Patent EP0247866A1 successfully refreshed from Google Patents.
EP0247866A1
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EP
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Coupling agents for radiolabeling proteins
Assignee: Mallinckrodt Inc
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Filing: 1987-05-28
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Granted: —
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Expires: 2007-05-28
Abstract
Abstract This invention relates to bifunctional coupling agents useful in forming conjugates with biologically useful molecules, such as antibodies. These conjugates can be complexed with radionuclide metal ions to provide materials useful for in vivo diagnostic and therapeutic applications.
Inventors
- 👤 Robert A. Nicolotti
- 👤 Richard T. Dean
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-11-08 05:41
CPC Classifications
C; C07; C07D; C07D231/00; C07D231/02; C07D231/10; C07D231/12; A; A61; A61K; A61K51/00; A61K51/02; A61K51/04; A61K51/08; A61K51/10; A61K51/1093; A61P; A61P35/00; C07D207/00; C07D207/46; C07D233/00; C07D233/54; C07D233/56; C07D249/00; C07D249/02; C07D249/08; A61K2121/00; A61K2123/00; Y; Y10; Y10S; Y10S530/00; Y10S530/866
Claims Analysis
Total Claims: 35
Claim 1
Independent Claim
138 words
A coupling agent for joining a radionuclide metal ion with a biologically useful protein or polypeptide molecule comprising a compound of the formula: wherein R₁, R₂, and R₃ are the same or different and each represents a radical selected from the group consisting of alkyls having from 1 to 6 carbon atoms, aryls having from 6 to 8 carbon atoms and alkaryls having 7 to 9 carbon atoms, any of which can be substituted with one or more hydroxyl, alkoxy, carboxy or sulfonate groups; n is either 1 or 2; AA are independently α or β amino acids linked to each other by amide bonds; i is an integer of from 2 to 6; and X is a activating group capable of forming an amide bond with an ε-amino group of said biologically useful protein or polypeptide molecule.
Claim 2
Dependent Claim
138 words
A coupling agent for joining a radionuclide metal ion with a biologically useful protein or polypeptide molecule comprising a compound of the formula: wherein R₁, R₂, and R₃ are the same or different and each represents a radical selected from the group consisting of alkyls having from 1 to 6 carbon atoms, aryls having from 6 to 8 carbon atoms and alkaryls having 7 to 9 carbon atoms, any of which can be substituted with one or more hydroxyl, alkoxy, carboxy or sulfonate groups; n is either 1 or 2; AA are independently α or β amino acids linked to each other by amide bonds; i is an integer of from 2 to 6; and X is a activating group capable of forming an amide bond with an ε-amino group of said biologically useful protein or polypeptide molecule.
Claim 3
Dependent Claim
20 words
The coupling agent of claim 1 wherein X is a member selected from the group consisting of a halogen, N₃,
Claim 4
Dependent Claim
15 words
The coupling agent of claim 1 or claim 2 wherein i is 3 or 4.
Claim 5
Dependent Claim
17 words
The coupling agent of any one of claims 1 to 3 wherein R₁ is methyl or phenyl.
Claim 6
Dependent Claim
18 words
The coupling agent of any one of claims 1 to 4 wherein R₂ and R₃ are both phenyl.
Claim 7
Dependent Claim
18 words
The coupling agent of any one of claims 1 to 4 wherein R₂ and R₃ are both methyl.
Claim 8
Dependent Claim
6 words
The compound N-(3-sulfosuccinimidyl) S-acetylmercaptoacetylglycylglycylglycylglycinate sodium salt.
Claim 9
Dependent Claim
6 words
The compound N-(3-sulfosuccinimidyl) S-acetylmercaptoacetylglycylglycylglycylglycinate sodium salt.
Claim 10
Dependent Claim
6 words
The compound N-(3-sulfosuccinimidyl) S-acetylmercaptoacetylglycylglycylglycinate sodium salt.
Claim 11
Dependent Claim
6 words
The compound N-(3-sulfosuccinimidyl) S-acetylmercaptoacetylglycylglycylglycinate sodium salt.
Claim 12
Dependent Claim
6 words
The compound N-(3-sulfosuccinimidyl) S-benzoylmercaptoacetylglycylglycylglycinate sodium salt.
Claim 13
Dependent Claim
6 words
The compound N-(3-sulfosuccinimidyl) S-benzoylmercaptoacetylglycylglycylglycinate sodium salt.
Claim 14
Dependent Claim
8 words
The compound N-(3-sulfosuccinimidyl) 2,3-bis (acetylmercaptoacetamido) propionate sodium salt.
Claim 15
Dependent Claim
8 words
The compound N-(3-sulfosuccinimidyl) 2,3-bis (acetylmercaptoacetamido) propionate sodium salt.
Claim 16
Dependent Claim
108 words
An antibody conjugate of the formula: wherein Ab is the residue of an antibody or fragment thereof; R₁, R₂, and R₃ are the same or different and each represents a radical selected from the group consisting of alkyls having from 1 to 6 carbon atoms, aryls having from 6 to 8 carbon atoms and alkaryls having 7 to 9 carbon atoms, any of which can be substituted with one or more hydroxyl, alkoxy, carboxy or sulfonate groups; n is either 1 or 2; AA are independently α or β amino acids linked to each other by amide bonds; and i is an integer of from 2 to 6.
Claim 17
Dependent Claim
108 words
An antibody conjugate of the formula: wherein Ab is the residue of an antibody or fragment thereof; R₁, R₂, and R₃ are the same or different and each represents a radical selected from the group consisting of alkyls having from 1 to 6 carbon atoms, aryls having from 6 to 8 carbon atoms and alkaryls having 7 to 9 carbon atoms, any of which can be substituted with one or more hydroxyl, alkoxy, carboxy or sulfonate groups; n is either 1 or 2; AA are independently α or β amino acids linked to each other by amide bonds; and i is an integer of from 2 to 6.
Claim 18
Dependent Claim
19 words
The antibody conjugate of claim 11, wherein Ab is the residue of a F(abʹ)₂ fragment of a monoclonal antibody.
Claim 19
Dependent Claim
24 words
The antibody conjugate of claim 11, wherein Ab is the residue of a Fabʹ fragment of a monoclonal antibody to a tumor associated antigen.
Claim 20
Dependent Claim
21 words
The antibody conjugate of claim 11, wherein Ab is the residue of a Fabʹ fragment of a monoclonal antibody to CEA.
Claim 21
Dependent Claim
17 words
The antibody conjugate of any one of claims 11 to 14, wherein i is 3 or 4.
Claim 22
Dependent Claim
17 words
The antibody conjugate of any one of claims 11 to 15, wherein R₁ is methyl or phenyl.
Claim 23
Dependent Claim
18 words
The antibody conjugate of any one of claims 11 to 16, wherein R₂ and R₃ are both phenyl.
Claim 24
Dependent Claim
18 words
The antibody conjugate of any one of claims 11 to 16, wherein R₂ and R₃ are both methyl.
Claim 25
Dependent Claim
26 words
An antibody-radionuclide complex comprising the antibody conjugate of any one of claims 11 to 18 and a radionuclide metal selected from radiosotopes of technetium and rhenium.
Claim 26
Dependent Claim
19 words
An antibody-radionuclide complex as claimed in claim 19, wherein the radionuclide is selected from Tc-99m, Re-186, Re-188 and Re-189.
Claim 27
Independent Claim
171 words
A method of producing an antibody conjugate for in vivo diagnostic or therapeutic use which comprises: (a) enzymatically cleaving the Fc fragment from an antibody to a tumor-associated antigen which cleaves to produce an F(ab)ʹ₂ dimer; (b) reducing the F(ab)ʹ₂ dimer to produce two Fabʹ fragments; and (c) reacting the Fabʹ fragments with a coupling agent of the formula: wherein R₁, R₂, and R₃ are the same or different and each represents a radical selected from the group consisting of alkyls having from 1 to 6 carbon atoms, aryls having from 6 to 8 carbon atoms and alkaryls having 7 to 9 carbon atoms, any of which can be substituted with one or more hydroxyl, or alkoxy, carboxy or sulfonate groups; n is either 1 or 2; AA are independently α or β amino acids linked to each other by amide bonds; i is an integer of from 2 to 6; and X is an activating group capable of forming an amide bond with an ε-amino group of said Fabʹ fragment.
Claim 28
Independent Claim
171 words
A method of producing an antibody conjugate for in vivo diagnostic or therapeutic use which comprises: (a) enzymatically cleaving the Fc fragment from an antibody to a tumor-associated antigen which cleaves to produce an F(ab)ʹ₂ dimer; (b) reducing the F(ab)ʹ₂ dimer to produce two Fabʹ fragments; and (c) reacting the Fabʹ fragments with a coupling agent of the formula: wherein R₁, R₂, and R₃ are the same or different and each represents a radical selected from the group consisting of alkyls having from 1 to 6 carbon atoms, aryls having from 6 to 8 carbon atoms and alkaryls having 7 to 9 carbon atoms, any of which can be substituted with one or more hydroxyl, or alkoxy, carboxy or sulfonate groups; n is either 1 or 2; AA are independently α or β amino acids linked to each other by amide bonds; i is an integer of from 2 to 6; and X is an activating group capable of forming an amide bond with an ε-amino group of said Fabʹ fragment.
Claim 29
Dependent Claim
19 words
The method of claim 21, wherein X is a member selected from the group consisting of a halogen, N₃,
Claim 30
Dependent Claim
16 words
The method of claim 21 or claim 22, wherein the antibody is cleaved with preactivated papain.
Claim 31
Independent Claim
19 words
The method of any one of claims 21 to 23, wherein the antibody is a monoclonal antibody to CEA.
Claim 32
Independent Claim
16 words
The method of any one of claims 21 to 24, wherein i is 3 or 4.
Claim 33
Independent Claim
13 words
The method of claims 21 to 25, wherein R₁ is methyl or phenyl.
Claim 34
Independent Claim
17 words
The method of any one of claims 21 to 26, wherein R₂ and R₃ are both phenyl.
Claim 35
Independent Claim
17 words
The method of any one of claims 21 to 26, wherein R₂ and R₃ are both methyl.
References Cited (Backward Citations)
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