Granted Patent B2

US 12,491,260 · App. 17/583,674 · Granted Dec 9, 2025

Inventors: Gilles Besin (Brookline, MA); Stephen Hoge (Brookline, MA); Joseph Senn (Cambridge, MA); Kerry Benenato (Sudbury, MA); Staci Sabnis (Cambridge, MA)

Assignee: ModernaTX, Inc.

A61K48/0033A61K9/127A61K9/1271A61K31/7115A61K31/713A61K39/39A61K47/10A61K47/14A61K47/18A61K47/543A61K47/544A61K47/60A61K47/6929A61K48/0066C08G65/3322C08G65/3326C08G65/33306C08G65/3331C08G65/33317C08G65/33324C08G65/3348C08G65/3356C12N15/117C12N15/88A61K2039/55555C08G2650/04C12N2310/141C12N2310/17C12N2320/32

Abstract

Claims (32)

1 . A lipid nanoparticle (LNP) comprising an mRNA coding for a therapeutic protein, an ionizable lipid, a helper lipid, a structural lipid, and a PEG-lipid;

wherein the mRNA comprises at least one miR binding site; and

wherein the PEG-lipid is a compound of Formula (V-OH):

or a pharmaceutically acceptable salt thereof, wherein:

r is an integer between 1 and 100, inclusive; and

R 5 is optionally substituted C 10-40 alkyl.

2 . The LNP of claim 1 , wherein the compound of Formula (V-OH) is Cmpd452:

3 . The LNP of claim 2 , wherein the PEG-lipid comprises a PEG molecule of an average molecular weight of 2,000 Da or less.

4 . The LNP of claim 3 , wherein the PEG-lipid is HO-PEG2000-ester-C18 (Cmpd403).

5 . The LNP of claim 1 , wherein the ionizable lipid is a compound of Formula (XI):

or a pharmaceutically acceptable salt thereof, wherein:

l is selected from 1, 2, 3, 4, and 5;

M and M′ are independently selected from —C(O)O— and —OC(O)—;

M 1 is M′;

R 2 and R 3 are both independently C 1-14 alkyl or C 2-14 alkenyl;

R 4 is —(CH 2 ) n Q, in which Q is —OH, and n is selected from 2, 3, and 4; and

R′ is a C 1 -C 18 linear alkyl.

6 . The LNP of claim 5 , wherein R′ is C 9 alkyl.

7 . The LNP of claim 5 , wherein n is 2.

8 . The LNP of claim 5 , wherein the compound of Formula (XI) has the structure of Cmpd18:

9 . The LNP of claim 1 , wherein the helper lipid comprises at least one fatty acid chain of at least 8 carbons in length and at least one polar headgroup moiety, and wherein the helper lipid is a zwitterionic non-cationic helper lipid, a DSPC analog, oleic acid, an oleic acid analog, 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), or a DSPC substitute.

10 . The LNP of claim 9 , wherein the helper lipid is DSPC.

11 . The LNP of claim 1 , wherein the helper lipid is oleic acid or an oleic acid analog.

12 . The LNP of claim 1 , wherein the structural lipid is cholesterol.

13 . The LNP of claim 1 , comprising a molar ratio of about 45-65% ionizable lipid; 5-25% helper lipid; 15-45% structural lipid; and 0.15-15% PEG-lipid.

14 . The LNP of claim 1 , wherein the PEG-lipid is present in an amount of less than 0.5% (w/w).

15 . The LNP of claim 1 , wherein the therapeutic protein replaces a protein in the subject that is deficient or abnormal, augments the function of an endogenous protein, or provides a novel function to a cell in the subject.

16 . The LNP of claim 1 , wherein the at least one miR binding site binds a microRNA expressed in an immune cell.

17 . The LNP of claim 1 , wherein the at least one miR binding site is in the 3′ untranslated region of the mRNA.

18 . The LNP of claim 1 , wherein the at least one miR binding site is selected from miR 122, 126, 155, and 142.3p.

19 . The LNP of claim 1 , wherein the mRNA is chemically-modified.

20 . The LNP of claim 1 , further comprising an additional agent that inhibits an immune response.

Assignments (2)

Continuity (13)

References Cited (400)