Substituted Benzyl-Triazole Compounds for CBL-B Inhibition Releasing the Brake on the Immune System

This patent covers a family of small molecules that block an enzyme called CBL-B, which acts as a natural brake on immune cells. Switching that brake off is a way of making the immune system attack tumours more aggressively. It comes from Nurix Therapeutics, Inc., a San Francisco biotechnology company built around the chemistry of protein degradation.

The Problem

The immune system has powerful mechanisms for killing abnormal cells, and it also has strong safeguards to stop those mechanisms turning on healthy tissue. T cells, the immune system’s targeted killers, carry several layers of built-in restraint. Tumours exploit those restraints. Much of the last fifteen years of cancer immunotherapy has been about lifting them, most famously with checkpoint inhibitor antibodies that block PD-1 and CTLA-4.

Checkpoint inhibitors work spectacularly for some patients and not at all for many others, and they act on the outside of the cell. Inside the T cell there is another brake: CBL-B, an E3 ubiquitin ligase that tags signalling proteins for destruction and thereby raises the threshold a T cell must clear before it activates. Blocking CBL-B should lower that threshold, but E3 ligases sit inside the cell and have historically been considered hard targets for drug molecules, so few tools existed to test the idea in patients.

What This Invention Does

The application discloses compounds of a defined chemical formula, built around a substituted benzyl-triazole scaffold, together with pharmaceutical compositions containing them and methods of using them to inhibit CBL-B within the ubiquitin-proteasome system. Because these are small molecules rather than antibodies, they can be taken orally and can reach a target that sits inside the cell.

The claimed uses run wider than a single therapy. The compounds are described for modulating the immune system generally, for treating diseases amenable to immune modulation, and for treating cells in the body, in the laboratory, or outside the body before being returned to a patient, which is the pattern used in cell therapy manufacturing. The application also specifically covers combinations: a CBL-B inhibitor together with a cancer vaccine, and a CBL-B inhibitor together with an oncolytic virus, along with methods of treating cancer using each pairing. The logic is that a vaccine or a virus generates the immune signal while the CBL-B inhibitor removes the brake that would otherwise damp the response.

Key Features

• Defined compound family. Compounds of a specified formula based on a substituted benzyl-triazole scaffold are claimed.
• CBL-B inhibition. The compounds inhibit the E3 enzyme CBL-B in the ubiquitin proteasome pathway.
• Broad immune modulation. Uses extend to any disease amenable to modulating the immune system, not only cancer.
• In vivo, in vitro and ex vivo treatment. Cells can be treated in the body, in the laboratory, or outside the body and returned.
• Cancer vaccine combination. Compositions and methods pairing a CBL-B inhibitor with a cancer vaccine are claimed.
• Oncolytic virus combination. Compositions and methods pairing a CBL-B inhibitor with an oncolytic virus are claimed.

Who Is Behind It

The applicant is Nurix Therapeutics, Inc., a clinical-stage biotechnology company in San Francisco founded in 2009 out of academic laboratories at the University of California, San Francisco, which specialises in targeted protein degradation and E3 ligase chemistry. The named inventors include Arthur T. Sands, Neil F. Bence, Christoph W. Zapf, Frederick Cohen, Chenbo Wang, Thomas Cummins, Hiroko Tanaka, Hunter Shunatona, Jennifa Gosling, Dahlia Weiss and Mario Cardozo. The application is a divisional of Australian application 2020303696, arising from PCT/US2020/039957 with priority from June 2019.

Why It Matters

Immunotherapy transformed the outlook for melanoma, lung cancer and several blood cancers, but most patients still do not respond, and finding the next lever to pull is one of oncology’s central questions. CBL-B has become one of the more closely watched targets because it acts inside the T cell and can be reached with a pill rather than an infusion. Australia has a strong record in early-phase oncology trials, and companies routinely seek Australian patent protection to cover both clinical work conducted here and eventual commercial supply. It is worth being clear that this is an application covering a compound class, not an approved medicine: whether any of these molecules proves safe and effective in patients is decided by clinical trials and regulators, not by a patent office.

Related Concepts

• Ubiquitin ligase – the enzyme family CBL-B belongs to.
• Cancer immunotherapy – the treatment field this compound class is aimed at.
• T cell – the immune cell whose activation threshold CBL-B controls.
• Checkpoint inhibitor – the established class of brake-releasing drugs this would complement.
• Oncolytic virus – one of the claimed combination partners.
• Targeted protein degradation – the broader field the applicant works in.

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AU 2026202030 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.