Patent US1592462A successfully refreshed from Google Patents.
US4877868A
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Radionuclide antibody coupling
Assignee: Poniard Pharmaceuticals Inc
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Filing: 1986-03-12
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Granted: 1989-10-31
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Expires: 2006-03-12
Abstract
Abstract Metal radionuclide labeled proteinaceous substances which contain, in their native states, disulfide (cysteine) linkages, which find use in diagnosis and treatment of a variety of pathologic conditions. The radionuclide labeled proteinaceous substances of the present invention are formed by the treatment of the proteinaceous substance of interest with a disulfide reducing agent, followed by reaction of the reduced proteinaceous substance ("H-treated product") with a suitable radionuclide species containing, for example, 99mTc, 186Re and 188Re, or 67Cu. It has been found that the H-treated products, e.g., antibodies, react specifically with radionuclide species to form stable radionuclide labeled antibodies or other radiolabeled products. The H-treated products may be stabilized or modified in a variety of ways prior to and subsequent to complexation with the metal radionuclide.
Inventors
- 👤 John M. Reno
- 👤 Becky J. Bottino
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-28 12:02
CPC Classifications
A; A61; A61K; A61K51/00; A61K51/02; A61K51/04; A61K51/08; A61K51/081; A61K51/10; A61K2121/00; A61K2123/00; Y; Y10; Y10S; Y10S424/00; Y10S424/06; Y10S435/00; Y10S435/81
Claims Analysis
Total Claims: 30
Claim 1
Independent Claim
69 words
A method of preparing a metal radionuclide-labeled protein from a protein precursor having at least oe disulfide linkage, the method comprising: reacting said protein precursor with a disulfide reducing agent to form a dimercaptoprotein; reacting said dimercaptoprotein with a divalent or trivalent cation to yield a cation-derivatized protien; and combining said cation-derivatized protein with 99m Tc, 186 Re, 188 Re or 67 Cu to form said metal radionuclide-labeled protein.
Claim 2
Independent Claim
69 words
A method of preparing a metal radionuclide-labeled protein from a protein precursor having at least oe disulfide linkage, the method comprising: reacting said protein precursor with a disulfide reducing agent to form a dimercaptoprotein; reacting said dimercaptoprotein with a divalent or trivalent cation to yield a cation-derivatized protien; and combining said cation-derivatized protein with 99m Tc, 186 Re, 188 Re or 67 Cu to form said metal radionuclide-labeled protein.
Claim 3
Dependent Claim
20 words
The method of claim 1 wherein said protein precursor is a monoclonal antibody polyclonal antibody or specific binding fragment thereof.
Claim 4
Independent Claim
10 words
The method of claim1 wherein the reducing agent is dithiothreitol.
Claim 5
Dependent Claim
11 words
The method of claim 1 wherein the cation is zinc ion.
Claim 6
Dependent Claim
33 words
The method of claim 1 further comprising, after the second reacting step, the steps of lyophilizing the cation-derivatized protein and solubilizing the cation-derivatized protein in aqueous buffered medium prior to said combining step.
Claim 7
Dependent Claim
24 words
The method of claim 1 further comprising, after the first reacting step, the step of freeing said dimercaptoprotein of spent and unreacted reducing agent.
Claim 8
Dependent Claim
25 words
The method of claim 1 further comprising, after the second reacting step, the step of freeing said cation-derivatized protein of spent and unreacted reducing agent.
Claim 9
Independent Claim
90 words
A method of preparing a metal radionuclide-labeled protein from a protein precursor having at least one disulfide linkage, the method comprising: reacting said protein precursor with a disulfide reducing agent to form a dimercaptoprotein; stabilizing said dmercaptoprotein against inactivation by reaction of the dimercaptoprotein with a derivatizing agent for mercapto groups, thereby producing a derivatized protein having regenerable mercapto groups; regenerating said mercapto groups, thereby forming a regenerated dimercaptoprotein; and combining said regenerated dimercaptoprotein with 99m Tc, 186 Re, 188 Re or 67 Cu to form said metal radionuclide-labeled protein.
Claim 10
Independent Claim
90 words
A method of preparing a metal radionuclide-labeled protein from a protein precursor having at least one disulfide linkage, the method comprising: reacting said protein precursor with a disulfide reducing agent to form a dimercaptoprotein; stabilizing said dmercaptoprotein against inactivation by reaction of the dimercaptoprotein with a derivatizing agent for mercapto groups, thereby producing a derivatized protein having regenerable mercapto groups; regenerating said mercapto groups, thereby forming a regenerated dimercaptoprotein; and combining said regenerated dimercaptoprotein with 99m Tc, 186 Re, 188 Re or 67 Cu to form said metal radionuclide-labeled protein.
Claim 11
Dependent Claim
12 words
The method of claim 8 wherein the derivatizing agent is cyanate ion.
Claim 12
Dependent Claim
13 words
The method of claim 8 further comprising the step of lyophilizing the dimercaptoprotein.
Claim 13
Dependent Claim
19 words
A product made by the method of any one of claims 1, 2, 3, 4, 5, 6 and 7.
Claim 14
Independent Claim
54 words
A method of preparing a storage-stable metal radionuclide complexing protein comprising reacting a disulfide-containing protein precursor with a disulfide reducing agent to form a dimercaptoprotein; and reacting said dimercaptoprotein with a divalent or trivalent cation to produce a derivatized product, or with a derivatizing agent for mercapto groups to produce a regenerable derivatized product.
Claim 15
Independent Claim
54 words
A method of preparing a storage-stable metal radionuclide complexing protein comprising reacting a disulfide-containing protein precursor with a disulfide reducing agent to form a dimercaptoprotein; and reacting said dimercaptoprotein with a divalent or trivalent cation to produce a derivatized product, or with a derivatizing agent for mercapto groups to produce a regenerable derivatized product.
Claim 16
Dependent Claim
20 words
The method of claim 12 wherein said protein precursor is a monoclonal antibody, polyclonal antibody or specific bonding fragment thereof.
Claim 17
Dependent Claim
11 words
The method of claim 12 wherein the reducing agent is dithiothreitol.
Claim 18
Dependent Claim
19 words
The method of claim 12 further comprising the step of lyophilizing the derivatized product or the regenerable derivatized product.
Claim 19
Dependent Claim
24 words
The method of claim 12 further comprising, after the first reacting step, the step of freeing said dimercaptoprotein of spent and unreacted reducing agent.
Claim 20
Dependent Claim
30 words
The method of claim 12 further comprising, after the second reacting step, the step of freeing said derivatized product or said regenerable derivatized product of spent and unreacted reducing agent.
Claim 21
Dependent Claim
16 words
A product made by the method of any one of claims 12, 13, 14, or 15.
Claim 22
Dependent Claim
23 words
A kit comprising a sterile package containing the product made by the method of any one of claims 12, 13, 14, or 15.
Claim 23
Independent Claim
56 words
A method for direct technetium-99m labeling of a disulfide-containing protein, comprising: forming a labile, soluble complex of reduced technetium-99m; reacting said disulfide-containing protein with dithiothreitol to form a dimercaptoprotein; and combining said dimercaptoprotein with said labile, soluble complex of reduced technetium-99m in a reaction solution or buffer having a pH from about 5 to about 10.
Claim 24
Independent Claim
56 words
A method for direct technetium-99m labeling of a disulfide-containing protein, comprising: forming a labile, soluble complex of reduced technetium-99m; reacting said disulfide-containing protein with dithiothreitol to form a dimercaptoprotein; and combining said dimercaptoprotein with said labile, soluble complex of reduced technetium-99m in a reaction solution or buffer having a pH from about 5 to about 10.
Claim 25
Dependent Claim
21 words
The method of claim 20 wherein the protein is a monoclonal antibody, a polyclonal antibody or a specific binding fragment thereof.
Claim 26
Dependent Claim
11 words
A product made by the method of claim 20 or 21.
Claim 27
Independent Claim
63 words
A method for directly labeling a storage-stable dimercaptoprotein with a metal radionuclide, comprising: reacting a disulfide-containing protein with a reducing agent to form a dimercaptoprotein; lyophilizing said dimercaptoprotein, thereby forming a storage-stable dimercaptoprotein; rehydrating said storage-stable dimercaptoprotein, thereby forming a regenerated dimercaptoprotein; and combining said regenerated dimercaptoprotein with 99m Tc, 186 Re, 188 Re or 67 Cu to obtain said metal radionuclide-labeled protein.
Claim 28
Independent Claim
63 words
A method for directly labeling a storage-stable dimercaptoprotein with a metal radionuclide, comprising: reacting a disulfide-containing protein with a reducing agent to form a dimercaptoprotein; lyophilizing said dimercaptoprotein, thereby forming a storage-stable dimercaptoprotein; rehydrating said storage-stable dimercaptoprotein, thereby forming a regenerated dimercaptoprotein; and combining said regenerated dimercaptoprotein with 99m Tc, 186 Re, 188 Re or 67 Cu to obtain said metal radionuclide-labeled protein.
Claim 29
Dependent Claim
21 words
The method of claim 23 wherein the protein is a monoclonal antibody, a polyclonal antibody or a specific binding fragment thereof.
Claim 30
Dependent Claim
11 words
The method of claim 23 wherein the reducing agent is dithiothreitol.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1992-10-30 | 1993-05-01 | 1993-10-31 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1996-10-30 | 1997-05-01 | 1997-10-31 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2000-10-30 | 2001-05-01 | 2001-10-31 | $7700.00 | Window Closed / Lapsed |