Claims for Patent: 7,998,923

Summary for Patent: 7,998,923

Title:	Bioactivation of particles
Abstract:	Particles are bioactivated by attaching bioactivation peptides to the particle surface. The bioactivation peptides are peptide-based compounds that impart one or more biologically important functions to the particles. Each bioactivation peptide includes a molecular or surface recognition part that binds with the surface of the particle and one or more functional parts. The surface recognition part includes an amino-end and a carboxy-end and is composed of one or more hydrophobic spacers and one or more binding clusters. The functional part(s) is attached to the surface recognition part at the amino-end and/or said carboxy-end.
Inventor(s):	Pinaud; Fabien (Berkeley, CA), King; David (San Francisco, CA), Weiss; Shimon (Los Angeles, CA)
Assignee:	The Regents of the University of California (Oakland, CA)
Application Number:	10/513,567
Patent Claims:	1. A bioactivated particle, comprising: a quantum dot that includes a surface; and at least one bioactivation peptide attached to said surface of said quantum dot, said bioactivation peptide comprising a molecular recognition part that is bound to the surface of said quantum dot and one or more functional parts, said molecular recognition part comprising an amino-end and a carboxy-end and comprising one or more hydrophobic spacers and one or more binding clusters and wherein said functional part(s) is attached to said molecular recognition part at said amino-end and/or said carboxy-end, wherein said binding cluster is directly bound to said surface of said quantum dot and comprises an amino acid independently selected from the group consisting of cysteine, methionine, and histidine, wherein said hydrophobic spacer comprises an amino acid modified to be hydrophobic independently selected from the group consisting of cyclohexyl-substituted alanine, cyclohexyl-substituted glycine, cyclohexyl-substituted isoleucine, cyclohexyl-substituted leucine, cyclohexyl-substituted methionine, cyclohexyl-substituted arginine, cyclohexyl-substituted valine, and cyclohexyl-substituted tryptophan, wherein said bioactivation peptide comprises the sequence Cha-C-C-Cha-C-C-Cha-C-C-Cha [SEQ. ID. NO. 1], and wherein Cha is cyclohexyl alanine and C is cysteine. 2. A bioactivated particle according to claim 1 where said binding cluster consists essentially of two cysteines. 3. A bioactivated particle according to claim 1 wherein said hydrophobic amino acid is cyclohexyl alanine. 4. A bioactivated particle according to claim 2 wherein said hydrophobic spacer is cyclohexyl alanine. 5. A bioactivated particle according to claim 1 wherein said molecular recognition part comprises at least three binding clusters which are located alternately between at least four hydrophobic spacers. 6. A bioactivated particle according to claim 5 wherein said binding cluster consists essentially of two cysteines and said hydrophobic spacer consists essentially of cyclohexyl alanine. 7. A bioactivated particle according to claim 1 wherein said quantum dot comprises inorganic material at said surface. 8. A bioactivated particle according to claim 1 wherein the diameter of said quantum dot is between 0.1 and 100 nanometers. 9. A bioactivated particle according to claim 7 wherein said inorganic material is selected from the group consisting of semiconductors comprising elements from column(s) II and VI, III and V, and/or IV of the periodic table, metallic materials, magnetic materials and dielectric materials. 10. A bioactivated particle according to claim 9 wherein the diameter of said quantum dot is between 0.1 and 100 nanometers. 11. A bioactivated particle according to claim 1 wherein said functional part(s) comprise one or more functional agent(s) selected from the group consisting of solubility agents, conjugation agents, targeting agents, therapeutic agents, imaging agents, detection agents, recognition, agents and diagnostic agents. 12. A bioactivated particle according to claim 1 wherein said functional part(s) consist essentially of one or more solubility agent(s). 13. A bioactivated particle according to claim 1 wherein said functional part(s) comprise a solubility agent attached to said molecular recognition part and one or more functional agent(s) attached to said one or more solubility agents) wherein said functional agent(s) is selected from the group consisting of conjugation agents, targeting agents, therapeutic agents, imaging agents, detection agents, recognition agents and diagnostic agents. 14. A bioactivated particle according to claim 12 wherein said solubility agent is selected from the group consisting of hydrophilic peptides, polyethylene glycol, poly(ethylene oxide), polyelectrolytes and sugars. 15. A bioactivated particle according to claim 14, wherein a first portion and second portion of said at least one bioactivation peptide, are attached to said particle surface and wherein said first portion comprises functional part(s) that are different from the functional part(s) of said second portion. 16. A bioactivated particle according to claim 15, wherein said first portion of said at least one bioactivation peptide includes a functional part that comprises a first solubility agent that consists of a hydrophilic peptide and wherein said second portion of said at least one bioactivation peptide includes a functional part that comprises a second solubility agent that consists of polyethylene glycol. 17. A bioactivation peptide for use in treating quantum dots having a surface to form bioactivated particles, said bioactivation peptide comprising: a molecular recognition part that is bindable to said surface of said quantum clot and one or more functional parts, said molecular recognition part including an amino-end and a carboxy-end and comprising one or more hydrophobic spacers and one or more binding clusters and wherein said functional part(s) is attached to said molecular recognition part at said amino-end and/or said carboxy-end, wherein said binding cluster is directly bindable to said surface of said quantum dot and comprises an amino acid independently selected from the group consisting of cysteine, methionine, and histidine and wherein said hydrophobic spacer comprises an amino acid modified to be hydrophobic independently selected from the group consisting of cyclohexyl-substituted alanine, cyclohexyl-substituted glycine, cyclohexyl-substituted isoleucine, cyclohexyl-substituted leucine, cyclohexyl-substituted methionine, cyclohexyl-substituted arginine, cyclohexyl-substituted valine, and cyclohexyl-substituted tryptophan, wherein the molecular recognition part comprises the sequence Cha-C-C-Cha-C-C-Cha-C-C-Cha [SEQ. ID. NO. 1], and wherein Cha is cyclohexyl alanine and C is cysteine. 18. A bioactivation peptide according to claim 17, wherein said binding cluster consists essentially of two cysteines. 19. A bioactivation peptide according to claim 17, wherein said hydrophobic amino acid is cyclohexyl alanine. 20. A bioactivation peptide according to claim 18 wherein said hydrophobic spacer is cyclohexyl alanine. 21. A bioactivation peptide according to claim 17 wherein said molecular recognition part comprises at least three binding clusters which are alternately located between at least four hydrophobic spacers. 22. A bioactivation peptide according to claim 21 wherein said binding clusters each consists essentially of two cysteines and said hydrophobic spacers each consists essentially of cyclohexyl alanine. 23. A bioactivation peptide according to claim 17 wherein said quantum dot to which said molecular recognition part is bindable comprises inorganic material at said surface. 24. A bioactivation peptide according to claim 23 wherein the diameter of said particle is between 0.1 and 100 nanometers. 25. A bioactivation peptide according to claim 17 wherein said functional part(s) comprises one or more functional agent(s) selected from the group consisting of solubility agents, conjugation agents, targeting agents, therapeutic agents, imaging agents, detection agents, recognition agents and diagnostic agents. 26. A bioactivation peptide according to claim 17 wherein said functional part(s) consist essentially of one or more solubility agent(s). 27. A bioactivation peptide according to claim 17 wherein said functional part(s) comprise one or more solubility agents attached to said molecular recognition part and one or more functional agent(s) attached to said one or more solubility agent(s) wherein said functional agents) is selected from the group consisting of conjugation agents, targeting agents, therapeutic agents, imaging agents, detection agents, recognition agents and diagnostic agents. 28. A bioactivation peptide according to claim 26 wherein said solubility agent is selected from the group consisting of hydrophilic peptides, polyethylene glycol, polyethylene oxide), polyelectrolytes and sugars. 29. A composition of matter comprising bioactivated particles according to claim 1 suspended in an aqueous medium. 30. A composition of matter comprising bioactivated particles according to claim 12 suspended in an aqueous medium. 31. A composition of matter comprising bioactivated particles according to claim 13 suspended in an aqueous medium. 32. A composition of matter comprising bioactivated particles according to claim 15 suspended in an aqueous medium. 33. A composition of matter comprising bioactivated particles according to claim 16 suspended in an aqueous medium. 34. A method for making a bioactivated particle that is soluble in an aqueous medium, said method comprising the steps of: providing a quantum dot that includes a surface; and treating the surface of said quantum dot with a sufficient amount of a bioactivation peptide according to claim 17 to make said bioactivated particle soluble in said aqueous medium. 35. A method for making a bioactivated particle that is soluble in an aqueous medium, said method comprising the steps of: providing a quantum dot that includes a surface; and treating the surface of said quantum dot with a sufficient amount of a bioactivation peptide according to claim 26 to make said bioactivated particle soluble in said aqueous medium. 36. A method for making a bioactivated particle that is soluble in an aqueous medium, said method comprising the steps of: providing a quantum dot that includes a surface; and treating the surface of said quantum dot with a sufficient amount of a bioactivation peptide according to claim 27 to make said bioactivated particle soluble in said aqueous medium. 37. A bioactivated particle having the formula ##STR00001## wherein [QD] is a quantum dot, wherein [BC] is a binding cluster comprising an amino acid independently selected from the group consisting of cysteine, methionine, histidine, and combinations, wherein [HS] is a hydrophobic spacer comprising an amino acid modified to be hydrophobic independently selected from the group consisting of cyclohexyl-substituted alanine, cyclohexyl-substituted glycine, cyclohexyl-substituted isoleucine, cyclohexyl-substituted leucine, cyclohexyl-substituted methionine, cyclohexyl-substituted arginine, c cyclohexyl-substituted valine, and cyclohexyl-substituted tryptophan, wherein m is at least 1, wherein [FP.sub.1] and [FP.sub.2] may be the same or different and are functional parts selected from the group consisting of a solubility agent, conjugation agent, targeting agent, therapeutic agent, imaging agent, detection agent, recognition agent, and diagnostic agent, wherein the sequence {[BC]-[HS]}.sub.m comprises the sequence Cha-C-C-Cha-C-C-Cha-C-C-Cha [SEQ. ID. NO. 1], and wherein Cha is cyclohexyl alanine and C is cysteine. 38. The bioactivated particle of claim 37, wherein [BC] is a binding cluster consisting of at least one cysteine. wherein [HS] is a hydrophobic spacer consisting of at least one cyclohexyl alanine, wherein m is at most 3, and wherein [FP.sub.1] and [FP.sub.2] may be the same or different and are functional parts selected from the group consisting of a hydrophilic peptide, polyethylene glycol, poly(ethylene oxide), a polyelectrolyte, polyethylene imine, a sugar, cellobiose, sucrose, sialic acid, and combinations. 39. A bioactivation peptide having the formula: [FP.sub.1]-[MRP], [MRP]-[FP.sub.2], or [FP.sub.1]-[MRP]-[FP.sub.2], wherein [FP.sub.1] and [FP.sub.2] may be the same or different and are functional parts selected from the group consisting of amide, acetyl, carboxamide, carboxyl, polyethylene glycol (PEG), NHS ester, keto, thiol, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), Ni-NTA, I, Yt, tritium, a metallo texaphyrin, taxol, herceptin, fluorescein, bromothymol blue, a hydrophilic peptide, biotin, avidin, streptavidin, lysine, cysteine, aspartic acid, DNA, transferrin, an antibody, a single chain fragment, G-S-E-S-G-G-S-E-S-G [SEQ. ID. NO. 6], G-S-S-S-G-G-S-S-S-G [SEQ. ID. NO. 7], G-P-K-K-K-R-K-V-G-G-S-E-S-G-G-S-E-S-G [SEQ.ID.NO. 8], K-G-S-E-S-G-G-S-E-S-G [SEQ. ID. NO. 9], and combinations, wherein [MRP] is a molecular recognition part consisting of Cha-C-C-Cha-C-C-Cha-C-C-Cha [SEQ. ID. NO. 1], and wherein Cha is cyclohexyl alanine, C is cysteine, G is glycine, S is serine, E is glutamic acid, P is proline, K is lysine, R is arginine, and V is valine. 40. The bioactivation peptide of claim 39, having the formula [MRP]-[FP.sub.2] wherein [FP.sub.2] is selected from the group consisting of PEG, PEG-biotin, hydrophilic peptide-transferrin, and hydrophilic peptide-tyrosine-DOTA-iodine. 41. The bioactivation peptide of claim 39, selected from the group consisting of NH.sub.2-Cha-C-C-Cha-C-C-Cha-C-C-Cha-carboxamide [SEQ. ID. NO. 1], acetylated-Cha-C-C-Cha-C-C-Cha-C-C-Cha-carboxamide [SEQ. ID. NO. 1], NH.sub.2-G-S-E-S-G-G-S-E-S-G-Cha-C-C-Cha-C-C-Cha-C-C-Cha-carboxamide [SEQ. ID. NO. 2], acetylated-G-S-E-S-G-G-S-E-S-G-Cha-C-C-Cha-C-C-Cha-C-C-Cha-carboxamide [SEQ. ID. NO. 10], acetylated-G-S-S-S-G-G-S-S-S-G-Cha-C-C-Cha-C-C-Cha-C-C-Cha-carboxamide [SEQ. ID. NO. 3], acetylated-G-P-K-K-K-R-K-V-G-G-S-E-S-G-G-S-E-S-G-Cha-C-C-Cha-C-C-Cha-C-C-- Cha-carboxamide [SEQ. ID. NO. 4], acetylated-K-G-S-E-S-G-G-S-E-S-G-Cha-C-C-Cha-C-C-Cha-C-C-Cha-carboxamide [SEQ. ID. NO. 5], and biotin-Cha-C-C-Cha-C-C-Cha-C-C-Cha-carboxamide [SEQ. ID. NO. 1]. 42. The bioactivated particle according to claim 1, wherein the at least one bioactivation peptide is selected from the group consisting of NH.sub.2-Cha-C-C-Cha-C-C-Cha-C-C-Cha-carboxamide [SEQ. ID. NO. 1], acetylated-Cha-C-C-Cha-C-C-Cha-C-C-Cha-carboxamide [SEQ. ID. NO. 1], NH.sub.2-G-S-E-S-G-G-S-E-S-G-Cha-C-C-Cha-C-C-Cha-C-C-Cha-carboxamide [SEQ. ID. NO. 2], acetylated-G-S-E-S-G-G-S-E-S-G-Cha-C-C-Cha-C-C-Cha-C-C-Cha-carboxamide [SEQ. ID. NO. 10], acetylated-G-S-S-S-G-G-S-S-S-G-Cha-C-C-Cha-C-C-Cha-C-C-Cha-carboxamide [SEQ. ID. NO. 3], acetylated-G-P-K-K-R-K-V-G-G-S-E-S-G-G-S-E-S-G-Cha-C-C-Cha-C-C-Cha-C-C-Ch- a-carboxamide [SEQ. ID. NO. 4], acetylated-K-G-S-E-S-G-G-S-E-S-G-Cha-C-C-Cha-C-C-Cha-C-C-Cha-carboxamide [SEQ. ID. NO. 5], and biotin-Cha-C-C-Cha-C-C-Cha-C-C-Cha-carboxamide [SEQ. ID. NO. 1], wherein G is glycine, S is serine, E is glutamic acid, P is proline, K is lysine, R is arginine, and V is valine. 43. The bioactivation peptide according to claim 17, selected from the group consisting of NH.sub.2-Cha-C-C-Cha-C-C-Cha-C-C-Cha-carboxamide [SEQ. ID. NO. 1], acetylated-Cha-C-C-Cha-C-C-Cha-C-C-Cha-carboxamide [SEQ. ID. NO. 1], NH.sub.2-G-S-E-S-G-G-S-E-S-G-Cha-C-C-Cha-C-C-Cha-C-C-Cha-carboxamide [SEQ. ID. NO. 2], acetylated-G-S-E-S-G-G-S-E-S-G-Cha-C-C-Cha-C-C-Cha-C-C-Cha-carboxamide [SEQ. ID. NO. 10], acetylated-G-S-S-S-G-G-S-S-S-G-Cha-C-C-Cha-C-C-Cha-C-C-Cha-carboxamide [SEQ. ID. NO. 3], acetylated-G-P-K-K-K-R-K-V-G-G-S-E-S-G-G-S-E-S-G-Cha-C-C-Cha-C-C-Cha-C-C-- Cha-carboxamide [SEQ. ID. NO. 4], acetylated-K-G-S-E-S-G-G-S-E-S-G-Cha-C-C-Cha-C-C-Cha-C-C-Cha-carboxamide [SEQ. ID. NO. 5], and biotin-Cha-C-C-Cha-C-C-Cha-C-C-Cha-carboxamide [SEQ. ID. NO. 1], wherein G is glycine, S is serine, E is glutamic acid, P is proline, K is lysine, R is arginine, and V is valine.

Details for Patent 7,998,923

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	09/25/1998		2022-05-07
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	02/10/2017		2022-05-07