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Publication Number
US-12006369-B2
Publication Date
2024-06-11
Expiration Date
Abstract
The invention provides improved compositions for adoptive T cell therapies for B cell related conditions.
Core Innovation
The invention relates to chimeric antigen receptor (CAR) compositions for human B cell maturation antigen (BCMA) targeting, including a variable light chain comprising the CDR sequences set forth in SEQ ID NOs: 1-3 and a variable heavy chain comprising the CDR sequences set forth in SEQ ID NOs: 4-6. The CDR sequences bind human BCMA, and the CAR comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 71.
The invention further encompasses a CAR comprising the amino acid sequence of SEQ ID NO: 71. The disclosed CAR constructs are described in connection with humanized anti-BCMA CARs and behavior in which certain humanized anti-BCMA CARs cause antigen-independent tonic cytokine release.
The description also addresses modifying a CAR transmembrane domain to make cytokine release antigen-dependent or to reduce cytokine release without antigen. The disclosed CAR architecture includes a humanized anti-BCMA extracellular binding domain with specified CDRs, together with hinge/spacer and transmembrane domain choices, co-stimulatory domains, and a primary signaling domain.
The constructs are also described in terms of encoding polynucleotides/vectors and genetically modified immune effector cells, including T lymphocytes and NK cells, and in terms of pharmaceutical compositions with pharmaceutically acceptable excipients for therapeutic use.
Claims Coverage
The partial content identifies two independent claims. Across these claims, the inventive scope is directed to a human BCMA-binding CAR defined by CDRs and sequence identity, and a CAR defined by a specific amino-acid sequence, with dependent claim coverage to CAR-containing cells and compositions.
Bcma-binding humanized car with defined cdrs and sequence identity
A chimeric antigen receptor (CAR) comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 71, wherein the CAR comprises a variable light chain comprising the CDR sequences set forth in SEQ ID NOs: 1-3 and a variable heavy chain comprising the CDR sequences set forth in SEQ ID NOs: 4-6, and wherein the CDR sequences bind human B cell maturation antigen (BCMA).
Car comprising the amino acid sequence of seq id no. 71
A CAR comprising the amino acid sequence of SEQ ID NO: 71.
Overall, the claim coverage focuses on CARs that bind human BCMA through specified light- and heavy-chain CDR sequences with at least 95% identity to SEQ ID NO: 71, and on a CAR defined by the amino-acid sequence of SEQ ID NO: 71, with dependent claim coverage for CAR-containing cells and compositions including pharmaceutically acceptable excipients.
Stated Advantages
Modifying the CAR transmembrane domain can make cytokine release antigen-dependent.
Modifying the CAR transmembrane domain can reduce cytokine release without antigen.
Humanized anti-BCMA CARs can be evaluated for tonic cytokine release behavior in association with cytolytic activity.
Documented Applications
BCMA-targeted cancer treatment using CAR-modified immune effector cell populations, including multiple myeloma and non-Hodgkin’s lymphoma.
Cryopreservation and thawing of CAR-expressing immune effector cells to maintain viability upon thawing.
Therapeutic administration framework for CAR T-cell infusion with in vivo expansion, persistence, and memory differentiation, including repeated blood draw, activation, and reinfusion.
Therapeutic treatment of multiple myeloma (MM).
Therapeutic treatment of non-Hodgkin’s lymphoma (NHL).
Treatment of B-cell related autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, myasthenia gravis, and ITP.
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