Gene delivery carrier
AssigneesMassachusetts Institute of Technology, Politecnico Di Milano
InventorsUmberto Capasso Palmiero, James C. Kaczmarek, Daniel Griffith Anderson, Davide Moscatelli
Life of this patent
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Abstract
Disclosed are methods, compositions, reagents, systems, and kits to prepare and utilize poly (β-amino ester) (PBAE) polymers, which are synthesized via Michael addition reactions of diacrylates and amines disclosed herein. Various embodiments utilize lactones and lactone derivatives to generate the diacrylate compounds. The PBAE polymers are shown to be effective biodegradable carriers for the delivery of an agent such as an organic molecule, inorganic molecule, nucleic acid, protein, peptide, polynucleotide, targeting agent, an isotopically labeled chemical compound, vaccine, or an immunological agent.
Claims39
A polymer of Formula (I):
- or a pharmaceutically acceptable salt thereof,
- wherein:
- is a single bond or a double bond
- A is hydrogen or —XR3;
- each B independently is a diradical of the formula:
- each D independently is:
- E is hydrogen or —XR4;
- each R, R′, and R″ independently is optionally substituted, cyclic or acyclic aliphatic;
- optionally substituted, cyclic or acyclic heteroaliphatic;
- or a combination thereof;
- each Ra independently is hydrogen or optionally substituted aliphatic;
- R1 and R2 independently are selected from hydrogen, optionally substituted, cyclic or acyclic aliphatic;
- optionally substituted, cyclic or acyclic heteroaliphatic;
- optionally substituted aryl;
- optionally substituted heteroaryl;
- and a nitrogen protecting group;
- or R1 and R2 are combined to form a ring;
- R3 and R4 independently are selected from hydrogen;
- optionally substituted, cyclic or acyclic aliphatic;
- optionally substituted, cyclic or acyclic heteroaliphatic;
- optionally substituted aryl;
- optionally substituted heteroaryl;
- and a protecting group;
- X is O, S, NH, or NRX, wherein RX is optionally substituted, aliphatic;
- optionally substituted carbocyclyl;
- optionally substituted heteroaliphatic;
- optionally substituted hetercyclyl;
- optionally substituted aryl;
- or optionally substituted heteroaryl;
- X′ is O or NRy, wherein Ry is hydrogen;
- optionally substituted, aliphatic;
- optionally substituted carbocyclyl;
- optionally substituted heteroaliphatic;
- optionally substituted hetercyclyl;
- optionally substituted aryl;
- or optionally substituted heteroaryl;
- each m independently is an integer between 1 and 100, inclusive;
- and
- n is an integer between 1 and 10,000, inclusive.
(canceled)
(canceled)
6-21. (canceled)
(canceled)
25-35. (canceled)
(canceled)
39-61. (canceled)
63-69. (canceled)
71-77. (canceled)
79-85. (canceled)
87-93. (canceled)
95-96. (canceled)
A compound of Formula (VI):
- wherein:
- R is optionally substituted, cyclic or acyclic aliphatic, optionally substituted, cyclic or acyclic heteroaliphatic, or a combination thereof;
- each R′ independently is optionally substituted, cyclic or acyclic aliphatic, optionally substituted, cyclic or acyclic heteroaliphatic, or a combination thereof;
- each Ra independently is hydrogen or optionally substituted aliphatic;
- and
- m is an integer between 1 and 100, inclusive.
98-112. (canceled)
115-117. (canceled)
119-123. (canceled)
(canceled)
127-135. (canceled)
(canceled)
139-140. (canceled)
Dependencies are inferred from the claim text.