Patent US5061641A successfully refreshed from Google Patents.
US5061641A
Expired / Lapsed
US
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Method for radiolabeling proteins
Assignee: Immunomedics Inc
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Filing: 1988-04-01
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Granted: 1991-10-29
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Expires: 2008-04-01
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 sulfhydral groups on the protein as endogenous ligands and optionally using an exogenous ligand which binds tightly to the radiometal ion to further stabilize the chelate.
Inventors
- 👤 Dan Shochat
- 👤 Hans J. Hansen
- 👤 Robert S. Wu
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-03 12:53
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: 37
Claim 1
Independent Claim
68 words
A method for direct radiolabeling of a protein, comprising the steps of: (a) 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 (b) contacting the resultant radiolabeled protein with an exogenous ligand which tightly binds to said radiometal ions, and recovering the resultant solution of stabilized radiolabeled protein.
Claim 2
Independent Claim
68 words
A method for direct radiolabeling of a protein, comprising the steps of: (a) 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 (b) contacting the resultant radiolabeled protein with an exogenous ligand which tightly binds to said radiometal ions, and recovering the resultant solution of stabilized radiolabeled protein.
Claim 3
Dependent Claim
18 words
The method of claim 1, wherein said protein solution is substantially free of low molecular weight thiol compounds.
Claim 4
Dependent Claim
63 words
The method of claim 1, 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
14 words
The method of claim 1, wherein the protein is an antibody or antibody fragment.
Claim 6
Dependent Claim
28 words
The method of claim 4, wherein the protein is an antibody fragment produced by reduction of disulfide bonds in a higher molecular weight antibody or antibody fragment precursor.
Claim 7
Dependent Claim
30 words
The method of claim 5, wherein the antibody fragment is a monovalent Fab--SH or Fab'--SH fragment produced by reductive cleavage of a divalent F(ab) 2 or F(ab') 2 precursor fragment.
Claim 8
Dependent Claim
23 words
The method of claim 5, wherein the antibody fragment is a monovalent Fabc'--SH light/heavy chain fragment produced by reductive cleavage of whole immunoglobulin.
Claim 9
Dependent Claim
24 words
The method of claim 6, wherein said radionuclide is selected from the group consisting of Tc-99 m, Re-186, Re-188, Cu-67, Hg-197, Pb-203 and Bi-212.
Claim 10
Dependent Claim
20 words
The method of claim 8, wherein said contacting is effected in the presence of a transchelator for reduced pertechnetate ions.
Claim 11
Dependent Claim
23 words
The method of claim 1, wherein said radionuclide is selected from the group consisting of Tc-99m, Re-186, Re-188, Cu-67, Hg-197, Pb-203 and Bi-212.
Claim 12
Dependent Claim
16 words
The method of claim 1, wherein said exogenous ligand is a monodentate sulfur or phosphorus compound.
Claim 13
Dependent Claim
19 words
The method of claim 11, wherein said compound is a C 1-30 mercaptoalkane, thioester, thioamide, thiourea, phosphine, or phosphonate.
Claim 14
Dependent Claim
17 words
The method of claim 1, wherein said exogenous ligand is a bidentate S/S, S/N or P/N ligand.
Claim 15
Dependent Claim
13 words
The method of claim 14, wherein said exogenous ligand is 6-mercaptopurine or 2-aminoethanethiol.
Claim 16
Dependent Claim
18 words
The method of claim 1, wherein said exogenous ligand is a tridentate S/S/N, S/N/N, P/P/N or P/N/N ligand.
Claim 17
Dependent Claim
22 words
The method of claim 1, wherein said exogenous ligand has a sugar, dextran or polyol moiety joined thereto to render it hypoimmunogenic.
Claim 18
Dependent Claim
22 words
The method of claim 1, wherein said radionuclide is a high energy beta emitter or an alpha emitter for cytotoxic targeted therapy.
Claim 19
Dependent Claim
14 words
The method of claim 17, wherein said exogenous ligand has a radiosensitizer joined thereto.
Claim 20
Dependent Claim
11 words
A stabilized radiolabeled protein labeled by the method of claim 1.
Claim 21
Dependent Claim
16 words
The stabilized radiolabeled protein of claim 19, wherein said protein is an antibody or antibody fragment.
Claim 22
Dependent Claim
17 words
The stabilized radiolabeled antibody or fragment of claim 20, which is a labeled Fab' or Fab fragment.
Claim 23
Dependent Claim
27 words
The stabilized radiolabeled antibody or fragment of claim 20, wherein said radiometal is selected from the group consisting of Tc-99m, Re-186, Re-188, Cu-67, Hg-197, Pb-203 and Bi-212.
Claim 24
Dependent Claim
13 words
The stabilized radiolabeled antibody fragment of claim 21, wherein said radiometal is Tc-99m.
Claim 25
Dependent Claim
45 words
A stabilized radiolabeled 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 said radiometal ion.
Claim 26
Dependent Claim
45 words
A stabilized radiolabeled 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 said radiometal ion.
Claim 27
Dependent Claim
16 words
The stabilized radiolabeled protein of claim 24, wherein said protein is an antibody or antibody fragment.
Claim 28
Dependent Claim
17 words
The stabilized radiolabeled antibody or fragment of claim 25, which is a labeled Fab' or Fab fragment.
Claim 29
Dependent Claim
27 words
The stabilized radiolabeled antibody or fragment of claim 25, wherein said radiometal is selected from the group consisting of Tc-99m, Re-186, Re-188, Cu-67, Hg-197, Pb-203 and Bi-212.
Claim 30
Dependent Claim
13 words
The stabilized radiolabeled antibody fragment of claim 26, wherein said radiometal is Tc-99m.
Claim 31
Dependent Claim
24 words
The stabilized radiolabeled protein of claim 24, wherein said exogenous ligand has a sugar, dextran or polyol moiety joined thereto to render it hypoimmunogenic.
Claim 32
Dependent Claim
34 words
The stabilized radiolabeled protein of claim 24, wherein said radionuclide is a high energy beta emitter or an alpha emitter for cytotoxic targeted therapy, and wherein said exogenous ligand has a radiosensitizer joined thereto.
Claim 33
Dependent Claim
18 words
The stabilized radiolabeled protein of claim 24, wherein said exogenous ligand is a monodentate sulfur or phosphorus compound.
Claim 34
Dependent Claim
21 words
The stabilized radiolabeled protein of claim 31, wherein said compound is a C 1-30 mercaptoalkane, thioester, thioamide, thiourea, phosphine, or phosphonate.
Claim 35
Dependent Claim
19 words
The stabilized radiolabeled protein of claim 24, wherein said exogenous ligand is a bidentate S/S, S/N or P/N ligand.
Claim 36
Dependent Claim
20 words
The stabilized radiolabeled protein of claim 24, wherein said exogenous ligand is a tridentate S/S/N, S/N/N, P/P/N or P/N/N ligand.
Claim 37
Dependent Claim
15 words
The stabilized radiolabeled protein of claim 34, wherein said exogenous ligand is 6-mercaptopurine or 2-aminoethanethiol.
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