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US4732864A
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Trace-labeled conjugates of metallothionein and target-seeking biologically active molecules
Assignee: Bristol Myers Squibb Pharma Co
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Filing: 1983-10-06
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Granted: 1988-03-22
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Expires: 2003-10-06
Abstract
Abstract Conjugates of target-seeking biologically active molecules and metallothionein in which all or part of the metal in the metallothionein is suitable for diagnostic or therapeutic applications.
Inventors
- 👤 Glen L. Tolman
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 14:37
CPC Classifications
A; A61; A61K; A61K51/00; A61K51/02; A61K51/04; A61K51/08; A61K51/10; A61K51/1093; A61K47/00; A61K47/50; A61K47/51; A61K47/68; A61K47/6835; A61K47/6887; A61K2121/00; A61K2123/00; Y; Y10; Y10S; Y10S436/00; Y10S436/804; Y10T; Y10T436/00; Y10T436/24
Claims Analysis
Total Claims: 50
Claim 1
Independent Claim
75 words
A conjugate of (a) a target-seeking biologically active molecule selected from the group consisting of antibodies, antibody fragments, hormones, peptides, proteins and drugs which bind to receptors and localize in certain organs, tissues and cells of the mammalian body and (b) metallothionein or metallothionein fragment in which at least a part of the metal in the metallothionein or fragment is a trace-labeled metal having sufficient affinity for the metallothionein or metallothionein fragment to bind thereto.
Claim 2
Dependent Claim
75 words
A conjugate of (a) a target-seeking biologically active molecule selected from the group consisting of antibodies, antibody fragments, hormones, peptides, proteins and drugs which bind to receptors and localize in certain organs, tissues and cells of the mammalian body and (b) metallothionein or metallothionein fragment in which at least a part of the metal in the metallothionein or fragment is a trace-labeled metal having sufficient affinity for the metallothionein or metallothionein fragment to bind thereto.
Claim 3
Dependent Claim
33 words
The conjugate of claim 1 wherein the trace-label metal is selected from the group consisting of Pb, Tc, Ru, Hg, Ag, Au, Pd, Cu, Re, Bi, Pt, W, Co, Ni, Rh and Os.
Claim 4
Dependent Claim
12 words
The conjugate of claim 1 wherein the trace-label metal is a radionuclide.
Claim 5
Dependent Claim
26 words
The conjugate of claim 3 wherein the radionuclide is selected from the group consisting of Tc-99m, Pb-203, Ru-97, Hg-197, Ag-111, Au-198, Pd-103, Cu-67, Re-188, Bi-212, Os-191.
Claim 6
Dependent Claim
24 words
The conjugate of claim 3 wherein the radionuclide is selected from the group consisting of Tc-99m, Hg-197, Ag-111, Au-198, Pd-103, Cu-67, Re-188, and Ru-97.
Claim 7
Dependent Claim
20 words
The conjugate of claim 3 wherein the radionuclide is selected from the group consisting of Tc-99m, Hg-197, Ag-111, and Au-198.
Claim 8
Dependent Claim
21 words
The conjugate of claim 4, 5 or 6 in which the target-seeking biologically active molecule is an antibody or fragment thereof.
Claim 9
Dependent Claim
12 words
The conjugate of claim 7 wherein the antibody is a monoclonal antibody.
Claim 10
Dependent Claim
24 words
The conjugate of claim 8 wherein the monoclonal antibody is selected from the group consisting of anti-THY 1.1 and anti human breast carcinoma B6.2.
Claim 11
Dependent Claim
13 words
The conjugate of claim 9 wherein the metallothionein or metallothionein fragment is mammalian.
Claim 12
Dependent Claim
13 words
The conjugate of claim 7 wherein the metallothionein or metallothionein fragment is mammalian.
Claim 13
Dependent Claim
82 words
A conjugate of (a) a target-seeking biologically active molecule selected from the group consisting of antibodies, antibody fragments, hormones, peptides, proteins and drugs which bind to receptors and localize in certain organs, tissues and cells of the mammalian body and (b) metallothionein or metallothionein fragment in which all metal in the metallothionein or fragment (a) is non-radioactive and (b) has an affinity for metallothionein less than that of the cations selected from the group consisting of Tc, Ag, Au, Hg and Cu.
Claim 14
Dependent Claim
82 words
A conjugate of (a) a target-seeking biologically active molecule selected from the group consisting of antibodies, antibody fragments, hormones, peptides, proteins and drugs which bind to receptors and localize in certain organs, tissues and cells of the mammalian body and (b) metallothionein or metallothionein fragment in which all metal in the metallothionein or fragment (a) is non-radioactive and (b) has an affinity for metallothionein less than that of the cations selected from the group consisting of Tc, Ag, Au, Hg and Cu.
Claim 15
Dependent Claim
11 words
The conjugate of claim 12 wherein the non-radioactive metal is Zn.
Claim 16
Dependent Claim
21 words
The conjugate of claim 12 or 13 in which the target seeking biologically active molecule is an antibody or fragment thereof.
Claim 17
Dependent Claim
12 words
The conjugate of claim 14 wherein the antibody is a monoclonal antibody.
Claim 18
Dependent Claim
23 words
The conjugate of claim 15 herein the monoclonal antibody is selected from the group consisting of anti-THY 1.1 and anti-human breast carcinoma B6.2.
Claim 19
Dependent Claim
13 words
The conjugate of claim 16 wherein the metallothionein or metallothionein fragment is mammalian.
Claim 20
Dependent Claim
13 words
The conjugate of claim 14 wherein the metallothionein or metallothionein fragment is mammalian.
Claim 21
Dependent Claim
33 words
A composition comprising purified metallothionein or metallothionein fragment in which at least a part of the metallothionein or fragment is Tc-99m, in a physiologically compatible vehicle in an amount sufficient for scintigraphic imaging.
Claim 22
Dependent Claim
33 words
A composition comprising purified metallothionein or metallothionein fragment in which at least a part of the metallothionein or fragment is Tc-99m, in a physiologically compatible vehicle in an amount sufficient for scintigraphic imaging.
Claim 23
Dependent Claim
13 words
The composition of claim 19 wherein the metallothionein or metallothionein fragment is mammalian.
Claim 24
Dependent Claim
64 words
In a method of diagnosing a disease state or monitoring organ function in a mammal which comprises administering a trace labeled conjugate of a target-seeking biologically active molecule, then subjecting the mammal to scintigraphic imaging, the improvement wherein the conjugate is a conjugate of claim 1, 2, 3, 4, 5 or 6 in a physiologically compatible vehicle in an amount effective for scintigraphic imaging.
Claim 25
Dependent Claim
58 words
A method of treating a disease state in a mammal which comprises administering a conjugate of claim 5 wherein the trace-label metal is a radionuclide and is selected from the group consisting of Ag-111, Au-198, Sb-119, Cu-67, Re-188 and Pd-103 and wherein said radionuclide is in a physiologically compatible vehicle in an amount sufficient to kill target cells.
Claim 26
Dependent Claim
35 words
A method of monitoring kidney function comprising intravenously administering to a mammal a composition of claim 19 or 20, then subjecting the mammal to scintigraphic imaging wherein the imaging is an indication of kidney function.
Claim 27
Independent Claim
97 words
A method of trace labeling a target-seeking biologically active molecule which comprises (a) reacting a metallothionein or fragment thereof with a salt or salt complex of a trace-label metal having a sufficient affinity for the metallothionein or fragment to bind thereto whereby the trace-label metal replaces at least a portion of the metal in the metallothionein, and then (b) conjugating the metallothionein to the biologically active molecule selected from the group consisting of antibodies, antibody fragments, hormones, peptides, proteins and drugs which bind to receptors and localize in certain organs, tissues and cells of the mammalian body.
Claim 28
Independent Claim
97 words
A method of trace labeling a target-seeking biologically active molecule which comprises (a) reacting a metallothionein or fragment thereof with a salt or salt complex of a trace-label metal having a sufficient affinity for the metallothionein or fragment to bind thereto whereby the trace-label metal replaces at least a portion of the metal in the metallothionein, and then (b) conjugating the metallothionein to the biologically active molecule selected from the group consisting of antibodies, antibody fragments, hormones, peptides, proteins and drugs which bind to receptors and localize in certain organs, tissues and cells of the mammalian body.
Claim 29
Dependent Claim
12 words
The method of claim 24 wherein the trace-label metal is a radionuclide.
Claim 30
Dependent Claim
18 words
The method of claim 24 or 25 wherein the biologically active molecule is an antibody or fragment thereof.
Claim 31
Dependent Claim
12 words
The method of claim 26 wherein the antibody is a monoclonal antibody.
Claim 32
Dependent Claim
23 words
The method of claim 27 wherein the monoclonal antibody is selected from the group consisting of anti-THY 1.1 and anti-human breast carcinoma B6.2.
Claim 33
Dependent Claim
20 words
The method of claim 25 wherein the radionuclide is selected from the group consisting of Tc-99m, Ag-111, Au-198 and Hg-197.
Claim 34
Independent Claim
91 words
A method of trace labeling a biologically active molecule body which comprises (a) reacting a thionein with a salt or salt complex in which at least a portion of the metal is a trace-label metal, whereby thionein is converted to a metallothionein containing at least a portion of trace-label metal, and then (b) conjugating the metallothionein to the biologically active molecule selected from the group consisting of antibodies, antibody fragments, hormones, peptides, proteins and drugs which bind to receptors and localize in certain organs, tissues and cells of the mammalian body.
Claim 35
Independent Claim
91 words
A method of trace labeling a biologically active molecule body which comprises (a) reacting a thionein with a salt or salt complex in which at least a portion of the metal is a trace-label metal, whereby thionein is converted to a metallothionein containing at least a portion of trace-label metal, and then (b) conjugating the metallothionein to the biologically active molecule selected from the group consisting of antibodies, antibody fragments, hormones, peptides, proteins and drugs which bind to receptors and localize in certain organs, tissues and cells of the mammalian body.
Claim 36
Dependent Claim
16 words
The method of claim 30 wherein the biologically active molecule is an antibody or fragment thereof.
Claim 37
Dependent Claim
12 words
The method of claim 31 wherein the antibody is a monoclonal antibody.
Claim 38
Dependent Claim
23 words
The method of claim 32 wherein the monoclonal antibody is selected from the group consisting of anti-THY 1.1 and anti-human breast carcinoma B6.2.
Claim 39
Dependent Claim
16 words
The method of claim 30, 31, 32 or 33 wherein the trace-label metal is a radionuclide.
Claim 40
Dependent Claim
18 words
The method of claim 34 wherein the radionuclide is selected from the group consisting of Ru-97, Pd-103 and.
Claim 41
Independent Claim
118 words
A method of trace-labeling a biologically active molecule which comprises (a) conjugating metallothionein, thionein, or a fragment thereof with a biolgically active molecule selected from the group consisting of antibodies, antibody fragments, hormones, peptides, proteins and drugs which bind to receptors and localize in certain organs, tissues and cells of the mammalian body and then (b) reacting a conjugate formed from step (a) with a salt or salt complex of a trace-label metal having a sufficient affinity for the metallothionein, thionein or fragment thereof to bind thereto, whereby the trace-label metal replaces at least a portion of the metal in the metallothionein or the thionein is converted to a metallothionein containing at least a portion of trace-label metal.
Claim 42
Independent Claim
118 words
A method of trace-labeling a biologically active molecule which comprises (a) conjugating metallothionein, thionein, or a fragment thereof with a biolgically active molecule selected from the group consisting of antibodies, antibody fragments, hormones, peptides, proteins and drugs which bind to receptors and localize in certain organs, tissues and cells of the mammalian body and then (b) reacting a conjugate formed from step (a) with a salt or salt complex of a trace-label metal having a sufficient affinity for the metallothionein, thionein or fragment thereof to bind thereto, whereby the trace-label metal replaces at least a portion of the metal in the metallothionein or the thionein is converted to a metallothionein containing at least a portion of trace-label metal.
Claim 43
Dependent Claim
16 words
The method of claim 36 wherein the biologically active molecule is an antibody or fragment thereof.
Claim 44
Dependent Claim
11 words
The method of claim 37 wherein the trace-metal is a radionuclide.
Claim 45
Dependent Claim
71 words
In a method of diagnosing a disease state or monitoring organ function in a mammal which comprises administering a trace-labeled conjugate of a target-seeking biologically active molecule, then subjecting the mammal to scintigraphic imaging, the improvement wherein the conjugate is a conjugate of claim 7 in a physiologically compatible vehicle in an amount effective for scintigraphic imaging wherein the imaging is an indication of a disease state or of organ function.
Claim 46
Dependent Claim
71 words
In a method of diagnosing a disease state or monitoring organ function in a mammal which comprises administering a trace-labeled conjugate of a target-seeking biologically active molecule, then subjecting the mammal to scintigraphic imaging, the improvement wherein the conjugate is a conjugate of claim 8 in a physiologically compatible vehicle in an amount effective for scintigraphic imaging wherein the imaging is an indication of a disease state or of organ function.
Claim 47
Dependent Claim
71 words
In a method of diagnosing a disease state or monitoring organ function in a mammal which comprises administering a trace-labeled conjugate of a target-seeking biologically active molecule, then subjecting the mammal to scintigraphic imaging, the improvement wherein the conjugate is a conjugate of claim 9 in a physiologically compatible vehicle in an amount effective for scintigraphic imaging wherein the imaging is an indication of a disease state or of organ function.
Claim 48
Dependent Claim
17 words
A method of claim 22 wherein the target-seeking biologically active molecule is an antibody or fragment thereof.
Claim 49
Dependent Claim
12 words
A method of claim 42 wherein the antibody is a monoclonal antibody.
Claim 50
Dependent Claim
23 words
A method of claim 43 wherein the monoclonal antibody is selected from the group consisting of anti-THY 1.1 and antihuman breast carcinoma B6.2.
References Cited (Backward Citations)
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 |