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US4741900A
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US
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Antibody-metal ion complexes
Assignee: Cytogen Corp
•
Filing: 1984-08-31
•
Granted: 1988-05-03
•
Expires: 2004-08-31
Abstract
Abstract This invention relates to antibody-metal ion complexes having a metal ion coordinately bound to a compatible chelator covalently bound to an antibody or antibody fragment. Also described are methods for intermediates in the preparation of antibody-metal ion complexes. Therapeutic and in vitro and in vivo diagnostic methods utilizing such antibody-metal ion complexes are described.
Inventors
- 👤 Vernon L. Alvarez
- 👤 John D. Rodwell
- 👤 Chyi Lee
- 👤 John W. F. Goers
- 👤 Richard C. Siegel
- 👤 Thomas J. McKearn
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 17:16
CPC Classifications
A; A61; A61K; A61K49/00; A61K49/06; A61K49/08; A61K49/10; A61K49/14; A61K49/16; A61K39/00; A61K39/395; A61K49/085; A61K51/00; A61K51/02; A61K51/04; A61K51/08; A61K51/10; A61K51/1093; G; G01; G01N; G01N33/00; G01N33/48; G01N33/50; G01N33/53; G01N33/531; G01N33/532; G01N33/534; G01N33/543; G01N33/54353; G01N33/577; A61K2121/00; A61K2123/00; Y; Y10; Y10S; Y10S435/00; Y10S435/972
Claims Analysis
Total Claims: 89
Claim 1
Independent Claim
137 words
A method for preparing an antibody-chelator conjugate, comprising: (a) reacting an antibody or antibody fragment with an oxidizing agent to form an aldehyde group in the carbohydrate moiety of the antibody or antibody fragment, in which the carbohydrate moiety is not part of nor directly involved with the antigen binding site of the antibody or antibody fragment; and (b) reacting the aldehyde group of the resultant oxidized antibody or antibody fragment with a compatible chelator containing an amine group selected from the group consisting of primary amine, hydrazine, hydrazide, hydroxylamine, phenylhydrazine, semicarbazide and thiosemicarbazide groups to form a water-soluble antibody-chelator conjugate being characterized by (i) substantially the same immunospecificity as the unconjugated antibody or antibody fragment; and (ii) aqueous solubility such that the antibody-chelator conjugate, when reacted with a metal ion, is suitable for in vivo administration.
Claim 2
Independent Claim
137 words
A method for preparing an antibody-chelator conjugate, comprising: (a) reacting an antibody or antibody fragment with an oxidizing agent to form an aldehyde group in the carbohydrate moiety of the antibody or antibody fragment, in which the carbohydrate moiety is not part of nor directly involved with the antigen binding site of the antibody or antibody fragment; and (b) reacting the aldehyde group of the resultant oxidized antibody or antibody fragment with a compatible chelator containing an amine group selected from the group consisting of primary amine, hydrazine, hydrazide, hydroxylamine, phenylhydrazine, semicarbazide and thiosemicarbazide groups to form a water-soluble antibody-chelator conjugate being characterized by (i) substantially the same immunospecificity as the unconjugated antibody or antibody fragment; and (ii) aqueous solubility such that the antibody-chelator conjugate, when reacted with a metal ion, is suitable for in vivo administration.
Claim 3
Dependent Claim
13 words
The method according to claim 1, wherein the oxidizing agent is an enzyme.
Claim 4
Dependent Claim
14 words
The method according to claim 1, wherein the oxidizing agent is an oxygen acid.
Claim 5
Dependent Claim
26 words
The method according to claim 1, wherein the antibody fragment is selected from the group consisting of Fab fragments, (Fab') 2 fragments and half antibody molecules.
Claim 6
Dependent Claim
21 words
The method according to claim 1, wherein the antibody or antibody fragment is a monoclonal antibody or a monoclonal antibody fragment.
Claim 7
Dependent Claim
17 words
The method according to claim 1, wherein the compatible chelator is an amine-containing derivative of diethylenetriaminepentaacetic acid.
Claim 8
Dependent Claim
47 words
The method according to claim 1, wherein the compatible chelator is selected from the group consisting of p-aminoaniline-diethylenetriaminepentaacetic acid, hydrazide-diethylenetriaminepentaacetic acid, phenylhydrazide-diethylenetriaminepentaacetic acid, hydroxylamine-diethylenetriaminepentaacetic acid, semicarbazide-diethylenetriaminepentaacetic acid, thiosemicarbazide-diethylenetriaminepentaacetic acid, polyethyleneimine-diethylenetriaminepentaacetic acid, p-phenylenediamine-diethylenetriaminepentaacetic acid, α-N-diethylenetriaminepentaacetic acid-L-lysine, glycyl-tyrosyl-lysine-diethylenetriaminepentaacetic acid, diethylenetriaminepentaacetic acid mono[(4-aminophenyl)methyl ] amide and L-lysine benzyl ester-diethylenetriaminepentaacetic acid.
Claim 9
Dependent Claim
31 words
The method according to claim 1, wherein the compatible chelator is an amine-containing derivative of a chelator selected from the group consisting of ethylenediaminetetraacetic acid, dimercaptosuccinic acid, 2,3-dimercaptopropanesulfonic acid and metallothioein.
Claim 10
Dependent Claim
17 words
The method according to claim 1, wherein thee compatible chelator is an amine-containing derivative of a cryptate.
Claim 11
Dependent Claim
22 words
The method according to claim 1, wherein the antibody-chelator conjugate is stabilized by exposure to an effective amount of a reducing agent.
Claim 12
Independent Claim
164 words
A method for preparing an antibody-metal ion complex, comprising: (a) reacting an antibody or antibody fragment with an oxidizing agent to form an aldehyde group in the carbohydrate moiety of the antibody or antibody fragment, in which the carbohydrate moiety is not part of nor directly involved with the antigen binding site of the antibody or antibody fragment; (b) reacting the aldehyde group of the resultant oxidized antibody or antibody fragment with a compatible chelator containing an amine group selected from the group consisting of primary amine, hydrazine, hydrazide, hydroxylamine, phenylhydrazine, semicarbazide and thiosemicarbazide groups to form a water-soluble antibody-chelator conjugate; and (c) combining the antibody-chelator conjugate with a metal ion under conditions which allow chelation of the metal ion to the antibody-chelator conjugate to form a water-soluble antibody-metal ion complex being characterized by (i) substantially the same immunospecificity as the unconjugated antibody or antibody fragment and (ii) an aqueous solubility such that the antibody metal ion complex is suitable for in vivo administration.
Claim 13
Independent Claim
164 words
A method for preparing an antibody-metal ion complex, comprising: (a) reacting an antibody or antibody fragment with an oxidizing agent to form an aldehyde group in the carbohydrate moiety of the antibody or antibody fragment, in which the carbohydrate moiety is not part of nor directly involved with the antigen binding site of the antibody or antibody fragment; (b) reacting the aldehyde group of the resultant oxidized antibody or antibody fragment with a compatible chelator containing an amine group selected from the group consisting of primary amine, hydrazine, hydrazide, hydroxylamine, phenylhydrazine, semicarbazide and thiosemicarbazide groups to form a water-soluble antibody-chelator conjugate; and (c) combining the antibody-chelator conjugate with a metal ion under conditions which allow chelation of the metal ion to the antibody-chelator conjugate to form a water-soluble antibody-metal ion complex being characterized by (i) substantially the same immunospecificity as the unconjugated antibody or antibody fragment and (ii) an aqueous solubility such that the antibody metal ion complex is suitable for in vivo administration.
Claim 14
Dependent Claim
13 words
The method according to claim 11, wherein the metal ion is a radioisotope.
Claim 15
Dependent Claim
12 words
The method according to claim 12, wherein the radioisotope emits data particles.
Claim 16
Dependent Claim
27 words
The method according to claim 13, wherein the radioisotope is selected from the group consisting of 46 Scandium, 47 Scandium, 48 Scandium, 72 Gallium and 73 Gallium.
Claim 17
Dependent Claim
12 words
The method according to claim 2, wherein the radioisotope emits alpha particles.
Claim 18
Dependent Claim
25 words
The method according to claim 15, wherein the radioisotope is selected from the group consisting of 211 Bismuth, 212 Bismuth, 213 Bismuth and 214 Bismuth.
Claim 19
Dependent Claim
12 words
The method according to claim 12, wherein the radioisotope emits positron particles.
Claim 20
Dependent Claim
27 words
The method according to claim 17, wherein the radioisotope is selected from the group consisting of 43 Scandium, 44 Scandium, 52 Iron, 55 Cobalt and 68 Gallium.
Claim 21
Dependent Claim
12 words
The method according to claim 11, wherein the metal ion is paramagnetic.
Claim 22
Dependent Claim
30 words
The method according to claim 19, wherein the metal ion is selected from the group consisting of 54 Iron, 56 Iron, 57 Iron, 58 Iron, 157 Gadolinium and 55 Manganese.
Claim 23
Dependent Claim
13 words
The method according to claim 11, wherein the oxidizing agent is an enzyme.
Claim 24
Dependent Claim
14 words
The method according to claim 11, wherein the oxidizing agent is an oxygen acid.
Claim 25
Dependent Claim
26 words
The method according to claim 11, wherein the antibody fragment is selected from the group consisting of Fab fragments, (Fab') 2 fragments and half antibody molecules.
Claim 26
Dependent Claim
20 words
The method according to claim 11, wherein the antibody or antibody fragment is a monoclonal antibody or monoclonal antibody fragment.
Claim 27
Dependent Claim
17 words
The method according to claim 11, wherein the compatible chelator is an amine-containing derivative of diethylenetriaminepentaacetic acid.
Claim 28
Dependent Claim
48 words
The method according to claim 11, wherein the compatible chelator is selected from the group consisting of p-aminoaniline-diethylenetriaminepentaacetic acid, hydrazide-diethylenetriaminepentaacetic acid, phenylhydrazide-diethylenetriaminepentaacetic acid, hydroxylamine-diethylenetriaminepentaacetic acid, semicarbazide-diethylenetriaminepentaacetic acid, thiosemicarbazide-diethylenetriaminepentaacetic acid, polyethyleneimine-diethylenetriaminepentaacetic acid, p-phenylenediamine-diethylenetriaminepentaacetic acid, α-N-diethylentriminepentacetic acid L-lysine, glycyl-tyrosyl-lysinediethylentriaminepentaacetic acid, diethylenetriaminepentaacetic acid mono [(4-aminophenyl)methyl ]amide and L-lysine benzyl ester-diethylenetriaminepentaacetic acid.
Claim 29
Dependent Claim
31 words
The method according to claim 11, wherein the compatible chelator is an amine-containing derivative of a chelator selected from the group consisting of ethylenediaminetetraacetic acid, dimercaptosuccinic acid, 2,3-dimercaptopropanesulfonic acid and metallothioein.
Claim 30
Dependent Claim
17 words
The method according to claim 11, wherein the compatible chelator is an amine-containing derivative of a cryptate.
Claim 31
Dependent Claim
23 words
The method according to claim 11, wherein the antibody-metal ion complex is stabilized by exposure to an effective amount of a reducing agent.
Claim 32
Dependent Claim
32 words
The method according to claim 11, further comprising the step of: (d) separating the antibody-metal ion complexes from non-chelated metal ions to obtain antibody-metal ion complexes substantially free of non-chelated metal ions.
Claim 33
Dependent Claim
18 words
The method according to claim 30, wherein the separation is accomplished by high performance gel permeation liquid chromatography.
Claim 34
Independent Claim
156 words
A method for preparing an antibody-metal ion complex, comprising: (a) reacting an antibody or antibody fragment with an oxidizing agent to form an aldehyde group in the carbohydrate moiety of the antibody or antibody fragment, in which the carbohydrate moiety is not part of nor directly involved with the antigen binding site of the antibody or antibody fragment; and (b) reacting the aldehyde group of the resultant oxidized antibody or antibody fragment with a chelator-metal ion complex, said chelator-metal ion complex comprising a compatible chelator-metal ion complex comprising a compatible chelator containing an amine group selected from the group consisting of primary amine, hydrazine, hydrazide, hydroxylamine, phenylhydrazine, semicarbazide and thiosemicarbazide groups coordinately bound to a metal ion, to form a water-soluble antibody-metal ion complex being characterized by (i) substantially the same immunospecificity as the unconjugated antibody or antibody fragment, and (ii) aqueous solubility such that the antibody-chelator metal ion complex is suitable for in vivo administration.
Claim 35
Independent Claim
156 words
A method for preparing an antibody-metal ion complex, comprising: (a) reacting an antibody or antibody fragment with an oxidizing agent to form an aldehyde group in the carbohydrate moiety of the antibody or antibody fragment, in which the carbohydrate moiety is not part of nor directly involved with the antigen binding site of the antibody or antibody fragment; and (b) reacting the aldehyde group of the resultant oxidized antibody or antibody fragment with a chelator-metal ion complex, said chelator-metal ion complex comprising a compatible chelator-metal ion complex comprising a compatible chelator containing an amine group selected from the group consisting of primary amine, hydrazine, hydrazide, hydroxylamine, phenylhydrazine, semicarbazide and thiosemicarbazide groups coordinately bound to a metal ion, to form a water-soluble antibody-metal ion complex being characterized by (i) substantially the same immunospecificity as the unconjugated antibody or antibody fragment, and (ii) aqueous solubility such that the antibody-chelator metal ion complex is suitable for in vivo administration.
Claim 36
Dependent Claim
13 words
The method according to claim 32, wherein the metal ion is a radioisotope.
Claim 37
Dependent Claim
12 words
The method according to claim 33, wherein the radioisotope emits beta particles.
Claim 38
Dependent Claim
27 words
The method according to claim 34, wherein the radioisotope is selected from the group consisting of 46 Scandium, 47 Scandium, 48 Scandium, 72 Gallium and 73 Gallium.
Claim 39
Dependent Claim
12 words
The method ccording to claim 33, wherein the radioisotope emits alpha particles.
Claim 40
Dependent Claim
24 words
The method according claim 36, wherein the radioisotope is selected from the group consisting of 211 Bismuth, 212 Bismuth, 213 Bismuth and 214 Bismuth.
Claim 41
Dependent Claim
12 words
The method according to claim 33, wherein the radioisotope emits positron particles.
Claim 42
Dependent Claim
27 words
The method according to claim 38, wherein the radioisotope is selected from the group consisting of 43 Scandium, 44 Scandium, 52 Iron, 55 Cobalt and 68 Gallium.
Claim 43
Dependent Claim
12 words
The method according to claim 32, wherein the metal ion is paramagnetic.
Claim 44
Dependent Claim
30 words
The method according to claim 40, wherein the metal ion is selected from the group consisting of 54 Iron, 56 Iron, 57 Iron, 58 Iron, 157 Gadolinium and 55 Manganese.
Claim 45
Dependent Claim
13 words
The method according to claim 32, wherein the oxidizing agent is an enzyme.
Claim 46
Dependent Claim
14 words
The method according to claim 32, wherein the oxidizing agent is an oxygen acid.
Claim 47
Dependent Claim
26 words
The method according to claim 32, wherein the antibody fragment is selected from the group consisting of Fab fragments, (Fab') 2 fragments and half antibody molecules.
Claim 48
Dependent Claim
20 words
The method according to claim 32, wherein the antibody or antibody fragment is a monoclonal antibody or monoclonal antibody fragment.
Claim 49
Dependent Claim
17 words
The method according to claim 32, wherein the compatible chelator is an amine-containing derivative of diethylenetriaminepentaacetic acid.
Claim 50
Dependent Claim
45 words
The method according to claim 32, wherein the compatible chelator is selected from the group consisting of p-aminoaniline-diethylenetriaminepentaacetic acid, hydrazide-diethylenetriaminepentaacetic acid, phenylhydrazide-diethylenetriaminepentaacetic acid, hydroxylamine-diethylenetriaminepentaacetic acid, semicarbazide-diethylenetriaminepentaacetic acid, thiosemicarbazide-diethylenetriaminepentaacetic acid, polyethyleneimine-diethylenetriaminepentaacetic acid, p-phenylenediamine-diethylenetriaminepentaacetic acid, α-N-diethylenetriaminepentaacetic acid-L-lysine, glycyl-tyrosyl-lysine-diethylenetriaminepentaacetic acid, diethylenetriaminepentaacetic acid mono[(4-aminophenyl)methyl]amide and L-lysine benzyl ester-diethylenetriaminepentaacetic acid.
Claim 51
Dependent Claim
31 words
The method according to claim 32, wherein the compatible chelator is an amine-containing derivative of a chelator selected from the group consisting of ethylenediaminetetraacetic acid, dimercaptosuccinic acid, 2,3-dimercaptopropanesulfonic acid and metallothioein.
Claim 52
Dependent Claim
17 words
The method according to claim 32, wherein the compatible chelator is an amine-containing derivative of a cryptate.
Claim 53
Dependent Claim
23 words
The method according to claim 32, werein the antibody-metal ion complex is stabilized by exposure to an effective amount of a reducing agent.
Claim 54
Dependent Claim
32 words
The method according to claim 32, further comprising the step of: (c) separating the antibody-metal ion complexes from non-chelated metal ions to obtain antibody-metal ion complexes substantially free of non-chelated metal ions.
Claim 55
Dependent Claim
18 words
The method according to claim 51, wherein the separation is accomplished by high performance gel permeation liquid chromatography.
Claim 56
Dependent Claim
85 words
An antibody-chelator conjugate, comprising: a compatible chelator attached through a covalent bond to a carbohydrate moiety of an oxidized antibody or antibody fragment, in which the carbohydrate moiety is not part or nor directly involved with the antigen binding site of the antibody or antibody fragment, said water-soluble antibody-chelator conjugate being characterized (i) substantially the same immunospecificity as the unconjugated antibody or antibody fragment, and (ii) aqueous solubility such that the antibody-chelator conjugate, when reacted with a metal ion, is suitable for in vivo administration.
Claim 57
Dependent Claim
85 words
An antibody-chelator conjugate, comprising: a compatible chelator attached through a covalent bond to a carbohydrate moiety of an oxidized antibody or antibody fragment, in which the carbohydrate moiety is not part or nor directly involved with the antigen binding site of the antibody or antibody fragment, said water-soluble antibody-chelator conjugate being characterized (i) substantially the same immunospecificity as the unconjugated antibody or antibody fragment, and (ii) aqueous solubility such that the antibody-chelator conjugate, when reacted with a metal ion, is suitable for in vivo administration.
Claim 58
Dependent Claim
24 words
The antibody-chelator conjugate according to claim 53, wherein the covalent bond is an enamine, hydrazone, oxime, phenylhydrazone, semicarbazone, thiosemicarbazone, or a reduced form thereof.
Claim 59
Dependent Claim
27 words
The antibody-chelator conjugate according to claim 53, wherein the antibody fragment is selected from the group consisting of Fab fragments, (Fab') 2 fragments and half antibody molecules.
Claim 60
Dependent Claim
21 words
The antibody-chelator conjugate according to claim 53, wherein the antibody or antibody fragment is a monoclonal antibody or monoclonal antibody fragment.
Claim 61
Dependent Claim
18 words
The antibody-chelator conjugate according to claim 53, wherein the compatible chelator is an amine-containing derivative of diethylenetriaminepentaacetic acid.
Claim 62
Dependent Claim
46 words
The antibody-chelator conjugate according to claim 57, wherein the compatible chelator is selected from the group consisting of p-aminoaniline-diethylenetriaminepentaacetic acid, hydrazide-diethylenetriaminepentaacetic acid, phenylhydrazide-diethylenetriaminepentaacetic acid, hydroxylamine-diethylenetriaminepentaacetic acid, semicarbazide-diethylenetriaminepentaacetic acid, thiosemicarbazide-diethylenetriaminepentaacetic acid, polyethyleneimine-diethylenetriaminetetraacetic acid p-phenylenediamine-diethylenetriaminepentaacetic acid, α-N-diethylenetriaminepentaacetic acid-L-lysine, glycyl-tyrosyl-lysine-diethylenetriaminepentaacetic acid, diethylenetriaminepentaacetic acid mono[(4-aminophenyl)methyl]amide and L-lysine benzyl ester-diethylenetriamine-pentaacetic acid.
Claim 63
Dependent Claim
32 words
The antibody-chelator conjugate according to claim 53, wherein the compatible chelator is an amine-containing derivative of a chelator selected from the group consisting of ethylenediaminetetraacetic acid, dimercaptosuccinic acid, 2,3-dimercaptopropanesulfonic acid and metallothioein.
Claim 64
Dependent Claim
18 words
The antibody-chelator conjugate according to claim 53, wherein the compatible chelator is an amine-containing derivative of a cryptate.
Claim 65
Dependent Claim
104 words
An antibody-metal ion complex, comprising: an antibody-chelator conjugate comprising a compatible chelator attached through a covalent bond to a carbohydrate moiety of an oxidized antibody or antibody fragment, in which the carbohydrate moiety is not part of nor directly involved with the antigen binding site of the antibody or antibody fragment; said water-soluble antibody-chelator conjugate coordinately bound through said compatible chelator to a metal ion to form a water-soluble antibody-metal ion complex being characterized by (i) substantially the same immunospecificity as the unconjugated antibody or antibody fragment, and (ii) aqueous solubility such that the antibody-chelator metal ion complex is suitable for in vivo administration.
Claim 66
Dependent Claim
104 words
An antibody-metal ion complex, comprising: an antibody-chelator conjugate comprising a compatible chelator attached through a covalent bond to a carbohydrate moiety of an oxidized antibody or antibody fragment, in which the carbohydrate moiety is not part of nor directly involved with the antigen binding site of the antibody or antibody fragment; said water-soluble antibody-chelator conjugate coordinately bound through said compatible chelator to a metal ion to form a water-soluble antibody-metal ion complex being characterized by (i) substantially the same immunospecificity as the unconjugated antibody or antibody fragment, and (ii) aqueous solubility such that the antibody-chelator metal ion complex is suitable for in vivo administration.
Claim 67
Dependent Claim
15 words
The antibody-metal ion complex according to claim 61, wherein the metal ion is a radioisotope.
Claim 68
Dependent Claim
14 words
The antibody-metal ion complex according to claim 62, wherein the radioisotope emits beta particles.
Claim 69
Dependent Claim
29 words
The antibody-metal ion complex according to claim 63, wherein the radioisotope is selected from the group consisting of 46 Scandium, 47 Scandium, 48 Scandium, 72 Gallium and 73 Gallium.
Claim 70
Dependent Claim
14 words
The antibody-metal ion complex according to claim 62, wherein the radioisotope emits alpha particles.
Claim 71
Dependent Claim
26 words
The antibody-metal ion complex according to claim 65, wherein the radioisotope is selected from the group consisting of 211 Bismuth, 212 Bismuth, 213 Bismuth 214 Bismuth.
Claim 72
Dependent Claim
14 words
The antibody-metal ion complex according to claim 62, wherein the radioisotope emits positron particles.
Claim 73
Dependent Claim
29 words
The antibody-metal ion complex according to claim 67, wherein the radioisotope is selected from the group consisting of 43 Scandium, 44 Scandium, 52 Iron, 55 Cobalt and 68 Gallium.
Claim 74
Dependent Claim
14 words
The antibody-metal ion complex according to claim 61, wherein the metal ion is paramagnetic.
Claim 75
Dependent Claim
32 words
The antibody-metal ion complex according to claim 69, wherein the metal ion is selected from the group consisting of 54 Iron, 56 Iron, 57 Iron, 58 Iron, 157 Gadolinium and 55 Manganese.
Claim 76
Dependent Claim
25 words
The antibody-metal ion complex according to claim 61, wherein the covalent bond is an imine, hydrazone, oxime, phenylhydrazone, semicarbazone, thiosemicarbazone or a reduced form thereof.
Claim 77
Dependent Claim
28 words
The antibody-metal ion complex according to claim 61, wherein the antibody fragment is selected from the group consisting of Fab fragments, (Fab') 2 fragments and half antibody molecules.
Claim 78
Dependent Claim
22 words
The antibody-metal ion complex according to claim 61, wherein the antibody or antibody fragment is a monoclonal antibody or monoclonal antibody fragment.
Claim 79
Dependent Claim
19 words
The antibody-metal ion complex according to claim 61, wherein the compatible chelator is an amine-containing derivative of diethylenetriaminepentaacetic acid.
Claim 80
Dependent Claim
47 words
The antibody-metal ion complex according to claim 61, wherein the compatible chelator is selected from the group consisting of p-aminoaniline-diethylenetriaminepentaacetic acid, hydrazide-diethylenetriaminepentaacetic acid, phenylhydrazide-diethylenetriaminepentaacetic acid, hydroxylamine-diethylenetriaminepentaacetic acid, semicarbazide-diethylenetriaminepentaacetic acid, thiosemicarbazide-diethylenetriaminepentaacetic acid, polyethyleneimine-diethylenetriaminepentaacetic acid, p-phenylenediamine-diethylenetriaminepentaacetic acid, α-N-diethylenetriaminepentaacetic acid-L-lysine, glycyl-tyrosyl-lysine-diethylenetriaminepentaacetic acid, diethylenetriaminepentaacetic acid mono[(4-aminophenyl)methyl]amide and L-lysine benzyl ester-diethylenetriaminepentaacetic acid.
Claim 81
Dependent Claim
33 words
The antibody-metal ion complex according to claim 61, wherein the compatible chelator is an amine-containing derivative of a chelator selected from the group consisting of ethylenediaminetetraacetic acid, dimercaptosuccinic acid, 2,3-dimercaptopropanesulfonic acid and metallothioein.
Claim 82
Dependent Claim
19 words
The antibody-metal ion complex according to claim 61, wherein the compatible chelator is an amine-containing derivative of a cryptate.
Claim 83
Dependent Claim
14 words
The antibody-metal ion complex according to claim 61, substantially free of non-chelated metal ions.
Claim 84
Independent Claim
164 words
A method for in vivo imaging a specific tissue, comprising: (a) administering to an animal or a human an effective amount of a water-soluble antibody metal ion complex which (i) is immunoreactive with and immunospecific for an antigenic determinant of the specific tissue and substantially non-immunoreactive with and non-immunospecific for non-specific tissue and the antigenic determinant is not found in substantial amounts in non-specific tissue; and (ii) comprises an antibody or antibody fragment, a compatible chelator and metal ion in which the compatible chelator is covalently bound to the antibody or antibody fragment at a carbohydrate moiety located outside the antigen binding region of the antibody or antibody fragment, and coordinately bound to the metal ion so that the antibody-metal ion complex is characterized by substantially the same immunospecificity as the antibody or antibody fragment and an aqueous solubility such that the antibody-metal ion complex is suitable for administration in vivo; and (b) detecting whether the antibody-metal ion complex localized at the specific tissue.
Claim 85
Independent Claim
164 words
A method for in vivo imaging a specific tissue, comprising: (a) administering to an animal or a human an effective amount of a water-soluble antibody metal ion complex which (i) is immunoreactive with and immunospecific for an antigenic determinant of the specific tissue and substantially non-immunoreactive with and non-immunospecific for non-specific tissue and the antigenic determinant is not found in substantial amounts in non-specific tissue; and (ii) comprises an antibody or antibody fragment, a compatible chelator and metal ion in which the compatible chelator is covalently bound to the antibody or antibody fragment at a carbohydrate moiety located outside the antigen binding region of the antibody or antibody fragment, and coordinately bound to the metal ion so that the antibody-metal ion complex is characterized by substantially the same immunospecificity as the antibody or antibody fragment and an aqueous solubility such that the antibody-metal ion complex is suitable for administration in vivo; and (b) detecting whether the antibody-metal ion complex localized at the specific tissue.
Claim 86
Independent Claim
152 words
A method for therapeutic treatment of a cellular disorder, comprising: administering to an animal or a human a therapeutically effective amount of a water-soluble antibody metal-ion complex which (a) is immunoreactive with and immunospecific for a target site associated with the cellular disorder and substantially non-immunoreactive with and non-immunospecific for tissue not associated with the cellular disorder; and (b) which comprises an antibody or antibody fragment, a compatible chelator and a metal ion which emits cytotoxic beta or alpha particles, in which the compatible chelator is covalently bound to the antibody or antibody fragment at a carbohydrate moiety located outside the antigen binding region of the antibody or antibody fragment, and coordinately bound to the metal ion so that the antibody-metal ion complex is characterized by substantially the same immunospecificity as the antibody or antibody fragment and an aqueous solubility such that the antibody-metal ion complex is suitable for administration in vivo.
Claim 87
Independent Claim
152 words
A method for therapeutic treatment of a cellular disorder, comprising: administering to an animal or a human a therapeutically effective amount of a water-soluble antibody metal-ion complex which (a) is immunoreactive with and immunospecific for a target site associated with the cellular disorder and substantially non-immunoreactive with and non-immunospecific for tissue not associated with the cellular disorder; and (b) which comprises an antibody or antibody fragment, a compatible chelator and a metal ion which emits cytotoxic beta or alpha particles, in which the compatible chelator is covalently bound to the antibody or antibody fragment at a carbohydrate moiety located outside the antigen binding region of the antibody or antibody fragment, and coordinately bound to the metal ion so that the antibody-metal ion complex is characterized by substantially the same immunospecificity as the antibody or antibody fragment and an aqueous solubility such that the antibody-metal ion complex is suitable for administration in vivo.
Claim 88
Independent Claim
134 words
A method for testing for an antigen, comprising: (a) mixing a sample suspected of containing the antigen with a water-soluble antibody metal ion complex which (i) is immunoreactive with and immunospecific for the antigen; and (ii) which comprises an antibody or antibody fragment, a compatible chelator and metal ion in which the compatible chelator is covalently bound to the antibody or antibody fragment at a carbohydrate moiety located outside the antigen binding region of the antibody or antibody fragment, and coordinately bound to the metal ion so that the antibody-metal ion complex is characterized by substantially the same immunospecificity as the antibody or antibody fragment and an aqueous solubility such that the antibody-metal ion complex is suitable for administration in vivo; and (b) detecting any interaction of the antibody-metal ion complex with the sample.
Claim 89
Independent Claim
134 words
A method for testing for an antigen, comprising: (a) mixing a sample suspected of containing the antigen with a water-soluble antibody metal ion complex which (i) is immunoreactive with and immunospecific for the antigen; and (ii) which comprises an antibody or antibody fragment, a compatible chelator and metal ion in which the compatible chelator is covalently bound to the antibody or antibody fragment at a carbohydrate moiety located outside the antigen binding region of the antibody or antibody fragment, and coordinately bound to the metal ion so that the antibody-metal ion complex is characterized by substantially the same immunospecificity as the antibody or antibody fragment and an aqueous solubility such that the antibody-metal ion complex is suitable for administration in vivo; and (b) detecting any interaction of the antibody-metal ion complex with the sample.
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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) | 1991-05-03 | 1991-11-02 | 1992-05-03 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1995-05-03 | 1995-11-02 | 1996-05-03 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1999-05-03 | 1999-11-02 | 2000-05-03 | $7700.00 | Window Closed / Lapsed |