Anti-CD20 antibodies and CAR-T structures
Inventors
Trinklein, Nathan • Harris, Katherine • Allen, Nicole • CHANG, Karen • Avanzino, Brian
Assignees
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Publication Number
US-12709644-B2
Publication Date
2026-08-18
Expiration Date
Abstract
Anti-CD20 antibodies (e.g., UniAbs™) and CAR-T structures are disclosed, along with methods of making such antibodies and CAR-T structures, compositions, including pharmaceutical compositions, comprising such antibodies and CAR-T structures, and their use to treat disorders that are characterized by the expression of CD20.
Core Innovation
The invention relates to anti-CD20 heavy-chain-only antibodies that include a heavy chain variable region with CDR1, CDR2, and CDR3 sequences embedded in a human VH framework. The disclosed antibody sequences are derived from UniAbs™/UniRat™ and include specific VH CDR sequences (SEQ ID NOs 1–6), embedded in a human VH framework, together with related VH sequences (SEQ ID NOs 7–8) and Fc/IgG subclass and variant configurations.
A central aspect is the use of these anti-CD20 heavy-chain-only antibody-derived heavy chain variable region features as an extracellular antigen-binding domain in a chimeric antigen receptor (CAR). The disclosed CAR comprises an extracellular antigen-binding domain that binds to CD20 and includes a heavy chain variable region that carries the specified CDR1, CDR2, and CDR3 sequences within the human VH framework.
The disclosure further positions these CAR extracellular antigen-binding domains in CAR-T constructs for treatment of disorders characterized by CD20 expression. The provided experimental evidence includes CD20 binding to Raji/Daudi cells, CAR-T mediated T-cell activation using a Jurkat NFAT luciferase reporter co-culture, in vitro killing of Raji-luc-GFP cells, and in vivo xenograft efficacy in a Raji-NSG model, with improved tumor control/survival for specific VH constructs.
Claims Coverage
Two independent claims are identified: one directed to a CAR T-cell with a CD20-binding extracellular antigen-binding domain containing specified CDR1/2/3 sequences in a human VH framework, and one directed to a CAR T-cell with a CD20-binding extracellular antigen-binding domain comprising a specified heavy chain variable region sequence (SEQ ID NO: 8). The independent claims focus on a limited set of inventive features centered on the CD20-binding heavy-chain variable region/CAR extracellular antigen-binding domain configuration.
CD20-binding CAR extracellular antigen-binding domain with specified CDR1/2/3 in a human VH framework
A CAR T-cell comprising a CAR with an extracellular antigen-binding domain that binds to CD20, wherein the CAR includes a heavy chain variable region sequence comprising a CDR1 sequence comprising SEQ ID NO: 4, a CDR2 sequence comprising SEQ ID NO: 5, and a CDR3 sequence comprising SEQ ID NO: 6; and wherein the CDR1, CDR2, and CDR3 sequences are present in a human VH framework.
CD20-binding CAR extracellular antigen-binding domain with a specific heavy chain variable region sequence (SEQ ID NO: 8)
A CAR T-cell comprising a CAR with an extracellular antigen-binding domain that binds to CD20, wherein the CAR includes a heavy chain variable region sequence comprising SEQ ID NO: 8.
Overall, the claim coverage is directed to CAR-T cells where CD20 binding is mediated by an extracellular antigen-binding domain comprising a heavy chain variable region defined by specific CDR1/2/3 sequences in a human VH framework (SEQ ID NOs 4–6) and, alternatively, by a specified heavy chain variable region sequence (SEQ ID NO: 8).
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treatment scope for disorders characterized by CD20 expression, including non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), acute lymphocytic leukemia (ALL), and marginal zone lymphoma (MZL) [as described in the partial content summary].
CAR-T constructs using the disclosed CD20-binding extracellular antigen-binding domains are documented with experimental evidence including CD20 binding, CAR-T mediated T-cell activation, in vitro killing, and in vivo xenograft efficacy in a Raji-NSG model [as described in the partial content summary].
Pharmaceutical composition formats including the CAR-T cell are documented [as described in the partial content summary].
Kit formats that include optional additional reagents including a chemotherapeutic drug are documented [as described in the partial content summary].
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