THERAPEUTIC COMPOSITIONS COMPRISING HYALURONAN AND THERAPEUTIC ANTIBODIES AS WELL AS METHODS OF TREATMENT

• US 20090220497A1
• Filed: 09/04/2006
• Published: 09/03/2009
• Est. Priority Date: 09/07/2005
• Status: Active Grant

• Current Assignee: Alchemia Oncology Pty Ltd. (The Sustainable Nutrition Group Ltd.)
• Original Assignee: Alchamia Opcology Pty Limisted
• Inventors: Brown, Tracey J., Brownlee, Gary
• Granted Patent: US 8,623,354 B2
• Time in Patent Office: Days
• US Class Current: 424/133.100
• 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 31/728 Hyaluronic acid
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 39/39558 against tumor tissues, cells, antigens
• 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 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention relates generally to treatment and prophylactic protocols for cellular diseases or disorders, such as diseases and disorders associated with abnormal cellular proliferation. More particularly, the present invention provides compositions comprising therapeutic antibodies and hyaluronan and their use in the treatment or prophylaxis of cellular diseases and disorders.

Claims

1. A formulation comprising hyaluronan (HA) or an analogue or a derivative or synthesized or chemically modified form or salt thereof wherein the hyaluronan is in the molecular weight range of about 400 kDaltons to 20,000 kDaltons, and a therapeutic antibody, or fragment, derivative, portion, chimera or fully de-immunized form thereof and optionally one or more, pharmaceutically acceptable carriers, diluents and/or excipients.

2. The formulation of claim 1 wherein the hyaluronan or analogue or derivative or synthesized or modified form thereof is in the molecular weight range of about 400 kDaltons to 10,000 kDaltons.

3. The formulation of claim 1 wherein the hyaluronan or analogue or derivative or synthesized or modified form thereof is in the molecular weight range of about 400 kDaltons to 2000 kDaltons.

4. The formulation of claim 1 wherein the hyaluronan or analogue or derivative or synthesized or modified form thereof is in the molecular weight range of about 400 kDaltons to 1,500 kDaltons.

5. The formulation of claim 1 wherein the hyaluronan or analogue or derivative or synthesized or modified form thereof is in the modal molecular weight range of about 860 kDaltons.

6. The formulation of claim 1, wherein the hyaluronan or analogue or derivative or synthesized or modified form thereof and the antibody are not covalently bound.

7. The formulation of claim 1 wherein the pH range of the composition is between pH 2.5 and 10.5.

8. The formulation of claim 1 wherein the pH range of the composition is between pH 5.0 and 8.5.

9. The formulation of claim 1, wherein the antibody, fragment, derivative, portion, chimera or fully de-immunized form thereof is for use in the treatment or prophylaxis of a cellular proliferative disease.

10. The formulation of claim 1, wherein the antibody, fragment, derivative or portion thereof is selected from the group of antibodies consisting of:

ABX-EGF;

Alemtuzumab;

Apolizumab;

Bevacizumab;

Cantuzumab;

Cetuximab;

cG250;

cmc-544;

Daclizumab;

Epratuzumab;

erlotinib;

Gemtuzumab ozogamicin;

hA20;

HCBE-11;

Hun901;

Ibritumomab tiuxetan;

IDEC 159;

Infliximab;

Lumiliximab;

mAb 3F8;

mAb b43.13;

mAb BC8;

mAb CC49-deltaCH₂;

mAb Ch14.18;

mAb CP-675, 206;

mAb HeFi-1;

mAb Hu3S193;

mAb HuG1-M195;

mAb huHMFG1;

mAb J591;

mAb MDX-CTLA4;

mAb MiK-beta-1;

MDX-010;

MEDI-507;

MLN2704;

Pertuzumab;

RAV12;

Rituximab;

SGN-30;

SGN-40;

Tositumomab;

Trastuzumab (herceptin);

TRM-1 (TRAIL R1 Mab); and

Yttrium-ibritumomab.

11. The formulation of claim 9 wherein the cellular proliferative disease is any one of cancer, neoplastic disease or any disease involving inflammation of tissue or release of inflammatory agents.

12. The formulation of claim 9 wherein the cellular proliferative disease results in one or more of a tumor, neoplasm, uncontrolled hyper-proliferation or metastasis.

13. The formulation of claim 9 wherein the cellular proliferative disease is present in one or more organs or tissues including the breast, lung, prostate, kidney, skin, neural tissue, ovary, uterus, liver, pancreas, epithelial cells, gastric tissue, intestine, exocrine, endocrine, lymphatic system, hematopoietic system, head tissue and neck tissue.

14. The formulation of claim 9 wherein the cellular proliferative disease occurs in a mammal.

15. The formulation of claim 1, wherein the antibody is cetuximab.

16. The formulation of claim 1, wherein the antibody is bevacizumab.

17. The formulation of claim 1, wherein the antibody is humanised.

19. The formulation of claim 14 wherein the mammal is selected from the group consisting of primate, bovine, canine, equine, feline and porcine animal.

20. The formulation of claim 19 wherein the primate is a human.

21. The formulation of claim 1, wherein the composition is in oral, topical or parenteral form.

22. The formulation of claim 21 wherein the oral form is presented as a tablet, pill, capsule, lozenge, troche, powder, granule, emulsion, liquid, aqueous or oily suspension, medicine, syrup, elixir or spray.

23. The formulation of claim 21 wherein the topical form is administered in the form of a cream, lotion, emulsion, gel, film, spray, paste or ointment.

24. The formulation of claim 21 wherein the parenteral form is formulated for subcutaneous injection, aerosol, intravenous, intramuscular, intrathecal, intracranial, intrasternal injection or infusion techniques in the form of a liquid, ointment, suppository or pessary.

25. The formulation of claim 1 together with a second agent or composition used in the treatment of cellular proliferative disease wherein the second agent is a chemotherapeutic agent or therapeutic antibody.

26. The formulation of claim 1, wherein the bioavailability of the antibody, fragment, derivative or portion thereof is enhanced.

31. The formulation of claim 1, wherein the HA is administered in an amount of about 0.01 to about 40 mg/kg of body weight.

32. The formulation of claim 1, wherein the HA is administered in an amount of about 0.1 to about 27 mg/kg of body weight.

64. The formulation of claim 1, wherein the antibody is herceptin.

65. The formulation of claim 25 wherein the second agent or composition is irinotecan or doxorubicin or fluorouracil or leucovorin or oxaliplatin or methotrexate or gemcitabine.

67. The formulation of claim 25 wherein the formulation comprises cetuximab and the second composition comprises irinotecan.

18. (canceled)

27. (canceled)

30. (canceled)

33. A method of treatment or prophylaxis for cellular diseases in a subject, the method comprising administering to a subject in need thereof a therapeutic antibody or a fragment, derivative, portion, chimera or fully de-immunized form thereof and HA or an analogue, a derivative or synthesized or chemically modified form or salt thereof wherein the hyaluronan is in the molecular weight range of about 360 Daltons to 20,000 kDaltons for a time and under conditions for the symptoms of the cellular disease to be ameliorated.

28. The method of claim 55 wherein the HA is administered prior to the administration of the second agent.

29. The method of claim 55 wherein the HA is administered subsequent to the administration of the second agent.

34. The method of claim 33 wherein the hyaluronan or an analogue or derivative or synthesized or modified form thereof is in the molecular weight range of 360 Dalton to 10,000 kDa.

35. The method of claim 33 wherein the hyaluronan or an analogue or derivative or synthesized or modified form thereof is in the molecular weight range of about 360 Daltons to 2000 kDaltons.

36. The method of claim 33 wherein the hyaluronan or an analogue or derivative or synthesized or modified form thereof is in the molecular weight range of about 20 kDaltons to 1,500 kDaltons.

37. The method of claim 33 wherein the hyaluronan or an analogue or derivative or synthesized or modified form thereof is in the modal molecular weight range of about 860 kDaltons.

38. The method of claim 33, wherein the hyaluronan or an analogue or derivative or synthesized or modified form thereof and the antibody are not covalently bound.

39. The method of claim 33 wherein the pH range of the composition is between pH 2.5 and 10.5.

40. The method of claim 33, wherein the antibody, fragment, derivative or portion thereof is selected from the group of antibodies consisting of:

ABX-EGF;

Alemtuzumab;

Apolizumab;

Bevacizumab;

Cantuzumab;

Cetuximab;

cG250;

cmc-544;

Daclizumab;

Epratuzumab;

erlotinib;

Gemtuzumab ozogamicin;

hA20;

HCBE-1;

Hun901;

Ibritumomab tiuxetan;

IDEC 159;

Infliximab;

Lumiliximab;

mAb 3F8;

mAb b43.13;

mAb BC8;

mAb CC49-deltaCH₂;

mAb Ch14.18;

mAb CP-675, 206;

mAb HeFi-1;

mAb Hu3S193;

mAb HuG1-M195;

mAb huHMFG1;

mAb J591;

mAb MDX-CTLA4;

mAb MiK-beta-1;

MDX-010;

MEDI-507;

MLN2704;

Pertuzumab;

RAV12;

Rituximab;

SGN-30;

SGN-40;

Tositumomab;

Trastuzumab (herceptin);

TRM-1 (TRAIL R1 Mab); and

Yttrium-ibritumomab.

41. The method of claim 33, wherein the cellular proliferative disease is any one of cancer, neoplastic disease or any disease involving inflammation of tissue or release of inflammatory agents.

42. The method of claim 33, wherein the cellular proliferative disease results in one or more of a tumor, neoplasm, uncontrolled hyper-proliferation or metastasis.

43. The method of claim 33, wherein the cellular proliferative disease is present in one or more organs or tissues including the breast, lung, prostate, kidney, skin, neural tissue, ovary, uterus, liver, pancreas, epithelial cells, gastric tissue, intestine, exocrine, endocrine, lymphatic system, hematopoietic system, head tissue and neck tissue.

44. The method of claim 33, wherein the cellular proliferative disease occurs in a mammal.

45. The method of claim 33, wherein the antibody is cetuximab.

46. The method of claim 33, wherein the antibody is bevacizumab.

47. The method of claim 33, for the treatment or prophylaxis of colorectal cancer.

48. The method of claim 44 wherein the mammal is selected from the group consisting of primate, bovine, canine, equine, feline and porcine animal.

49. The method of claim 48 wherein the primate is a human.

50. The method of claim 33, wherein the administering is oral, topical or parenteral.

51. The method of claim 50 wherein the orally administered form is tablet, pill, capsule, lozenge, troche, powder, granule, emulsion, liquid, aqueous or oily suspension, medicine, syrup, elixir or spray.

52. The method of claim 50 wherein the topically administered form is a cream, lotion, emulsion, gel, film, spray, paste or ointment.

53. The method of claim 50 wherein the parental administration is by subcutaneous injection, aerosol, intravenous, intramuscular, intrathecal, intracranial, intrasternal injection or infusion techniques in the form of a liquid, ointment, suppository or pessary.

54. The method of claim 33, wherein the hyaluronan or an analogue or a derivative or synthesized or modified form thereof is administered simultaneously, sequentially, prior to, in combination, during or subsequent to the administration of the antibody, fragment, derivative or portion thereof.

55. The method of claim 33, wherein a second agent or composition is administered when used in the treatment of cellular proliferative disease wherein the second agent is a chemotherapeutic agent or therapeutic antibody.

56. The method of claim 55 wherein the second agent or composition comprises HA formulated with irinotecan or doxorubicin or fluorouracil or leucovorin or oxaliplatin or methotrexate or gemcitabine.

57. The method of claim 56 wherein the second agent or composition comprises HA formulated with any of the antibodies selected from the group consisting of:

ABX-EGF;

Alemtuzumab;

Apolizumab;

Bevacizumab;

Cantuzumab;

Cetuximab;

cG250;

cmc-544;

Daclizumab;

Epratuzumab;

erlotinib;

Gemtuzumab ozogamicin;

hA20;

HCBE-1;

Hun901;

Ibritumomab tiuxetan;

IDEC 159;

Infliximab;

Lumiliximab;

mAb 3F8;

mAb b43.13;

mAb BC8;

mAb CC49-deltaCH2;

mAb Ch14.18;

mAb CP-675, 206;

mAb HeFi-1;

mAb Hu3S193;

mAb HuG1-M195;

mAb huHMFG1;

mAb J591;

mAb MDX-CTLA4;

mAb MiK-beta-1;

MDX-010;

MEDI-507;

MLN2704;

Pertuzumab;

RAV12;

Rituximab;

SGN-30;

SGN-40;

Tositumomab;

Trastuzumab (herceptin);

TRM-1 (TRAIL R1 Mab); and

Yttrium-ibritumomab.

58. The method of claim 55 wherein the second agent or composition comprises irinotecan or doxorubicin or fluorouracil or leucovorin or oxaliplatin or methotrexate or gemcitabine.

59. The method of claim 55 wherein the second agent or composition comprises any of the antibodies selected from the group consisting of:

ABX-EGF;

Alemtuzumab;

Apolizumab;

Bevacizumab;

Cantuzumab;

Cetuximab;

cG250;

cmc-544;

Daclizumab;

Epratuzumab;

erlotinib;

Gemtuzumab ozogamicin;

hA20;

HCBE-1;

Hun901;

Ibritumomab tiuxetan;

IDEC 159;

Infliximab;

Lumiliximab;

mAb 3F8;

mAb b43.13;

mAb BC8;

mAb CC49-deltaCH₂;

mAb Ch14.18;

mAb CP-675, 206;

mAb HeFi-1;

mAb Hu3S193;

mAb HuG1-M195;

mAb huHMFG1;

mAb J591;

mAb MDX-CTLA4;

mAb MiK-beta-1;

MDX-010;

MEDI-507;

MLN2704;

Pertuzumab;

RAV12;

Rituximab;

SGN-30;

SGN-40;

Tositumomab;

Trastuzumab (herceptin);

TRM-1 (TRAIL R1 Mab); and

Yttrium-ibritumomab.

60. The method of claim 55, wherein the second agent or composition comprises the treatment regime FOLFOX (fluorouracil, leucovorin and oxaliplatin), FOLFIR1 (comprising irinotecan, leucovorin and fluorouracil) and IFL (comprising irinotecan, fluorouracil and leucovorin).

61. The method of claim 33, wherein the bioavailability of the antibody, fragment, derivative or portion thereof is enhanced.

62-63. -63. (canceled)

66. (canceled)

68-69. -69. (canceled)