US4837003A
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Radiolabeled antibody fragments
Assignee: Mallinckrodt Inc
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Filing: 1984-09-13
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Granted: 1989-06-06
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Expires: 2004-09-13
Abstract
Abstract Methods and reagents for attaching radionuclide metal ions to antibody fragments are disclosed. A coupling agent is employed which contains a maleimidyl group linked, through a divalent organic moiety, to a group capable of forming a chelate complex with the radionuclide metal ion. Antibody fragments labeled with radionuclide metal ions by the disclosed procedure are useful for in vivo diagnostic or therapeutic applications.
Inventors
- 👤 Robert A. Nicolotti
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-08 05:51
CPC Classifications
C; C07; C07D; C07D207/00; C07D207/02; C07D207/44; C07D207/444; C07D207/448; C07D207/452; A; A61; A61K; A61K51/00; A61K51/02; A61K51/04; A61K51/08; A61K51/10; A61K51/1093; A61P; A61P35/00; A61K2121/00; A61K2123/00; Y; Y10; Y10S; Y10S436/00; Y10S436/804; Y10S436/811; Y10S436/813; Y10S530/00; Y10S530/866
Claims Analysis
Total Claims: 19
Claim 1
Independent Claim
108 words
An antibody conjugate of the formula: ##STR8## wherein Ab is the residue of a Fab' fragment of a monoclonal antibody, said antibody being one which retains antigen-binding activity following enzymatic removal of the F c fragment and reductive cleavage of the disulfide bond joining the heavy chains; --S-- is the residue of the free sulfhydryl group of the Fab' fragment; R is a divalent organic linker; and R' is a non-toxic, weakly acidic chelating group capable of forming a chelate with a radionuclide metal ion that is thermodynamically stable under physiological conditions and has a higher stability constant than a chelate of the radionuclide with transferrin in vivo.
Claim 2
Dependent Claim
108 words
An antibody conjugate of the formula: ##STR8## wherein Ab is the residue of a Fab' fragment of a monoclonal antibody, said antibody being one which retains antigen-binding activity following enzymatic removal of the F c fragment and reductive cleavage of the disulfide bond joining the heavy chains; --S-- is the residue of the free sulfhydryl group of the Fab' fragment; R is a divalent organic linker; and R' is a non-toxic, weakly acidic chelating group capable of forming a chelate with a radionuclide metal ion that is thermodynamically stable under physiological conditions and has a higher stability constant than a chelate of the radionuclide with transferrin in vivo.
Claim 3
Dependent Claim
27 words
An antibody conjugate as claimed in clain 1, wherein Ab is the residue of a Fab' fragment of a monoclonal antibody of the subclass IgG 1 .
Claim 4
Dependent Claim
26 words
An antibody conjugate as claimed in claim 1 wherein Ab is the residue of a Fab' fragment of a monoclonal antibody to a tumor associated antigen.
Claim 5
Dependent Claim
23 words
An antibody conjugate as claimed in claim 1, wherein Ab is the residue of a Fab' fragment of a monoclonal antibody to CEA.
Claim 6
Dependent Claim
48 words
An antibody conjugate as claimed in claim 1, wherein R is --(CH 2 ) n -- and R' is --N[CH 2 CH 2 N(CH 2 CO 2 H) 2 ] 2 or --CH[N(CH 2 COOH) 2 ]CH 2 N(CH 2 COOH) 2 wherein n is 1 to 20.
Claim 7
Dependent Claim
12 words
An antibody conjugate as claimed in claim 5, wherein n is 7.
Claim 8
Dependent Claim
110 words
An antibody-radionuclide conjugate of the formula: ##STR9## wherein Ab is the residue of a Fab' fragment of a monoclonal antibody, said antibody being one which retains antigen-binding activity following enzymatic removal of the F c fragment and reductive cleavage of the disulfide bond joining the heavy chains; --S-- is the residue of the free sulfhydryl group of the Fab' fragment; R is a divalent organic linker; and R" is a chelate complex between a radionuclide metal ion and a group that is capable of forming a chelate complex therewith, said complex being thermodynamically stable and having a higher stability constant than a chelate of the radionuclide with transferrin in vivo.
Claim 9
Dependent Claim
110 words
An antibody-radionuclide conjugate of the formula: ##STR9## wherein Ab is the residue of a Fab' fragment of a monoclonal antibody, said antibody being one which retains antigen-binding activity following enzymatic removal of the F c fragment and reductive cleavage of the disulfide bond joining the heavy chains; --S-- is the residue of the free sulfhydryl group of the Fab' fragment; R is a divalent organic linker; and R" is a chelate complex between a radionuclide metal ion and a group that is capable of forming a chelate complex therewith, said complex being thermodynamically stable and having a higher stability constant than a chelate of the radionuclide with transferrin in vivo.
Claim 10
Dependent Claim
27 words
An antibody-radionuclide conjugate as claimed in claim 7, wherein Ab is the residue of a Fab' fragment of a monoclonal antibody of the subclass IgG 1 .
Claim 11
Dependent Claim
26 words
An antibody-radionuclide conjugate as claimed in claim 7 wherein Ab is the residue of a Fab' fragment of a monoclonal antibody to a tumor associated antigen.
Claim 12
Dependent Claim
23 words
An antibody-radionuclide conjugate as claimed in claim 7, wherein Ab is the residue of a Fab' fragment of a monoclonal antibody to CEA.
Claim 13
Dependent Claim
64 words
An antibody-radionuclide conjugate as claimed in claim 7, wherein R is --(CH 2 ) n -- wherein n is 1 to 20 and R" is a chelate complex between a radionuclide metal ion and a chelating group of the formula --N[CH 2 CH 2 N(CH 2 CO 2 H) 2 ] 2 or --CH[N(CH 2 COOH) 2 ]CH 2 N(CH 2 COOH) 2 .
Claim 14
Dependent Claim
48 words
An antibody-radionuclide conjugate as claimed in claim 11, wherein n is 7 and R" is a chelate complex between indium-111 and the chelating group --N[CH 2 CH 2 N(CH 2 CO 2 H) 2 ] 2 or --CH[N(CH 2 COOH) 2 ]CH 2 N(CH 2 COOH) 2 .
Claim 15
Dependent Claim
52 words
An antibody-radionuclide conjugate as claimed in claim 11, wherein n is 7 and R" is a chelate complex between technetium-99m and the chelating group --N[CH 2 CH 2 N(CH 2 CO 2 H) 2 ] 2 or --CH[N(CH 2 CO 2 H) 2 ]CH 2 N(CH 2 CO 2 H) 2 .
Claim 16
Dependent Claim
18 words
An antibody-radionuclide conjugate as claimed in claim 8, wherein the chelated radionuclide metal ion is a beta-emitting radionuclide.
Claim 17
Dependent Claim
18 words
An antibody-radionuclide conjugate as claimed in claim 7, wherein the chelated radionuclide metal ion is a gamma-emitting radionuclide.
Claim 18
Dependent Claim
41 words
A method of detecting and localizing a tumor in vivo which comprises parenterally administering an antibody-radionuclide conjugate of claim 9 in which the radionuclide is a gamma-emitting radionuclide and photoscanning the subject to determine the site of the conjugate in vivo.
Claim 19
Dependent Claim
14 words
A method as claimed in claim 16, wherein the antibody-radionuclide conjugate is administered intravenously.
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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) | 1992-06-05 | 1992-12-05 | 1993-06-06 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1996-06-05 | 1996-12-05 | 1997-06-06 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2000-06-05 | 2000-12-05 | 2001-06-06 | $7700.00 | Window Closed / Lapsed |