Methods of treating disease with random copolymers

• US 7,655,221 B2
• Filed: 11/17/2005
• Issued: 02/02/2010
• Est. Priority Date: 05/07/2004
• Status: Expired due to Fees

• Current Assignee: Ares Trading SA (Merck & Co., Inc.)
• Original Assignee: Peptimmune, Inc..
• Inventors: Johnson, Keith, Zhang, Jianxin, Rasmussen, James, Yu, Bei, Baldwin, Sam, Bonnin, Dustan, Zanelli, Eric
• Primary Examiner(s): Russel; Jeffrey E
• Application Number:
  US11/283,406
• Publication Number:
  US 20060189527A1
• Time in Patent Office: 1,538 Days
• Field of Search: None
• US Class Current: 424/78.08
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 38/02 Peptides of undefined number of amino acids; Derivatives thereof
• CPC Class Codes: A61K 38/16 Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof enzyme inhibitors A61K38/005
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14

Abstract

The invention relates to novel methods and kits for treating or preventing disease through the administration of random copolymers comprising amino acids tyrosine (Y), phenylalanine (F), alanine (A), and lysine (K). The invention also relates to the treatment of autoimmune diseases, such as multiple sclerosis, and to the administration of random copolymers in treatment regimen comprising formulations that are administered at intervals greater than 24 hours, or to sustained release formulations which administer the copolymer over a period greater than 24 hours. The invention further relates to methods for conducting a pharmaceutical business comprising manufacturing, licensing, or distributing kits containing or relating to the formulations or dosing regimens of random copolymer described herein.

Claims

1. A method of reducing the severity of one or more symptoms of multiple sclerosis comprising the step of administering to a subject in need thereof an effective amount of a random copolymer composition, wherein said effective amount is delivered to said subject in two or more doses, each additional dose after the first dose being administered at least one week after the conclusion of administration of the immediately preceding dose, and wherein the random copolymer composition comprises YFAK (L-tyrosine, L-phenylalanine, L-alanine and L-lysine) in an output molar ratio of about 1.0:

1.2;

XA;

6.0 respectively, and has a length of at least 35 amino acids wherein XA=18.0 to 30.0.

2. The method of claim 1, wherein the random copolymer composition comprises YFAK (L-tyrosine, L-phenylalanine, L-alanine and L-lysine) in an output molar ratio of about 1.0:

1.2;

XA;

6.0 respectively, and has a length of at least 35 amino acids wherein the composition is selected from the group consisting of;

(a) a random copolymer composition comprising YFAK (L-tyrosine, L-phenylalanine, L-alanine and L-lysine) in an output molar ratio of about 1.0;

1.2;

20;

6.0 respectively, and has a length of at least 35 amino acids; and

(b) a random copolymer composition comprising YFAK (L-tyrosine, L-phenylalanine, L-alanine and L-lysine) in an output molar ratio of about 1.0;

1.2;

22;

6.0 respectively, and has a length of at least 35 amino acids; and

(c) a random copolymer composition comprising YFAK (L-tyrosine, L-phenylalanine, L-alanine and L-lysine) in an output molar ratio of about 1.0;

1.2;

24;

6.0 respectively, and has a length of at least 35 amino acids.

3. The method of claim 1, wherein the multiple sclerosis is relapsing-remitting multiple sclerosis.

4. The method of claim 1, wherein the subject is a human.

5. The method of claim 1, wherein the effective amount of the random copolymer is between 0.02 mg per dose and 2000 mg per dose.

6. The method of claim 1, wherein the effective amount is about 1 mg.

7. The method of claim 1, wherein the random copolymer composition is administered in a dosing regimen comprising a dose of between 10 and 65 mg per m² of the body surface area of the subject per dose.

8. The method of claim 7, wherein the dosing regimen comprises a dose of about 22 mg per m² of the body surface area of the subject per dose.

9. The method of claim 1, wherein the random copolymer composition is administered in a dosing regimen comprising a dose of between about 0.05 mg and 0.4 mg per kg of the body weight of the subject per dose.

10. The method of claim 1, wherein the random copolymer composition is administered in a dosing regimen comprising a maximum dose of about 140 mg per m² of the body surface area of the subject weekly.

11. The method of claim 1, wherein the random copolymer composition is administered in a dosing regimen comprising a dose of between 0.35 and 2.8 mg per kg of the body weight of the subject weekly.

12. The method of claim 1, wherein the dosing regimen comprises continuous administration of the random copolymer composition.

13. The method of claim 12, wherein the administration of the random copolymer composition is via devices designed to deliver the random copolymer composition continuously.

14. The method of claim 13, wherein the device is an implantable device, a sustained release capsule, controlled release formulation, or a pump.

15. The method of claim 12, wherein said effective amount is delivered to the subject using a sustained-release formulation which administers the random copolymer over a period of at least 3 days.

16. The method of claim 1, further comprising administering an additional therapeutically active agent to the subject.

17. The method of claim 16, wherein the additional agent is one or more random copolymers useful in treating multiple sclerosis.

18. The method of claim 16, wherein the additional agent is an anti-inflammatory agent.

19. The method of claim 1, further comprising administering to said subject a T-cell depletion therapy.

20. The method of claim 1, further comprising administering to said subject an anti-lymphocyte therapy.

21. The method of claim 20, wherein said anti-lymphocyte therapy comprises administering an agent selected from the group consisting of a polyclonal antibody and a monoclonal antibody.

22. The method of claim 21, wherein said polyclonal antibody is antithymocyte gamma globulin (ATGAM).

23. The method of claim 21, wherein said monoclonal antibody is selected from the group consisting of alemtuzumab, muromonab, daclizumab, and basiliximab.

24. The method of claim 1, further comprising administering to said subject an anti B-cell therapy.

25. The method of claim 24, wherein said anti-B-cell therapy comprises administering anti CD-20 antibody.

28. The method according to claim 1, wherein the effective amount is delivered subcutaneously.

26. A method for decreasing the frequency of recurrences of episodes of multiple sclerosis comprising the step of administering to a subject in need thereof an effective amount of a random copolymer composition, wherein said effective amount is delivered to said subject in two or more doses, each additional dose after the first dose being administered at least one week after the administration of the immediately preceding dose, and wherein the random copolymer composition comprises YFAK (L-tyrosine, L-phenylalanine, L-alanine and L-lysine) in an output molar ratio of about 1.0:

1.2;

XA;

6.0 respectively, and has a length of at least 35 amino acids wherein XA=18.0 to 30.0.

27. The method of claim 26, wherein the random copolymer composition comprises YFAK (L-tyrosine, L-phenylalanine, L-alanine and L-lysine) in an output molar ratio of about 1.0:

1.2;

XA;

6.0 respectively, and has a length of at least 35 amino acids wherein the composition is selected from the group consisting of;

(a) a random copolymer composition comprising YFAK (L-tyrosine, L-phenylalanine, L-alanine and L-lysine) in an output molar ratio of about 1.0;

1.2;

20;

6.0 respectively, and has a length of at least 35 amino acids;

(b) a random copolymer composition comprising YFAK (L-tyrosine, L-phenylalanine, L-alanine and L-lysine) in an output molar ratio of about 1.0;

1.2;

22;

6.0 respectively, and has a length of at least 35 amino acids; and

(c) a random copolymer composition comprising YFAK (L-tyrosine, L-phenylalanine, L-alanine and L-lysine) in an output molar ratio of about 1.0;

1.2;

24;

6.0 respectively, and has a length of at least 35 amino acids.

29. The method according to claim 26, wherein the effective amount is delivered subcutaneously.