Viral treatment

Inventors

Connaris, Helen • Yang, Lei • Potter, Jane Alexandra

Assignees

Pneumagen Ltd

Abstract

The disclosure provides molecules for use in compositions, medicaments and methods for the treatment or prevention of RSV infections, its symptoms and associated pathologies and potentially infections caused or contributed to by viral pathogens which do not bind or do not primarily bind sialic acid containing receptors during pathogenesis. Specifically, the disclosure is based on the finding that molecules with affinity for (or an ability to bind to) sialic acid (and in particular sialoglycoconjugates) on cell surfaces (these including sialic acid containing glycoproteins and cell surface sialic acid receptors), find utility in the treatment and/or prevention of symptoms, infections, diseases and/or conditions associated with respiratory syncytial vims (RSV).

Core Innovation

The invention relates to using a sialic acid binding molecule to treat a respiratory syncytial virus (RSV) infection in a subject in need thereof. The sialic acid binding molecule comprises one or more family 40 carbohydrate binding modules (CBM40), and the rationale described is that RSV does not bind host sialylated receptors, but CBM40 binds sialylated RSV surface glycoproteins terminating in sialic acid and/or blocks access to host targets.

The core constructs described are CBM40-based multivalent sialic acid binding molecules, including CBM40/TD-linked architectures and engineered variants. The description specifies a fusion structure comprising CBM40 linked to a trimerisation domain (TD) and multivalent examples including named constructs and engineered hexameric constructs, including HEX17, with defined CBM40-derived elements and SEQ ID-defined variants and mutation sets.

The description further states optional functional exclusions and binding/property constraints for the sialic acid binding molecules. These include exclusion of sialidase activity and exclusion of heparin/heparin sulfate binding, including non-binding and/or exclusion of a GAG-binding domain, while maintaining sialic acid binding functionality. Experimental support described includes evidence of CBM-RSV interaction and modulation of inflammatory mediators, including IL-8, along with binding assays such as ELISA and competition with sialyllactose, and reports using in vitro and in vivo models.

Claims Coverage

The document provides two independent claims, both centered on administering a sialic acid binding molecule that comprises one or more family 40 carbohydrate binding modules (CBM40). Across the dependent claims, the coverage is refined by defining modified CBM40(s) and specifying sequence- and domain-level constraints, including functional exclusions and defined CBM1/CBM2-TD fusion structures and variants.

Overall, the claim set covers prophylaxis/treatment and neutralising/blocking of RSV by administering CBM40-containing sialic acid binding molecules, with dependent coverage specifying additional functional exclusions including sialidase activity and heparin/heparin sulfate or GAG-binding-related properties, and tighter definition of modified CBM40(s) via mutation-relative reference sequences and specified CBM1/CBM2-TD fusion architectures.

Stated Advantages

Documented Applications