Granted Patent B2

US 12,704,501 · App. 17/442,487 · Granted Aug 11, 2026

Inventors: Miguel Garcia-Guzman (San Diego, CA); Roger Heim (Del Mar, CA); Eileen Sun Chin (San Diego, CA); Jerry Fong (San Diego, CA); Deepak Yadav (San Diego, CA); Nikolai Suslov (San Diego, CA); C. Daniel De Magalhaes Filho (La Jolla, CA); Chung-Wein Lee (San Diego, CA)

Assignee: Rakuten Medical, Inc.

G01N33/5011A61K39/3955A61K41/008A61K47/6803A61K47/6849A61P35/00A61K2039/505

Abstract

Claims (39)

1 . A method of treating a tumor that is a head or neck cancer in a subject, the method comprising administering to the subject a photoimmunotherapy (PIT) treatment, thereby treating the tumor,

wherein the PIT treatment comprises a conjugate comprising a silicon phthalocyanine dye and an EGFR binding molecule; and

wherein the subject has been selected for treatment by:

a) measuring in a sample from the subject a first level of an immune checkpoint biomarker comprising a PD-L1 expression;

b) comparing the first level of PD-L1 from the subject to a first threshold level of PD-L1 expression, wherein the first threshold level is a Combined Positive Score (CPS) of PD-L1 expression equal to 30; and

c) selecting the subject for treatment if the first level from the subject is lower than the first threshold level.

2 . The method of claim 1 , wherein the sample is a tumor sample, a blood sample, or a serum sample.

3 . The method of claim 1 , wherein the first threshold level is measured as a Combined Positive Score (CPS) equal to the number of cells staining positive for the immune checkpoint biomarker, divided by the total number of tumor cells, multiplied by 100.

4 . The method of claim 1 , wherein the PIT treatment comprises irradiating an area proximal to the tumor at a wavelength of at or about 660 nm to at or about 740 nm.

5 . The method of claim 1 , wherein the EGFR binding molecule is cetuximab or a fragment thereof.

6 . The method of claim 1 , wherein the method further comprises:

measuring a second level of the immune checkpoint biomarker in a second sample from the subject after the PIT treatment;

determining whether the second level of the immune checkpoint biomarker is increased in the subject relative to the first level measured prior to the PIT treatment; and

if the second level is increased relative to the first level, administering an immune checkpoint inhibitor to the subject.

7 . The method of claim 1 , wherein the PIT treatment comprises exposing the conjugate to light that has a wavelength within a range of at or about 660 nm to at or about 740 nm.

8 . The method of claim 1 , wherein the PIT treatment comprises exposing the conjugate to light that has a wavelength of at or about 690 nm.

9 . The method of claim 1 , wherein the silicon phthalocyanine dye comprises the formula:

wherein:

L is a linker;

Q is a reactive group for attachment of the dye to the EGFR binding molecule;

R 2 , R 3 , R 7 , and R 8 are each independently selected from among substituted alkyl and substituted aryl;

R 4 , R 5 , R 6 , R 9 , R 10 , and R 11 are each independently selected from among hydrogen, substituted alkyl, substituted alkanoyl, substituted alkoxycarbonyl, substituted alkylcarbamoyl, and a chelating ligand, wherein at least one of R 4 , R 5 , R 6 , R 9 , R 10 , and R 11 comprises a water soluble group;

R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , R 22 and R 23 are each independently selected from among hydrogen, halogen, substituted alkylthio, substituted alkylamino and substituted alkoxy; and

X 2 and X 3 are each independently C 1 -C 10 alkylene.

10 . The method of claim 7 , wherein the silicon phthalocyanine dye is IR700.

11 . The method of claim 7 , wherein the EGFR binding molecule is cetuximab or a fragment thereof.

12 . The method of claim 7 , wherein the silicon phthalocyanine dye comprises the formula:

wherein:

L is a linker;

Q is a reactive group for attachment of the dye to the EGFR binding molecule;

R 2 , R 3 , R 7 , and R 8 are each independently selected from among substituted alkyl and substituted aryl;

R 4 , R 5 , R 6 , R 9 , R 10 , and R 11 are each independently selected from among hydrogen, substituted alkyl, substituted alkanoyl, substituted alkoxycarbonyl, substituted alkylcarbamoyl, and a chelating ligand, wherein at least one of R 4 , R 5 , R 6 , R 9 , R 10 , and R 11 comprises a water soluble group;

R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , R 22 and R 23 are each independently selected from among hydrogen, halogen, substituted alkylthio, substituted alkylamino and substituted alkoxy; and

X 2 and X 3 are each independently C 1 -C 10 alkylene.

13 . The method of claim 8 , wherein the silicon phthalocyanine dye is IR700.

14 . The method of claim 8 , wherein the EGFR binding molecule is cetuximab or a fragment thereof.

15 . The method of claim 10 , wherein the EGFR binding molecule is cetuximab or a fragment thereof.

16 . The method of claim 12 , wherein the EGFR binding molecule is cetuximab or a fragment thereof.

17 . The method of claim 1 , wherein the silicon phthalocyanine dye is IR700.

Assignments (1)

Continuity (3)

References Cited (400)