Polypeptides that bind complement component C5 or serum albumin and fusion proteins thereof
Inventors
Puffer, Bridget • Chandler, Julian • GERA, NIMISH • Sheridan, Douglas L. • JINDAL, SIDDHARTH • Tamburini, Paul P.
Assignees
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Publication Number
US-12221473-B2
Publication Date
2025-02-11
Expiration Date
Abstract
The disclosure provides engineered polypeptides that specifically bind to human complement component C5 and/or serum albumin. The disclosure also provides fusion proteins comprising such engineered polypeptides, wherein such fusion proteins may be multivalent and multi-specific fusion proteins. The disclosure further provides nucleic acid molecules that encode such engineered polypeptides or fusion proteins, and methods of making such engineered polypeptides or fusion proteins. The disclosure further provides pharmaceutical compositions that comprise such engineered polypeptides or fusion proteins, and methods of treatment using such engineered polypeptides or fusion proteins.
Core Innovation
The invention relates to an engineered polypeptide that specifically binds to human serum albumin. The engineered polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOS:22-25 and 27-34 and fragments thereof.
The disclosure further provides engineered binding domains configured as fusion proteins combining C5-binding and human serum albumin-binding functions, including multi-specific and multivalent arrangements. The fusion proteins include linker peptide options and defined domain orientation arrangements for combining the complement C5-binding domain with an HSA-binding polypeptide.
Phage-display panning is used to identify anti-albumin VHHs, with human serum albumin as the target antigen. Selected binding polypeptides are expressed and purified as VHH-His proteins, and their binding to human serum albumin is characterized, including binding behavior against additional serum albumins and non-competitive albumin binding versus FcRn for at least one set of albumin-binding polypeptides.
Claims Coverage
The provided independent claims cover sequence-defined engineered polypeptides that specifically bind human serum albumin, and additional fusion-protein embodiments combining C5-binding and HSA-binding functions. Across the items, two inventive features are identified for the albumin-binding polypeptide claim coverage.
Engineered polypeptide specifically binding to human serum albumin
An engineered polypeptide that specifically binds to human serum albumin.
Defined sequence selection (SEQ ID NOS:22-25 and 27-34) or fragments thereof
The engineered polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOS:22-25 and 27-34 and fragments thereof.
The claim coverage is directed to sequence-defined engineered polypeptides that specifically bind human serum albumin, with fusion-protein embodiments also described in the disclosure.
Stated Advantages
The disclosure states that an HSA-binding VHH does not significantly disrupt FcRn binding.
The disclosure presents the albumin-binding function as supporting an extended albumin half-life pathway via FcRn.
Documented Applications
Bispecific C5/HSA fusion constructs for complement-related disorders.
Pharmaceutical compositions and therapeutic kits for treating complement-mediated disorders.
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