Patent US4732974A successfully refreshed from Google Patents.
US4732974A
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Metal ion labeling of carrier molecules
Assignee: Mallinckrodt Inc
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Filing: 1986-03-05
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Granted: 1988-03-22
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Expires: 2006-03-05
Abstract
Abstract A conjugate of a protein or polypeptide and a metal ion is prepared by reacting a metal ion transfer complex comprising a chelate of 4,5-dihydroxyl-m-benzenedisulfonic acid or a salt thereof with a protein or polypeptide that is covalently bound to an exogenous chelating group having a greater affinity than 4,5-dihydroxyl-m-benzenedisulfonic acid for the metal ion.
Inventors
- 👤 Robert A. Nicolotti
- 👤 Alan R. Ketring
- 👤 Koon Y. Pak
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-06 20:09
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; A61K51/1093; C; C07; C07K; C07K1/00; C07K1/107; C07K1/1072; C07K1/1077; A61K2121/00; A61K2123/00
Claims Analysis
Total Claims: 13
Claim 1
Independent Claim
87 words
A method of preparing a conjugate of a protein or polypeptide and a metal ion which comprises reacting a metal ion transfer complex comprising a chelate of 4,5-dihydroxyl-m-benzenedisulfonic acid or a salt thereof and a metal ion with a protein or polypeptide that is covalently bound to an exogenous chelating group, said exogenous chelating group having a greater chelating affinity than 4,5-dihydroxyl-m-benzenedisulfonic acid for the metal ion, the reaction being carried out in an aqueous medium at a pH at which the protein or polypeptide is stable.
Claim 2
Independent Claim
87 words
A method of preparing a conjugate of a protein or polypeptide and a metal ion which comprises reacting a metal ion transfer complex comprising a chelate of 4,5-dihydroxyl-m-benzenedisulfonic acid or a salt thereof and a metal ion with a protein or polypeptide that is covalently bound to an exogenous chelating group, said exogenous chelating group having a greater chelating affinity than 4,5-dihydroxyl-m-benzenedisulfonic acid for the metal ion, the reaction being carried out in an aqueous medium at a pH at which the protein or polypeptide is stable.
Claim 3
Dependent Claim
18 words
A method as claimed in claim 1, wherein the protein or polypeptide is an antibody or fragment thereof.
Claim 4
Dependent Claim
22 words
A method as claimed in claim 1, wherein the protein or polypeptide is an antibody or fragment thereof to a tumor-associated antigen.
Claim 5
Dependent Claim
21 words
A method as claimed in claim 1, wherein the protein or polypeptide is an antibody or fragment thereof to carcinoembryonic antigen.
Claim 6
Dependent Claim
71 words
A method as claimed in claim 1, wherein the metal ion is selected from the group consisting of Mg, Al, Ca, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Ga, Sr, Y, Zr, Mo, Tc, Pd, Cd, In, Sn, Sb, Ba, Hf, W, Re, Hg, Tl, Rh, Pb, Bi, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Th, U and Pu and isotopes thereof.
Claim 7
Dependent Claim
24 words
A method as claimed in claim 1, wherein the metal ion is selected from the group consisting of indium, gallium, technetium and isotopes thereof.
Claim 8
Independent Claim
113 words
A method of preparing a conjugate of a protein or polypeptide and a technetium ion which comprises: (a) reacting 4,5-dihydroxyl-m-benzenedisulfonic acid and pertechnetate ions in an aqueous reaction medium; (b) electrolytically reducing the pertechnetate ions in the reaction medium of step (a) to an oxidation state less than +7; and (c) reacting the chelate of reduced technetium produced in steps (a) and (b) with a protein or polypeptide that is covalently bound to an exogenous chelating group, said exogenous chelating group having a greater chelating affinity than 4,5-dihydroxyl-m-benzenedisulfonic acid for the technetium ion, the reaction being carried out in an aqueous medium at a pH at which the protein or polypeptide is stable.
Claim 9
Independent Claim
113 words
A method of preparing a conjugate of a protein or polypeptide and a technetium ion which comprises: (a) reacting 4,5-dihydroxyl-m-benzenedisulfonic acid and pertechnetate ions in an aqueous reaction medium; (b) electrolytically reducing the pertechnetate ions in the reaction medium of step (a) to an oxidation state less than +7; and (c) reacting the chelate of reduced technetium produced in steps (a) and (b) with a protein or polypeptide that is covalently bound to an exogenous chelating group, said exogenous chelating group having a greater chelating affinity than 4,5-dihydroxyl-m-benzenedisulfonic acid for the technetium ion, the reaction being carried out in an aqueous medium at a pH at which the protein or polypeptide is stable.
Claim 10
Dependent Claim
13 words
A method as claimed in claim 7, wherein the technetium ion is Tc-99m.
Claim 11
Dependent Claim
25 words
A method as claimed in claim 2, 3 or 4, wherein the metal ion is selected from the group consisting of In-111, Ga-67 and Tc-99m.
Claim 12
Dependent Claim
55 words
A method as claimed in claim 2, 3 or 4, wherein the protein or polypeptide is an antibody or fragment thereof which has been covalently joined to an exogenous chelating group by reacting it with a coupling agent of the formula ##STR16## wherein R is a divalent organic radical and R' is a chelating group.
Claim 13
Dependent Claim
157 words
A method as claimed in claim 1, wherein the protein or polypeptide has been covalently joined to an exogenous chelating agent by reacting it with a coupling agent selected from the group consisting of ##STR17## wherein R 1 , R 2 and R 3 are the same or different and each represents a radical selected from the group consisting of alkyls having from 1 to 6 carbon atoms, aryls having from 6 to 8 carbon atoms and aralkyls having from 7 to 9 carbon atoms, any of which can be substituted with one or more hydroxyl, alkoxy, carboxy or sulfonate groups; n is either 1 or 2; AA are independently α or β amino acid residues linked to each other by amide bonds; i is an integer of from 2 to 6; and X is an activating group capable of forming an amide bond with an ε-amino group or an amino terminus of the protein or polypeptide.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 1991-03-22 | 1991-09-21 | 1992-03-22 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1995-03-22 | 1995-09-21 | 1996-03-22 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1999-03-22 | 1999-09-21 | 2000-03-22 | $7700.00 | Window Closed / Lapsed |