activation disorders.
• Upstream action. Lowering protein production reduces bradykinin generation before attacks occur.
• Compositions and methods. The filing protects both the RNAi agents and how they are used to treat patients.

Who Is Behind It

The applicant is Alnylam Pharmaceuticals, Inc., a biopharmaceutical company based in Cambridge, Massachusetts, that built its business on translating RNA interference, the gene-silencing mechanism recognised by a Nobel Prize, into approved therapies. The named inventors are Akin Akinc, Gregory Hinkle, Martin Maier, James Butler, and Jingxuan Liu. This filing is a divisional application from an earlier related Australian application.

Why It Matters

Hereditary angioedema patients live with the constant threat of sudden attacks, and treatments that prevent attacks rather than only treating them are highly valuable. An RNAi approach that reduces the proteins driving the disease at the genetic level fits a broader shift toward therapies that act on the root cause. Protecting these compositions in Australia supports the company’s research and any clinical or commercial activity in the local market.

Related Concepts

• RNA interference – the gene-silencing mechanism the drugs use.
• Hereditary angioedema – the disease the methods aim to treat.
• Kinin-kallikrein system – the protein pathway the agents target.
• Bradykinin – the molecule that causes the swelling.
• Factor XII – one of the target proteins in the pathway.

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AU 2026201961 was published in the Australian Official Journal of Patents on 2 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.