NZ739780B2 - Compositions, combinations and related methods for photoimmunotherapy - Google Patents

Compositions, combinations and related methods for photoimmunotherapy Download PDF

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Publication number
NZ739780B2
NZ739780B2 NZ739780A NZ73978016A NZ739780B2 NZ 739780 B2 NZ739780 B2 NZ 739780B2 NZ 739780 A NZ739780 A NZ 739780A NZ 73978016 A NZ73978016 A NZ 73978016A NZ 739780 B2 NZ739780 B2 NZ 739780B2
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New Zealand
Prior art keywords
conjugate
cancer
administered
hours
medicament
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NZ739780A
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NZ739780A (en
Inventor
Merrill Biel
Eileen Sun Chin
Jerry Fong
Guzman Miguel Garcia
Roger Heim
Lewis R Makings
Deepak Yadav
Original Assignee
Rakuten Medical Inc
Filing date
Publication date
Application filed by Rakuten Medical Inc filed Critical Rakuten Medical Inc
Priority claimed from PCT/US2016/047640 external-priority patent/WO2017031367A1/en
Publication of NZ739780A publication Critical patent/NZ739780A/en
Publication of NZ739780B2 publication Critical patent/NZ739780B2/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18—Growth factors; Growth regulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A61K41/0057—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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A61K41/0057—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
    • A61K41/0071—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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6849—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6851—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Provided herein are conjugates, compositions and methods for use in photoimmunotherapy, such as photoimmunotherapy induced by activation of a phthalocyanine dye conjugated to a targeting molecule that binds a protein on cell, for example, an IR700-antibody conjugate. In some embodiments, the phthalocyanine-dye conjugate can be activated by irradiation with near-infrared light. Features of the conjugates, compositions and methods, including the dose of the conjugate, provide various advantages, such as lower toxicity and/or improved efficacy. In some embodiments, also provided is a dual label phthalocyanine-dye conjugate in which the targeting molecule is conjugated to an additional fluorescent dye, which can be used for photoimmunotherapy while, for example, also exhibiting improved performance for imaging or detection. Also provided are therapeutic methods using the conjugates and compositions for treatment of diseases and conditions, including tumors or cancers.

Claims (46)

THE CLAIMS DEFINING THE INVENTION ARE AS FOLLOWS:
1. Use of a conjugate comprising an IR700 linked to cetuximab or an antigen- binding fragment thereof in the manufacture of a medicament for treating a lesion associated with a cancer, tumor or hyperplasia in a subject, wherein the medicament is to be administered in a dosing schedule, wherein the dosing schedule comprises: a) that the medicament is to be intravenously administered to the subject, wherein the amount of conjugate to be administered is or is about 320 mg/m or is or is about 640 mg/m ; b) after administration of the medicament, the lesion is to be irradiated at a wavelength of 600 nm to 850 nm, at a dose from at or about 25 J cm to at or about 400 J cm or from at or about 25 J/cm fiber length to at or about 500 J/cm fiber length.
2. The use of claim 1, wherein the amount of conjugate to be administered is or is about 640 mg/m .
3. Use of a conjugate comprising an IR700 linked to cetuximab or an antigen- binding fragment thereof in the manufacture of a medicament for treating a tumor in a subject having a head or neck cancer, wherein the medicament is to be administered in a dosing schedule, wherein the dosing schedule comprises: a) that the medicament is to be intravenously administered to the subject, wherein the amount of conjugate to be administered is or is about 640 mg/m ; and b) after administration of the medicament, the lesion is to be irradiated at a wavelength of at or about 690 ± 50 nm, at a dose of at least at or about 50 J cm or at least at or about 100 J/cm of fiber length.
4. The use of any one of claims 1-3, wherein the irradiation is to be carried out between at or about 30 minutes and at or about 96 hours after administration of the medicament.
5. The use of any one of claims 1-4, wherein the irradiation is to be carried out 24 hours ± 3 hours after administration of the medicament.
6. The use of claim 1, wherein the lesion is to be irradiated at a wavelength of at or about 690 ± 50 nm.
7. The use of any one of claims 1-6, wherein the lesion is to be irradiated at a dose of at or about 50 J cm or at or about 100 J/cm of fiber length.
8. The use of any one of claims 1-7, wherein the dosing schedule is to be repeated, whereby steps (a) and (b) are to be repeated.
9. The use of claim 8, wherein the dosing schedule is to be repeated if a residual lesion remains at a time that is more than or about 2 weeks, 3 weeks, 4 weeks, 2 months, 6 months or 1 year after initiation of the prior administration of the medicament.
10. The use of claim 8 or 9, wherein the dosing schedule is to be repeated if a residual lesion remains at or about 4 weeks after initiation of the prior administration of the medicament.
11. The use of any one of claims 1-10, wherein the lesion is a tumor that is a superficial tumor.
12. The use of claim 11, wherein the irradiation step comprises illumination of the superficial tumor with a microlens-tipped fiber for surface illumination.
13. The use of any one of claims 1-10, wherein the lesion is a tumor that is a subcutaneous tumor or an interstitial tumor.
14. The use of claim 13, wherein the irradiation step is to be carried out using cylindrical diffusing fibers; and, wherein the cylindrical diffusing fibers comprise a diffuser length of 0.5 cm to 10 cm and spaced 1.8 ± 0.2 cm apart.
15. The use of any one of claims 1-14, wherein the medicament is to be administered in a dosing schedule in which: the administration of the medicament is performed only one time as a single injection or infusion; or the dosing schedule does not comprise a subsequent dose of the medicament; or the dosing schedule does not comprise a subsequent dose of the targeting molecule that is not so conjugated.
16. The use of any one of claims 1-15, wherein the cancer is selected from the group consisting of bladder cancer, cancer of the larynx, stomach cancer, lung cancer, colon cancer, head or neck cancer, and pancreatic cancer.
17. The use of claim 16, wherein the cancer is a head or neck cancer.
18. The use of claim 16 or 17, wherein the cancer is a head or neck cancer that cannot be successfully treated with surgery, radiation or chemotherapy.
19. The use of any one of claims 1-18, wherein the lesion is a squamous cell carcinoma.
20. The use of any one of claims 1-19, wherein the dosing schedule further comprises administration of an additional therapeutic agent or anti-cancer treatment.
21. Use of a first conjugate comprising an IR700 linked to cetuximab or an antigen-binding fragment thereof and an immune checkpoint inhibitor in the manufacture of a medicament for treating a lesion associated with a cancer, tumor or hyperplasia in a subject, wherein the first conjugate and immune checkpoint inhibitor are to be administered in a dosing schedule, wherein the dosing schedule comprises: a) that an immune checkpoint inhibitor is to be administered to the subject; b) that the first conjugate is to be intravenously administered to the subject, wherein the amount of first conjugate to be administered is or is about 320 mg/m or is or is about 640 mg/m ; and c) that an area around or near the lesion is to be irradiated at a wavelength of 600 nm -2 -2 to 850 nm, at a dose from at or about 25 J cm to at or about 400 J cm or from at or about 25 J/cm fiber length to at or about 500 J/cm fiber length.
22. The use of claim 21, wherein the immune checkpoint inhibitor specifically binds a molecule selected from the group consisting of PD-1, PD-L1, CTLA-4, and CD25.
23. The use of claim 21 or 22, wherein administering the first conjugate followed by light irradiation primes activation of immune cells.
24. The use of any one of claims 21-23, wherein the immune checkpoint inhibitor is to be administered at least at or about 12 hours, 24 hours, 48 hours, 96 hours, one week, two weeks, three weeks or four weeks prior to the administration of the first conjugate.
25. The use of any one of claims 21-23, wherein the immune checkpoint inhibitor is to be administered three times a week, two times a week, once every week, once every two weeks, once every three weeks or once a month subsequent to administering the first conjugate.
26. The use of any one of claims 21-25, wherein the administration of the immune checkpoint inhibitor is to be continued three times a week, two times a week, once every week, once every two weeks, once every three weeks or once a month subsequent to the irradiation.
27. The use of any one of claims 21-26, wherein the irradiation is carried out between at or about 30 minutes and at or about 96 hours after administering the first conjugate.
28. The use of any one of claims 21-27, wherein the irradiation is carried out at or about 24 hours ± 3 hours after administering the first conjugate.
29. The use of any one of claims 21-28, wherein the immune checkpoint inhibitor is comprised in a second conjugate comprising a phthalocyanine dye linked to the immune checkpoint inhibitor.
30. Use of a first conjugate comprising an IR700 linked to cetuximab or an antigen-binding fragment thereof and a second conjugate comprising an IR700 linked to an immune checkpoint inhibitor in the manufacture of a medicament for treating a lesion associated with a cancer in a subject, wherein the first and second conjugates are to be administered in a dosing schedule, wherein the dosing schedule comprises: a) that the first conjugate is to be intravenously administered to the subject, wherein the amount of conjugate to be administered is or is about 320 mg/m or is or is about 640 mg/m ; b) that the second conjugate is to be intravenously administered to the subject; and c) that an area around or near the lesion is to be irradiated at a wavelength of 600 nm -2 -2 to 850 nm, at a dose from at or about 25 J cm to at or about 400 J cm or from at or about 25 J/cm fiber length to at or about 500 J/cm fiber length.
31. The use of claim 30, wherein the immune checkpoint inhibitor specifically binds a molecule selected from the group consisting of PD-1, PD-L1, CTLA-4, and CD25
32. The use of claim 30 or 31, wherein the first conjugate and the second conjugate are to be administered prior to the irradiation.
33. The use of any one of claims 30-32, wherein the first conjugate and the second conjugate are to be administered simultaneously.
34. The use of any one of claims 30-32, wherein the first conjugate and the second conjugate are to be administered separately.
35. The use of claim 30 or 31, wherein the first conjugate is to be administered prior to the irradiation step, the second conjugate is to be administered after the irradiation step and the dosing schedule further comprises repeating step c) after administration of the second conjugate.
36. The use of any one of claims 30-35, wherein the irradiation is to be carried out between at or about 30 minutes and at or about 96 hours after administering the first conjugate or the second conjugate.
37. The use of any one of claims 30-35, wherein the irradiation is to be carried out between at or about 30 minutes and at or about 96 hours after administering the first conjugate.
38. The use of any one of claims 30-35, wherein the irradiation is to be carried out between at or about 30 minutes and at or about 96 hours after administering the second conjugate.
39. The use of any one of claims 30-35, wherein the irradiation is to be carried out at or about 24 hours ± 3 hours after administering the first conjugate or the second conjugate.
40. The use of any one of claims 21-35, wherein the irradiation is to be carried out 24 hours ± 3 hours after administering the first conjugate.
41. The use of any one of claims 21-35, wherein the irradiation is to be carried out 24 hours ± 3 hours after administering the second conjugate.
42. The use of any one of claims 21-41, wherein the immune checkpoint inhibitor is selected from among nivolumab, pembrolizumab, pidilizumab, MK-3475, BMS-936559, MPDL3280A, ipilimumab, tremelimumab, UVIP31, MEDI4736, AMP-224, MSB001078C, and an antigen-binding fragment of any of the foregoing.
43. The use of any one of claims 21-42, wherein the cancer is selected from the group consisting of bladder cancer, cancer of the larynx, stomach cancer, lung cancer, colon cancer, head or neck cancer, and pancreatic cancer.
44. The use of any one of claims 21-43, wherein the cancer is a head or neck cancer.
45. The use of any one of claims 21-44, wherein the cancer is a head or neck cancer that cannot be successfully treated with surgery, radiation or chemotherapy.
46. The use of any one of claims 21-45, wherein the lesion is a squamous cell carcinoma.
NZ739780A 2016-08-18 Compositions, combinations and related methods for photoimmunotherapy NZ739780B2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201562206776P 2015-08-18 2015-08-18
US201562249085P 2015-10-30 2015-10-30
PCT/US2016/047640 WO2017031367A1 (en) 2015-08-18 2016-08-18 Compositions, combinations and related methods for photoimmunotherapy

Publications (2)

Publication Number Publication Date
NZ739780A NZ739780A (en) 2024-02-23
NZ739780B2 true NZ739780B2 (en) 2024-05-24

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