Thermotherapy via targeted delivery of nanoscale magnetic particles

• US 6,997,863 B2
• Filed: 07/19/2002
• Issued: 02/14/2006
• Est. Priority Date: 07/25/2001
• Status: Expired due to Fees

• Current Assignee: Aspen Medisys, LLC (Rhinomed Ltd.)
• Original Assignee: Triton Biosystems Inc (Novartis Ag)
• Inventors: Ellis-Busby, Diane, Foreman, Allan, Ivkov, Robert, Handy, Erik S., Braunhut, Susan J., Ardman, Blair, Gwost, Douglas U.
• Primary Examiner(s): Lacyk, John P.
• Application Number:
  US10/200,082
• Publication Number:
  US 20030032995A1
• Time in Patent Office: 1,306 Days
• Field of Search: 600 9- 15, 607/103, 607/105, 424422-423, 424/426, 424/428, 424/430, 424434-437, 424489-491, 424493-502, 424647-648, 424/1.29, 424/1.33, 424/1.53, 424 932- 9323, 977/DIG.1
• US Class Current: 600/9
• CPC Class Codes: A61N 1/406 using implantable thermoseeds or injected particles for localized hyperthermia preparations of seeds and particles A61K41/0052
• CPC Class Codes: A61N 2/02 using magnetic fields produced by coils, including single turn loops or electromagnets A61N2/12 takes precedence
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• 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 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: Y10S 977/904 for medical, immunological, body treatment, or diagnosis

Abstract

Disclosed are therapeutic methods for the treatment of disease material involving administration of a thermotherapeutic magnetic composition, which contains single-domain magnetic particles attached to a target-specific ligand, to a patient and application of an alternating magnetic field to inductively heat the thermotherapeutic magnetic composition. Also disclosed are methods of administering the thermotherapeutic magnetic material composition. The thermotherapeutic methods may be used where the predetermined target is associated with diseases, such as cancer, diseases of the immune system, and pathogen-borne diseases, and undesirable targets, such as toxins, reactions associated with organ transplants, hormone-related diseases, and non-cancerous diseased cells or tissue.

Claims

1. A method for treating a patient, comprising:

administering a magnetic material composition to at least a position of the patient, the magnetic material composition comprising at least one, single domain magnetic particle attached to a ligand specific to a predetermined target in the patient, said single domain magnetic particle capable of producing heat by Neé

l relaxation in response to ap alternating magnetic field; and

applying an alternating magnetic field to the magnetic material composition combined with the predetermined target to inductively heat the magnetic material composition.

2. The method as recited in claim 1, wherein the predetermined target is associated with a cancer.

3. The method as recited in claim 2, wherein the predetermined target is one of a) a member of vascular endothelial growth factor receptor (VEGFR) family, b) a member of carcinoembryonic antigen (CEA) family, c) an anti-idiotypic mAR, d) a ganglioside mimic, e) a member of cluster designation/differentiation (CD) antigen family, f) a member of epidermal growth factor receptor (EGFR) family. g) a cellular adhesion molecule, h) a member of MUC-type inucin family, i) a cancer antigen (CA), j) a matrix metalloproteinase, k) a glycoprotein antigen, l) a melanoma associated antigen (MAA), m) a proteolytic enzyme, n) a calmodulin, o) a tumor necrosis factor (TNF) receptor family, p) an angiogenic marker, q) a melanoma antigen recognized by T cells (MART) antigen, r) a member of melanoma antigen encoding gene (MAGE) family, s) a prostate membrane specific antigen (PMSA), t) a small cell lung carcinoma antigen (SCLCA), u) a proliferating cell nuclear antigen 10 (PC10), v) pS2, w) a T/Tn antigen, x) a hormone receptor, y) a tumor suppressor gene antigen, z) a cell cycle regulator antigen, aa) an oncogene antigen, bb) an oncogene receptor antigen, cc) a proliferation marker, dd) a proteinase involved in degradation of extracellular matrix, ee) a malignant transformation related factor, ff) an apoptosis-related factor gg) a human carcinoma antigen and hh) any combination of a) through gg).

4. The method as recited in claim 3, wherein the ganglioside mimic is GD3.

5. The method as recited in claim 3, wherein the epidermal growth factor receptor (EGFR) includes at least one of Her-1, Her-2, Her-3, Her-4, and any combination thereof.

6. The method as recited in claim 3, wherein the cluster designation/differentiation antigen includes at least one of CD20 antigen, CD22 antigen, CD52 antigen, CD64 antigen, CD31 antigen, CD33 antigen and any combination thereof.

7. The method as recited in claim 3, wherein the cellular adhesion molecule is epithelial cellular adhesion molecule (Ep-CAM) antigen.

8. The method as recited in claim 3, wherein to MUC-type mucin includes at least one of polymorphic epithelial mucin (PEM), and MUC-1, and any combination thereof.

9. The method as recited in claim 3, wherein the cancer antigen is at least one of CA125, CA19-9, CA15-3 (breast tumor antigen), and CA242, and any combination thereof.

10. The method as recited in claim 3, wherein the matrix metalloproteinase is matrix metalloproteinase 2 (MMP-2).

11. The method as recited in claim 3, wherein the glycoprotein antigen is epithelial associated glycoprotein (HMFGI antigen).

12. The method as recited in claim 3, wherein the proteolytic enzyme is at least one of cathepsin G, cathepsin D, cathepsin L, cathepsin B, cathepsin C, and cathepsin S, and any combination thereof.

13. The method as recited in claim 3, wherein the calmodulin is calponin.

14. The method as recited in claim 3, wherein the tumor necrosis factor receptor is a TRAIL Receptor-1 protein.

15. The method as recited in claim 3, wherein the angiogenic marker is at least one of vascular endothelial growth factor receptor (VEGFR), Integrin alpha.v.beta.3, and any combination thereof.

16. The method as recited in claim 1, wherein the predetermined target is associated with a disease of a patient'"'"'s immune system.

17. The method as recited in claim 16, wherein the predetermined target is an antigen associated with one of rheumatoid arthritis, vasculitis and multiple sclerosis.

18. The method as recited in claim 17, wherein the predetermined target is a cluster designation/differentiation antigen.

19. The method as recited in claim 1, wherein the predetermined target is a virus.

20. The method as recited in claim 19, wherein the predetermined target is Epstein-Barr virus (EBV).

21. The method as recited in claim 19, wherein the predetermined target is a Hepatitis virus.

22. The method as recited in claim 19, wherein the predetermined target is a human immunodeficiency virus (HIV).

23. The method as recited in claim 19, wherein the predetermined target is a Herpes virus.

24. The method as recited in claim 1, wherein the predetermined target is one of an undesirable material and associated with an undesirable material.

25. The method as recited in claim 24, wherein the predetermined target is undesired adipose tissue.

26. The method as recited in claim 24, wherein the predetermined target is a gastric inhibitory polypeptide receptor.

27. The method as recited in claim 24, wherein the predetermined target is low density lipoprotein (LDL).

28. The method as recited in claim 24, wherein the predetermined target is clotted blood.

29. The method as recited in claim 1, wherein the predetermined target is associated with a reaction to an organ transplanted into the patient.

30. The method as recited in claim 29, wherein the predetermined target is at least one of human T cell receptor CD3 antigen, CD4 antigen, CD8 antigen, CD18 antigen, CD52 antigen and CD154 antigen.

31. The method as recited in claim 1, wherein the predetermined target is one of non-cancerous disease material and associated with non-cancerous disease material.

32. The method as recited in claim 31, wherein the predetermined target is one of a non-cancerous disease deposit and a non-cancerous disease precursor deposit.

33. The method as recited in claim 32, wherein the predetermined target is associated with Alzheimer'"'"'s disease.

34. The method as recited in claim 33, wherein the predetermined target is an amyloid protein.

35. The method as recited in claim 33, wherein the predetermined target is an apolipoprotein.

36. The method as recited in claim 31, wherein the predetermined target is associated with an HIV infected cell.

37. The method as recited in claim 36, wherein the predetermined target is CTLA4 protein.

38. The method as recited in claim 1, wherein administering the magnetic material composition further comprises administering the material to a specific area of a patient'"'"'s body via an administration technique being at least one of injecting the composition intravenously, injecting the composition intraperitoneally, injecting the composition intravascularly, injecting the composition intramuscularly, injecting the composition subcutaneously, applying the composition topically, applying the composition via a wash, lavage or rinse perisurgically, inhaling the composition, orally ingesting the composition, and rectally inserting the composition.

39. The method as recited in claim 1, wherein administering the magnetic material composition further comprises:

administering the ligand and the magnetic particle to the patient separately; and

combining the ligand with the magnetic particle in the patient'"'"'s body.

40. The method as recited in claim 39, wherein administering the magnetic material composition further comprises:

administering the ligand, having one of a binder and a receptor, to the patient;

administering the magnetic particle, having the other of the binder and the receptor to the patient; and

combining the ligand with the magnetic particle by uniting the binder and receptor in the patient'"'"'s body.

41. The method as recited in claim 40, wherein the binder is biotinylated and the receptor is an avidin.

42. The method as recited in claim 39, wherein administering the magnetic material composition further comprises:

administering a bispecific ligand to the patient;

administering a magnetic material conjugated to a target molecule to the patient; and

combining the magnetic particle with the ligand in the patient'"'"'s body.

43. The method as recited in claim 1, wherein applying the alternating magnetic field includes applying the alternating magnetic field when the magnetic material composition is outside the patient'"'"'s body.

44. The method as recited in claim 43, wherein administering comprises providing the magnetic material composition within the patient'"'"'s body and extracting the magnetic material composition from the patient'"'"'s body after attaching to the target.

45. The method recited in claim 43, further comprising removing, after applying the alternating magnetic field, the magnetic material composition from extracted bodily materials and prior to returning the extracted bodily materials to the patient'"'"'s body.

46. The method as recited in claim 43, wherein administering comprises extracorporeal administration of the magnetic material composition into a patient'"'"'s bodily materials.

47. The method as recited in claim 46, wherein extracorporeal administration comprises:

extracting bodily materials from the patient;

administering the magnetic material composition to the extracted bodily materials; and

exposing the extracted bodily materials to the alternating magnetic field.

48. The method as recited in claim 43, further comprising returning extracted bodily materials to the patient'"'"'s body after exposure to the alternating magnetic field.

49. The method as recited in claim 43, further comprising returning extracted bodily materials to the patient'"'"'s body before exposure to the magnetic field.

50. The method as recited in claim 43, wherein the magnetic material composition is in at least one of blood and blood products extracted from the patient.

51. The method as recited in claim 1, further comprising detecting at least one location of accumulation of the magnetic material composition within the patient'"'"'s body.

52. The method as recited in claim 51, wherein detecting the at least one location of accumulation of the magnetic material includes using at least one of i) magnetic resonance imaging (MRI) and ii) a superconducting quantum interference device (SQUID) after administering the composition to the patient and prior to application of the alternating magnetic field.

53. The method as recited in claim 52, further comprising determining an amount of the magnetic material composition taken up by the target by direct or indirect detection of the particles via at least one of MRI and the SQUID.

54. The method as recited in claim 53, wherein the determined amount of magnetic material composition taken up by the target is used to calculate a condition and duration of the alternating magnetic field to be applied.

55. The method as recited in claim 1, further comprising inducing a desired pathological effect by inductively heating the magnetic material causing one of necrosis, apoptosis and deactivation of disease material.

56. The method as recited in claim 1, further comprising applying the alternating magnetic field to a region of the patient containing the predetermined target and to a region of the patient adjacent to the region containing the predetermined target.

57. The method as recited in claim 1, further comprising localizing the magnetic material composition to a region containing the predetermined target by applying a d.c. component of the alternating magnetic field to the region of the patient containing the predetermined target.

58. The method as recited in claim 1, further comprising monitoring at least one physical characteristic of a portion of the patient.

59. The method as recited in claim 58, wherein monitoring the at least one physical characteristic comprises monitoring temperature.

60. The method as recited in claim 58, wherein monitoring the at least one physical characteristic comprises monitoring tissue impedance.

61. The method as recited in claim 1, wherein the alternating magnetic field is applied to the patient during a treatment duration, and applying the alternating magnetic field comprises pulsing the alternating magnetic field with a pulse length less than the treatment duration.

62. The method as recited in claim 61, further comprising applying at least two pulses of the alternating magnetic field to the patient.

63. The method as recited in claim 1, further comprising generating with a magnetic field generator an alternating magnetic field having a strength in the range of about 100 Oersteds (Oe) to about 2,000 Oe proximate the magnetic field generator.

64. The method as recited in claim 1, wherein the alternating magnetic field has one of a triangular waveform, square waveform, sinusoidal waveform, trapezoidal waveform and a sawtooth waveform.

65. The method as recited in claim 1, wherein applying the alternating magnetic field comprises modulating the alternating magnetic field.

66. The method as recited in claim 65, wherein modulating the magnetic field comprises applying a modulation having one of a sinusoidal envelope, a triangular envelope, a square wave envelope, a trapezoidal envelope, and a sawtooth envelope.

67. The method as recited in claim 1, wherein applying the alternating magnetic field comprises providing and positioning auxiliary coils to influence a magnetic field pattern generated by a primary coil.

68. The method as recited in claim 67, further comprising driving at least one of the primary and auxiliary coils with a d.c. component to influence the magnetic field pattern.

69. The method as recited in claim 68, wherein the d.c. component has a magnitude sufficient to influence the magnetic field pattern by causing the alternating magnetic field to have at least one of i) a unidirectional nature with varying intensity and ii) a time-averaged, non-zero value.

70. The method as recited in claim 67, further comprising driving the auxiliary coils in series with the primary coil.

71. The method as recited in claim 67, further comprising driving the auxiliary coils in parallel with the primary coil.

72. The method as recited in claim 67, further comprising electrically matching the auxiliary coils with a phase relationship so as to maximize the field strength in a specific area and minimizing the field strength in areas which may experience detrimental effects from the alternating magnetic field.

73. The method as recited in claim 67, further comprising influencing the magnetic field pattern to separate the patient from an electric field component associated with the magnetic field, so as to reduce dielectric heating of the patient.

74. The method as recited in claim 67, wherein applying the alternating magnetic field comprises applying the alternating magnetic field using only the primary coil.

75. The method as recited in claim 1, wherein applying the alternating magnetic field further comprises providing a primary coil as a core-less coil.

76. The method as recited in claim 1, wherein applying the alternating magnetic field includes generating the alternating magnetic field with a magnetic field generator and further comprises cooling the magnetic field generator with liquid.

77. The method as recited in claim 76, further comprising cooling a core of the magnetic field generator with liquid.

78. The method as recited in claim 1, wherein applying the alternating magnetic field includes driving a primary coil formed of at least first and second coils, the first and second coils disposed proximate respective first and second pole pieces of a magnetic core.

79. The method as recited in claim 1, wherein applying the alternating magnetic field further includes driving a plurality of coils located along a magnetic core.