Therapeutic delivery compositions and methods of use thereof

• US 20040248833A1
• Filed: 08/02/2004
• Published: 12/09/2004
• Est. Priority Date: 03/19/1991
• Status: Abandoned Application

• Current Assignee: CytRx Corporation
• Original Assignee: CytRx Corporation
• Inventors: Emanuele, R Martin, Allaudeen, Hameedsulthan S, Kousoulas, Konstantin G, Newman, Mark
• Application Number:
  US10/485,610
• Publication Number:
  US 20040248833A1
• Time in Patent Office: Days
• US Class Current: 514/44
• CPC Class Codes: A61K 2039/53 DNA (RNA) vaccination
• CPC Class Codes: A61K 2039/6093 Synthetic polymers, e.g. polyethyleneglycol [PEG], Polymers or copolymers of (D) glutamate and (D) lysine
• CPC Class Codes: A61K 31/765 Polymers containing oxygen
• CPC Class Codes: A61K 31/77 of oxiranes
• CPC Class Codes: A61K 38/50 acting on carbon-nitrogen bonds, other than peptide bonds (3.5), e.g. asparaginase
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/245 Herpetoviridae, e.g. herpes simplex virus
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/56 the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: C08G 65/08 Saturated oxiranes
• CPC Class Codes: C08G 65/2624 containing aliphatic amine groups
• CPC Class Codes: C08G 65/30 Post-polymerisation treatment, e.g. recovery, purification, drying
• CPC Class Codes: C12N 2710/16634 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Abstract

The present invention relates to compositions and methods for treating infectious diseases and genetic disorders through gene therapy and intracellular delivery of antisense oligonucleotides or other nucleic acid sequences. The present invention comprises a therapeutic delivery composition effective for treating a disease state comprising an administerable admixture of an effective amount of a therapeutic compound capable of altering nucleic acid sequence function and an effective amount of a block copolymer having the following general formula: Wherein, the mean aggregate molecular weight of the portion of the octablock copolymer represented by polyoxypropylene is between about 5000 and about 7000 Daltons; a is a number such that the portion represented by polyoxyethylene constitutes between about 10% to about 40% of the compound by weight; and bi s a number such that the polyoxypropylene portion of the total molecular weight of the octablock copolymer constitutes between about 30 60% and about 90% of the compound by weight. The present invention also includes compositions and methods using biologically active reverse block copolymers. The reverse copolymers.

Claims

1. A therapeutic composition for treating a human or animal comprising,

a compound capable of altering nucleic acid function admixed with an octablock copolymer, wherein the octablock copolymer has the following formula:

Wherein,

the mean aggregate molecular weight of the portion of the octablock copolymer represented by polyoxypropylene (POP) is between about 5000 and about 7000 Daltons;

a is a number such that the portion represented by polyoxyethylene (POE) constitutes between about 10% to about 40% of the compound by weight; and

b is a number such that the polyoxypropylene portion of the total molecular weight of the octablock copolymer constitutes between about 60% and about 90% of the compound by weight.

2. The composition of claim 1, wherein,

the mean aggregate molecular weight of the portion of the octablock copolymer represented by polyoxypropylene is about 6750 Daltons;

a is a number such that the portion represented by polyoxyethylene constitutes about 10% of the compound by weight; and

b is a number such that the polyoxypropylene portion of the total molecular weight of the octablock copolymer constitutes about 90% of the compound by weight.

3. The composition of claim 1, wherein,

the mean aggregate molecular weight of the portion of the octablock copolymer represented by polyoxypropylene is about 5750 Daltons;

a is a number such that the portion represented by polyoxyethylene constitutes approximately 10% of the compound by weight; and

b is a number such that the polyoxypropylene portion of the total molecular weight of the octablock copolymer constitutes about 90% of the compound by weight.

4. The composition of claim 1, wherein,

the mean aggregate molecular weight of the portion of the octablock copolymer represented by polyoxypropylene is about 5220 Daltons;

a is a number such that the portion represented by polyoxyethylene constitutes about 10% of the compound by weight; and

b is a number such that the polyoxypropylene portion of the total molecular weight of the octablock copolymer constitutes about 90% of the compound by weight.

5. The composition of claim 1, wherein,

the mean aggregate molecular weight of the portion of the octablock copolymer represented by polyoxypropylene is between about 5000 and about 7000 Daltons;

a is a number such that the portion represented by polyoxyethylene constitutes between about 5% to about 20% of the compound by weight; and

b is a number such that the polyoxypropylene portion of the total molecular weight of the octablock copolymer constitutes between about 80% and about 95% of the compound by weight.

6. The composition of claim 1, wherein the compound capable of altering nucleic acid sequence function is selected from nucleic acids, vector constructs, genes, oligonucleotides, antisense oligonucleotides, triplex DNA compounds, or ribozymes.

7. A therapeutic composition for treating a human or animal comprising,

a compound capable of altering nucleic acid function admixed with an octablock copolymer, wherein the block copolymer has the following formula:

Wherein,

the mean aggregate molecular weight of the portion of the octablock copolymer represented by polyoxypropylene is between about 5000 and about 7000 Daltons;

a is a number such that the portion represented by polyoxyethylene constitutes between about 10% to about 40% of the compound by weight; and

b is a number such that the polyoxypropylene portion of the total molecular weight of the octablock copolymer constitutes between about 60% and about 90% of the compound by weight.

8. The composition of claim 7, wherein:

the mean aggregate molecular weight of the portion of the octablock copolymer represented by polyoxypropylene is about 6750 Daltons;

a is a number such that the portion represented by polyoxyethylene constitutes about 10% of the compound by weight; and

b is a number such that the polyoxypropylene portion of the total molecular weight of the octablock copolymer constitutes about 90% of the compound by weight.

9. The composition of claim 7, wherein,

the mean aggregate molecular weight of the portion of the octablock copolymer represented by polyoxypropylene is about 5750 Daltons;

a is a number such that the portion represented by polyoxyethylene constitutes approximately 10% of the compound by weight; and

b is a number such that the polyoxypropylene portion of the total molecular weight of the octablock copolymer constitutes about 90% of the compound by weight.

10. The composition of claim 7, wherein,

the mean aggregate molecular weight of the portion of the octablock copolymer represented by polyoxypropylene is about 5220 Daltons;

a is a number such that the portion represented by polyoxyethylene constitutes about 10% of the compound by weight; and

b is a number such that the polyoxypropylene portion of the total molecular weight of the octablock copolymer constitutes about 90% of the compound by weight.

11. The composition of claim 7, wherein the compound capable of altering nucleic acid sequence function is selected from nucleic acids, vector constructs, genes, oligonucleotides, antisense oligonucleotides, triplex DNA compounds, or ribozymes.

12. A method of delivering a compound capable of altering nucleic acid sequence function to a human or animal comprising,

administering to a human or animal a composition comprising a compound capable of altering nucleic acid sequence function admixed with an octablock copolymer, wherein the octablock copolymer has the following formula:

wherein,

the mean aggregate molecular weight of the portion of the octablock copolymer represented by polyoxypropylene is between about 5000 and about 7000 Daltons;

a is a number such that the portion represented by polyoxyethylene constitutes between about 10% to about 40% of the compound by weight; and

b is a number such that the polyoxypropylene portion of the total molecular weight of the octablock copolymer constitutes between about 60% and about 90% of the compound by weight.

13. The method of claim 12, wherein,

the mean aggregate molecular weight of the portion of the octablock copolymer represented by polyoxypropylene is about 6750 Daltons;

a is a number such that the portion represented by polyoxyethylene constitutes about 10% of the compound by weight; and

b is a number such that the polyoxypropylene portion of the total molecular weight of the octablock copolymer constitutes about 90% of the compound by weight.

14. The method of claim 12, wherein,

the mean aggregate molecular weight of the portion of the octablock copolymer represented by polyoxypropylene is about 5750 Daltons;

a is a number such that the portion represented by polyoxyethylene constitutes approximately 10% of the compound by weight; and

b is a number such that the polyoxypropylene portion of the total molecular weight of the octablock copolymer constitutes about 90% of the compound by weight.

15. The method of claim 12, wherein:

the mean aggregate molecular weight of the portion of the octablock copolymer represented by polyoxypropylene is about 5220 Daltons;

a is a number such that the portion represented by polyoxyethylene constitutes about 10% of the compound by weight; and

b is a number such that the polyoxypropylene portion of the total molecular weight of the octablock copolymer constitutes about 90% of the compound by weight.

16. The method of claim 12, wherein the compound capable of altering nucleic acid sequence function is selected from nucleic acids, vector constructs, genes, oligonucleotides, antisense oligonucleotides, triplex DNA compounds, or ribozymes.

17. A method of delivering a compound capable of altering nucleic acid sequence function to a human or animal comprising, administering to a human or animal a composition comprising a compound capable of altering nucleic acid sequence function admixed with an octablock copolymer, wherein the octablock copolymer has the following formula:

18. The method of claim 17, wherein,

the mean aggregate molecular weight of the portion of the octablock copolymer represented by polyoxypropylene is about 6750 Daltons;

a is a number such that the portion represented by polyoxyethylene constitutes about 10% of the compound by weight; and

b is a number such that the polyoxypropylene portion of the total molecular weight of the octablock copolymer constitutes about 90% of the compound by weight.

19. The method of claim 17, wherein,

the mean aggregate molecular weight of the portion of the octablock copolymer represented by polyoxypropylene is about 5750 Daltons;

a is a number such that the portion represented by polyoxyethylene constitutes approximately 10% of the compound by weight; and

b is a number such that the polyoxypropylene portion of the total molecular weight of the octablock copolymer constitutes about 90% of the compound by weight.

20. The method of claim 17, wherein,

the mean aggregate molecular weight of the portion of the octablock copolymer represented by polyoxypropylene is about 5220 Daltons;

a is a number such that the portion represented by polyoxyethylene constitutes about 10% of the compound by weight; and

b is a number such that the polyoxypropylene portion of the total molecular weight of the octablock copolymer constitutes about 90% of the compound by weight.

21. The method of claim 17, wherein the compound capable of altering nucleic acid sequence function is selected from nucleic acids, vector constructs, genes, oligonucleotides, antisense oligonucleotides, triplex DNA compounds, or ribozymes.

22. The method of claim 17, wherein,

the mean aggregate molecular weight of the portion of the octablock copolymer represented by polyoxypropylene is between about 5000 and about 7000 Daltons;

a is a number such that the portion represented by polyoxyethylene constitutes between about 5% to about 20% of the compound by weight; and

b is a number such that the polyoxypropylene portion of the total molecular weight of the octablock copolymer constitutes between about 80% and about 95% of the compound by weight.

23. A therapeutic composition for treating a human or animal comprising,

a compound capable of altering nucleic acid function admixed with a block copolymer, wherein the block copolymer has the following formula:

wherein “

b”

represents a number such that the molecular weight of the hydrophobe (C₃H₆O)_b is between approximately 2,000 and 20,000, and “

a”

represents a number such that the percentage of hydrophile (C₂H₄O)_a is between approximately 1% and 90%.

24. The composition of claim 23, wherein, wherein “

b”

represents a number such that the molecular weight of the hydrophobe (C₃H₆O)_b is approximately 5,000, and “

a”

represents a number such that the percentage of hydrophile (C₂H₄O)_a is approximately 90%.

25. The composition of claim 23, wherein, wherein “

b”

represents a number such that the molecular weight of the hydrophobe (C₃H₆O)_b is approximately 5750, and “

a”

represents a number such that the percentage of hydrophile (C₂H₄O)_a is between approximately 10%.

26. The composition of claim 23, wherein, wherein “

b”

represents a number such that the molecular weight of the hydrophobe (C₃H₆O)_b is approximately 5220, and “

a”

represents a number such that the percentage of hydrophile (C₂H₄O)_a is approximately 10%.

27. The composition of claim 23, wherein the compound capable of altering nucleic acid sequence function is selected from nucleic acids, vector constructs, genes, oligonucleotides, antisense oligonucleotides, triplex DNA compounds, or ribozymes.

28. The composition of claim 23, wherein wherein “

b”

represents a number such that the molecular weight of the hydrophobe (C₃H₆O)_b is between approximately 2,000 and 10,000, and “

a”

represents a number such that the percentage of hydrophile (C₂H₄O)_a is between approximately 5% and 30%.

29. The composition of claim 23, wherein, wherein “

b”

represents a number such that the molecular weight of the hydrophobe (C₃H₆O)_b is approximately 6750 Daltons, and “

a”

represents a number such that the percentage of hydrophile (C₂H₄O)_a is approximately 10%.

30. A method of delivering a compound capable of altering nucleic acid sequence function to a human or animal comprising,

administering to a human or animal a composition comprising a compound capable of altering nucleic acid sequence function admixed with a block copolymer, wherein the block copolymer has the following formula,

wherein “

b”

represents a number such that the molecular weight of the hydrophobe (C₃H₆O)_b is between approximately 2,000 and 20,000, and “

a”

represents a number such that the percentage of hydrophile (C₂H₄O)_a is between approximately 1% and 90%.

31. The method of claim 30,

wherein “

b”

represents a number such that the molecular weight of the hydrophobe (C₃H₆O)_b is approximately 6750, and “

a”

represents a number such that the percentage of hydrophile (C₂H₄O)_a is approximately 10%.

32. The method of claim 30,

wherein “

b”

represents a number such that the molecular weight of the hydrophobe (C₃H₆O)_b is approximately 5750, and “

a”

represents a number such that the percentage of hydrophile (C₂H₄O)_a is approximately 10%.

33. The method of claim 30,

wherein “

b”

represents a number such that the molecular weight of the hydrophobe (C₃H₆O)_b is approximately 5220, and “

a”

represents a number such that the percentage of hydrophile (C₂H₄O)_a is approximately 10%.

34. The method of claim 30, wherein the compound capable of altering nucleic acid sequence function is selected from nucleic acids, vector constructs, genes, oligonucleotides, antisense oligonucleotides, triplex DNA compounds, or ribozymes.

35. The method of claim 30,

wherein “

b”

represents a number such that the molecular weight of the hydrophobe (C₃H₆O)_b is between approximately 2,000 and 10,000, and “

a”

represents a number such that the percentage of hydrophile (C₂H₄O)_a is between approximately 5% and 30%.