EP0284071A2
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EP
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Metal-radionuclide-labeled proteins and glycoproteins for diagnosis and therapy
Assignee: Poniard Pharmaceuticals Inc
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Filing: 1988-03-24
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Granted: —
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Expires: 2008-03-24
Abstract
Abstract Chelated radionuclide compositions are provided for conjugation to polypeptides and carbohydrates. The resulting conjugates may be used in diagnosis and therapy.
Inventors
- 👤 Alan R. Fritzberg
- 👤 Sudhakar Kasina
- 👤 Jean-Luc Vanderheyden
- 👤 Ananthachari Srinivasan
- 👤 Tripuraneni N. Rao
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-10-30 22:21
CPC Classifications
G; G01; G01N; G01N33/00; G01N33/48; G01N33/50; G01N33/53; G01N33/531; G01N33/532; G01N33/534; A; A61; A61K; A61K51/00; A61K51/02; A61K51/04; A61K51/0474; A61K51/0478; A61K51/08; A61K51/088; A61K51/10; A61K51/1045; A61K51/1066; A61K51/1093; C; C07; C07B; C07B59/00; C07B59/004; C07F; C07F13/00; C07F13/005; A61K2121/00; A61K2123/00
Claims Analysis
Total Claims: 30
Claim 1
Independent Claim
102 words
A compound of the formula: wherein: T is H or a sulfur protecting group, each X independently represents H₂ or O; each R independently represents a substitutent selected from the group consisting of hydrogen; a non-alkyl side chain of an amino acid other than cysteine; alkyl; geminal dialkyl; and -(CH₂) n -Z; Z represents -COOH, a conjugation group, or a targeting compound; n is an integer of from 1 to about 4; and Rʹ is H₂; -(CH₂) n -Z; or an alkyl group having one or more polar groups substituted thereon; wherein the compound comprises at least one -(CH₂) n -Z substituent.
Claim 2
Dependent Claim
102 words
A compound of the formula: wherein: T is H or a sulfur protecting group, each X independently represents H₂ or O; each R independently represents a substitutent selected from the group consisting of hydrogen; a non-alkyl side chain of an amino acid other than cysteine; alkyl; geminal dialkyl; and -(CH₂) n -Z; Z represents -COOH, a conjugation group, or a targeting compound; n is an integer of from 1 to about 4; and Rʹ is H₂; -(CH₂) n -Z; or an alkyl group having one or more polar groups substituted thereon; wherein the compound comprises at least one -(CH₂) n -Z substituent.
Claim 3
Dependent Claim
32 words
The compound of Claim 1 wherein the sulfur protecting group is selected from the group consisting of alkyl, aryl, acyl, thioacyl, and organothio groups comprising from 1 to about 10 carbon atoms.
Claim 4
Dependent Claim
24 words
The compound of Claim 1 wherein the sulfur protecting group, when taken together with the sulfur atom to be protected, is a hemithioacetal group.
Claim 5
Dependent Claim
26 words
The compound of Claim 3 wherein the hemithioacetal group is selected from the group consisting of tetrahydrofuranyl, 2-methyl tetrahydrofuranyl, tetrahydropyranyl, 2-methyl tetrahydropyranyl, ethoxyethyl, and methoxymethyl groups.
Claim 6
Dependent Claim
17 words
The compound of Claim 1 wherein the sulfur protecting group is selected from the group consisting of:
Claim 7
Dependent Claim
103 words
A compound of the formula: and water soluble salts thereof, wherein: M is a radionuclide; each X independently represents H₂ or O; each Rʹ independently represents a substituent selected from the group consisting of hydrogen; a non-alkyl side chain of an amino acid other than cysteine; alkyl; geminal dialkyl; and -(CH₂) n -Z; Z represents -COOH, a conjugation group, or a targeting compound; n is an integer of from 1 to about 4; and Rʹ is H₂; -(CH₂) n -Z; or an alkyl group having one or more polar groups substituted thereon; wherein the compound comprises at least one -(CH₂) n -Z substituent.
Claim 8
Dependent Claim
103 words
A compound of the formula: and water soluble salts thereof, wherein: M is a radionuclide; each X independently represents H₂ or O; each Rʹ independently represents a substituent selected from the group consisting of hydrogen; a non-alkyl side chain of an amino acid other than cysteine; alkyl; geminal dialkyl; and -(CH₂) n -Z; Z represents -COOH, a conjugation group, or a targeting compound; n is an integer of from 1 to about 4; and Rʹ is H₂; -(CH₂) n -Z; or an alkyl group having one or more polar groups substituted thereon; wherein the compound comprises at least one -(CH₂) n -Z substituent.
Claim 9
Dependent Claim
28 words
The compound of Claim 6 wherein M is a radionuclide selected from the group consisting of 99m Tc, ¹⁸⁶Re, ¹⁸⁸Re, ⁶⁷Cu, ⁶⁴Cu, ²⁰³Pb, ²¹²Pb, ²¹²Pb, ²¹²Bi, and ¹⁰⁹Pd.
Claim 10
Dependent Claim
15 words
The compound of Claim 1 or 6 wherein at least one substituent X is O.
Claim 11
Dependent Claim
12 words
The compound of Claim 8 wherein all three substituents X represent O.
Claim 12
Dependent Claim
34 words
The compound of Claim 1 or 6 wherein the conjugation group is selected from the group consisting of active esters, imidate esters, primary or secondary amines, hydrazines, isothiocyanates, maleimides, and other Michael acceptor groups.
Claim 13
Dependent Claim
14 words
The compound of Claim 10 wherein the conjugation group is a 2,3,5,6-tetrafluorophenyl ester group.
Claim 14
Dependent Claim
24 words
The compound of Claim 1 or 6 wherein the targeting compound is selected from the group consisting of proteins, glycoproteins, carbohydrates, and fragments thereof.
Claim 15
Dependent Claim
17 words
The compound of Claim 12 wherein the targeting compound is a monoclonal antibody or a fragment thereof.
Claim 16
Dependent Claim
17 words
The compound of Claim 13 wherein the monoclonal antibody or fragment thereof is specific for cancer cells.
Claim 17
Dependent Claim
22 words
The compound of Claim 1 or 6 wherein said compound comprises at least one substituent -(CH₂) n -Z wherein Z is -COOH.
Claim 18
Dependent Claim
24 words
The compound of Claim 1 or 6 wherein said compound comprises a substituent -(CH₂)₃-Z wherein Z is a conjugation group or a targeting compound.
Claim 19
Dependent Claim
7 words
The compounds of Figures 1A to 1I.
Claim 20
Dependent Claim
7 words
The compounds of Figures 1A to 1I.
Claim 21
Dependent Claim
87 words
A method for radionuclide labeling of a glycoprotein comprising: reacting said glycoprotein with a glycol cleaving agent to cleave at least one sugar to produce a dialdehyde or higher polyaldehyde to provide a polyaldehyde product; reacting said polyaldehyde product with a compound according to Claim 1 wherein Z is amino, hydrazine, or an amino salt to produce a glycoprotein having a chelating compound conjugated thereto; and reacting said glycoprotein having a chelating compound conjugated thereto with a radionuclide under conditions sufficient to form a glycoprotein-radionuclide chelate conjugate.
Claim 22
Dependent Claim
62 words
A method for radionuclide labeling of a glycoprotein comprising: reacting said glycoprotein with a glycol cleaving agent to cleave at least one sugar to produce a dialdehyde or higher polyaldehyde to provide a polyaldehyde product; and reacting said polyaldehyde product with a compound according to Claim 6, wherein Z is amino, hydrazine or an amino salt to produce a radionuclide chelate-conjugated glycoprotein.
Claim 23
Dependent Claim
37 words
A method for radionuclide labeling of a polypeptide, comprising reacting the polypeptide with a compound of Claim 6, wherein said compound comprises a conjugation group which reacts with the polypeptide, thereby binding the compound to the polypeptide.
Claim 24
Dependent Claim
53 words
A method for radionuclide labeling of a polypeptide, comprising: reacting the polypeptide with a compound of Claim 1, wherein said compound comprises a conjugation group which reacts with the polypeptide, thereby binding the compound to the polypeptide, reacting the compound bound to the polypeptide with a radionuclide metal to form a chelate-polypeptide conjugate.
Claim 25
Dependent Claim
21 words
The method of Claim 18, 19, 20, or 21, wherein the glycoprotein or polypeptide is a monoclonal antibody or fragment thereof.
Claim 26
Dependent Claim
17 words
The method of Claim 22 wherein the monoclonal antibody or fragment thereof is specific for cancer cells.
Claim 27
Dependent Claim
25 words
The method of Claim 22, wherein the radionuclide is selected from the group consisting of 99m Tc, ¹⁸⁶Re, ¹⁸⁸Re, ¹⁰³Pb, ²¹²Pb, ²¹²Bi, ¹⁹⁸Au, and ¹⁰⁹Pd.
Claim 28
Dependent Claim
31 words
The compound according to Claim 6 wherein Z is a targeting compound which binds to target cells and M is a therapeutically effective radionuclide, for use as an active therapeutic substance.
Claim 29
Dependent Claim
30 words
The compound according to Claim 6, wherein Z is a targeting compound which binds to target cells and M is a diagnostically effective radionuclide, for use as a diagnostic agent.
Claim 30
Dependent Claim
31 words
The method of Claim 25 or 26 wherein the target cells are cancer cells and the targeting compound is a monoclonal antibody or fragment thereof which binds to the cancer cells.
References Cited (Backward Citations)
No citation records indexed.
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