EP0174853A2
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EP
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Radiolabeled antibody fragments
Assignee: Mallinckrodt Inc
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Filing: 1985-09-12
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Granted: —
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Expires: 2005-09-12
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
EP
Data Source
google_patents
Last Synchronized
2026-11-07 04:11
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
65 words
An antibody conjugate of the formula: 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 Fc fragment and reductive cleavage of the disulfide bond joining the heavy chains; R is a divalent organic linker; and R' is a group which is capable of chelating a radionuclide metal ion.
Claim 2
Dependent Claim
65 words
An antibody conjugate of the formula: 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 Fc fragment and reductive cleavage of the disulfide bond joining the heavy chains; R is a divalent organic linker; and R' is a group which is capable of chelating a radionuclide metal ion.
Claim 3
Dependent Claim
27 words
An antibody conjugate as claimed in claim 1, wherein Ab is the residue of a Fab' fragment of a monoclonal antibody of the subclass IgG l .
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
49 words
An antibody conjugate as claimed in any one of claims 1 to 4, wherein R is -(CH2)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
40 words
- An antibody-radionuclide conjugate of the formula: derived from an antibody conjugate according to any one of the preceding claims wherein the group R' has formed a chelate complex with a radionuclide metal ion to form a chelate complex R".
Claim 9
Dependent Claim
17 words
An antibody-radionuclide conjugate as claimed in claim 7, wherein the radionuclide metal ion is indium-III or technetium-99m.
Claim 10
Dependent Claim
18 words
An antibody-radionuclide conjugate as claimed in claim 7, wherein the chelated radionuclide metal ion is a beta-emitting radionuclide.
Claim 11
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 12
Dependent Claim
59 words
A method of detecting and localizing a tumor in vivo which comprises parenterally administering an antibody-radionuclide conjugate of claim 7 in which the radionuclide is a gamma-emitting radionuclide and Ab is the residue of a Fab' fragment of a monoclonal antibody to a tumor associated antigen, and photoscanning the subject to determine the srze of the conjugate in vivo.
Claim 13
Dependent Claim
14 words
A method as claimed in claim 11, wherein the antibody-radionuclide conjugate is administered intravenously.
Claim 14
Independent Claim
96 words
A method of producing an antibody conjugate for in vivo diagnostic or therapeutic use which comprises: (a) enzymatically cleaving the Fc fragment from a monoclonal antibody to a tumor-associated antigen which cleaves to produce an F(ab') 2 dimer in which the heavy chains are joined by a single disulfide bond; (b) reducing the F(ab') 2 dimer to produce two Fab' fragments each having a free sulfhydryl group; and (c) reacting the Fab' fragments with a coupling agent of the formula wherein R and R' are as defined in any one of claims 1, 5 or 6.
Claim 15
Dependent Claim
22 words
A method as claimed in claim 3, wherein the monoclonal antibody is an antibody of the murine subclass I gG l .
Claim 16
Dependent Claim
17 words
A method as claimed in claim 13 or 14, wherein the antibody is cleaved with preactivated papain.
Claim 17
Dependent Claim
19 words
A method as claimed in claim 13, 14 or 15 wherein the antibody is a monoclonal antibody to CEA.
Claim 18
Independent Claim
27 words
A method as claimed in any one of claims 13 to 16, which further comprises forming a chelate complex between-the -R' group and a radionuclide metal ion.
Claim 19
Dependent Claim
16 words
A method as claimed in claim 17, wherein the radionuclide metal ion is indium-111 or technetium-99m.
References Cited (Backward Citations)
No citation records indexed.
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