US 12,220,456 B2
Compositions and methods for organ-protective expression and modulation of coding ribonucleic acids
Romain Micol, Wilmington, DE (US); and Valerie Duval, Wilmington, DE (US)
Assigned to Combined Therapeutics, Inc., Wilmington, DE (US)
Filed by Combined Therapeutics, Inc., Wilmington, DE (US)
Filed on Feb. 8, 2024, as Appl. No. 18/436,426.
Application 18/436,426 is a continuation of application No. 18/108,248, filed on Feb. 10, 2023, granted, now 11,931,409.
Application 18/108,248 is a continuation of application No. 17/689,908, filed on Mar. 8, 2022, granted, now 11,596,685, issued on Mar. 7, 2023.
Application 17/689,908 is a continuation of application No. PCT/US2021/019028, filed on Feb. 22, 2021.
Claims priority of provisional application 63/059,458, filed on Jul. 31, 2020.
Claims priority of provisional application 62/979,619, filed on Feb. 21, 2020.
Prior Publication US 2024/0252618 A1, Aug. 1, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 39/215 (2006.01); C12N 15/11 (2006.01); C12N 15/113 (2010.01); A61K 39/00 (2006.01)
CPC A61K 39/215 (2013.01) [C12N 15/113 (2013.01); A61K 2039/53 (2013.01)] 31 Claims
 
1. A composition comprising:
at least a first mRNA construct comprising at least a first open reading frame (ORF), wherein the first ORF encodes a tumor antigen;
at least a second mRNA construct comprising at least a second open reading frame (ORF), wherein the second ORF encodes a product associated with vaccine induced immunity selected from the group consisting of: IL-1; IL-2; IL-3; IL-4; IL-5; IL-6; IL-7; IL-8; IL-9; IL-10; IL-11; IL-12; IL-15; IL-17; IL-21; TGF-beta; IFNγ; IFNα; IFNβ; TNFα; M-CSF; G-CSF; GM-CSF; CCL2; CCL3; CCL4; CCL5; CCL20; CCL22; CCL28; CXCL8; CXCL9; CXCL10; CXCL11; CXCL12; and XCL1 and wherein the second ORF is operatively linked to at least one untranslated region (UTR), wherein the UTR comprises at least a first, second, and a third micro-RNA (miRNA) target sequence, and wherein each of the at least first, second, and third miRNA target sequences are optimised to each hybridise with a different corresponding miRNA sequence; and
an in vivo delivery composition;
wherein the first and second mRNA constructs are comprised within or adsorbed to the delivery composition.