Theralase Technologies Inc. V.TLT

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[Gustoes]

CLAIMS

WHAT IS CLAIMED IS:

1. A method for treating a tumor in a patient, said method comprising:

administering to the patient an immunogenic composition comprising antigenic material inactivated by treatment with a metal-based coordination complex and electromagnetic radiation,

wherein the immunogenic composition is effective to elicit an immune response to the antigenic material in the patient after administration and the metal-based coordination complex is represented by one of the following formulas:

(a) formula (I):

 

including hydrates, solvates, pharmaceutically acceptable salts, prodrugs and complexes thereof, wherein:

M at each occurrence is independently selected from the group consisting of osmium, ruthenium and rhodium;

X is selected from the group consisting of 

n = 0, 1, 2, 3, 4, or 5;

q is independently at each occurrence 0, 1, or 2;

y is independently at each occurrence 0, 1, or 2;

z is independently at each occurrence 1, 2, or 3;

Lig¹ is a bidentate ligand that at each occurrence is each independently selected from the

 

group consisting of

Lig² is a bidentate ligand that at each occurrence is each independently selected from the group consisting of

Lig³ is a bidentate li and that at each occurrence is each independentl selected from the

 

group consisting o

R¹ is selected from the group consisting of hydrogen, optionally substituted phenyl, optionally substituted aryl, optionally substituted heteroaryl, 4-pyridyl, 3-pyridyl, 2- thiazole, 2-pyrolyl, 2-furanyl, 

 

u is an integer;

R^2a, R^2b, R^2c, R^2d, R^2e, R^2f, R^2g, R^2h, R²ⁱ, R^2j, R^2k, and R^2l at each occurrence are each independently selected from the group consisting of hydrogen, C_1-6optionally substituted alkyl, C_1-6 optionally substituted branched alkyl, C_3-7 optionally substituted cycloalkyl, C_1-6 optionally substituted haloalkyl, C_1-6 optionally substituted alkoxy, CO₂R⁵, CONR⁶

₂, NR⁷

₂, SO₃H, sulfate, sulfonate, optionally substituted aryl, optionally substituted aryloxy, optionally substituted heteroaryl, and optionally substituted heterocycle;

R^3a, R^3b, R^3c, R^3d, R^3e, R^3f, R^3g, R^3h R³ⁱ, R^3j, R^3k, and R^3l at each occurrence are each independently selected from the group consisting of hydrogen, C_1-6optionally substituted alkyl, C_1-6 optionally substituted branched alkyl, C_1-6 optionally substituted haloalkyl, C_1-6 optionally substituted alkoxy, optionally substituted phenyl, and CO₂R⁸;

R^4a, R^4b, and R^4c at each occurrence are each independently selected from the group consisting of hydrogen, C_1-6 optionally substituted alkyl, C_1-6 optionally substituted

branched alkyl, C_1-6 optionally substituted cycloalkyl, C_1-6 optionally substituted haloalkyl, C_1-6 optionally substituted alkoxy, CO₂R⁵, CONR⁶

₂, NR7

₂ , sulfate, sulfonate, optionally substituted aryl, optionally substituted aryloxy, optionally substituted heteroaryl, and optionally substituted heterocycle;

R^4a and R^4b at each occurrence on a thiophene ring are taken together with the atom to which they are bound to form an optionally substituted ring having from 6 ring atoms containing 2 oxygen atoms;

R⁵ at each occurrence are each independently selected from the group consisting of hydrogen and optionally substituted alkyl;

R⁶ at each occurrence are each independently selected from the group consisting of hydrogen and optionally substituted alkyl;

R⁷ at each occurrence are each independently selected from the group consisting of hydrogen and optionally substituted alkyl; and

R⁸ at each occurrence are each independently selected from the group consisting of hydrogen and optionally substituted alkyl.

(b) formula (VI):

 

including hydrates, solvates, pharmaceutically acceptable salts, prodrugs and complexes thereof wherein;

M¹ and M² at each occurrence is independently selected from the group consisting of osmium, manganese, molybdenum, rhenium, ruthenium, iron, cobalt, rhodium, iridium, nickel, platinum, and copper;

A² is selected from the group consisting of 

t is an integer;

(c) formula (VIIa):

 

including hydrates, solvates, pharmaceutically acceptable salts, prodrugs and complexes thereof wherein:

 

A³ is selected from the group consisting of  
, ,

 

Lig¹ is a bidentate ligand that at each occurrence is each independently selected from the

 

group consisting of 

Lig³ is a bidentate ligand that at each occurrence is each independently selected from the

 

group consisting of

R¹ is selected from the group consisting of hydrogen, optionally substituted phenyl, optionally substituted aryl, optionally substituted heteroaryl, 4-pyridyl, 3-pyridyl, 2-

 

thiazole, 2-pyrolyl, 2-furanyl, 

 

u is an integer;

R^2a, R^2b, R^2c, R^2d, R^2e, R^2f, R^2g, R^2h, R²ⁱ, R^2j, R^2k, and R^2l at each occurrence are each independently selected from the group consisting of hydrogen, C_1-6optionally substituted alkyl, C_1-6 optionally substituted branched alkyl, C_3-7 optionally substituted cycloalkyl, C_1-6 optionally substituted haloalkyl, C_1-6 optionally substituted alkoxy, CO₂R⁵, CONR⁶

₂, NR⁷

₂, SO₃H, sulfate, sulfonate, optionally substituted aryl, optionally substituted aryloxy, optionally substituted heteroaryl, and optionally substituted heterocycle;

R^3a, R^3b, R^3c, R^3d, R^3e, R^3f, R^3g, R^3h R³ⁱ, R^3j, R^3k, and R^3l at each occurrence are each independently selected from the group consisting of hydrogen, C_1-6optionally substituted alkyl, C_1-6 optionally substituted branched alkyl, C_1-6 optionally substituted haloalkyl, C_1-6 optionally substituted alkoxy, optionally substituted phenyl, and CO₂R⁸;

R^4a, R^4b, and R^4c at each occurrence are each independently selected from the group consisting of hydrogen, C_1-6 optionally substituted alkyl, C_1-6 optionally substituted branched alkyl, C_1-6 optionally substituted cycloalkyl, C_1-6 optionally substituted haloalkyl, C_1-6 optionally substituted alkoxy, CO₂R⁵, CONR⁶

₂, NR7

₂ , sulfate, sulfonate, optionally substituted aryl, optionally substituted aryloxy, optionally substituted heteroaryl, and optionally substituted heterocycle;

R^4a and R^4b at each occurrence on a thiophene ring are taken together with the atom to which they are bound to form an optionally substituted ring having from 6 ring atoms containing 2 oxygen atoms;

R⁵ at each occurrence are each independently selected from the group consisting of hydrogen and optionally substituted alkyl;

R⁶ at each occurrence are each independently selected from the group consisting of hydrogen and optionally substituted alkyl;

R⁷ at each occurrence are each independently selected from the group consisting of hydrogen and optionally substituted alkyl; and

R⁸ at each occurrence are each independently selected from the group consisting of hydrogen and optionally substituted alkyl

p is independently at each occurrence 0, 1, or 2;

q is independently at each occurrence 0, 1, or 2; and

n is 0, 1, 2, 3, 4, or 5.

(d) formula (II):

 

including hydrates, solvates, pharmaceutically acceptable salts, prodrugs and complexes thereof, wherein:

M is selected from the group consisting of manganese, molybdenum, rhenium, iron, ruthenium, osmium, cobalt, rhodium, iridium, nickel, platinum, and copper;

X is selected from the group consisting of

and SO 

₄^-2_;

n = 0, 1, 2, 3, 4, or 5;

y = 1, 2, or 3;

z = 0, 1, or 2;

Lig at each occurrence is inde endentl selected from the rou consistin of

 

 
;

 

R¹ is selected from the group consisting of  
, , 

u is an integer;

R^2a, R^2b, R^2c, R^2d, R^2e, and R^2f at each occurrence are each independently selected from the group consisting of hydrogen, C1-6 optionally substituted alkyl, C1-6 optionally substituted branched alkyl, C3-7 optionally substituted cycloalkyl, C1-6 optionally substituted haloalkyl, C1-6 optionally substituted alkoxy, CO₂R⁵, CONR⁶

₂, NR7 ₂ , sulfate, sulfonate, optionally substituted aryl, optionally substituted aryloxy, optionally substituted heteroaryl, and optionally substituted heterocycle;

R^3a, R^3b, R^3c, R^3d, R^3e, R^3f, R^3g, R^3h R³ⁱ, R^3j, R^3k, R^3l, and R^3m at each occurrence are each independently selected from the group consisting of hydrogen, C1-6 optionally substituted alkyl, C1-6 optionally substituted branched alkyl, C1-6 optionally substituted haloalkyl, C1-6 optionally substituted alkoxy, and CO₂R⁸;

R^4a, R^4b, and R^4c at each occurrence are each independently selected from the group consisting of hydrogen, C1-6 optionally substituted alkyl, C1-6 optionally substituted branched alkyl, C1-6 optionally substituted cycloalkyl, C1-6 optionally substituted haloalkyl, C1-6 optionally substituted alkoxy, CO₂R⁵, CONR⁶

₂, NR7 ₂ , sulfate, sulfonate, optionally substituted aryl, optionally substituted aryloxy, optionally substituted heteroaryl, and optionally substituted heterocycle;

R^4a and R^4b at each occurrence on a thiophene ring are taken together with the atom to which they are bound to form an optionally substituted ring having from 6 ring atoms containing 2 oxygen atoms;

R⁵ at each occurrence is independently selected from the group consisting of hydrogen and optionally substituted alkyl;

R⁶ at each occurrence is independently selected from the group consisting of hydrogen and optionally substituted alkyl;

R⁷ at each occurrence is independently selected from the group consisting of hydrogen and optionally substituted alkyl; and

R⁸ at each occurrence is independently selected from the group consisting of hydrogen and optionally substituted alkyl.

2. The method of claim 1, wherein the immunogenic composition is prepared by collecting tumor cells from a donor, preparing a composition comprising the tumor cells and the metal-based coordination complex, and exposing the composition to the electromagnetic radiation to provide the immunogenic composition.

3. The method of claim 2, wherein the electromagnetic radiation is laser light having a wavelength from 500-950 nm.

4. The method of claim 2, wherein the electromagnetic radiation is X-rays or Gamma rays.

5. The method of claim 2, wherein the donor is the patient and is a human, and the tumor cells are cancer cells.

6. The method of claim 2, wherein the metal-based coordination complex further comprises transferrin.

7. The method of claim 2, wherein M is at least one of Ru, Rh, Os and Ir. 8. The method of claim 2, wherein the metal-based coordination complex has the following structure:

 

 .

9. A method for preparing an immunogenic composition, said method comprising:

collecting tumor cells from a donor;

preparing a composition comprising the tumor cells and a metal-based coordination complex; and

exposing the composition to electromagnetic radiation to provide the immunogenic composition,

wherein the immunogenic composition is effective to elicit an immune response to the antigenic material in a patient to whom the immunogenic composition is administered, and the metal-based coordination complex is represented by one of the following formulas:

(a) formula (I):

 

including hydrates, solvates, pharmaceutically acceptable salts, prodrugs and complexes thereof, wherein:

M at each occurrence is independently selected from the group consisting of osmium, ruthenium and rhodium;

X is selected from the group consisting of Cl-, PF - ₆ , Br-, BF - ₄ , ClO - ₄ , CF₃SO - ₃ , and SO ^-2

₄ ; n = 0, 1, 2, 3, 4, or 5;

q is independently at each occurrence 0, 1, or 2;

y is independently at each occurrence 0, 1, or 2;

z is independently at each occurrence 1, 2, or 3;

Lig¹ is a bidentate ligand that at each occurrence is each independently selected from the

 

group consisting of  
, , , ,

 

Lig² is a bidentate ligand that at each occurrence is each independently selected from the group consisting of  
, , , ,

Lig³ is a bidentate ligand that at each occurrence is each independently selected from the

 

group consisting of 

R¹ is selected from the group consisting of hydrogen, optionally substituted phenyl, optionally substituted aryl, otionall substituted heteroarl 4- ridl 3- ridl 2-

 

thiazole, 2-pyrolyl, 2-furanyl, 

 g ;

R^2a, R^2b, R^2c, R^2d, R^2e, R^2f, R^2g, R^2h, R²ⁱ, R^2j, R^2k, and R^2l at each occurrence are each independently selected from the group consisting of hydrogen, C_1-6optionally substituted alkyl, C_1-6 optionally substituted branched alkyl, C_3-7 optionally substituted cycloalkyl, C_1-6 optionally substituted haloalkyl, C_1-6 optionally substituted alkoxy, CO₂R⁵, CONR⁶

₂, NR⁷

₂, SO₃H, sulfate, sulfonate, optionally substituted aryl, optionally substituted aryloxy, optionally substituted heteroaryl, and optionally substituted heterocycle;

R^3a, R^3b, R^3c, R^3d, R^3e, R^3f, R^3g, R^3h R³ⁱ, R^3j, R^3k, and R^3l at each occurrence are each independently selected from the group consisting of hydrogen, C_1-6optionally substituted alkyl, C_1-6 optionally substituted branched alkyl, C_1-6 optionally substituted haloalkyl, C_1-6 optionally substituted alkoxy, optionally substituted phenyl, and CO₂R⁸;

R^4a, R^4b, and R^4c at each occurrence are each independently selected from the group consisting of hydrogen, C_1-6 optionally substituted alkyl, C_1-6 optionally substituted branched alkyl, C_1-6 optionally substituted cycloalkyl, C_1-6 optionally substituted haloalkyl, C_1-6 optionally substituted alkoxy, sulfate, sulfonate, 

optionally substituted aryl, optionally substituted aryloxy, optionally substituted heteroaryl, and optionally substituted heterocycle;

R^4a and R^4b at each occurrence on a thiophene ring are taken together with the atom to which they are bound to form an optionally substituted ring having from 6 ring atoms containing 2 oxygen atoms;

R⁵ at each occurrence are each independently selected from the group consisting of hydrogen and optionally substituted alkyl;

R⁶ at each occurrence are each independently selected from the group consisting of hydrogen and optionally substituted alkyl;

R⁷ at each occurrence are each independently selected from the group consisting of hydrogen and optionally substituted alkyl; and

R⁸ at each occurrence are each independently selected from the group consisting of hydrogen and optionally substituted alkyl.

(b) formula (VI):

 

including hydrates, solvates, pharmaceutically acceptable salts, prodrugs and complexes thereof wherein;

M¹ and M² at each occurrence is independently selected from the group consisting of osmium, manganese, molybdenum, rhenium, ruthenium, iron, cobalt, rhodium, iridium, nickel, platinum, and copper;

A² is selected from the group consisting of 

t is an integer;

(c) formula (VIIa):

 

including hydrates, solvates, pharmaceutically acceptable salts, prodrugs and complexes thereof wherein:

 

A³ is selected from the group consisting o  
, ,

 

Lig¹ is a bidentate ligand that at each occurrence is each independently selected from the

 

group consisting of  
, , , , 

Lig³ is a bidentate ligand that at each occurrence is each independently selected from the

 

group consisting of

R¹ is selected from the group consisting of hydrogen, optionally substituted phenyl, optionally substituted aryl, optionally substituted heteroaryl, 4-pyridyl, 3-pyridyl, 2-

 

thiazole, 2-pyrolyl, 2-furanyl,  
, , , ,

 

u is an integer;

R^2a, R^2b, R^2c, R^2d, R^2e, R^2f, R^2g, R^2h, R²ⁱ, R^2j, R^2k, and R^2l at each occurrence are each independently selected from the group consisting of hydrogen, C_1-6optionally substituted alkyl, C_1-6 optionally substituted branched alkyl, C_3-7 optionally substituted cycloalkyl, C_1-6 optionally substituted haloalkyl, C_1-6 optionally substituted alkoxy, CO₂R⁵, CONR⁶

₂, NR⁷

₂, SO₃H, sulfate, sulfonate, optionally substituted aryl, optionally substituted aryloxy, optionally substituted heteroaryl, and optionally substituted heterocycle;

R^3a, R^3b, R^3c, R^3d, R^3e, R^3f, R^3g, R^3h R³ⁱ, R^3j, R^3k, and R^3l at each occurrence are each independently selected from the group consisting of hydrogen, C_1-6optionally substituted alkyl, C_1-6 optionally substituted branched alkyl, C_1-6 optionally substituted haloalkyl, C_1-6 optionally substituted alkoxy, optionally substituted phenyl, and CO₂R⁸;

R^4a, R^4b, and R^4c at each occurrence are each independently selected from the group consisting of hydrogen, C_1-6 optionally substituted alkyl, C_1-6 optionally substituted branched alkyl, C_1-6 optionally substituted cycloalkyl, C_1-6 optionally substituted haloalkyl, C_1-6 optionally substituted alkoxy, CO₂R⁵, CONR⁶

₂, NR7

₂ , sulfate, sulfonate, optionally substituted aryl, optionally substituted aryloxy, optionally substituted heteroaryl, and optionally substituted heterocycle;

R^4a and R^4b at each occurrence on a thiophene ring are taken together with the atom to which they are bound to form an optionally substituted ring having from 6 ring atoms containing 2 oxygen atoms;

R⁵ at each occurrence are each independently selected from the group consisting of hydrogen and optionally substituted alkyl;

R⁶ at each occurrence are each independently selected from the group consisting of hydrogen and optionally substituted alkyl;

R⁷ at each occurrence are each independently selected from the group consisting of hydrogen and optionally substituted alkyl; and

R⁸ at each occurrence are each independently selected from the group consisting of hydrogen and optionally substituted alkyl

p is independently at each occurrence 0, 1, or 2;

q is independently at each occurrence 0, 1, or 2; and

n is 0, 1, 2, 3, 4, or 5.

(d) formula (II):

 

including hydrates, solvates, pharmaceutically acceptable salts, prodrugs and complexes thereof, wherein:

M is selected from the group consisting of manganese, molybdenum, rhenium, iron, ruthenium, osmium, cobalt, rhodium, iridium, nickel, platinum, and copper;

- - - - - -X is selected from the group consisting of Cl , PF₆ , Br , BF₄ , ClO₄ , CF₃SO₃ ,

and SO₄^-2_;

n = 0, 1, 2, 3, 4, or 5;

y = 1, 2, or 3;

z = 0, 1, or 2;

Lig at each occurrence is inde endentl selected from the rou consistin of

 

 , , 

R¹ is selected from the group consisting of 

u is an integer;

R^2a, R^2b, R^2c, R^2d, R^2e, and R^2f at each occurrence are each independently selected from the group consisting of hydrogen, C1-6 optionally substituted alkyl, C1-6 optionally substituted branched alkyl, C3-7 optionally substituted cycloalkyl, C1-6 optionally substituted haloalkyl, C1-6 optionally substituted alkoxy, CO₂R⁵, CONR⁶

₂, NR7 ₂ , sulfate, sulfonate, optionally substituted aryl, optionally substituted aryloxy, optionally substituted heteroaryl, and optionally substituted heterocycle;

R^3a, R^3b, R^3c, R^3d, R^3e, R^3f, R^3g, R^3h R³ⁱ, R^3j, R^3k, R^3l, and R^3m at each occurrence are each independently selected from the group consisting of hydrogen, C1-6 optionally substituted alkyl, C1-6 optionally substituted branched alkyl, C1-6 optionally substituted haloalkyl, C1-6 optionally substituted alkoxy, and CO₂R⁸;

R^4a, R^4b, and R^4c at each occurrence are each independently selected from the group consisting of hydrogen, C1-6 optionally substituted alkyl, C1-6 optionally substituted branched alkyl, C1-6 optionally substituted cycloalkyl, C1-6 optionally substituted haloalkyl, C1-6 optionally substituted alkoxy, CO₂R⁵, CONR⁶

₂, NR7 ₂ , sulfate, sulfonate, optionally substituted aryl, optionally substituted aryloxy, optionally substituted heteroaryl, and optionally substituted heterocycle;

R^4a and R^4b at each occurrence on a thiophene ring are taken together with the atom to which they are bound to form an optionally substituted ring having from 6 ring atoms containing 2 oxygen atoms;

R⁵ at each occurrence is independently selected from the group consisting of hydrogen and optionally substituted alkyl;

R⁶ at each occurrence is independently selected from the group consisting of hydrogen and optionally substituted alkyl;

R⁷ at each occurrence is independently selected from the group consisting of hydrogen and optionally substituted alkyl; and

R⁸ at each occurrence is independently selected from the group consisting of hydrogen and optionally substituted alkyl.

10. The method of claim 9, wherein the electromagnetic radiation is laser light having a wavelength from 500-950 nm.

11. The method of claim 9, wherein the electromagnetic radiation is X-rays or Gamma rays.

12. The method of claim 9, wherein the donor is a human and the tumor cells are cancer cells.

13. The method of claim 9, wherein the metal-based coordination complex further comprises transferrin.

14. The method of claim 9, wherein M is at least one of Ru, Rh, Os and Ir. 15. The method of claim 9, wherein the metal-based coordination complex has the following structure:

 

 .

16. The method of claim 9, wherein the immunogenic composition is incubated with dendritic cells from the patient so as to prepare armed dendritic cells having tumor antigens,

the armed dendritic cells are administered to the patient optionally in combination with transferrin, and/or

the armed dendritic cells are co-cultured with CD4+ or CD8+ to provide expanded CD4+ or CD8+ cells which are administered to the patient optionally in combination with transferrin.

17. An immunogenic composition prepared by the method of claim 9.

18. The immunogenic composition of claim 17, wherein the metal-based coordination complex further comprises transferrin.

19. The immunogenic composition of claim 17, wherein M is at least one of Ru, Rh, Os and Ir.

20. The immunogenic composition of claim 17, wherein the metal-based coordination complex has the following structure:

 .

Gustoes wrote:

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1. (WO2018209203) VACCINE CONTAINING CANCER CELLS INACTIVATED BY PHOTODYNAMIC TREATMENT WITH METAL-BASED COORDINATION COMPLEXES, AND IMMUNOTHERAPY METHOD USING SAME

 

 

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