Binding proteins 1
Inventors
Campbell, James • DUBLJEVIC, Valentina • Hansen, James • RATTRAY, Zahra • Zhou, Jiangbing
Assignees
Nucleus Therapeutics Pty Ltd • Yale University
Publication Number
US-12312417-B2
Publication Date
2025-05-27
Expiration Date
2038-07-17
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Abstract
The present disclosure relates to cell penetrating anti-DNA binding proteins. Compositions comprising these binding proteins may be may be useful for delivering agents to cells and treating diseases such as cancer.
Core Innovation
The invention relates to cell penetrating anti-DNA binding proteins, specifically antibodies with particular variable region sequences that bind DNA. The core innovation is the identification and use of antibody modifications that significantly increase nuclear penetration, and, in some cases, improve physical stability and reduce immunogenicity. These proteins can be conjugated to therapeutic agents or nucleic acids for the targeted delivery of such agents into cells.
The disclosed binding proteins comprise specific complementarity determining regions (CDRs) in the heavy and light chains, with sequences defined by SEQ ID NOs: 1, 3, 4 (heavy chain) and SEQ ID NOs: 6, 7, 8 (light chain). The invention also covers proteins at least 95% identical to particular reference sequences, and conjugation of these antibodies to therapeutic compounds or nucleic acids, optionally through a cathepsin-cleavable linker.
The problem being solved is the need for improved cell penetrating anti-DNA binding proteins as therapeutic agents, particularly to selectively impair DNA repair pathways or deliver therapeutic payloads to target cells. The approach addresses the clinical need for more effective, stable, and less immunogenic agents for diseases such as cancer, where targeted nuclear delivery of therapeutics is desirable.
Claims Coverage
The patent contains several independent claims, each focusing on inventive features involving cell penetrating anti-DNA antibodies with defined sequences and specific conjugations.
Cell penetrating anti-DNA antibody with defined CDR sequences conjugated to a therapeutic compound
An antibody comprising: - A heavy chain variable region (VH) with: - CDR1: NYGMH (SEQ ID NO: 1) - CDR2: YISSGSSTIYYADSVKG (SEQ ID NO: 3) - CDR3: RGLLLDY (SEQ ID NO: 4) - A light chain variable region (VL) with: - CDR1: RASKTVSTSSYSYMH (SEQ ID NO: 6) - CDR2: YASYLES (SEQ ID NO: 7) - CDR3: QHSREFPWT (SEQ ID NO: 8) - The antibody is conjugated to a therapeutic compound. Optional features include: - VH and VL with at least 95% identity to specified SEQ ID NOs - The therapeutic compound includes cytotoxic agents, chemotherapeutics, anti-inflammatories, or radioisotopes - Conjugation via a linker cleavable by cathepsin
Cell penetrating anti-DNA antibody with defined CDR sequences conjugated to a nucleic acid
An antibody comprising: - A heavy chain variable region (VH) with: - CDR1: NYGMH (SEQ ID NO: 1) - CDR2: YISSGSSTIYYADSVKG (SEQ ID NO: 3) - CDR3: RGLLLDY (SEQ ID NO: 4) - A light chain variable region (VL) with: - CDR1: RASKTVSTSSYSYMH (SEQ ID NO: 6) - CDR2: YASYLES (SEQ ID NO: 7) - CDR3: QHSREFPWT (SEQ ID NO: 8) - The antibody is conjugated to a nucleic acid. Optional features include: - VH and VL with at least 95% identity to specified SEQ ID NOs - Conjugation via a linker cleavable by cathepsin
The main inventive features cover cell-penetrating anti-DNA antibodies with specific CDR and variable region sequences, conjugation to therapeutic compounds or nucleic acids, and the delivery of these agents via defined linkers to treat diseases such as cancer.
Stated Advantages
The disclosed modifications increase nuclear penetration of the binding proteins.
Some modifications improve the physical stability of the proteins.
Some modifications reduce the immunogenicity of the binding proteins.
Documented Applications
Treatment of cancer, including but not limited to glioblastoma, BRCA2 deficient cancers, and PTEN deficient cancers.
Targeted delivery of therapeutic agents (such as cytotoxic drugs or radioisotopes) and nucleic acids into cells.
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