IP Library Granted Patent US 12,195,746
Granted Patent B2
US 12,195,746 · App. 17/706,522 · Granted Jan 14, 2025

Compositions and processes for targeted delivery, expression and modulation of coding ribonucleic acids in tissue

Inventor: Romain Micol (London, GB)
Assignee: Combined Therapeutics, Inc.
C12N15/86A61K31/7088A61K35/763A61K45/06A61K48/0058C12N2310/141C12N2710/16632C12N2710/16643
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Quick Facts
Patent No.
US 12,195,746
App. No.
17/706,522
Granted
Jan 14, 2025
Kind
B2
Abstract

A composition for expressing a polypeptide within a target organ including a delivery particle, and at least a first mRNA sequence complexed with, encapsulated by, or otherwise associated with the delivery particle. The mRNA sequence includes a coding sequence which codes for the polypeptide, at least a first untranslated region (UTR) sequence, and at least one micro-RNA (miRNA) binding site sequence, wherein the miRNA binding site sequence is located within, immediately 5′ to, or immediately 3′ to, the first UTR sequence. The miRNA binding site sequence is selected so as to provide for differential expression of the coding sequence between first and second cell types comprised within the target organ. Methods for making and using the composition are provided, particularly in treatment of disease, such as cancer.

Claims (18)

1. A composition comprising at least two delivery particles comprising: a first delivery particle, wherein the first delivery particle comprises a first mRNA sequence complexed with, encapsulated by, or otherwise associated with the first delivery particle, the first mRNA sequence comprising a coding sequence which codes for tumor-associated antigen, an untranslated region (UTR) sequence; at least three micro-RNA (miRNA) binding site sequences, wherein the at least three miRNA binding site sequences are comprised of substantially different sequences and located within, immediately 5′ to, or immediately 3′ to, the UTR sequence; and

a second delivery particle, wherein the second delivery particle comprises a second mRNA sequence complexed with, encapsulated by, or otherwise associated with the second delivery particle, the second mRNA sequence comprising a coding sequence which codes for an immunomodulatory molecule, an UTR sequence; at least three micro-RNA (miRNA) binding site sequences, wherein the at least three miRNA binding site sequences are comprised of substantially different sequences and located within, immediately 5′ to, or immediately 3′ to, the UTR sequence, and wherein upon administration to a subject, the composition stimulates an immune response to the tumor-associated antigen.

2. The composition of claim 1 , wherein the first and/or second mRNA sequence comprises greater than four miRNA binding site sequences.

3. The composition of claim 1 , wherein the at least three miRNA binding site sequences provide for differential expression of the coding sequence between a first and a second cell type comprised within a target organ selected from the group consisting of liver; brain; lung; breast; and pancreas.

4. The composition of claim 1 , wherein the at least three miRNA binding site sequences comprise one or more miRNA-122 binding site sequences.

5. The composition of claim 1 , wherein the first and second delivery particles comprise aminoalcohol lipidoids.

6. The composition of claim 5 , wherein the first and second mRNA sequences are encapsulated by the first and second delivery particles, respectively.

7. The composition of claim 1 , wherein the second mRNA codes for an immunomodulatory molecule selected from the group consisting of:

(i) cytokines involved in immune response and inflammation selected from one or more of: TNF α, TNFβ, IFNα, IFNβ, IFNgamma, IL1, IL2, IL3, IL4, IL5, IL6, IL7, IL8, IL9, IL10, IL11, IL12, CCL 2, CCL3, CCL4, CCL5 CXCL 9, and CXCL10;

(ii) dendritic cell activators selected from one or more of: GM-CSF, TLR7 and TLR9;

(iii) molecules targeting the following cellular receptors and their ligands selected from one or more of: CD40, CD40L, CD160, 2B4, Tim-3, GP-2, B7H3 and B7H4;

(iv) TGF β inhibitors;

(v) T-cell membrane protein 3 inhibitors;

(vi) inhibitors of programmed death 1 (PD1), programmed death-ligand 1 (PDL1), programmed death-ligand 2 (PDL2), cytotoxic T-lymphocyte antigen 4 (CTLA4), and lymphocyte-activation gene 3 (LAG3); and

(vii) NF-κB inhibitors.

8. The composition of claim 7 , wherein the second mRNA codes for IL12.

9. The composition of claim 7 , wherein the second mRNA codes for GM-CSF.

10. A method of treating cancer in a subject comprising: systemically administering to the subject a composition as in one of claim 2-4 or 1-9 , thereby treating the subject.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 21, 2025
From: MICOL, ROMAIN
To: COMBINED THERAPEUTICS, INC.
Reel/Frame 074160/0541 →
Priority Claims (1)
GB 1714430 · Sep 7, 2017 · national
Continuity (4)
Continuation 16811504 · Mar 6, 2020
Continuation PCTUS2018049772 · Sep 6, 2018
Provisional Application 62632056 · Feb 19, 2018
Related Publication 20220220506A1 · Jul 14, 2022
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