Granted Patent B2

US 12,648,959 · App. 17/893,918 · Granted Jun 9, 2026

Inventors: Yizhou Dong (Dublin, OH); Kevin Thomas Love (Boston, MA); Robert S. Langer (Newton, MA); Daniel Griffith Anderson (Framingham, MA); Delai Chen (Cambridge, MA); Yi Chen (Cambridge, MA); Arturo Jose Vegas (Belmont, MA); Akinleye C. Alabi (Ithaca, NY); Yunlong Zhang (Cambridge, MA)

Assignee: Massachusetts Institute of Technology

A61K31/7105A61K31/711A61K47/22C07C229/12C07C229/22C07C229/24C07C229/26C07C229/36C07C237/08C07C237/12C07C271/22C07C279/14C07C323/58C07D207/16C07D209/20C07D209/24C07D233/64C07D241/08C07D265/32C07D403/06C07D413/06C07D487/04C07D487/06C12N15/87C12N15/88C12Q1/025G01N33/15A61K2121/00Y02A50/30

Abstract

Claims (59)

1 . A method of delivering an agent to a subject or a cell, the method comprising contacting with the cell or administering to the subject a composition comprising the agent and a compound of formula (III):

or a salt thereof;

wherein:

p is 1;

each instance of Q is O;

each instance of R 1 is independently hydrogen, alkyl, or a group of formula (iv);

provided at least one instance of R 1 is a group of formula (iv):

L is alkylene;

R 6 and R 7 are each independently hydrogen, alkyl, a nitrogen protecting group, or a group of formula (i), (ii), or (iii);

each instance of R 2 is independently hydrogen, alkyl, a nitrogen protecting group, or a group of formula (i), (ii), or (iii);

formulae (i), (ii), and (iii) are:

wherein each instance of formula (i) is independently formula (i-a) or (i-b):

each instance of R′ is independently hydrogen or alkyl;

X is O, S, or NR X , wherein R X is hydrogen or a nitrogen protecting group;

Y is O;

R P is hydrogen, alkyl, or an oxygen protecting group when attached to an oxygen atom; and

R L is C 6-50 alkyl,

provided that at least one instance of R 2 , R 6 , or R 7 is a group of the formula (i), (ii), or (iii);

wherein each alkyl and alkylene is independently unsubstituted or substituted at one or more positions with a group selected from halogen, —CN, —NO 2 , —OH, —OR aa , —N(R bb ) 2 , —N(R bb ) 3 + X − , —N(OR cc )R bb , —SH, —SR aa , —C(═O)R aa , —CO 2 H, —CHO, —C(OR) 2 , —CO 2 R aa , —OC(═O)R aa , —OCO 2 R aa , —C(═O)N(R bb ) 2 , —OC(═O)N(R bb ) 2 , —NR bb C(═O)R aa , —NR bb CO 2 R aa , —NR bb C(═O)N(R bb ) 2 , —C(═NR bb )R aa , —C(═NR bb )OR aa , —OC(═NR bb )R aa , —OC(═NR bb )OR aa , —C(═NR bb )N(R bb ) 2 , —OC(═NR bb )N(R bb ) 2 , —NR bb C(═NR bb )N(R bb ) 2 , C 3-14 carbocyclyl, 3-14 membered heterocyclyl, C 6-14 aryl, and 5-14 membered heteroaryl, wherein each alkyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 groups selected from halogen, —OH, —OR ee , and C 1-50 alkyl;

or two geminal hydrogens on a carbon atom are replaced with the group ═O;

each instance of R aa is, independently, selected from C 1-50 alkyl;

each instance of R bb is, independently, selected from hydrogen and C 1-50 alkyl;

each instance of R ee is, independently, selected from C 1-50 alkyl and C 3-10 carbocyclyl; and

X − is a counterion.

2 . The method of claim 1 , wherein each instance of R 1 is a group of formula (iv).

3 . The method of claim 1 , wherein the compound is selected from the group consisting of:

and salts thereof, wherein:

R 1 is selected from the group consisting of H, —CH 3 , —CH(CH 3 ) 2 , —CH(CH 3 )(CH 2 CH 3 ), —CH 2 CH(CH 3 ) 2 ,

provided at least one R 1 is a group of formula:

4 . The method of claim 1 , wherein the compound is selected from the group consisting of:

and salts thereof.

5 . The method of claim 1 , wherein the compound is selected from the group consisting of:

and salts thereof.

6 . The method of claim 5 , wherein the compound is:

or a salt thereof.

7 . The method of claim 5 , wherein the compound is:

or a salt thereof.

8 . The method of claim 1 , wherein X is NR X , wherein R X is hydrogen or a nitrogen protecting group.

9 . The method of claim 1 , wherein X is O.

10 . The method of claim 1 , wherein the composition is a pharmaceutical composition.

11 . The method of claim 1 , wherein the agent is an organic molecule, inorganic molecule, small molecule, nucleic acid, protein, peptide, or polynucleotide.

12 . The method of claim 11 , wherein the agent is a polynucleotide.

13 . The method of claim 12 , wherein the polynucleotide is RNA.

14 . The method of claim 13 , wherein the RNA is RNAi, dsRNA, siRNA, shRNA, miRNA, or antisense RNA.

15 . The method of claim 12 , wherein the polynucleotide encodes a protein or peptide.

16 . The method of claim 15 , wherein the encoded protein is pharmaceutically active.

17 . The method of claim 12 , wherein the polynucleotide comprises a sequence encoding an antigenic protein or peptide.

18 . The method of claim 17 , wherein the antigenic protein or peptide is an antigen of a virus.

19 . The method of claim 18 , wherein the virus is selected from the group consisting of influenza A, influenza B, and respiratory syncytial viruses.

20 . The method of claim 17 , wherein administration of the composition to the subject induces an immunologic response sufficient to decrease the chance of a subsequent infection and/or lessen the symptoms associated with such an infection.

21 . The method of claim 12 , wherein the polynucleotide is capable of fixing an error in the genome of the cell or the subject.

22 . The method of claim 12 , wherein the polynucleotide is chemically or biologically modified.

23 . The method of claim 13 , wherein upon delivery of the RNA, the RNA is able to interfere with the expression of a specific gene in a biological cell.

24 . The method of claim 12 , wherein the polynucleotide is DNA.

25 . The method of claim 1 , wherein the subject has been diagnosed with a disease or disorder.

26 . The method of claim 25 , wherein the disease, disorder, or condition is selected from the group consisting of proliferative disorders, inflammatory disorders, autoimmune disorders, painful conditions, liver diseases, and familial amyloid neuropathies.

27 . The method of claim 25 , wherein the disease, disorder, or condition is cancer, liver disease, or an infection.

28 . The method of claim 1 , wherein the agent is a targeting agent, an isotopically labeled chemical compound, vaccine, or immunological agent.

29 . The method of claim 18 , wherein the virus is selected from the group consisting of smallpox, influenza A and B, respiratory syncytial virus, parainfluenza, measles, HIV, varicella-zoster, herpes simplex 1 and 2, cytomegalovirus, Epstein-Barr virus, rotavirus, rhinovirus, adenovirus, papillomavirus, poliovirus, mumps, rabies, rubella, coxsackieviruses, equine encephalitis, Japanese encephalitis, yellow fever, Rift Valley fever, and hepatitis A, B, C, D, and E virus.

Assignments (1)

Continuity (6)

References Cited (400)