Claims for Patent: 11,592,396

Summary for Patent: 11,592,396

Title:	Methods and systems for spatially identifying abnormal cells
Abstract:	The present invention provides compositions and methods for imaging tumor resections.
Inventor(s):	W. David Lee, Moungi G. Bawendi, Jorge Ferrer
Assignee:	Lumicell Inc
Application Number:	US16/829,498
Patent Claims:	1. A composition comprising: a molecular imaging probe having the formula: [S1]i-P-[([S2]j-F)-A-([S3]k-Q)-[S4]m]n and wherein S1, S2, S3, and S4 are spacers that each independently comprise a group selected from PEG2, PEG2 attached to an amino acid, aminohexanoic acid, an amino acid sequence SRK, an amino acid D, and an amino acid C; i is 0 or 1; P is a pharmacokinetic modifier comprising polyethylene glycol (PEG) or methoxyPEG molecule (MPEG); F is a Cy5 fluorochrome; A is an amino acid sequence selected from GRKL or GGRK; Q is a QSY21 dark quencher; j is 0 or 1; k is 0 or 1; m is 0 or 1; and n is 1, 2, or 4; or a pharmaceutically acceptable salt or prodrug of the molecular imaging probe. 2. The composition of claim 1, wherein the composition includes the molecular imaging probe. 3. The composition of claim 1, wherein the composition includes the pharmaceutically acceptable salt of the molecular imaging probe. 4. The composition of claim 1, wherein the molecular imaging probe has optical properties in the visible spectrum. 5. The composition of claim 1, wherein the Cy5 fluorochrome and the QSY21 dark quencher are separated by an enzyme cleavage site such that the molecular imaging probe does not emit fluorescence until the enzyme cleavage site is cleaved. 6. The composition of claim 5, wherein the enzyme cleavage site is cleaved by cathespin. 7. The composition of claim 5, wherein the enzyme cleavage site is an amino acid sequence. 8. The composition of claim 1, wherein the pharmacokinetic modifier comprises a PEG molecule between 500 g/mol and 100,000 g/mol. 9. The composition of claim 1, wherein the molecular imaging probe has the following formula: PEG-SRK(Cy5)-GGRK(QSY21)-D. 10. The composition of claim 9, wherein the PEG is between 500 g/mol and 100,000 g/mol. 11. The composition of claim 9, wherein the PEG is about 20,000 g/mol. 12. The composition of claim 1, wherein the molecular imaging probe has the following formula: C(PEG)-SRK(Cy5)-GGRK(QSY21)-D. 13. The composition of claim 12, wherein the PEG is between 500 g/mol and 100,000 g/mol. 14. The composition of claim 12, wherein the PEG is about 20,000 g/mol. 15. The composition of claim 1, wherein the molecular imaging probe has a formula selected from: [QSY21-Ahx-GGRK(Cy5)-PEG2-C]n-PEG, wherein n=1, 2 or 4, Cy5-Ahx-GGRK(QSY21)-PEG2-C(PEG) and QSY21-LRGGRK(Cy5)-PEG2-C(PEG). 16. A molecular imaging probe comprising the formula: [S1]i-P-[([S2]j-F)-A-([S3]k-Q)-[S4]m]n and wherein S1, S2, S3, and S4 are spacers that each independently comprise a group selected from PEG2, PEG2 attached to an amino acid, aminohexanoic acid, an amino acid sequence SRK, an amino acid D, and an amino acid C; i is 0 or 1; P is a pharmacokinetic modifier comprising polyethylene glycol (PEG) or methoxyPEG molecule (MPEG); F is a Cy5 fluorochrome; A is an amino acid sequence selected from GRKL or GGRK; Q is a QSY21 dark quencher; j is 0 or 1; k is 0 or 1; m is 0 or 1; and n is 1, 2, or 4. 17. The molecular imaging probe of claim 16, wherein the molecular imaging probe has the formula: [S1]i-P-[([S2]j-F)-A-([S3]k-Q)-[S4]m]n. 18. The molecular imaging probe of claim 16, wherein the molecular imaging probe has optical properties in the visible spectrum of 350-670 nm. 19. The molecular imaging probe of claim 16, wherein the Cy5 fluorochrome and the QSY21 dark quencher of the molecular imaging probe are separated by an enzyme cleavage site such that the molecular imaging probe does not emit fluorescence until the enzyme cleavage site is cleaved. 20. The molecular imaging probe of claim 19, wherein the enzyme cleavage site is cleaved by cathepsin. 21. The molecular imaging probe of claim 19, wherein the enzyme cleavage site is an amino acid sequence. 22. The molecular imaging probe of claim 16, wherein the pharmacokinetic modifier comprises a PEG molecule between 500 g/mol and 100,000 g/mol. 23. The molecular imaging probe of claim 16, wherein the molecular imaging probe has the following formula: PEG-SRK(Cy5)-GGRK(QSY21)-D. 24. The molecular imaging probe of claim 23, wherein the PEG is between 500 g/mol and 100,000 g/mol. 25. The molecular imaging probe of claim 23, wherein the PEG is about 20,000 g/mol. 26. The molecular imaging probe of claim 16, wherein the molecular imaging probe has the following formula: C(PEG)-SRK(Cy5)-GGRK(QSY21)-D. 27. The molecular imaging probe of claim 26, wherein the PEG is between 500 g/mol and 100,000 g/mol. 28. The molecular imaging probe of claim 26, wherein the PEG is about 20,000 g/mol. 29. The molecular imaging probe of claim 16, wherein the molecular imaging probe has a formula selected from: [QSY21-Ahx-GGRK(Cy5)-PEG2-C]n-PEG, wherein n=1, 2 or 4, Cy5-Ahx-GGRK(QSY21)-PEG2-C(PEG) and QSY21-LRGGRK(Cy5)-PEG2-C(PEG). 30. A pharmaceutically acceptable salt of the molecular imaging probe of claim 16. 31. A prodrug of the molecular imaging probe of claim 16. 32. A molecular imaging probe comprising the formula QSY21-Ahx-GGRK(Cy5)-PEG2-C]n-PEG, wherein n=1, 2 or 4. 33. A pharmaceutically acceptable salt of molecular imaging probe of claim 32. 34. A prodrug of the molecular imaging probe of claim 32. 35. The molecular imaging probe of claim 32, wherein Cy5 and QSY21 are separated by an enzyme cleavage site such that the molecular imaging probe does not emit fluorescence until the enzyme cleavage site is cleaved. 36. The molecular imaging probe of claim 32, wherein the PEG is between 500 g/mol and 100,000 g/mol. 37. The molecular imaging probe of claim 32, wherein the PEG is about 20,000 g/mol. 38. A composition comprising: a molecular imaging probe having the formula QSY21-Ahx-GGRK(Cy5)-PEG2-C]n-PEG, wherein n=1, 2 or 4; or a pharmaceutically acceptable salt or prodrug of the molecular imaging probe. 39. The composition of claim 38, wherein the composition includes the molecular imaging probe. 40. The composition of claim 38, wherein the composition includes the pharmaceutically acceptable salt of the molecular imaging probe. 41. The composition of claim 38, wherein Cy5 and QSY21 are separated by an enzyme cleavage site such that the molecular imaging probe does not emit fluorescence until the enzyme cleavage site is cleaved. 42. The composition of claim 38, wherein the PEG is between 500 g/mol and 100,000 g/mol. 43. The composition of claim 38, wherein the PEG is about 20,000 g/mol.