Granted Patent B2

US 12,433,847 · App. 17/689,314 · Granted Oct 7, 2025

Inventors: Carlo Giovanni Traverso (Newton, MA); Ameya R. Kirtane (Minneapolis, MN); Robert S. Langer (Newton, MA); Hyunjoon Kim (Cambridge, MA); Gary W Liu (Cambridge, MA); James Byrne (Boston, MA); Daniel Reker (Durham, NC); Yunhua Shi (Belmont, MA); Grace Junyue Zhong (Cambridge, MA); Netra Rajesh (Brampton, CA)

Assignees: Massachusetts Institute of Technology; The Brigham and Women's Hospital, Inc.

A61K9/5153A61K39/0011A61K48/0041A61P35/00C08G63/685A61K2039/53

Abstract

Claims (142)

1. A branched polymer of Formula (I):

L-(R) n   (I)

or a salt thereof, wherein:

L is a substituted or unsubstituted heteroalkylene;

n is 3, 4, 5, or 6; and

each R is independently hydrogen, Formula (II), or Formula (III);

wherein Formula (II) is:

wherein:

m is an integer of 1-1000, inclusive;

A is optionally substituted alkylene or optionally substituted heteroalkylene;

X is —CH═CH 2 , —CH 2 CH 2 OR 2 , —CH 2 CH 2 SR 3 , —CH 2 CH 2 N(R 2 )(R 3 ), or —CH 2 CH 2 L(R 4 ) q ;

q is 2, 3, 4, or 5;

R 1 is optionally substituted alkyl or optionally substituted heteroalkyl;

R 2 is hydrogen, optionally substituted alkyl, or optionally substituted heteroalkyl;

R 3 is optionally substituted alkyl or optionally substituted heteroalkyl; or

R 2 and R 3 combine to form a 4-7 membered ring; and

each R 4 is independently hydrogen, Formula (II), or Formula (III);

wherein Formula (III) is:

wherein:

p is an integer of 1-1000, inclusive;

B is optionally substituted alkylene or optionally substituted heteroalkylene;

Z is —CH═CH 2 , —CH 2 CH 2 OR 6 , —CH 2 CH 2 SR 7 , —CH 2 CH 2 N(R 6 )(R 7 ), or —CH 2 CH 2 L(R 8 ) v ;

v is 2, 3, 4, or 5;

R 5 is optionally substituted alkyl or optionally substituted heteroalkyl;

R 6 is hydrogen, optionally substituted alkyl, or optionally substituted heteroalkyl;

R 7 is optionally substituted alkyl or optionally substituted heteroalkyl; or

R 6 and R 7 combine to form a 4-7 membered ring; and

each R 8 is independently hydrogen, Formula (II), or Formula (III);

provided that at least one R is Formula (II) and at least one R is Formula (III), and provided that Formula (II) and Formula (III) are not the same.

2. The polymer of claim 1 , wherein each R is independently Formula (II) or Formula (III).

3. The polymer of claim 1 , wherein each L is independently of the formula:

wherein

each Y is independently:

each L 1 is independently substituted or unsubstituted C 1-10 alkylene or substituted or unsubstituted C 1-10 heteroalkylene; and

each R L is independently hydrogen, halogen, substituted or unsubstituted C 1-5 alkylene, or substituted or unsubstituted C 1-5 heteroalkylene.

4. The polymer of claim 1 , wherein at least one R 4 is Formula (II) or Formula (III).

5. The polymer of claim 1 , wherein at least one R 8 is Formula (II) or Formula (III).

6. The polymer of claim 1 , wherein:

n is 3;

L is

wherein in Formula (II):

A is —(CH 2 ) 6 —;

X is —CH 2 CH 2 N(R 2 )(R 3 ) or —CH 2 CH 2 L(R 4 ) q ;

R is —(CH 2 ) 3 OH;

R 2 is hydrogen;

R 3 is

and

wherein in Formula (III):

B is —(CH 2 ) 4 —;

Z is —CH 2 CH 2 N(R 6 )(R 7 ) or —CH 2 CH 2 L(R 8 ) v ;

R 5 is —(CH 2 ) 5 OH;

R 6 is hydrogen; and

R 7 is

7. The polymer of claim 1 , wherein:

n is 3;

L is

wherein in Formula (II):

A is —(CH 2 ) 6 —;

X is —CH 2 CH 2 N(R 2 )(R 3 );

R is —(CH 2 ) 3 OH;

R 2 is hydrogen; and

R 3 is

and

wherein in Formula (III):

B is —(CH 2 ) 4 —;

Z is —CH 2 CH 2 N(R 6 )(R 7 );

R 5 is —(CH 2 ) 5 OH;

R 6 is hydrogen; and

R 7 is

8. The polymer of claim 1 , wherein:

n is 4;

L is

wherein in Formula (II):

A is —(CH 2 ) 3 —;

X is —CH 2 CH 2 N(R 2 )(R 3 ) or —CH 2 CH 2 L(R 4 ) q ;

R 1 is —(CH 2 ) 5 OH;

R 2 is hydrogen; and

R 3 is

and

wherein in Formula (III):

B is —(CH 2 ) 6 —;

Z is —CH 2 CH 2 N(R 6 )(R 7 ) or —CH 2 CH 2 L(R 8 ) v ;

R 5 is —(CH 2 ) 3 OH;

R 6 is hydrogen; and

R 7 is

9. The polymer of claim 1 , wherein:

n is 4;

L is

wherein in Formula (II):

A is —(CH 2 ) 3 —;

X is —CH 2 CH 2 N(R 2 )(R 3 );

R 1 is —(CH 2 ) 5 OH;

R 2 is hydrogen; and

R 3 is

and

wherein in Formula (III):

B is —(CH 2 ) 6 —;

Z is —CH 2 CH 2 N(R 6 )(R 7 );

R 5 is —(CH 2 ) 3 OH;

R 6 is hydrogen; and

R 7 is

10. The polymer of claim 1 , wherein:

n is 3;

L is

wherein in Formula (II):

A is —(CH 2 ) 4 —;

X is —CH 2 CH 2 N(R 2 )(R 3 ) or —CH 2 CH 2 L(R 4 ) q ;

R 1 is —(CH 2 ) 5 OH;

R 2 is hydrogen; and

R 3 is

and

wherein in Formula (III):

B is —(CH 2 ) 6 —;

Z is —CH 2 CH 2 N(R 6 )(R 7 ) or —CH 2 CH 2 L(R 8 ) v ;

R 5 is —CH 2 CH(OH)CH 2 OH;

R 6 is hydrogen; and

R 7 is

11. The polymer of claim 1 , wherein:

n is 3;

L is

wherein in Formula (II):

A is —(CH 2 ) 4 —;

X is —CH 2 CH 2 N(R 2 )(R 3 );

R 1 is —(CH 2 ) 5 OH;

R 2 is hydrogen; and

R 3 is

and

wherein in Formula (III):

B is —(CH 2 ) 6 —;

Z is —CH 2 CH 2 N(R 6 )(R 7 );

R 5 is —CH 2 CH(OH)CH 2 OH;

R 6 is hydrogen; and

R 7 is

12. A composition comprising the polymer of claim 1 , or a salt thereof; an agent; and optionally an excipient.

13. The composition of claim 12 , wherein the agent is an organic molecule, inorganic molecule, nucleic acid, protein, peptide, polynucleotide, targeting agent, an isotopically labeled chemical compound, vaccine, an immunological agent, or an agent useful in bioprocessing.

14. The composition of claim 12 , wherein the agent is a polynucleotide.

15. The composition of claim 14 , wherein the agent is an RNA.

16. A kit comprising a polymer of claim 1 ; and instructions for using the kit.

17. A method of delivering an agent to a subject or cell, the method comprising administering to the subject or contacting the cell with a composition of claim 12 .

18. The method of claim 17 , wherein the cell is a liver cell, kidney cell, spleen cell, lung cell, skin cell, brain cell, epithelial cell, or a cell of the gastrointestinal tract.

19. A method of treating or preventing a disease in a subject in need thereof, the method comprising administering to the subject a composition of claim 12 .

20. The method of claim 19 , wherein the disease is a genetic disease, proliferative disease, hematological disease, neurological disease, liver disease, kidney disease, spleen disease, lung disease, painful condition, psychiatric disorder, musculoskeletal disease, a metabolic disorder, inflammatory disease, or autoimmune disease.

Assignments (4)

Continuity (2)

References Cited (382)