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US 12,599,679 B2Granted
Circular RNA compositions
AssigneeOrna Therapeutics, Inc.
InventorsAmy M. Becker, Robert Alexander Wesselhoeft, IV, Akinola O. Emmanuel, Jui Dutta-Simmons, Allen T. Horhota, Kevin J. Kauffman, Bun Chau, Thomas Lee
Life of this patent
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Abstract
Provided herein are circular RNA constructs comprising an IRES, and at least one expression sequence encoding binding molecule, compositions thereof, and methods of treatment, including for cancer and autoimmune disease. In particular, circular RNA comprising an IRES and a CD19 binder, a HER2 binder, or a BCMA binder are provided, optionally formulated with a delivery vehicle. Precursor polynucleotides comprising an IRES, and at least one expression sequence encoding a CAR construct are also described herein.
Claims48
A circular RNA construct comprising:
- (A) a translation initiation element comprising a sequence that is at least 80% identical to the corresponding RNA sequence of any one of SEQ ID NO:
- 8, SEQ ID NOs:
- 1-7, and SEQ ID NOs:
- 9-18, and
- (B) at least one expression sequence that encodes a chimeric antigen receptor (CAR), wherein the CAR comprises an antigen binding domain, a hinge domain, a transmembrane domain, a costimulatory domain, and a signaling domain, wherein:
- a. the antigen binding domain specifically binds to CD19 and comprises a light chain variable region (VL) comprising VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO:
- 29, and a heavy chain variable region (VH) comprising VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO:
- 29, wherein the VL and VH are linked by a linker;
- b. the antigen binding domain specifically binds to BCMA and comprises a first variable heavy domain of heavy chain (VHH) comprising VHH CDR1, VHH CDR2, and VHH CDR3 of SEQ ID NO:
- 122, and a second VHH comprising a VHH CDR4, VHH CDR5, and VHH CDR6 of SEQ ID NO:
- 122;
- c. the antigen binding domain specifically binds to BCMA and comprises a VL comprising a VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO:
- 121, and a VH comprising a VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO:
- 121, wherein the VL and VH are linked by a linker;
- or
- d. the antigen binding domain specifically binds to HER2 and comprises a VL comprising VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO:
- 117, and VH comprising VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO:
- 117, wherein the VL and VH are linked by a linker.
15 more elements
A linear precursor RNA polynucleotide comprising:
- (A) a translation initiation element comprising a sequence that is at least 80% identical to any one of SEQ ID NO:
- 8, SEQ ID NOs:
- 1-7, SEQ ID NOs:
- 9-18, or fragment thereof, and
- (B) at least one expression sequence that encodes a chimeric antigen receptor (CAR), wherein the CAR comprises an antigen binding domain, a hinge domain, a transmembrane domain, a costimulatory domain, and a signaling domain, wherein:
- a. the antigen binding domain specifically binds to CD19 and comprises a light chain variable region (VL) comprising a VL CDR1, VL CDR2, VL CDR3 of SEQ ID NO:
- 29, and a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO:
- 29, wherein the VL and VH are linked by a linker;
- b. the antigen binding domain specifically binds to BCMA and comprises a first variable heavy domain of heavy chain (VHH) comprising a VHH CDR1, VHH CDR2, VHH CDR3 of SEQ ID NO:
- 122, and a second VHH comprising a VHH CDR4, VHH CDR5, and VHH CDR6 of SEQ ID NO:
- 122;
- c. the antigen binding domain specifically binds to BCMA and comprises a VL comprising a VL CDR1, VL CDR2, VL CDR3 of SEQ ID NO:
- 121, and a VH comprising a VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO:
- 121, wherein the VL and VH are linked by a linker;
- and/or
- d. the antigen binding domain specifically binds to HER2 and comprises a VL comprising a VL CDR1, VL CDR2, VL CDR3 of SEQ ID NO:
- 117, and VH comprising a VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO:
- 117, wherein the VL and VH are linked by a linker.
15 more elements
A DNA vector encoding a linear RNA polynucleotide comprising:
- (A) a translation initiation element comprising a sequence that is at least 80% identical to the corresponding RNA sequence of any one of SEQ ID NO:
- 8, SEQ ID NOs:
- 1-7, or SEQ ID NOs:
- 9-18, and
- (B) at least one expression sequence that encodes a chimeric antigen receptor (CAR), wherein the CAR comprises an antigen binding domain, a hinge domain, a transmembrane domain, a costimulatory domain, and a signaling domain, wherein:
- a. the antigen binding domain specifically binds to CD19 and comprises a light chain variable region (VL) comprising VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO:
- 29, and a heavy chain variable region (VH) comprising VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO:
- 29, wherein the VL and VH are linked by a linker;
- b. the antigen binding domain specifically binds to BCMA and comprises a first variable heavy domain of heavy chain (VHH) comprising VHH CDR1, VHH CDR2, and VHH CDR3 of SEQ ID NO:
- 122, and a second VHH comprising a VHH CDR4, VHH CDR5 and VHH CDR6 of SEQ ID NO:
- 122;
- c. the antigen binding domain specifically binds to BCMA and comprises a VL comprising a VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO:
- 121, and a VH comprising a VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO:
- 121, wherein the VL and VH are linked by a linker;
- or
- d. the antigen binding domain specifically binds to HER2 and comprises a VL comprising VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO:
- 117, and VH comprising VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO:
- 117, wherein the VL and VH are linked by a linker.
15 more elements
Dependencies are inferred from the claim text.