Modified Polymers for Delivery of Polynucleotides, Method of Manufacture, and Methods of Use Thereof

• US 20130109817A1
• Filed: 01/07/2013
• Published: 05/02/2013
• Est. Priority Date: 03/26/2010
• Status: Abandoned Application

• Current Assignee: Mersana Therapeutics, Inc.
• Original Assignee: Mersana Therapeutics, Inc.
• Inventors: Yurkovetskiy, Aleksandr V., Yin, Mao, Lowinger, Timothy B., Cabral, Carolina B., Hammond, Charles E., Stevenson, Cheri A.
• Application Number:
  US13/735,872
• Publication Number:
  US 20130109817A1
• Time in Patent Office: Days
• US Class Current: 525/467
• CPC Class Codes: A61K 47/59 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
• CPC Class Codes: A61K 48/0041 the non-active part being polymeric
• CPC Class Codes: C08G 63/914 derived from polycarboxylic acids and polyhydroxy compounds
• CPC Class Codes: C08L 59/00 Compositions of polyacetals; Compositions of derivatives of polyacetals of polyvinyl acetals C08L29/14
• CPC Class Codes: C12N 15/111 General methods applicable to biologically active non-coding nucleic acids
• CPC Class Codes: C12N 15/87 Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
• CPC Class Codes: C12N 2310/11 Antisense
• CPC Class Codes: C12N 2310/12 catalytic nucleic acids, e.g. ribozymes
• CPC Class Codes: C12N 2310/14 interfering N.A.
• CPC Class Codes: C12N 2320/32 Special delivery means, e.g. tissue-specific

Abstract

A modified polymer is provided herein, the modified polymer having the following formula:

in which W₁, W₂, W₃, W₄, W₅, W₆, Z₁, Z₂, Z₃, Z₄, Z₅, Z₉′, R₁, R₂, R₃, R₄, R₅, n₁, n₂, n₃, n₄, n₅, and n_6′ are defined herein. The modified polymer is useful for delivering a polynucleotide to the cytoplasm of a selected tissue type or cell type.

Claims

1. A modified polyacetal of Formula (V) useful to conjugate with R₆:

2. The modified polyacetal of claim 1 being of Formula (Va):

3. The modified polyacetal of claim 2, wherein R₂ is:

4. The modified polyacetal of claim 3, wherein R₂ is:

5. The modified polyacetal of claim 4, wherein R₂ is a linear polyethylenimine having a molecular weight of about 500 to 2500 dalton, a branched polyethylenimine having a molecular weight of about 500 to about 800 dalton or

6. The modified polyacetal of claim 5, wherein the unit containing R₂ is a unit of Formula (XII) or Formula (XIII):

7. The modified polyacetal of claim 5, wherein the unit containing R₂ is a unit of Formula (XIV) or Formula (XV):

8. The modified polyacetal of claim 2, wherein Z₂ is ethylenediamine, piperazine, bis(piperidine), 1,3-diaminopropane, 1,4-diaminobutane, 1,5-diaminopentane, decamethylenediamine, hexamethylenediamine, lysine, histidine, arginine, tryptophan, agmatine or ornithine.

9. The modified polyacetal of claim 8, wherein Z₂ is

10. The modified polyacetal of claim 9, wherein the unit containing Z₂ is a unit of Formula (VII) or (VIII):

11. The modified polyacetal of claim 2, wherein the modified polyacetal is:

12. The modified polyacetal of claim 1 being of Formula (Vb):

13. The modified polyacetal of claim 12, wherein

n is between about 0.01 and about 0.9996 inclusive;

and

n₂ is between about 0.02 and about 0.90 inclusive.

14. The modified polyacetal of claim 12, wherein Z₆ is ethylenediamine, piperazine, bis(piperidine), 1,3-diaminopropane, 1,4-diaminobutane, 1,5-diaminopentane, decamethylenediamine, hexamethylenediamine, lysine, histidine, arginine, tryptophan, agmatine or ornithine.

15. The modified polyacetal of claim 14, wherein Z₆ is

16. The modified polyacetal of claim 12, wherein Z₇ is:

17. The modified polyacetal of claim 16, wherein Z₇ is:

18. The modified polyacetal of claim 12, wherein the modified polyacetal is:

19. The modified polyacetal of claim 1, wherein:

the ratio (m₁) of the number of R₁ to the total number of polyacetal units of the polyacetal is 0 to 0.25;

the ratio (m₃) of the number of R₃ to the total number of polyacetal units of the polyacetal is 0 to 100;

the ratio (m₄) of the number of R₄ to the total number of polyacetal units of the polyacetal is 0 to 30;

the ratio (m₅) of the number of R₅ to the total number of polyacetal units of the polyacetal is 0 to 0.03.

20. The modified polyacetal of claim 19, wherein

m₁ is 0.002 to 0.25;

m₃ is 0.002 to 100;

m₄ is 0.03 to 0.30; and

m₅ is 0.01 to 0.03.