EP0251494A2
Expired / Lapsed
EP
⏱️ 0.0 years remaining
Therapeutic or radiodiagnostic compound
Assignee: Leland Stanford Junior University
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Filing: 1987-05-29
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Granted: —
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Expires: 2007-05-29
Abstract
Abstract A system for localizing a diagnostic or therapeutic agent to an internal target site. The system includes (1) a biotinylated compound, (2) an avidin-containing binding protein capable of localizing selectively at the target tissue, when administered parenterally, and (3) a clearing agent which can bind to and cross-link the binding protein, to form a protein aggregate which is readily cleared from the subject's bloodstream. In practicing the method of the invention, the binding protein is administered to the subject parenterally, and allowed to localize at the target site, typically within 1-4 days. This is followed by a chase with the clearing agent to remove circulating, but not target-localized binding protein. When the biotinylated compound is administered, binding of the compound to the localized binding protein, and rapid clearance of unbound compound by the kidneys, results in selective localization of the compound at the target site.
Inventors
- 👤 David A. Goodwin
- 👤 Claude Meares
- 👤 Michael Mccall
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-10-23 10:25
CPC Classifications
B; B82; B82Y; B82Y5/00; A; A61; A61K; A61K47/00; A61K47/50; A61K47/51; A61K47/68; A61K47/6891; A61K47/6897; A61K47/6898; A61K51/00; A61K51/02; A61K51/04; A61K51/08; A61K51/10; A61K51/1093; A61K2123/00
Claims Analysis
Total Claims: 13
Claim 1
Independent Claim
128 words
A method of preparing a system for administering a diagnostic or therapeutic agent to an internal target site of a subject, the method comprising: (a) derivatizing a compound comprising, or for containing, the agent with biotin and forming a biotinylated compound containing the agent; (b) derivatizing a protein comprising avidin with an antibody or antibody fragment to form a binding protein capable of localizing selectively at the target tissue when administered to the subject parenterally; (c) derivatizing a human protein with biotin to form a clearing agent capable of reacting with the binding protein when circulating in the bloodstream of the subject to form a macromolecular aggregate which is cleared by the subject's reticuloendothelial system; (d) providing the products of steps (a), (b) and (c) as said system.
Claim 2
Independent Claim
128 words
A method of preparing a system for administering a diagnostic or therapeutic agent to an internal target site of a subject, the method comprising: (a) derivatizing a compound comprising, or for containing, the agent with biotin and forming a biotinylated compound containing the agent; (b) derivatizing a protein comprising avidin with an antibody or antibody fragment to form a binding protein capable of localizing selectively at the target tissue when administered to the subject parenterally; (c) derivatizing a human protein with biotin to form a clearing agent capable of reacting with the binding protein when circulating in the bloodstream of the subject to form a macromolecular aggregate which is cleared by the subject's reticuloendothelial system; (d) providing the products of steps (a), (b) and (c) as said system.
Claim 3
Dependent Claim
16 words
A method as claimed in claim 1 wherein the protein comprising avidin is avidin or streptavidin.
Claim 4
Dependent Claim
34 words
A method as claimed in claim 1 or claim 2, wherein the biotinylated compound containing the agent is a biotinylated chelate compound complexed with a metal ion to form a stable metal chelate complex.
Claim 5
Dependent Claim
20 words
A method as claimed in claim 3 wherein the chelate compound is a metal chelate of 1-phenyl or 1-benzyl EDTA.
Claim 6
Dependent Claim
25 words
A method as claimed in claim 4 wherein the epitope-chelate compound is a metal chelate having a thiobutane spacer arm linked to the benzyl moiety.
Claim 7
Independent Claim
46 words
A method as claimed in any one of claims 3 to 5 wherein the metal chelate is a chelate of: (a) ⁹⁰Y, ¹⁹⁷Hg or ⁶⁷Cu, or (b) ¹¹¹In, ⁶⁷Ga, ⁶⁴Cu, 99m Tc, ⁶⁸Ga, ⁶²Zn, ⁶⁷Cu, ¹⁹⁷Hg, ⁹⁷Ru, ⁵⁷Co or ⁵³Co, or (c) iron, copper or ruthenium.
Claim 8
Independent Claim
23 words
A method as claimed in any one of the preceding claims, wherein the binding protein is selectively permeable across walls of tumor-supplying capillaries.
Claim 9
Independent Claim
153 words
A method of preparing a system for administering a diagnostic or therapeutic agent to an internal target site of a subject, the method comprising: (a) reacting the N-hydroxysuccinimide ester of biotin (biotin-NHS) with an amine group in a compound comprising, or for containing, the agent to form a biotinylated compound and, if necessary, combining the biotinylated compound with the agent; (b) condensing or coupling an antibody or antibody fragment with avidin or steptavidin to form a binding protein capable of localising selectively at the target tissue when administered to the subject parenterally; (c) reacting a human protein with biotin-NHS or condensing a human protein with biotin to form a clearing agent capable of reacting with the binding protein when circulating in the bloodstream of the subject for form a macromolecular aggregate which is cleared by the subject's reticuloendothelial system; and (d) providing the products of steps (a), (b) and (c) as a kit.
Claim 10
Independent Claim
153 words
A method of preparing a system for administering a diagnostic or therapeutic agent to an internal target site of a subject, the method comprising: (a) reacting the N-hydroxysuccinimide ester of biotin (biotin-NHS) with an amine group in a compound comprising, or for containing, the agent to form a biotinylated compound and, if necessary, combining the biotinylated compound with the agent; (b) condensing or coupling an antibody or antibody fragment with avidin or steptavidin to form a binding protein capable of localising selectively at the target tissue when administered to the subject parenterally; (c) reacting a human protein with biotin-NHS or condensing a human protein with biotin to form a clearing agent capable of reacting with the binding protein when circulating in the bloodstream of the subject for form a macromolecular aggregate which is cleared by the subject's reticuloendothelial system; and (d) providing the products of steps (a), (b) and (c) as a kit.
Claim 11
Dependent Claim
93 words
(a) A method as claimed in claim 8 wherein in step (a) the compound reacted with biotin-NHS is an EDTA derivative, especially a compound of the formula (b) A method as claimed in claim 8 or claim 9(a) wherein in step (b) the antibody or antibody fragment is condensed or coupled with avidin or streptavidin using 2-imminothiolane and succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate as cross-linking reagents or a soluble carbodiimide or di-N-hydroxysuccinimide compound as coupling agent, (c) a method as claimed in claim 8, claim 9(a) or Claim 9(b) wherein the human protein is human transferrin.
Claim 12
Dependent Claim
35 words
A modification of a method as claimed in any one of claims 1, 3 to 6 when dependent on claim 1, 8 or 9, wherein step (b) comprises providing avidin or steptavidin as binding protein.
Claim 13
Dependent Claim
210 words
(A) A method of preparing a substance for use in administering a diagnostic of therapeutic agent to an internal target site of a subject by sequentially administering parenterally to the patient: (a) a biotinylated compound containing the agent derivatised with biotin, (b) an avidin-containing binding protein capable of localising selectively at the target tissue when administered to the subject, and (c) a clearing agent capable of reacting with the binding protein when circulating in the bloodstream of the subject to form a macromolecular aggregate which is cleared by the subject's reticuloendothelial system, the method comprising: (i) performing a method as defined in any one of claims 1(a), 3 to 6, 8a or 9a to prepare the biotinylated compound containing the agent derivalised with biotin, or (ii) performing a method as defined in any one of claims 1(b), 2, 7, 8b or 9b to prepare the avidin-containing binding protein, or (iii) performing a method as defined in any one of claims 1(c), 8(c) or 9(c) to prepare the clearing agent; or (B) the use of a method defined in (i), (ii) or (iii) above for preparing, respectively, the resultant biotinylated compound, binding protein or clearing agent for use in sequentially administering parenterally to the patient substances (a), (b) and (c) above.
References Cited (Backward Citations)
No citation records indexed.
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