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Publication Number
US-12459994-B2
Publication Date
2025-11-04
Expiration Date
Abstract
Provided herein are albumin binding proteins and methods of making and using thereof.
Core Innovation
The invention relates to a humanized albumin binding protein comprising a VHH domain. The VHH domain comprises three complementarity determining regions (CDRs), including CDR1, CDR2, and CDR3, defined by specific amino acid sequences represented by SEQ ID NOs, with CDR2 and CDR3 including allowed residue substitutions at indicated positions.
The invention further provides that the humanized albumin binding protein can comprise a second component, denoted as D2, linked via a peptide linker (L). The linked format can be in an N-to-C order as D1-L-D2 or D2-L-D1, and D2 is either a second antigen binding protein or a non-antigen binding moiety.
The disclosed fusion proteins are characterized for albumin binding using surface plasmon resonance (SPR), including binding affinities (KD) and binding behavior at different pH conditions. The orientation of the components affects the measured affinity, and linking D1 to D2 is associated with increased half-life relative to D2 alone.
Claims Coverage
The independent claim is directed to a humanized albumin binding protein defined by specific VHH CDR sequences, with additional dependent claim coverage adding a linked second component (D2) via a peptide linker, including selectable linker sequences and broad D2 moiety options. The inventive features center on the defined VHH CDR1, CDR2, and CDR3 constraints.
Humanized albumin binding VHH domain with defined CDR sequences
A humanized albumin binding protein comprising a VHH domain, wherein the VHH domain comprising three complementarity determining regions (CDRs) includes a CDR1 having an amino acid sequence represented by SEQ ID NO: 104, a CDR2 having an amino acid sequence represented by SEQ ID NO: 141 with X63 being S or T, and a CDR3 having an amino acid sequence represented by SEQ ID NO: 142 with X101 being T or A.
N-to-C linked second component D2 via peptide linker orientation
A humanized albumin binding protein wherein a peptide linker (L) links a first component (D1) to a second component (D2) in N-to-C order as D1-L-D2 or D2-L-D1, and wherein D2 is either a second antigen binding protein or a non-antigen binding moiety.
Specific peptide linker sequence options
A humanized albumin binding protein wherein the peptide linker has an amino acid sequence matching one of SEQ ID NOs 58-73.
Broad D2 moiety selection including named antibody formats and Fc variants
A humanized albumin binding protein wherein the D2 region includes an antigen-binding or non-antigen-binding moiety selected from various named antibody and binding protein formats and Fc variants, including single chain antibody and multivalent antibody fragments and Fc domain variants.
Overall, the claim coverage is centered on a humanized albumin-binding VHH domain with defined CDR sequence constraints, and is expanded by dependent claim features that add an oriented D1-L-D2 or D2-L-D1 fusion with a peptide linker whose sequence can be selected from specified SEQ ID NOs. The D2 region is further covered by broad selectable moieties spanning antigen-binding and non-antigen-binding formats, including multiple named antibody formats and Fc variant categories.
Stated Advantages
Half-life enhancement associated with linking D1 to D2, as described relative to D2 alone.
Improved albumin binding characterization using SPR including binding affinity values and orientation-dependent affinity differences at specified pH conditions.
Documented Applications
Albumin binding characterization and fusion protein evaluation using surface plasmon resonance (SPR) and half-life enhancement assessment, including comparisons of component orientation and linkage.
Formulation and administration routes for pharmaceutical compositions are discussed, including intravenous and subcutaneous administration, as part of pharmaceutical composition aspects.
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