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US 12,403,194 B2Granted
Compositions for treating cancer
AssigneeKelonia Therapeutics, Inc.
InventorsKevin M. Friedman, Molly R. Perkins, Connor S. Dobson, Stephen L. Sazinsky, Shannon G. Contrastano, Emily Thompson Beura, Cory Ahonen, Andrew Avery
Life of this patent
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Abstract
The present disclosure provides compositions and methods comprising recombinant particles suitable for specifically delivering one or more chimeric antigen receptors to immune effector cells in vivo.
Claims25
A recombinant lentiviral particle comprising:
- (a) a viral envelope comprising (i) a vesicular stomatitis Indiana virus envelope glycoprotein (VSIV-G) comprising amino acid substitutions selected from the group consisting of:
- K47A and R354A;
- K47A and R354Q;
- K47Q and R354A;
- and K47Q and R354Q;
- and (ii) a non-viral membrane-bound tropism polypeptide comprising an anti-CD3ε scFv and a human CD8α hinge and transmembrane domain;
- and
- (b) a recombinant lentiviral vector comprising a polynucleotide encoding a myeloproliferative sarcoma virus enhancer, negative control region deleted, d1587rev primer-binding site substituted (MND) U3 promoter or an EF1α promoter operably linked to a polynucleotide encoding a signal peptide and an anti-BCMA chimeric antigen receptor comprising an anti-BCMA scFv comprising a heavy chain variable region (VH) comprising a CDRH1, a CDRH2, and a CDRH3 comprising the amino acid sequences of SEQ ID NOs:
- 82, 83, and 84, and a light chain variable region (VL) comprising a CDRL1, a CDRL2, and a CDRL3 comprising the amino acid sequences of SEQ ID NOs:
- 86, 87, and 88;
- a CD8α hinge and transmembrane domain;
- a CD137 costimulatory domain;
- and a CD3ζ primary signaling domain.
10 more elements
A recombinant lentiviral particle comprising:
- (a) a viral envelope comprising (i) a mutated viral envelope glycoprotein comprising the amino acid sequence of any one of SEQ ID NOs:
- 332, 333, 334, and 335 and (ii) a non-viral membrane-bound tropism polypeptide comprising the amino acid sequence of any one of SEQ ID NOs:
- 324, 325, 326, 327, 328, 329, 330, and 331;
- and
- (b) a recombinant lentiviral vector comprising a 5′ long terminal repeat (LTR) comprising R and U5 regions;
- a Psi (Ψ) packaging signal;
- a cPPT/FLAP;
- a rev response element (RRE);
- a polynucleotide encoding an MND promoter or an EF1α promoter operably linked to a polynucleotide encoding a signal peptide and an anti-BCMA chimeric antigen receptor (CAR) comprising the amino acid sequence of SEQ ID NO:
- 270;
- optionally a WPRE;
- a 3′ LTR comprising U3 and R regions;
- a polyadenylation signal;
- and a poly(A) tail.
11 more elements
A recombinant lentiviral particle comprising:
- (a) a viral envelope comprising (i) a mutated viral envelope glycoprotein comprising the amino acid sequence of SEQ ID NO:
- 335 and (ii) a non-viral membrane-bound tropism polypeptide comprising the amino acid sequence of SEQ ID NO:
- 324;
- and
- (b) a recombinant lentiviral vector comprising a 5′ LTR comprising R and U5 regions;
- a Ψ packaging signal;
- a cPPT/FLAP;
- a rev response element (RRE);
- a polynucleotide encoding an EF1α promoter operably linked to a polynucleotide encoding a signal peptide and an anti-BCMA CAR comprising the amino acid sequence of SEQ ID NO:
- 270;
- optionally a WPRE;
- a 3′ LTR comprising U3 and R regions;
- a polyadenylation signal;
- and a poly(A) tail.
11 more elements
Dependencies are inferred from the claim text.