IP Library › Granted Patent US 12,599,679
Granted Patent B2
US 12,599,679 · App. 19/200,761 · Granted Apr 14, 2026

Circular RNA compositions

Inventors: Amy M. Becker (Lexington, MA); Robert Alexander Wesselhoeft, IV (Somerville, MA); Akinola O. Emmanuel (Cambridge, MA); Jui Dutta-Simmons (Sudbury, MA); Allen T. Horhota (Westford, MA); Kevin J. Kauffman (Newton, MA); Bun Chau (Needham, MA); Thomas Lee (Watertown, MA)
Assignee: Orna Therapeutics, Inc.
A61K48/005A61K9/1272A61K9/5123A61K40/11A61K40/15A61K40/17A61K40/31A61K40/4205A61K40/4211A61P35/00C07K16/2803C07K16/32C12N15/85C12N15/88A61K2239/13A61K2239/17A61K2239/21C07K2317/565C07K2317/622C12N2800/22C12N2830/50C12N2840/203
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,599,679
App. No.
19/200,761
Granted
Apr 14, 2026
Kind
B2
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.

Claims (83)

1 . 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.

2 . The circular RNA construct of claim 1 , wherein the translation initiation element comprises a sequence that is at least 90% identical to SEQ ID NO: 8.

3 . The circular RNA construct of claim 1 , wherein 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 the VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 29, wherein the VL and VH are linked by a linker.

4 . The circular RNA construct of claim 1 , wherein the expression sequence encodes a single chain antibody fragment (scFv).

5 . The circular RNA construct of claim 1 , wherein the circular RNA further comprises a polyA region, at least one miRNA binding site, and/or at least one miR-122 binding site.

6 . The circular RNA construct of claim 1 , wherein the expression sequence is codon optimized.

7 . The circular RNA construct of claim 1 , wherein the expression sequence further encodes a signal peptide.

8 . The circular RNA construct of claim 1 , wherein:

(a) the hinge domain is derived from a ErbB2, glycophorin A (GpA), CD2, CD3 delta, CD3 epsilon, CD3 gamma, CD4, CD7, CD8a, CD8b, CD11a (IT GAL), CD11b (IT GAM), CD11c (ITGAX), CD11d (IT GAD), CD18 (ITGB2), CD19 (B4), CD27 (TNFRSF7), CD28, CD28T, CD29 (ITGB1), CD30 (TNFRSF8), CD40 (TNFRSF5), CD48 (SLAMF2), CD49a (ITGA1), CD49d (ITGA4), CD49f (ITGA6), CD66a (CEACAM1), CD66b (CEACAM8), CD66c (CEACAM6), CD66d (CEACAM3), CD66e (CEACAM5), CD69 (CLEC2), CD79A (B-cell antigen receptor complex-associated alpha chain), CD79B (B-cell antigen receptor complex-associated beta chain), CD84 (SLAMF5), CD96 (Tactile), CD100 (SEMA4D), CD103 (ITGAE), CD134 (0X40), CD137 (4-1BB), CD150 (SLAMF1), CD158A (KIR2DL1), CD158B1 (KIR2DL2), CD158B2 (KIR2DL3), CD158C (KIR3DP1), CD158D (KIRDL4), CD158F1 (KIR2DL5A), CD158F2 (KIR2DL5B), CD158K (KIR3DL2), CD160 (BY55), CD162 (SELPLG), CD226 (DNAM1), CD229 (SLAMF3), CD244 (SLAMF4), CD247 (CD3-zeta), CD258 (LIGHT), CD268 (BAFFR), CD270 (TNFSF14), CD272 (BTLA), CD276 (B7-H3), CD279 (PD-1), CD314 (NKG2D), CD319 (SLAMF7), CD335 (NK-p46), CD336 (NK-p44), CD337 (NK-p30), CD352 (SLAMF6), CD353 (SLAMF8), CD355 (CRT AM), CD357 (TNFRSF18), inducible T cell co-stimulator (ICOS), LFA-1 (CD11a/CD18), NKG2C, DAP-10, ICAM-1, NKp80 (KLRF1), IL-2R beta, IL-2R gamma, IL-7R alpha, LFA-1, SLAMF9, LAT, GADS (GrpL), SLP-76 (LCP2), or PAG1/CBP;

(b) the transmembrane domain is derived from ErbB2, glycophorin A (GpA), 4-1BB/CD137, activating NK cell receptors, an immunoglobulin protein, B7-H3, BAFFR, BFAME (SEAMF8), BTEA, CD100 (SEMA4D), CD103, CD160 (BY55), CD18, CD19, CD19a, CD2, CD247, CD27, CD276 (B7-H3), CD28, CD29, CD3 delta, CD3 epsilon, CD3 gamma, CD30, CD4, CD40, CD49a, CD49D, CD49f, CD69, CD7, CD84, CD8alpha, CD8beta, CD96 (Tactile), CD11a, CD11b, CD11c, CD11d, CDS, CEACAM1, CRT AM, cytokine receptor, DAP-10, DNAMI (CD226), Fc gamma receptor, GADS, GITR, HVEM (EIGHTR), IA4, ICAM-1, ICAM-1, Ig alpha (CD79a), IE-2R beta, IE-2R gamma, IE-7R alpha, inducible T cell costimulator (ICOS), integrins, ITGA4, ITGA4, ITGA6, IT GAD, ITGAE, ITGAE, IT GAM, ITGAX, ITGB2, ITGB7, ITGB1, KIRDS2, EAT, LFA-1, LFA-1, a ligand that specifically binds with CD83, LIGHT, LIGHT, LTBR, Ly9 (CD229), lymphocyte function-associated antigen-1 (LFA-1; CD11a/CD18), MHC class 1 molecule, NKG2C, NKG2D, NKp30, NKp44, NKp46, NKp80 (KLRF1), OX-40, PAG/Cbp, programmed death-1 (PD-1), PSGL1, SELPLG (CD162), Signaling Lymphocytic Activation Molecules (SLAM proteins), SLAM (SLAMF1; CD150; IPO-3), SLAMF4 (CD244; 2B4), SLAMF6 (NTB-A; Ly108), SLAMF7, SLP-76, TNF receptor proteins, TNFR2, TNFSF14, a Toll ligand receptor, TRANCE/RANKL, VLA1, or VLA-6;

(c) the costimulatory domain is selected from a CD137 costimulatory domain or CD28 costimulatory domain; and

(d) the signaling domain is derived from B7-H3, BAFFR, BLAME (SLAMF8), BTLA, CD100 (SEMA4D), CD103, CD160 (BY55), CD18, CD19, CD 19a, CD2, CD247, CD27, CD276 (B7-H3), CD28, CD29, CD3 delta, CD3 epsilon, CD3 gamma, CD3 zeta, CD30, CD4, CD40, CD49a, CD49D, CD49f, CD69, CD7, CD84, CD8alpha, CD8beta, CD96 (Tactile), CD11a, CD11b, CD11c, CD11d, CDS, CEACAM1, CRT AM, cytokine receptor, DAP-10, DNAMI (CD226), Fc gamma receptor, GADS, GITR, HVEM (LIGHTR), IA4, ICAM-1, Ig alpha (CD79a), IL-2R beta, IL-2R gamma, IL-7R alpha, inducible T cell costimulator (ICOS), integrins, ITGA4, ITGA6, ITGAD, ITGAE, ITGAL, ITGAM, ITGAX, ITGB2, ITGB7, ITGB1, KIRDS2, LAT, LFA-1, ligand that specifically binds with CD83, LIGHT, LTBR, Ly9 (CD229), Ly108, lymphocyte function-associated antigen-1 (LFA-1; CD11a/CD18), MHC class 1 molecule, NKG2C, NKG2D, NKp30, NKp44, NKp46, NKp80 (KLRF1), OX-40, PAG/Cbp, programmed death-1 (PD-1), PSGL1, SELPLG (CD162), Signaling Lymphocytic Activation Molecules (SLAM proteins), SLAM (SLAMF1; CD150; IPO-3), SLAMF4 (CD244; 2B4), SLAMF6 (NTB-A), SLAMF7, SLP-76, TNF receptor proteins, TNFR2, TNFSF14, a Toll ligand receptor, TRANCE/RANKL, VLA1, or VLA-6.

9 . A pharmaceutical composition comprising the circular RNA construct of claim 1 ; and a transfer vehicle.

10 . The pharmaceutical composition of claim 9 , wherein the transfer vehicle comprises: (i) an ionizable lipid of Formula (I)

wherein n is an integer between 1 and 4;

R a is hydrogen or hydroxyl; and

R 1 and R 2 are each independently a linear or branched C 6 -C 30 alkyl, C 6 -C 30 alkenyl, or C 6 -C 30 heteroalkyl, optionally substituted by one or more substituents selected from a group consisting of oxo, halo, hydroxy, cyano, alkyl, alkenyl, aldehyde, heterocyclylalkyl, hydroxyalkyl, dihydroxyalkyl, hydroxyalkylaminoalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, (heterocyclyl)(alkyl) aminoalkyl, heterocyclyl, heteroaryl, alkylheteroaryl, alkynyl, alkoxy, amino, dialkylamino, aminoalkylcarbonylamino, aminocarbonylalkylamino, (aminocarbonylalkyl)(alkyl)amino, alkenylcarbonylamino, hydroxycarbonyl, alkyloxycarbonyl, aminocarbonyl, aminoalkylaminocarbonyl, alkylaminoalkylaminocarbonyl, dialkylaminoalkylaminocarbonyl, heterocyclylalkylaminocarbonyl, (alkylaminoalkyl)(alkyl) aminocarbonyl, alkylaminoalkylcarbonyl, dialkylaminoalkylcarbonyl, heterocyclylcarbonyl, alkenylcarbonyl, alkynylcarbonyl, alkylsulfoxide, alkylsulfoxidealkyl, alkylsulfonyl, and alkylsulfonealkyl;

or

(ii) an ionizable lipid of Formula (II)

wherein each n is independently an integer from 2-15;

L 1 and L 3 are each independently —OC(O)—* or —C(O)O—*, wherein “*” indicates the attachment point to R 1 or R 3 ;

R 1 and R 3 are each independently a linear or branched C 9 -C 20 alkyl or C 9 -C 20 alkenyl, optionally substituted by one or more substituents selected from a group consisting of oxo, halo, hydroxy, cyano, alkyl, alkenyl, aldehyde, heterocyclylalkyl, hydroxyalkyl, dihydroxyalkyl, hydroxyalkylaminoalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, (heterocyclyl) (alkyl) aminoalkyl, heterocyclyl, heteroaryl, alkylheteroaryl, alkynyl, alkoxy, amino, dialkylamino, aminoalkylcarbonylamino, aminocarbonylalkylamino, (aminocarbonylalkyl) (alkyl) amino, alkenylcarbonylamino, hydroxycarbonyl, alkyloxycarbonyl, aminocarbonyl, aminoalkylaminocarbonyl, alkylaminoalkylaminocarbonyl, dialkylaminoalkylaminocarbonyl, heterocyclylalkylaminocarbonyl, (alkylaminoalkyl) (alkyl) aminocarbonyl, alkylaminoalkylcarbonyl, dialkylaminoalkylcarbonyl, heterocyclylcarbonyl, alkenylcarbonyl, alkynylcarbonyl, alkylsulfoxide, alkylsulfoxidealkyl, alkylsulfonyl, and alkylsulfonealkyl; and

R 2 is selected from a group consisting of:

11 . The pharmaceutical composition of claim 9 , wherein the transfer vehicle has a lipid molar ratio formation selected from a Compound:Phospholipid:Phytosterol:PEG-DMG ratio of:40:20:38.5:1.5, 45:15:38.5:1.5, 50:10:38.5:1.5, 55:5:38.5:1.5, 60:5:33.5:1.5, 45:20:33.5:1.5, 50:20:28.5:1.5, 55:20:23.5:1.5, 60:20: 18.5:1.5, 40:15:43.5:1.5, 50:15:33.5:1.5, 55:15:28.5:1.5, 60:15:23.5:1.5, 40:10:48.5:1.5, 45:10:43.5:1.5, 55:10:33.5:1.5, 60:10:28.5:1.5, 40:5:53.5:1.5, 45:5:48.5:1.5, 50:5:43.5:1.5, 40:20:40:0, 45:20:35:0, 50:20:30:0, 55:20:25:0, 60:20:20:0, and 40:15:45:0.

12 . The pharmaceutical composition of claim 9 , wherein the transfer vehicle comprises an ionizable lipid selected from:

13 . The pharmaceutical composition of claim 9 , wherein the transfer vehicle further comprises (a) a helper lipid, a structural lipid, and/or a PEG-lipid; and (b) a pharmaceutical salt, buffer, or diluent, or combination thereof.

14 . The pharmaceutical composition of claim 13 , wherein the transfer vehicle comprises PEG-DSPC.

15 . The pharmaceutical composition of claim 9 , wherein the transfer vehicle is a lipid nanoparticle.

16 . The pharmaceutical composition of claim 9 , wherein the transfer vehicle further comprises a targeting moiety selected from a small molecule, scFv, nanobody, peptide, cyclic peptide, di or tri cyclic peptide, minibody, polynucleotide aptamer, engineered scaffold protein, heavy chain variable region, light chain variable region, or a fragment thereof.

17 . A method of treating cancer or an autoimmune disorder in a subject by administering an effective amount of a composition comprising the circular RNA construct of claim 1 or a pharmaceutical composition thereof, thereby treating the cancer or autoimmune disorder.

18 . The circular RNA of claim 1 , wherein:

a. the antigen binding domain specifically binds to CD19 and comprises a VL comprising amino acids 22-128 of SEQ ID NO: 29; and a VH comprising amino acids 143-262 of SEQ ID NO: 29;

b. the antigen binding domain specifically binds to BCMA and comprises a first VHH comprising amino acids 22-140 of SEQ ID NO: 122; and a second VHH comprising amino acids 156-273 of SEQ ID NO: 122;

c. the antigen binding domain specifically binds to BCMA and comprises a VL comprising amino acids 22-132 of SEQ ID NO: 121, and a VH comprising amino acids 151-267 of SEQ ID NO: 121;

d. the antigen binding domain specifically binds to HER2 and comprises a VL comprising amino acids 22-128 of SEQ ID NO: 117; and a VH comprising amino acids 146-265 of SEQ ID NO: 117.

19 . The circular RNA of claim 1 , wherein the antigen binding domain specifically binds to CD19 and comprises a VL comprising amino acids 22-128 of SEQ ID NO: 29; and a VH comprising amino acids 143-262 of SEQ ID NO: 29.

20 . The circular RNA construct of claim 1 , wherein the translation initiation element comprises a sequence that is at least 95% identical to the corresponding RNA sequence of SEQ ID NO: 8.

21 . The circular RNA construct of claim 1 , wherein the translation initiation element comprises a sequence that is identical to the corresponding sequence of SEQ ID NO: 8.

22 . The circular RNA construct of claim 1 , wherein 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, 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.

23 . The circular RNA of claim 1 , wherein 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.

24 . The circular RNA of claim 1 , wherein the antigen binding domain specifically binds to HER2 and comprises a VL comprising a VL CDR1, VL CDR2, and 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.

25 . The circular RNA of claim 1 , wherein the antigen binding domain specifically binds to BCMA and comprises a first VHH comprising amino acids 22-140 of SEQ ID NO: 122; and a second VHH comprising amino acids 156-273 of SEQ ID NO: 122.

26 . The circular RNA of claim 1 , wherein the antigen binding domain specifically binds to BCMA and comprises a VL comprising amino acids 22-132 of SEQ ID NO: 121, and a VH comprising amino acids 151-267 of SEQ ID NO: 121.

27 . The circular RNA of claim 1 , wherein the antigen binding domain specifically binds to HER2 and comprises a VL comprising amino acids 22-128 of SEQ ID NO: 117; and a VH comprising amino acids 146-265 of SEQ ID NO: 117.

28 . 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.

29 . A method of preparing a circular RNA construct, the method comprising incubating the linear RNA polynucleotide of claim 22 under suitable conditions for circularization.

30 . The linear precursor RNA of claim 28 , wherein the translation initiation element comprises a sequence that is at least 90% identical to SEQ ID NO: 8.

31 . The linear precursor RNA of claim 28 , wherein the antigen binding domain specifically binds to CD19 and comprises a light chain variable region (VL) comprising the VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 29, and a heavy chain variable region (VH) comprising the VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 29, wherein the VL and VH are linked by a linker.

32 . The linear precursor RNA of claim 28 , wherein 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, 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.

33 . The linear precursor RNA of claim 28 , wherein 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.

34 . The linear precursor RNA of claim 28 , wherein the antigen binding domain specifically binds to HER2 and comprises a VL comprising a VL CDR1, VL CDR2, and 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.

35 . The linear precursor RNA of claim 28 , wherein the antigen binding domain specifically binds to CD19 and comprises a VL comprising amino acids 22-128 of SEQ ID NO: 29; and a VH comprising amino acids 143-262 of SEQ ID NO: 29.

36 . The linear precursor RNA of claim 28 , wherein the antigen binding domain specifically binds to BCMA and comprises a first VHH comprising amino acids 22-140 of SEQ ID NO: 122; and a second VHH comprising amino acids 156-273 of SEQ ID NO: 122.

37 . The linear precursor RNA of claim 28 , wherein the antigen binding domain specifically binds to BCMA and comprises a VL comprising amino acids 22-132 of SEQ ID NO: 121, and a VH comprising amino acids 151-267 of SEQ ID NO: 121.

38 . The linear precursor RNA of claim 28 , wherein the antigen binding domain specifically binds to HER2 and comprises a VL comprising amino acids 22-128 of SEQ ID NO: 117; and a VH comprising amino acids 146-265 of SEQ ID NO: 117.

39 . 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.

40 . The DNA vector of claim 39 , wherein the translation initiation element comprises a sequence that is at least 90% identical to SEQ ID NO: 8.

41 . The DNA vector of claim 39 , wherein the antigen binding domain specifically binds to CD19 and comprises a light chain variable region (VL) comprising the VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 29, and a heavy chain variable region (VH) comprising the VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 29, wherein the VL and VH are linked by a linker.

42 . The DNA vector of claim 39 , wherein 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, 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.

43 . The DNA vector of claim 39 , wherein 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.

44 . The DNA vector of claim 39 , wherein the antigen binding domain specifically binds to HER2 and comprises a VL comprising a VL CDR1, VL CDR2, and 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.

45 . The DNA vector of claim 39 , wherein the antigen binding domain specifically binds to CD19 and comprises a VL comprising amino acids 22-128 of SEQ ID NO: 29; and a VH comprising amino acids 143-262 of SEQ ID NO: 29.

46 . The DNA vector of claim 39 , wherein the antigen binding domain specifically binds to BCMA and comprises a first VHH comprising amino acids 22-140 of SEQ ID NO: 122; and a second VHH comprising amino acids 156-273 of SEQ ID NO: 122.

47 . The DNA vector of claim 39 , wherein the antigen binding domain specifically binds to BCMA and comprises a VL comprising amino acids 22-132 of SEQ ID NO: 121, and a VH comprising amino acids 151-267 of SEQ ID NO: 121.

48 . The DNA vector of claim 39 , wherein the antigen binding domain specifically binds to HER2 and comprises a VL comprising amino acids 22-128 of SEQ ID NO: 117; and a VH comprising amino acids 146-265 of SEQ ID NO: 117.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 9, 2025
From: WESSELHOEFT, ROBERT ALEXANDER, IV; BECKER, AMY M.; EMMANUEL, AKINOLA O.; DUTTA-SIMMONS, JUI; LEE, THOMAS; HORHOTA, ALLEN T.; KAUFFMAN, KEVIN J.; CHAU, BUN
To: ORNA THERAPEUTICS, INC.
Reel/Frame 071638/0641 →
Continuity (5)
Continuation PCTUS2023078875 · Nov 7, 2023
Provisional Application 63509361 · Jun 21, 2023
Provisional Application 63501820 · May 12, 2023
Provisional Application 63423760 · Nov 8, 2022
Related Publication 20250262324A1 · Aug 21, 2025
References Cited (238)
US 4897355A · Eppstein et al. · 1990 [cited by applicant]
US 5171678A · Behr et al. · 1992 [cited by applicant]
US 5334761A · Gebeyehu et al. · 1994 [cited by applicant]
US 5378825A · Cook et al. · 1995 [cited by applicant]
US 5585481A · Arnold, Jr. et al. · 1996 [cited by applicant]
US 5744335A · Wolff et al. · 1998 [cited by applicant]
US 5885613A · Holland et al. · 1999 [cited by applicant]
US 5948902A · Honkanen et al. · 1999 [cited by applicant]
US 6319494B1 · Capon et al. · 2001 [cited by applicant]
US 6417326B1 · Cullis et al. · 2002 [cited by applicant]
US 7741465B1 · Eshhar et al. · 2010 [cited by applicant]
US 8158601B2 · Chen et al. · 2012 [cited by applicant]
US 8492359B2 · Yaworski et al. · 2013 [cited by applicant]
US 8734853B2 · Sood et al. · 2014 [cited by applicant]
US 9708628B2 · Tange et al. · 2017 [cited by applicant]
US 9765022B2 · Xu et al. · 2017 [cited by applicant]
US 12175354B1 · Dehghanpoor et al. · 2024 [cited by applicant]
US 20030022649A1 · Voyer · 2003 [cited by applicant]
US 20050222064A1 · Vargeese et al. · 2005 [cited by applicant]
US 20060008910A1 · MacLachlan et al. · 2006 [cited by applicant]
US 20060051405A1 · MacLachlan et al. · 2006 [cited by applicant]
US 20060083780A1 · Heyes et al. · 2006 [cited by applicant]
US 20090023673A1 · Manoharan et al. · 2009 [cited by applicant]
US 20100062967A1 · Keil et al. · 2010 [cited by applicant]
US 20100130588A1 · Yaworski et al. · 2010 [cited by applicant]
US 20100324120A1 · Chen et al. · 2010 [cited by applicant]
US 20110076335A1 · Yaworski et al. · 2011 [cited by applicant]
US 20110117125A1 · Hope et al. · 2011 [cited by applicant]
US 20110256175A1 · Hope et al. · 2011 [cited by applicant]
US 20120027796A1 · Manoharan et al. · 2012 [cited by applicant]
US 20120058144A1 · Manoharan et al. · 2012 [cited by applicant]
US 20120101148A1 · Aking et al. · 2012 [cited by applicant]
US 20120128760A1 · Manoharan et al. · 2012 [cited by applicant]
US 20120149894A1 · Cameron et al. · 2012 [cited by applicant]
US 20120178702A1 · Huang et al. · 2012 [cited by applicant]
US 20120202871A1 · Heyes et al. · 2012 [cited by applicant]
US 20130065939A1 · Judge et al. · 2013 [cited by applicant]
US 20130090372A1 · Budzik et al. · 2013 [cited by applicant]
US 20130116307A1 · Heyes et al. · 2013 [cited by applicant]
US 20130123338A1 · Heyes et al. · 2013 [cited by applicant]
US 20130156845A1 · Manoharan et al. · 2013 [cited by applicant]
US 20130164400A1 · Knopov et al. · 2013 [cited by applicant]
US 20130178541A1 · Stanton et al. · 2013 [cited by applicant]
US 20130195920A1 · Maier et al. · 2013 [cited by applicant]
US 20130202684A1 · Geall et al. · 2013 [cited by applicant]
US 20130274504A1 · Colletti et al. · 2013 [cited by applicant]
US 20130274523A1 · Bawiec, III et al. · 2013 [cited by applicant]
US 20130303587A1 · Yaworski et al. · 2013 [cited by applicant]
US 20130323269A1 · Manoharan et al. · 2013 [cited by applicant]
US 20130338210A1 · Manoharan et al. · 2013 [cited by applicant]
US 20140039032A1 · Kuboyama et al. · 2014 [cited by applicant]
US 20140141070A1 · Geall et al. · 2014 [cited by applicant]
US 20140200257A1 · Rajeev et al. · 2014 [cited by applicant]
US 20140255472A1 · Geall et al. · 2014 [cited by applicant]
US 20140308304A1 · Manoharan et al. · 2014 [cited by applicant]
US 20150057373A1 · Stanton et al. · 2015 [cited by applicant]
US 20150064242A1 · Heyes et al. · 2015 [cited by applicant]
US 20150140070A1 · Heartlein et al. · 2015 [cited by applicant]
US 20150141678A1 · Payne et al. · 2015 [cited by applicant]
US 20150203446A1 · Manoharan et al. · 2015 [cited by applicant]
US 20150239926A1 · Payne et al. · 2015 [cited by applicant]
US 20150376115A1 · Ansell et al. · 2015 [cited by applicant]
US 20160151284A1 · Heyes et al. · 2016 [cited by applicant]
US 20160311759A1 · Brito et al. · 2016 [cited by applicant]
US 20160317458A1 · Brito et al. · 2016 [cited by applicant]
US 20160376224A1 · Du et al. · 2016 [cited by applicant]
US 20170114010A1 · Payne et al. · 2017 [cited by applicant]
US 20170119904A1 · Ansell et al. · 2017 [cited by applicant]
US 20170190661A1 · Payne et al. · 2017 [cited by applicant]
US 20170210697A1 · Benenato et al. · 2017 [cited by applicant]
US 20180005363A1 · Nagatomo et al. · 2018 [cited by applicant]
US 20180028664A1 · Besin et al. · 2018 [cited by applicant]
US 20180153822A1 · Karve et al. · 2018 [cited by applicant]
US 20190091164A1 · Horhota et al. · 2019 [cited by applicant]
US 20190314284A1 · Guild et al. · 2019 [cited by applicant]
US 20190314524A1 · Ansell et al. · 2019 [cited by applicant]
US 20190321489A1 · Guild et al. · 2019 [cited by applicant]
WO 9313121A1 · 1993 [cited by applicant]
WO 9532305A1 · 1995 [cited by applicant]
WO 2005120152A2 · 2005 [cited by applicant]
WO 2005121348A1 · 2005 [cited by applicant]
WO 2006007712A1 · 2006 [cited by applicant]
WO 2006069782A2 · 2006 [cited by applicant]
WO 2008042973A2 · 2008 [cited by applicant]
WO 2008103276A2 · 2008 [cited by applicant]
WO 2009086558A1 · 2009 [cited by applicant]
WO 2009127060A1 · 2009 [cited by applicant]
WO 2009132131A1 · 2009 [cited by applicant]
WO 2010042877A1 · 2010 [cited by applicant]
WO 2010048536A2 · 2010 [cited by applicant]
WO 2010053572A2 · 2010 [cited by applicant]
WO 2010054384A1 · 2010 [cited by applicant]
WO 2010054401A1 · 2010 [cited by applicant]
WO 2010054405A1 · 2010 [cited by applicant]
WO 2010054406A1 · 2010 [cited by applicant]
WO 2010088537A2 · 2010 [cited by applicant]
WO 2010129709A1 · 2010 [cited by applicant]
WO 2010144740A1 · 2010 [cited by applicant]
WO 2011000106A1 · 2011 [cited by applicant]
WO 2011000107A1 · 2011 [cited by applicant]
WO 2011022460A1 · 2011 [cited by applicant]
WO 2011038160A2 · 2011 [cited by applicant]
WO 2011066651A1 · 2011 [cited by applicant]
WO 2011068810A1 · 2011 [cited by applicant]
WO 2011071860A2 · 2011 [cited by applicant]
WO 2011075656A1 · 2011 [cited by applicant]
WO 2011090965A1 · 2011 [cited by applicant]
WO 2011127255A1 · 2011 [cited by applicant]
WO 2011141704A1 · 2011 [cited by applicant]
WO 2011141705A1 · 2011 [cited by applicant]
WO 2011153120A1 · 2011 [cited by applicant]
WO 2012000104A1 · 2012 [cited by applicant]
WO 2012016184A2 · 2012 [cited by applicant]
WO 2012024526A2 · 2012 [cited by applicant]
WO 2012031043A1 · 2012 [cited by applicant]
WO 2012040184A2 · 2012 [cited by applicant]
WO 2012044638A1 · 2012 [cited by applicant]
WO 2012054365A2 · 2012 [cited by applicant]
WO 2012099755A1 · 2012 [cited by applicant]
WO 2012162210A1 · 2012 [cited by applicant]
WO 2013006825A1 · 2013 [cited by applicant]
WO 2013016058A1 · 2013 [cited by applicant]
WO 2013033563A1 · 2013 [cited by applicant]
WO 2013049328A1 · 2013 [cited by applicant]
WO 2013086322A1 · 2013 [cited by applicant]
WO 2013086354A1 · 2013 [cited by applicant]
WO 2013086373A1 · 2013 [cited by applicant]
WO 2013089151A1 · 2013 [cited by applicant]
WO 2013093648A2 · 2013 [cited by applicant]
WO 2013116126A1 · 2013 [cited by applicant]
WO 2013126803A1 · 2013 [cited by applicant]
WO 2013148541A1 · 2013 [cited by applicant]
WO 2014136086A1 · 2014 [cited by applicant]
WO 2015061467A1 · 2015 [cited by applicant]
WO 2015074085A1 · 2015 [cited by applicant]
WO 2015095340A1 · 2015 [cited by applicant]
WO 2015095346A1 · 2015 [cited by applicant]
WO 2015130584A2 · 2015 [cited by applicant]
WO 2015199952A1 · 2015 [cited by applicant]
WO 2016081029A1 · 2016 [cited by applicant]
WO 2017004143A1 · 2017 [cited by applicant]
WO 2017049245A2 · 2017 [cited by applicant]
WO 2017075531A1 · 2017 [cited by applicant]
WO 2017099823A1 · 2017 [cited by applicant]
WO 2017117528 · 2017 [cited by applicant]
WO 2017173054A1 · 2017 [cited by applicant]
WO 2017185054A1 · 2017 [cited by applicant]
WO 2018011633A1 · 2018 [cited by applicant]
WO 2019067999A1 · 2019 [cited by applicant]
WO 2019089828A1 · 2019 [cited by applicant]
WO 2019094486A1 · 2019 [cited by applicant]
WO 2019131770A1 · 2019 [cited by applicant]
WO 2019152557A1 · 2019 [cited by applicant]
WO 2019152848A1 · 2019 [cited by applicant]
WO 2019191780A1 · 2019 [cited by applicant]
WO 2019236673A1 · 2019 [cited by applicant]
WO 2020237227A1 · 2020 [cited by applicant]
WO 2020257611A1 · 2020 [cited by applicant]
WO 2021021634A1 · 2021 [cited by applicant]
WO 2021041473A1 · 2021 [cited by applicant]
WO 2021113777A2 · 2021 [cited by applicant]
WO 2021189059A2 · 2021 [cited by applicant]
WO 2021226597A2 · 2021 [cited by applicant]
WO 2021236855A1 · 2021 [cited by applicant]
WO 2022261490A2 · 2022 [cited by applicant]
WO 2023056033A1 · 2023 [cited by applicant]
WO 2023081526A1 · 2023 [cited by applicant]
WO 2023141586A1 · 2023 [cited by applicant]
WO 2023250375A1 · 2023 [cited by applicant]
WO 2024102677A1 · 2024 [cited by applicant]
WO 2024102730A1 · 2024 [cited by applicant]
WO 2024102762A1 · 2024 [cited by applicant]
WO 2024129982A2 · 2024 [cited by applicant]
WO 2024205657A2 · 2024 [cited by applicant]
WO 2024233308A2 · 2024 [cited by applicant]
WO 2024263729A1 · 2024 [cited by applicant]
WO 2025007148A1 · 2025 [cited by applicant]
WO 2025049690A1 · 2025 [cited by applicant]
WO 2025101501A1 · 2025 [cited by applicant]
WO 2025117969A1 · 2025 [cited by applicant]
WO 2025128871A2 · 2025 [cited by applicant]
WO 2025166238A1 · 2025 [cited by applicant]
Ahmad, et al. (2022) Chimeric antigen receptor T cell structure, its manufacturing, and related toxicities; A comprehensive review, Advances in Cancer Biology: Metastasis, 4: Article 100035, 6 pages. (Year: 2022). [cited by examiner]
Ahmad (2012) “scFv Antibody: Principles and Clinical Application”, Clinical and Developmental Immunology, Article 980250, 15 pages. (Year: 2012). [cited by examiner]
Goel et al. (2004) “Plasticity within the Antigen Combining Site May Manifest as Molecular Mimicry in the Humoral Immune Response”, The Journal of Immunology 173(12):7358-7367. (Year: 2004). [cited by examiner]
Lloyd et al. (2009) “Modelling the human immune response: performance of a 1011 human antibody repertoire against a broad panel of therapeutically relevant antigens”, Protein Engineering, Design & Selection 22(3):159-16… [cited by examiner]
Edwards et al. (2003) “The remarkable flexibility of the human antibody repertoire; isolation of over one thousand different antibodies to a single protein, BlyS”, Journal of Molecular Biology 334:103-118 (Year: 2003). [cited by examiner]
Xue, Hui Yi et al., “Lipid-Based Nanocarriers for RNA Delivery”, Current Pharmaceutical Design, 2015, 21, 3140-3147. [cited by applicant]
Behr et al. “Efficient gene transfer into mammalian primary endocrine cells with lipopolyamine-coated DNA,” PNAS 1989, 86(18):6982-6986. [cited by applicant]
Berge et al. “Pharmaceutical salts,” J. Pharmaceutical Sciences, 1977, 66(1):1-19. [cited by applicant]
Budker, V. et al., “Protein/Amphipathic Polyamine Complexes Enable Highly Efficient Transfection with Minimal Toxicity”, BioTechniques, (1997), 23:1, 139-147. [cited by applicant]
Caplen et al. “In vitro liposome-mediated DNA transfection of epithelial cell lines using the cationic liposome DC-Chol/DOPE,” Gene Ther, 1995, 2(9):603-13 (abstract). [cited by applicant]
Chen, Tao et al., “Polyanionic Polymers Which Enhance Fusogenicity”, U.S. Appl. No. 60/083,294, filed Apr. 28, 1998. [cited by applicant]
DeRosa, Frank et al., “Ionizable Cationic Lipids”, U.S. Appl. No. 61/617,468, filed Mar. 29, 2012. [cited by applicant]
Dobrikova et al. “Activity of a type 1 picornavirus internal ribosomal entry site is determined by sequences within the 3′ nontranslated region,” PNAS, 2003, 100(25):15125-15130. [cited by applicant]
Eshhar et al., “Tumor-specific T-bodies: toward clinical application,” Cancer Immunol Immunotherapy (1997) 45: 131-136. [cited by applicant]
Felgner et al. “Lipofection: A highly efficient, lipid-mediated DNA-transfection procedure,” PNAS, 1987, 84:7413-7417. [cited by applicant]
Finney et al. “Chimeric receptors providing both primary and costimulatory signaling in T cells from a single gene product,” J Immunol, 1998, 161(6):2791-7. [cited by applicant]
Gao et al. “A novel cationic liposome reagent for efficient transfection of mammalian cells,” Biochem Biophys Res Commun, 1991, 179(1):280-5. [cited by applicant]
Garlapati et al. “Identification of a novel internal ribosome entry site in giardiavirus that extends to both sides of the initiation codon,” J Biol Chem, 2004, 279(5):3389-97. [cited by applicant]
Godet, Anne-Claire et al., “IRES Trans-Acting Factors, Key Actors of the Stress Response”, Int. J. Mol. Sci. 2019, 20; 294: 29 pages. [cited by applicant]
Gross et al. “Therapeutic Potential of T Cell Chimeric Antigen Receptors (CARs) in Cancer Treatment: Counteracting Off-Tumor Toxicities for Safe CAR T Cell Therapy,” Annu Rev Pharmacol Toxicol, 2016, 56:59-83. [cited by applicant]
Gurtu et al. “IRES bicistronic expression vectors for efficient creation of stable mammalian cell lines,” Biochem Biophys Res Commun, 1996, 229(1):295-8. [cited by applicant]
Haney, Matthew J. et al., “Exosomes as Drug Delivery Vehicles for Parkinson's Disease Therapy”, J Control Release, 2015; 207: 18-30. [cited by applicant]
Heyes et al. “Cationic lipid saturation influences intracellular delivery of encapsulated nucleic acids,” Journal of Controlled Release, 2005, 107:276-287. [cited by applicant]
Holdt, Lesca M. et al., “Circular RNAs as Therapeutic Agents and Targets”, Front. Physiol. 2018, 9:1262, 16 pages. [cited by applicant]
Jang et al. “Initiation of Protein Synthesis by Internal Entry of Ribosomes into the 5′ Nontranslated Region of Encephalomyocarditis Virus RNA in Vivo,” J. Virol., 1989, 63(4):1651-1660. [cited by applicant]
Jayaraman et al. “Maximizing the potency of siRNA lipid nanoparticles for hepatic gene silencing in vivo,” Angew. Chem. Int. Ed., 2012, 51(34):8529-8533. [cited by applicant]
Kalos et al. “T Cells with Chimeric Antigen Receptors Have Potent Antitumor Effects and Can Establish Memory in Patients with Advanced Leukemia,” Sci Transl Med, 2011, 3:95. [cited by applicant]
Katano, Ikumi et al., “Long-term maintenance of peripheral blood derived human NK cells in a novel human IL-15-transgenic NOG mouse”, Scientific Reports, 2017, 7:17230, 14 pages. [cited by applicant]
Kaufman et al. “Improved vectors for stable expression of foreign genes in mammalian cells by use of the untranslated leader sequence from EMC virus,” Nucleic Acids Res, 1991, 19(16):4485-90. [cited by applicant]
Klibanov et al. “Amphipathic polyethyleneglycols effectively prolong the circulation time of liposomes,” FEBS Lett., 1990, 268(1):235-7. [cited by applicant]
Kobayashi et al. “Improved dicistronic mRNA expression vectors for efficient selection of transfectants highly expressing foreign genes,” Biotechniques, 1996, 21(3):398-402. [cited by applicant]
Koltover, et al. “An inverted hexagonal phase of cationic liposome-DNA complexes related to DNA release and delivery,” Science (1998) 281: 78-81. [cited by applicant]
Krause et al. “Antigen-dependent CD28 signaling selectively enhances survival and proliferation in genetically modified activated human primary T lymphocytes,” J Exp Med., 1998, 188(4):619-26. [cited by applicant]
Lasic et al. “Gelation of liposome interior. A novel method for drug encapsulation,” FEBS Lett, 1992, 312(2-3):255-8. [cited by applicant]
Li et al. “In vivo gene transfer via intravenous administration of cationic lipid-protamine-DNA (LPD) complexes,” Gene Ther, 1997, 4(9):891-900. [cited by applicant]
Luan, Xin et al., “Engineering exosomes as refined biological nanoplatforms for drug delivery”, Acta Pharmacologica Sinica, 2017, 38: 754-763. [cited by applicant]
Mackensen, Andreas et al., “Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus”, Nature Medicine, 2022, 28:2124-2132. [cited by applicant]
Maier et al. “Biodegradable Lipids Enabling Rapidly Eliminated Lipid Nanoparticles for Systemic Delivery of RNAi Therapeutics,” Mol. Ther., 2013, 21(8):1570-78. [cited by applicant]
Mendes, Livia Palmerston et al., “Dendrimers as Nanocarriers for Nucleic Acid and Drug Delivery in Cancer Therapy”, Molecules 2017, 22(1401), 21 pages. [cited by applicant]
Morrissey et al. “Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs,” Nat Biotechnol, 2005, 23(8):1002-7. [cited by applicant]
Mosser et al. “Use of a dicistronic expression cassette encoding the green fluorescent protein for the screening and selection of cells expressing inducible gene products,” Biotechniques, 1997, 22(1):150-4, 156, 158-61. [cited by applicant]
Mukherjee, Anubhab et al., “Lipid-polymer hybrid nanoparticles as a next-generation drug delivery platform: state of the art, emerging technologies, and perspectives”, International Journal of Nanomedicine 2019, 14, 193… [cited by applicant]
Nikonov, O.S et al., “Enteroviruses: Classification, Diseases They Cause, and Approaches to Development of Antiviral Drugs”, Biochemistry (Moscow), 2017, 82(13): 1615-1631. [cited by applicant]
Nunez, Daniel et al., “Cytokine and reactivity profiles in SLE patients following anti-CD19 CART therapy”, Molecular Therapy: Methods & Clinical Development, 2023, vol. 31, 6 pages. [cited by applicant]
PCT International Search Report and Written Opinion from PCT/US2023/078875, mailed Feb. 28, 2024, 20 pages. [cited by applicant]
Porter et al. “Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia,” N Engl J Med, 2011, 365 (8):725-33. [cited by applicant]
Ramesh, N. et al., “High-titer bicistronic retroviral vectors employing foot-and-mouth disease virus internal ribosome entry site”, Nucleic Acids Research, 1996, 24(14): 2697-2700. [cited by applicant]
Rees et al. “Bicistronic vector for the creation of stable mammalian cell lines that predisposes all antibiotic-resistant cells to express recombinant protein,” Biotechniques, 1996, 20(1):102-4, 106, 108-10. [cited by applicant]
Semple et al. “Rational design of cationic lipids for siRNA delivery,” Nat Biotechnol, 2010, 28(2):172-6. [cited by applicant]
Shah, Nina et al., “B-cell maturation antigen (BCMA) in multiple myeloma: rationale for targeting and current therapeutic approaches”, Leukemia (2020) 34: 985-1005. [cited by applicant]
Shobaki et al. “Mixing lipids to manipulate the ionization status of lipid nanoparticles for specific tissue targeting,” Int J Nanomedicine, 2018, 13:8395-8410. [cited by applicant]
Son, Siejin, “Sugar-Nanocapsules Imprinted with Microbial Molecular Patterns for mRNA Vaccination”, Nano Lett. 2020; 20(3) 1499-1509. [cited by applicant]
Song et al. “CD27 costimulation augments the survival and antitumor activity of redirected human T cells in vivo,” Blood, 2012, 119(3):696-706. [cited by applicant]
Wang et al., “A combinatorial library of unsaturated lipidoids for efficient intracellular gene delivery,” ACS Synthetic Biology, 1, 403-07 (2012). [cited by applicant]
Wang, Laixin et al., “Oligoribonucleotide circularization by template-mediated ligation with T4 Rna ligate: synthesis of circular hammerhaed ribozymes”, Nucleic Acids Research, 1998, 26(10): 2502-2504. [cited by applicant]
Wender, et al., “The design of guanidinium-rich transporters and their internalization mechanisms,” Adv. Drug Del. Rev., 2008, 60(4-5): 452-472. [cited by applicant]