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EP0137457A2 Expired / Lapsed EP ⏱️ 0.0 years remaining

Trace-labeled conjugates of metallothionein and target-seeking biologically active molecules

Assignee: Bristol Myers Squibb Pharma Co
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Filing: 1984-10-04
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Granted: —
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Expires: 2004-10-04
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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 Lewis Tolman

Bibliographic Details

Application Number —
Jurisdiction EP
Data Source google_patents
Last Synchronized 2026-10-26 07:35
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: 40
Claim 1
Independent Claim 43 words
A conjugate of a target-seeking biologically active molecule and metallothionein or metallothionein fragment in which at least a part of the metal in the metallothionein or fragment is a trace-label metal having sufficient affinity for the metallothionein or metallothionein fragment to bind thereto.
Claim 2
Dependent Claim 43 words
A conjugate of a target-seeking biologically active molecule and metallothionein or metallothionein fragment in which at least a part of the metal in the metallothionein or fragment is a trace-label metal having sufficient affinity for the metallothionein or metallothionein fragment to bind thereto.
Claim 3
Dependent Claim 36 words
The conjugate of Claim 1 wherein the trace-label metal is selected from the group consisting of In, Pb, Tc, Ru, Hg, Ag, Au, Pd, Cu, Re, Sb, Bi, Ga, 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 31 words
The conjugate of Claim 3 wherein the radionuclide is selected from the group consisting of Tc-99m, tn-111, In-l13m, Pb-203, Ru-97, Hg-197, Ag-111, Au-198, Pd-103, Cu-67, Re-188, Sb-119, Bi-212, Ga-67, Ga-68, Os-191.
Claim 6
Dependent Claim 25 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, Sb-119 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 20 words
The conjugate of Claim 1,2,3,4,5 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 15 words
The conjugate of Claim 1,2,3,4,5,6,8 or 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 49 words
A conjugate of a target-seeking biologically active molecule and a metallothionein or metallothionein fragment in which all metal in the metallothionein or fragment (a) is non-radioactive and (b) has as affinity for metallothionein less than the cations selected from the group consisting of Tc, Ag, Au, Hg and Cu(ll).
Claim 14
Dependent Claim 49 words
A conjugate of a target-seeking biologically active molecule and a metallothionein or metallothionein fragment in which all metal in the metallothionein or fragment (a) is non-radioactive and (b) has as affinity for metallothionein less than the cations selected from the group consisting of Tc, Ag, Au, Hg and Cu(ll).
Claim 15
Dependent Claim 11 words
The conjugate of Claim 12 wherein the non-radioactive metal is 2n.
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 15 words
The conjugate of Claim 12,13,15 or 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 20 words
A metallothionein or metallothionein fragment in which at least a part of the metal in metallothionein or fragment is Tc-99m.
Claim 22
Dependent Claim 20 words
A metallothionein or metallothionein fragment in which at least a part of the metal in metallothionein or fragment is Tc-99m.
Claim 23
Dependent Claim 13 words
The composition of Claim 19 wherein the metallothionein or metallothionein fragment is mammalian.
Claim 24
Dependent Claim 41 words
A method of diagnosing a disease state of monitoring organ function in a mammal which comprises administering a conjugate of Claim 1,2,3,4,5,6,7,8,9,10 or 11 wherein said trace-label metal is in a physiologically compatible vehicle in an amount effective for scintigraphic imaging.
Claim 25
Dependent Claim 61 words
A method of treating a disease state in a mammal which comprises administering a conjugate of Claim 1,2,3,4,5,6,7,8,9,10 or 11 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 30 words
A method of monitoring kidney function comprising intravenously administering a metallothionein of Claim 19 or 20, the Tc-99m therein being in physiological saline in an amount sufficient for scintigraphic imaging.
Claim 27
Independent Claim 65 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, then b. conjugating the metallothionein to the biologically active molecule.
Claim 28
Independent Claim 65 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, then b. conjugating the metallothionein to the biologically active molecule.
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 59 words
A method of trace-labeling a biologically active molecule which comprises a.. reacting a thionein with a metal 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, then b. conjugating the metallothionein to the biologically active molecule.
Claim 35
Independent Claim 59 words
A method of trace-labeling a biologically active molecule which comprises a.. reacting a thionein with a metal 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, then b. conjugating the metallothionein to the biologically active molecule.
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 20 words
3S. The method of Claim 34 wherein the radionuclide is selected from the group consisting of Ru-97, Pd-103 and Sb-119.

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