Photodynamic therapy treatment for eye disease

• US 20060088530A1
• Filed: 12/07/2005
• Published: 04/27/2006
• Est. Priority Date: 01/12/2000
• Status: Active Grant

• Current Assignee: Light Sciences Oncology, Inc.
• Original Assignee: Light Sciences Oncology, Inc.
• Inventors: Chen, James C.
• Granted Patent: US 7,320,786 B2
• Time in Patent Office: Days
• US Class Current: 424/143.100
• CPC Class Codes: A61K 41/0057 Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
• CPC Class Codes: A61K 41/0071 PDT with porphyrins having exactly 20 ring atoms, i.e. based on the non-expanded tetrapyrrolic ring system, e.g. bacteriochlorin, chlorin-e6, or phthalocyanines
• CPC Class Codes: A61K 41/0076 PDT with expanded (metallo)porphyrins, i.e. having more than 20 ring atoms, e.g. texaphyrins, sapphyrins, hexaphyrins, pentaphyrins, porphocyanines
• CPC Class Codes: A61K 47/62 the modifying agent being a protein, peptide or polyamino acid
• CPC Class Codes: A61K 47/6843 the antibody targeting a material from animals or humans
• CPC Class Codes: A61K 47/6847 the antibody targeting a hormone or a hormone-releasing or -inhibiting factor
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system

Abstract

This invention discloses methods, kits, and instructions to treat neovasculature diseases of the eye through the administration of a targeted photosensitizing agent and subsequent exposure to light of specific wavelength sufficient to photoactivate photosensitizing agent. The photosensitizing agent is bound to a composition that mediates site specific delivery to a neovasculature target tissue of a therapeutically effective amount of a photosensitizing agent that is activated by a relatively low fluence rate of light over a prolonged period of time. Diseases treatable under this invention, include: diabetic retinopathy; macular degeneration; and malignant uveal melanomas.

Claims

1. A method of treating neovascular disease of the eye, comprising:

administering a conjugate to targeted neovascular tissue of the eye comprising;

a photosensitizing compound that absorbs light in a range of about 500 nm to about 1100 nm; and

a targeting moiety that selectively binds to abnormal endothelium in the eye selected from the group consisting of a VEGF ligand, a VEGF receptor, an antibody or an antibody fragment thereof that binds to VEGF receptor, fibronectin extracelluar domain B (ED-B), α

vβ

3 integrin, or carcinoembryonic antigen, and a bispecific antibody construct consisting of VEGF ligand and VEGF receptor on abnormal endothelium lining or composing neovascular target tissue in the eye;

allowing sufficient time for the conjugate to clear from non-targeted tissue of the eye; and

illuminating the eye for a sufficient time interval with a light having a wave length or waveband that matches the excitation wave length or waveband of the photosensitizing compound to activate the photosensitizing compound, and

wherein the light has an intensity and a duration of illumination that produces a sufficient total fluence of irradiation which destroys the targeted neovascular tissue while the non-targeted tissue remains undamaged.

2. The method of claim 1, wherein the photosensitizing compound administered is a member selected from the group consisting of chlorines, bacteriochlorophylls, phthalocyanines, porphyrins, purpurins, merocyanines, psoralens, porfimer sodium, δ

-aminolevulinic acid protoporphyrin, indocyanine green, benzoporphyrin, methylene blue, toluidine blue, texaphyrins, pyropheophorbide compounds, verteporfin, derivatives thereof, and combinations thereof.

3. The method of claim 1, wherein sufficient time for the conjugate to clear from non-targeted tissue of the eye is about 24 hours or less.

4. The method of claim 1, wherein the sufficient time interval for illuminating the eye is between about 2 minutes to about 148 hours.

5. The method of claim 4, wherein the sufficient time interval for illuminating the eye is between about 24 hours to about 72 hours.

6. The method of claim 5, wherein the sufficient time interval for illuminating the eye is between about 4 minutes to about 60 minutes.

7. The method of claim 1, wherein the duration of illumination is 4 minutes.

8. The method of claim 1, wherein the duration of illumination is 20 minutes.

9. The method of claim 1, wherein the duration of illumination is 1 hour.

10. The method of claim 1, wherein the duration of illumination is 24 hours.

11. The method of claim 1, wherein the sufficient total fluence of irradiation is between about 30 J/cm² to about 25,000 J/cm².

12. The method of claim 11, wherein the sufficient total fluence of irradiation is between about 100 J/cm² and about 20,000 J/cm².

13. The method of claim 12, wherein the sufficient total fluence of irradiation is between about 500 J/cm² and about 10,000 J/cm².

14. The method of claim 13, wherein the sufficient total fluence of irradiation is between about 240 J/cm² to about 900 J/cm².

15. The method of claim 1, wherein the intensity of light is about 500 mW/cm² or less.

16. The method of claim 1, wherein the intensity of light is about 400 mW/cm² or less.

17. The method of claim 1, wherein the intensity of light is about 250 mW/cm² or less.

18. The method of claim 1, wherein the light is non-coherent light.

19. The method of claim 18, wherein the non-coherent light is a light emitting diode.

20. The method of claim 18, wherein the non-coherent light is ambient light.

21. The method of claim 1, wherein the light is coherent light.

22. The method of claim 1, wherein the targeted neovascular tissue is present in retina, choroid or both.

23. The method of claim 1, wherein the neovascular disease is diabetic retinopathy.

24. The method of claim 1, wherein the neovascular disease is macular degeneration.

25. The method of claim 1, wherein the conjugate is incorporated into a liposomal preparation.

26. The method of treating neovascular disease of the eye of claim 1, wherein the method is performed one time or multiple times in the eye.

27. A method of instructing a person to treat neovascular disease of the eye, comprising instructing a person to conduct a method according to claim 1.

28. A method of treating neovascular disease of the eye, comprising:

administering a conjugate to targeted neovascular tissue of the eye comprising;

a photosensitizing compound consisting essentially of chlorines, bacteriochlorophylls, phthalocyanines, porphyrins, purpurins, merocyanines, psoralens, porfimer sodium, δ

-aminolevulinic acid protoporphyrin, indocyanine green, benzoporphyrin, methylene blue, toluidine blue, texaphyrins, pyropheophorbide compounds, verteporfin, derivatives thereof, or combinations thereof; and

a targeting moiety that selectively binds to abnormal endothelium consisting essentially of a VEGF ligand, a VEGF receptor, an antibody or an antibody fragment thereof that binds to VEGF receptor, fibronectin extracelluar domain B (ED-B), α

vβ

3 integrin, or carcinoembryonic antigen, and a bispecific antibody construct consisting of VEGF ligand and VEGF receptor on abnormal endothelium lining or composing neovascular target tissue in the eye;

allowing sufficient time for the conjugate to clear from non-targeted tissue of the eye; and

illuminating the eye with a light having a wave length or waveband that matches the excitation wave length or waveband of the photosensitizing compound to activate the photosensitizing compound, and

wherein the light has a combination of an intensity of light of less than 500 mW/cm² and a duration of illumination of about 4 minutes to produce a total fluence of light irradiation from between about 30 J/cm² to about 25,000 J/cm² which destroys the targeted neovascular tissue while the non-targeted tissue remains undamaged.

29. The method of claim 28, wherein the sufficient time for the conjugate to clear from the non-targeted tissue is about 24 hours or less.

30. The method of treating neovascular disease of the eye of claim 28, wherein the method is performed one time or multiple times in the eye.

31. A method of treating choroidal neovasculature lesions of the eye, comprising:

administering a conjugate to targeted neovascular tissue of the eye comprising;

a verteporfin photosensitizing compound; and

an L19 antibody that binds to the ED-B of fibronectin targeting moiety;

allowing sufficient time for the conjugate to clear from non-targeted tissue of the eye; and

illuminating the eye for a period of about 10 minutes with 400 mW/cm² of collimated LED light having a wavelength of about 690 nm for a total fluence of 240 J/cm² to activate the photosensitizing compound and produce a total fluence of irradiation which destroys the targeted neovascular tissue while the non-targeted tissue remains undamaged.

32. The method of claim 31, wherein the sufficient time for the conjugate to clear from the non-targeted tissue is about 6 hours or less.

33. The method of treating choroidal neovasculature lesions of the eye of claim 31, wherein the method is performed one time or multiple times in the eye.

34. A method of treating choroidal tumors of the eye, comprising:

administering a conjugate to targeted neovascular tissue of the eye comprising;

a benzoporphyrin or benzoporphyrin derivative sensitizing compound; and

a carcinoembryonic antigen antibody targeting moiety;

allowing sufficient time for the conjugate to clear from non-targeteded tissue of the eye; and

illuminating the eye for a period of about 60 minutes with 250 mW/cm² of collimated LED light having a wavelength of about 690 nm for a total fluence of 240 J/cm² to activate the photosensitizing compound and produce a total fluence of irradiation which destroys the targeted neovascular tissue while the non-targeted tissue remains undamaged.

35. The method of claim 34, wherein the sufficient time for the conjugate to clear from the non-targeted tissue is about 6 hours or less.

36. The method of treating choroidal tumors of the eye of claim 34, wherein the method is performed one time or multiple times in the eye.

37. A method of treating retinal neovaculature lesions of the eye, comprising:

administering a conjugate to targeted neovascular tissue of the eye comprising;

a liposomal benzoporphyrin derivative photosensitizing compound; and

a VEGF targeting moiety;

allowing sufficient time for the conjugate to clear from non-targeteded tissue of the eye; and

illuminating the eye for a period of about 60 minutes with 250 mW/cm² of collimated LED light having a wavelength of about 690 nm for a total fluence of 240 J/cm² to activate the photosensitizing compound and produce a total fluence of irradiation which destroys the targeted neovascular tissue while the non-targeted tissue remains undamaged.

38. The method of claim 37, wherein the sufficient time for the conjugate to clear from the non-targeted tissue is about 6 hours or less.

39. The method of treating retinal neovaculature lesions of the eye of claim 37, wherein the method is performed one time or multiple times in the eye.

40. A method of treating vascular tumors of the eye, comprising:

administering a conjugate to targeted neovascular tissue of the eye comprising;

a texaphyrin photosensitizing compound; and

an α

vβ

3 antibody targeting moiety;

allowing sufficient time for the conjugate to clear from non-targeteded tissue of the eye; and

illuminating the eye for a period of about 60 minutes with 250 mW/cm² of collimated LED light having a wavelength of about 690 nm for a total fluence of 240 J/cm² to activate the photosensitizing compound and produce a total fluence of irradiation which destroys the targeted neovascular tissue while the non-targeted tissue remains undamaged.

41. The method of claim 40, wherein the sufficient time for the conjugate to clear from the non-targeted tissue is about 6 hours or less.

42. The method of treating vascular tumors of the eye of claim 40, wherein the method is performed one time or multiple times in the eye.

43. A method to treat neovascular disease of the eye, comprising:

administering a conjugate comprising a photosensitizing compound selected from the group consisting of chlorins, bacteriochlorophylls, phthalocyanines, porphyrins, purpurins, merocyanines, psoralens, porfimer sodium, δ

-aminolevulinic acid protoporphyrin, indocyanine green, methylene blue, toluidine blue, texaphyrins, pyropheophorbide compounds, and verteporfin conjugated to a targeting moiety selected which is a member selected from the group consisting of a VEGF ligand, a VEGF receptor, an antibody or antibody fragment that binds to VEGF receptor, a complete or functional bindable fragment of human antibody L19, α

vβ

3 integrin, the extra-domain B of fibronectin, and a carcinoembryonic antigen;

allowing sufficient time to permit the non-specifically bound conjugate to clear from on-target tissue; and

illuminating the neovascular tissue with light including a wavelength corresponding at least in part with the characteristic light absorption wavelength of the photosensitizing compound for a period of time sufficient to activate the photosensitizing compound;

wherein;

a combination of an intensity of light used for the step of illuminating and a duration of illumination is selected to produce a total fluence of irradiation such that the neovascular target tissue is destroyed and the non-targeted tissue through which the light passes remains undamaged; and

the neovascular tissue is treated with a total fluence of light irradiation from between about 240 J/cm² to about 900 J/cm².

44. The method of claim 43, wherein the light is non-coherent light.

45. The method of claim 43, wherein the light is coherent light.

46. The method of claim 43, wherein the neovascular tissue is present in retina, choroids or both.

47. The method of claim 43, wherein the photosensitized neovascular tissue is illuminated for a time interval of between 4 minutes and 72 hours.

48. The method of claim 43, wherein the sufficient time to permit the non-specifically bound conjugate to clear from on-target tissue is about 24 hours or less.

49. The method of treating neovascular disease of the eye of claim 43, wherein the method is performed one time or multiple times in the eye.