Therapeutic molecules
Inventors
MCGUINNESS, Brian • OSUCH, Isabelle • Rossant, Chris • ROMANOS, Mike • Royle, Nikki • Sandal, Thomas • Thompson, Lorraine • Writer, Michele
Assignees
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Publication Number
US-11746158-B2
Publication Date
2023-09-05
Expiration Date
Abstract
The invention relates to binding molecules that bind specifically to prostate specific membrane antigen (PSMA), in particular, single human variable heavy chain domain antibodies and related methods for treatment of cancer.
Core Innovation
The invention relates to binding molecules that bind human prostate specific membrane antigen (PSMA) and comprise a single human variable heavy chain (V_H) domain antibody. The binding molecule is defined by CDR1, CDR2 and CDR3 sequences selected from multiple specified sets of SEQ ID NOs, including family-by-family sequence listings and variant homologs with specified sequence identity.
The disclosed V_H-only antibodies provide binding capability through the heavy chain variable domain sequences comprising the CDR1, CDR2 and CDR3 regions, and the disclosure associates the selected V_H domains with binding and kinetic parameter information, including KD, Koff, Ka, IC50 and EC50. The invention addresses the need for PSMA-targeted anti-prostate cancer agents directed to human PSMA.
The disclosed binding molecules are described in multiple formats and contexts, including toxin conjugates, pharmaceutical compositions or medicaments, diagnostic immunoassay detection for PSMA detection, nucleic acids encoding the binding molecules, host cells or recombinant expression systems for producing the binding molecules, and combinations and multimodal binding molecule constructs such as bivalent, bispecific and multispecific fusions. Optional additional moieties include an albumin-binding moiety, and conjugated forms may include a toxin, labeled conjugate, enzyme, radioisotope, or other chemical moiety.
Claims Coverage
The independent claims center on PSMA-binding binding molecules defined by a single human V_H-only antibody whose CDR1, CDR2, and CDR3 sequences are selected from enumerated SEQ ID NO combinations. Across the provided claims, the main coverage centers on this V_H domain definition, with dependent refinements that specify additional V_H sequence choice, conjugate, composition, detection, and therapeutic embodiments.
Psma-binding single human variable heavy chain domain antibody
A binding molecule capable of binding human PSMA comprising a single human variable heavy chain (V_H) antibody comprising CDR1, CDR2 and CDR3 sequences selected from the enumerated SEQ ID NO combinations.
Further enumerated V_H sequence selection constraint
The binding molecule includes a V_H domain that comprises or consists of one of SEQ ID NO. 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, or 80.
Conjugation to a toxin, enzyme, radioisotope, or other chemical moiety
The binding molecule is conjugated to a toxin, enzyme, radioisotope, or another chemical moiety.
Pharmaceutical composition comprising the binding molecule and a pharmaceutical carrier
A pharmaceutical composition includes the binding molecule together with a pharmaceutical carrier.
Therapeutic treatment of prostate cancer or PSMA-expressing cancer
A method of treating prostate cancer or a PSMA-expressing cancer by administering a therapeutically effective amount of the binding molecule.
Diagnostic immunoassay detection for PSMA detection
The binding molecule is used as a detection agent in an immunoassay format for PSMA detection.
Overall, the claim coverage centers on PSMA-binding V_H-only antibodies defined by enumerated CDR1/CDR2/CDR3 SEQ ID selections, with dependent coverage that adds toxin, enzyme, radioisotope, or other chemical moiety conjugates, pharmaceutical compositions, diagnostic immunoassay detection, and therapeutic treatment of prostate cancer or PSMA-expressing cancer.
Stated Advantages
High-affinity native-form PSMA binding.
Monovalent targeting.
Reduced immunogenicity.
High stability.
High expression.
Utility in multiple formats, including toxin conjugates, medicaments or pharmaceutical compositions, diagnostic immunoassay detection, and nucleic acid or host cell production systems.
Documented Applications
Cancer therapy via PSMA-targeting, including treatment of prostate cancer or PSMA-expressing cancer by administering the binding molecule.
Toxin-conjugated immunoconjugate formats for therapeutic use.
Diagnostic immunoassay detection for PSMA detection.
PSMA inhibition in vitro or in vivo.
Production of the binding molecules using nucleic acids encoding the binding molecules and host cell or recombinant expression systems.
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