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US 2025/0320291 A1Published application
Compositions and uses of cd19 targeted chimeric antigen receptor modified immune cells
AssigneeCity of Hope
InventorsChristine E. Brown, Lawrence Stern, Stephen J. Forman, Xiuli Wang, John Williams
Life of this patent
Estimating the term…
Abstract
CD19 scFv, methods for using such scFv, CAR that include such scFv, methods for making and using such CD19 targeted CAR T cells and CD19 targeted CAR natural killer (NK) cells are described as a methods to treat a variety of cancers.
Claims23
A polypeptide comprising a CD19 scFv comprising:
- (a) the amino acid sequence:
- DIQMTQSPSSLSASVGDRVTITCRASQDISKYLNWYQQKPGGAPKLLIYHTSRLHSGVPS RFSGSGSGTDFTFTISSLQQEDIATYYCQQGNTLPYTFGQGTKLEIKGSTSGSGKPGSGEG STKGQVQLQESGPGLVAPSQTLSLTCTVSGVSLPDYGVSWIRQPPRKGLEWIGVIWGSET TYYNSALKSRVTISVDNSKNQFSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQG TLVTVSS (SEQ ID NO:
- 1) with up to 5 or up to 10 single amino acid substitutions;
- or
- (b) a light chain variable region that is at least 95% identical to:
- (SEQ ID NO:
- 50)
- DIQMTQSPSSLSASVGDRVTITCRASQDISKYLNWYQQKPGGAPKLLIYH
- TSRLHSGVPSRFSGSGSGTDFTFTISSLQQEDIATYYCQQGNTLPYTFGQ
- GTKLEIKGST
- and a heavy chain variable region that is at least 95% identical to:
- (SEQ ID NO:
- 54)
- QVQLQESGPGLVAPSQTLSLTCTVSGVSLPDYGVSWIRQPPRKGLEWIGV
- IWGSETTYYNSALKSRVTISVDNSKNQFSLKLSSVTAADTAVYYCAKHYY
- YGGSYAMDYWGQGTLVTVSS.
13 more elements
(canceled)
A polypeptide comprising a CD19 scFv comprising (a) the amino acid sequence:
- DIQMTQSPSSLSASVGDRVTITCRASQDISKYLNWYQQKPGKAPKLLIYHTSRLHSGVPS RFSGSRSGTDFTLTISSLQPEDFATYYCQQGNTLPYTFGQGTKVEIKGSTSGSGKPGSGEG STKGEVQLVESGGGLVQPGGSLRLSCAASGVSLPDYGVSWVRQAPGKGLEWVAVIWG SETTYYADSVKGRFTISADT SKNTAYLQMNSLRAEDTAVYYCSRHYYYGGSYAMDYW GQGTLVTVSS (SEQ ID NO:32) with up to 5 or up to 10 single amino acid substitutions;
- or
- (b) a light chain variable region that is at least 95% identical to:
- DIQMTQSPSSLSASVGDRVTITCRASQDISKYLNWYQQKPGKAPKLLIYHTSRLHSGVPS RFSGSRSGTDFTLTISSLQPEDFATYYCQQGNTLPYTFGQGTKVEIKGST (SEQ ID NO:
- 55 and a heavy chain variable region that is at least 95% identical to:
- (SEQ ID NO:
- 56)
- EVQLVESGGGLVQPGGSLRLSCAASGVSLPDYGVSWVRQAPGKGLEWVAV
- IWGSETTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRHYY
- YGGSYAMDYWGQGTLVTVSS.
7 more elements
(canceled)
A chimeric antigen receptor comprising a CD19 scFv;
- a spacer;
- a transmembrane domain;
- a co-stimulatory domain;
- and a CD3ζ signaling domain, wherein the CD19 scFv is selected from the group consisting of:
- (a) an scFv comprising the amino acid sequence DIQMTQSPSSLSASVGDRVTITCRASQDISKYLNWYQQKPGGAPKLLIYHTSRLHSGVPS RFSGSGSGTDFTFTISSLQQEDIATYYCQQGNTLPYTFGQGTKLEIKGSTSGSGKPGSGEG STKGQVQLQESGPGLVAPSQTLSLTCTVSGVSLPDYGVSWIRQPPRKGLEWIGVIWGSET TYYNSALKSRVTISVDNSKNQFSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQG TLVTVSS (SEQ ID NO:
- 1) with up to 5 or up to 10 single amino acid substitutions;
- (b) an scFv comprising a light chain variable region that is at least 95% identical to:
- (SEQ ID NO:
- 50)
- DIQMTQSPSSLSASVGDRVTITCRASQDISKYLNWYQQKPGGAPKLLIYH
- TSRLHSGVPSRFSGSGSGTDFTFTISSLQQEDIATYYCQQGNTLPYTFGQ
- GTKLEIKGST
- and a heavy chain variable region that is at least 95% identical to:
- (SEQ ID NO:
- 54)
- QVQLQESGPGLVAPSQTLSLTCTVSGVSLPDYGVSWIRQPPRKGLEWIGV
- IWGSETTYYNSALKSRVTISVDNSKNQFSLKLSSVTAADTAVYYCAKHYY
- YGGSYAMDYWGQGTLVTVSS;
- (c) an scFv comprising a light chain variable region that comprises a CDR1 comprising:
- RASQDISKYLN (SEQ ID NO:
- 51), a CDR2 comprising HTSRLHS (SEQ ID NO:
- 52);
- and a CDR3 comprising QQGNTLPYT (SEQ ID NO:
- 53);
- and a heavy chain variable region that comprises a CDR1 comprising:
- DYGVS (SEQ ID NO:
- 57), a CDR2 comprising VIWGSETTYYNSALKS (SEQ ID NO:
- 60);
- and a CDR3 comprising HYYYGGSYAMDY (SEQ ID NO:
- 59);
- (d) an scFv comprising the amino acid sequence:
- DIQMTQSPSSLSASVGDRVTITCRASQDISKYLNWYQQKPGKAPKLLIYHTSRLHSGVPS RFSGSRSGTDFTLTISSLQPEDFATYYCQQGNTLPYTFGQGTKVEIKGSTSGSGKPGSGEG STKGEVQLVESGGGLVQPGGSLRLSCAASGVSLPDYGVSWVRQAPGKGLEWVAVIWG SETTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRHYYYGGSYAMDYW GQGTLVTVSS (SEQ ID NO:32) with up to 5 or up to 10 single amino acid substitutions;
- (e) an scFv comprising a light chain variable region that is at least 95% identical to:
- DIQMTQSPSSLSASVGDRVTITCRASQDISKYLNWYQQKPGKAPKLLIYHTSRLHSGVPS RFSGSRSGTDFTLTISSLQPEDFATYYCQQGNTLPYTFGQGTKVEIKGST (SEQ ID NO:
- 55) and a heavy chain variable region that is at least 95% identical to:
- EVQLVESGGGLVQPGGSLRLSCAASGVSLPDYGVSWVRQAPGKGLEWVAVIWGSETTY YADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRHYYYGGSYAMDYWGQGTL VTVSS (SEQ ID NO:
- 56);
- and
- (f) a scFv comprising a light chain variable region that comprises a CDR1 comprising:
- RASQDISKYLN (SEQ ID NO:
- 51), a CDR2 comprising HTSRLHS (SEQ ID NO:
- 52);
- and a CDR3 comprising QQGNTLPYT (SEQ ID NO:
- 53) and a heavy chain variable region that comprises a CDR1 comprising:
- DYGVS (SEQ ID NO:
- 57), a CDR2 comprising VIWGSETTYYADSVKG (SEQ ID NO:
- 58);
- and a CDR3 comprising HYYYGGSYAMDY (SEQ ID NO:
- 59).
46 more elements
-20. (canceled)
A nucleic acid molecule comprising a nucleotide sequence encoding a chimeric antigen receptor (CAR), wherein the chimeric antigen receptor comprises:
- an scFv targeting CD19 comprising an amino acid sequence selected from SEQ ID NO:
- 1 or a variant thereof having 1-5 single amino acid substitutions or the amino acid sequence of SEQ ID NO:32 or variant thereof having 1-5 single amino acid substitutions;
- a spacer;
- a transmembrane domain;
- a co-stimulatory domain;
- and a CD3ζ signaling domain.
3 more elements
-30. (canceled)
-36. (canceled)
Dependencies are inferred from the claim text.