Eradication of Bacterial Biofilm Using Anti-Amyloid Monoclonal Antibodies Antibodies Targeting Curli to Disrupt Biofilm Matrix

This patent covers antibody-based compositions and methods that target curli, the major amyloid protein in Enterobacteriaceae biofilms, to disrupt biofilm architecture and prevent or treat the antibiotic-resistant infections associated with indwelling medical devices and chronic wounds.

The Problem

Bacterial biofilms are involved in more than two thirds of human infections, including catheter-associated urinary tract infections, infected heart valves, prosthetic joint infections, chronic wounds, and ventilator-associated pneumonia. Inside a biofilm, bacteria are shielded by a dense extracellular matrix of polysaccharide, DNA, and protein. They become up to a thousand times more tolerant of antibiotics than the same organisms growing freely, and they evade innate immune cells. Once a biofilm has formed on an indwelling device, there is no medical treatment that reliably eradicates it. Clinicians have to remove and replace the catheter, valve, or joint, with high morbidity and cost. The rise of antibiotic resistance has made the problem worse: even the high-dose, prolonged courses needed to overcome biofilm protection are increasingly ineffective. A treatment that disrupts the biofilm matrix itself, restoring antibiotic and immune access to the organisms inside, would change the calculus for device-associated and chronic infections.

What This Invention Does

The invention provides compositions and methods that use antibodies specific for curli, the principal amyloid protein expressed by Enterobacteriaceae (including E. coli and Salmonella) and a major structural component of their biofilms. Curli forms beta-sheet amyloid fibrils that, together with cellulose, build the three-dimensional scaffold inside which bacteria live. The patent claims compositions comprising a therapeutic antibody specific for binding to an epitope of curli, where the epitope has sequence homology to the antibody binding site of one or more heterologous amyloid proteins. The antibody can prevent fibrillisation of curli and of heterologous amyloids (including human amyloid beta), prevent biofilm formation, and disrupt formed biofilms, making the bacteria susceptible to antibiotics and host immune clearance. The invention also covers methods of treating microbial infection and treating or preventing biofilms using the composition. The application is a divisional of AU 2019274591, the national phase of PCT/US2019/033897, with priority from US Provisional 62/676,390 filed 25 May 2018. The work was supported by NIH grant AI132996.

Key Features

• Anti-curli antibody class. The antibodies bind the curli amyloid that builds the structural scaffold of Enterobacteriaceae biofilms. Without curli, the biofilm cannot form a mature three-dimensional structure and existing biofilms are destabilised.
• Cross-amyloid epitope strategy. The patent specifies antibodies whose epitope on curli has sequence homology with antibody-binding sites on heterologous amyloid proteins. That cross-reactive epitope strategy can leverage immunotherapeutic antibodies developed for human amyloid diseases.
• Prevention and disruption of biofilm. The antibody compositions are claimed both for preventing biofilm formation in the first place and for disrupting biofilms after they have formed, supporting use both prophylactically on indwelling devices and as treatment for established device-associated infections.
• Antibody-led restoration of antibiotic sensitivity. Because the antibody disrupts the biofilm matrix, antibiotics that fail at biofilm-tolerant concentrations become effective again, potentially saving devices that would otherwise have to be removed.
• Inhibition of fibrillisation across amyloid families. The same antibodies inhibit fibrillisation of heterologous amyloid proteins, including amyloid beta, raising the possibility of dual use against bacterial biofilms and human amyloid disease.

Who Is Behind It?

The applicants are Temple University, of the Commonwealth System of Higher Education, and the Lankenau Institute for Medical Research in Pennsylvania. The named inventors are Professor Cagla Tukel Wilson, a microbiologist at Temple’s Lewis Katz School of Medicine whose laboratory has been central to the curli-as-target hypothesis, and Dr Scott Dessain of the Lankenau Institute. The Australian patent attorney is FB Rice in Sydney. The application is a divisional of AU 2019274591, the national phase of PCT/US2019/033897, with priority from US provisional 62/676,390 filed 25 May 2018.

Why It Matters

Device-associated and chronic wound infections sit at the centre of the antimicrobial resistance crisis. Australia has approximately 200,000 hospital-acquired infections per year and the National Centre for Antimicrobial Stewardship has flagged biofilm-mediated infections as a priority area. Catheter-associated UTI, prosthetic joint infections, and chronic wound infections in particular drive long inpatient stays, repeated surgery, and recurrent antibiotic exposure. Antibody-based biofilm disruption is a structurally different modality from new antibiotics: it does not exert selection pressure for resistance in the same way, and it can be combined with existing antibiotics. Patent protection in Australia gives Temple and Lankenau the ability to license to local diagnostic, biotech, or pharmaceutical partners and influences whether anti-amyloid antibody products from related programs can be deployed off-label or in combination for Australian patients with biofilm-related disease.

Related Concepts

This application sits at the intersection of immunotherapy and antimicrobial resistance, using monoclonal antibodies rather than new antibiotics to disrupt the protective matrix that protects bacteria from drugs and the immune system.

Because curli shares structural features with human amyloid proteins, the work overlaps with anti-amyloid drug development for diseases such as Alzheimer’s disease, and may help reduce reliance on broad-spectrum antibiotics in device-associated and chronic wound infections.

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AU 2026201863 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.