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EP0336678A2
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EP
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Method for radiolabeling proteins
Assignee: Immunomedics Inc
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Filing: 1989-04-03
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Granted: —
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Expires: 2009-04-03
Abstract
Abstract A protein containing at least one pendant sulfhydryl group is directly radiolabeled with a radiometal which binds tightly to sulfhydryl groups, using one or more pendant sulfhydryl groups on the protein as endogenous ligands and optionally using an exogenous ligand which binds tightly to the radiometal ion further to stabilize the chelate.
Inventors
- 👤 Dan Shochat
- 👤 Hans J. Hansen
- 👤 Robert Sundoro-Wu
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-11-08 06:03
CPC Classifications
G; G01; G01N; G01N33/00; G01N33/48; G01N33/50; G01N33/53; G01N33/531; G01N33/532; G01N33/534; A; A61; A61K; A61K51/00; A61K51/02; A61K51/04; A61K51/08; A61K51/10; A61K51/1045; A61K51/1048; A61K2123/00; Y; Y10; Y10S; Y10S436/00; Y10S436/804
Claims Analysis
Total Claims: 22
Claim 1
Independent Claim
48 words
A method for direct radiolabeling of a preotein, comprising the step of contacting a solution of a protein containing at least one pendant sulfhydryl group with a solution of radiometal ions of a radionuclide which tightly binds to sulfhydryl groups, and recovering the resultant solution of radiolabeled protein.
Claim 2
Independent Claim
48 words
A method for direct radiolabeling of a preotein, comprising the step of contacting a solution of a protein containing at least one pendant sulfhydryl group with a solution of radiometal ions of a radionuclide which tightly binds to sulfhydryl groups, and recovering the resultant solution of radiolabeled protein.
Claim 3
Dependent Claim
20 words
A method as claimed in claim 1, wherein said protein solution is substantially free of low molecular weight thiol compounds.
Claim 4
Dependent Claim
67 words
A method as claimed in claim 1 or 2, wherein said protein solution is produced by passing a solution of a protein containing at least one pendant sulfhydryl group, said solution also containing low molecular weight molecules or ions for reducing disulfide groups and for stabilizing sulfhydryl groups, through a sizing column to remove said low molecular weight molecules and ions, and recovering the resultant protein solution.
Claim 5
Dependent Claim
40 words
A method as claimed in claim 1, 2 or 3, wherein the protein is an antibody or antibody fragment, the antibody fragment optionally being produced by reduction of disulfide bonds in a higher molecular weight antibody or antibody fragment precursor.
Claim 6
Dependent Claim
46 words
A method as claimed in claim 4, wherein the antibody fragment is (i) a monovalent Fab-SH or Fab′-SH fragment produced by reductive cleavage of a divalent F(ab)₂ or F(ab′)2 precursor fragment or (ii) a monovalent Fabc′-SH light/heavy chain fragment produced by reductive cleavage of whole immunoglobulin.
Claim 7
Dependent Claim
28 words
A method as claimed in claim 4, wherein the antibody or antibody fragment is partially reduced whole immunoglobulin, partially reduced F(ab′)₂, partially reduced F(ab)2, Fab′-SH, Fab-SH or Fabc′-SH.
Claim 8
Independent Claim
25 words
A method as claimed in any one of claims 1 to 6, wherein said radionuclide is Re-186, Re-188, Cu-67, Hg-197, Pb-203, Bi-212 or, preferably, Tc-99m.
Claim 9
Independent Claim
27 words
A method as claimed in any one of claims 1 to 7, wherein said contacting is effected in the presence of a transchelator for reduced pertechnetate ions.
Claim 10
Independent Claim
37 words
A method as claimed in any one of claims 1 to 8, wherein said resultant radiolabeled protein is contacted with an exogenous ligand which tightly binds to said radiometal ions, and recovering the resultant stabilized, radiometallabeled protein.
Claim 11
Independent Claim
117 words
A method as claimed in any one of claims 1 to 9, wherein said protein solution contains low molecular weight molecules or ions for reducing or stabilizing the sulfhydryl groups, said solution is applied to a molecular sizing gel column to which has been applied a solution of radiometal ions of said radionuclide which tightly binds to sulfhydryl groups, and said column is eluted, after which the resultant solution of radiometal-labeled protein, substantially free of low molecular weight molecules and unbound radiometal ions is recovered, and wherein said sizing gel column may further contain a transchelator for said radiometal ions and wherein said column may be eluted with a solution of a transchelator for said radiometal ions.
Claim 12
Dependent Claim
34 words
A method as claimed in claim 9, wherein said exogenous ligand: (i) is 6-mercaptopurine or 2-aminoethanethiol; and/or (ii) includes a sugar, dextran or polyol moiety to render it hypoimmunogenic; and/or (iii) includes a radiosensitizer.
Claim 13
Independent Claim
29 words
A method as claimed in any one of claims 1 to 11, wherein said radionuclide is a high energy beta emitter or an alpha emitter for cytotoxic targeted therapy.
Claim 14
Dependent Claim
43 words
A radiometal-labeled protein, comprising a protein containing at least one pendant sulfhydryl group bound to a radiometal ion of a radionuclide that binds tightly to sulfhydryl groups, said radiometal ion also being bound to an exogenous ligand which tightly binds to sulfhydryl groups.
Claim 15
Dependent Claim
43 words
A radiometal-labeled protein, comprising a protein containing at least one pendant sulfhydryl group bound to a radiometal ion of a radionuclide that binds tightly to sulfhydryl groups, said radiometal ion also being bound to an exogenous ligand which tightly binds to sulfhydryl groups.
Claim 16
Dependent Claim
25 words
A radiolabeled protein as claimed in claim 13, wherein said protein is an antibody or antibody fragment, such as a labeled Fab′ or Fab fragment.
Claim 17
Dependent Claim
15 words
A radiolabeled protein as claimed in claim 13 or 14, wherein said radiometal is Tc-99m.
Claim 18
Dependent Claim
34 words
A kit suitable for radiolabeling a protein with Tc-99m, comprising, in suitable containers: (a) a protein containing at least one free sulfhydryl group; and (b) a source of stannous ions for reduction of pertechnetate.
Claim 19
Dependent Claim
34 words
A kit suitable for radiolabeling a protein with Tc-99m, comprising, in suitable containers: (a) a protein containing at least one free sulfhydryl group; and (b) a source of stannous ions for reduction of pertechnetate.
Claim 20
Dependent Claim
23 words
A kit as claimed in claim 16, wherein said protein is an antibody or antibody fragment, such as (optionally lyophilized) Fab-SH or Fab′-SH.
Claim 21
Dependent Claim
21 words
A kit as claimed in claim 16 or 17, wherein said source of stannous ions is stannous chloride or stannous glucoheptonate.
Claim 22
Dependent Claim
23 words
A kit as claimed in claim 16, 17 or 18, which further comprises a transchelator for reduced pertechnetate, optionally bound to said gel.
References Cited (Backward Citations)
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