Heavy chain antibodies binding to PSMA
Inventors
van Schooten, Wim • Clarke, Starlynn • Dang, Kevin • Buelow, Ben
Assignees
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Publication Number
US-12180298-B2
Publication Date
2024-12-31
Expiration Date
Abstract
Anti-PSMA heavy chain antibodies are disclosed, along with methods of making such antibodies, compositions, including pharmaceutical compositions, comprising such antibodies, and their use to treat disorders that are characterized by the expression of PSMA.
Core Innovation
The document describes human anti-PSMA heavy chain-only antibodies (UniAbs™) and related multi-specific formats. The antibodies include antigen-binding regions defined by specific CDR1, CDR2, and CDR3 sequence sets in a human VH framework, and the disclosure allows limited substitutions while requiring heavy-chain-only framework requirements, including heavy chain constant region designs lacking CH1.
The disclosure further provides antibody and molecule formats including monovalent and bivalent configurations and multi-specific constructs including bispecific antibodies (PSMA×CD3) and three-chain antibody-like molecules (TCA/T-chain antibody-like). The multi-specific molecules are characterized through selection of particular variable-region polypeptide sequences and defined linker and Fc design elements in the disclosed formats.
The problem addressed is the need for anti-PSMA binding antibodies and multi-specific constructs that bind PSMA-positive cells while not binding PSMA-negative cells, and that demonstrate functional T-cell redirected activity and anti-tumor effects in PSMA-expressing settings. The document supports this by describing antibody families with PSMA-positive cell binding without PSMA-negative binding, and by reporting characterization including competition epitope binning and affinity estimation.
Claims Coverage
The partial claim set includes four independent claims. Across these, the inventive features mainly cover specific anti-PSMA heavy chain-only antigen-binding regions defined by CDR sequence assignments, antibodies incorporating those antigen-binding regions with defined configuration and optional CD3 binding, and three-chain antibody-like molecules defined by specific PSMA-binding and CD3-binding variable-region polypeptide sequences.
Anti-PSMA antigen-binding region with CDR1/2/3 SEQ ID NOs
An antigen-binding region of an anti-PSMA heavy chain antibody comprising a CDR1 sequence of SEQ ID NO: 2, a CDR2 sequence of SEQ ID NO: 11, and a CDR3 sequence of SEQ ID NO: 18.
Anti-PSMA antibody with defined CDR1/2/3 SEQ ID NOs
An antibody comprising an antigen-binding region of an anti-PSMA heavy chain antibody, wherein the antigen-binding region comprises a CDR1 sequence of SEQ ID NO: 2, a CDR2 sequence of SEQ ID NO: 11, and a CDR3 sequence of SEQ ID NO: 18.
Three-chain antibody-like molecule with CD3 and PSMA binding polypeptide sequences
A three-chain antibody-like molecule that binds to a CD3 protein and a PSMA protein, comprising a first polypeptide comprising the sequence of SEQ ID NO: 86, a second polypeptide comprising the sequence of SEQ ID NO: 87, and a third polypeptide comprising the sequence of SEQ ID NO: 88, 89, 90, 91, 92, or 93.
Three-chain antibody-like molecule with specified PSMA and CD3 variable-region CDR constraints
A three-chain antibody-like molecule comprising a PSMA-binding heavy chain variable region with a CDR1 sequence of SEQ ID NO: 67, a CDR2 sequence of SEQ ID NO: 68, and a CDR3 sequence of SEQ ID NO: 18, and a CD3-binding heavy chain variable region paired with a light chain variable region, wherein the CD3-binding heavy chain variable region comprises CDR1 of SEQ ID NO: 59, CDR2 of SEQ ID NO: 60, and CDR3 of SEQ ID NO: 61, and the light chain variable region comprises CDR1 of SEQ ID NO: 62, CDR2 sequence of GAS, and CDR3 of SEQ ID NO: 64.
Overall, the claim coverage is centered on anti-PSMA heavy chain antibody antigen-binding regions defined by specific CDR1/CDR2/CDR3 sequence assignments, and on constructing multi-specific three-chain antibody-like molecules that bind PSMA and CD3 using specified PSMA-binding variable-region constraints and specified CD3-binding heavy- and light-chain variable-region CDR sequences.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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