Patent US4885153A successfully refreshed from Google Patents.
US4885153A
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US
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Radiohalogenated for proteins
Assignee: Poniard Pharmaceuticals Inc
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Filing: 1989-04-13
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Granted: 1989-12-05
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Expires: 2009-04-13
Abstract
Abstract Haloaryl compounds bearing a defined functional group or precursor are metalated with either Sn(n-Bu) 3 or SnMe 3 . The resulting aryltin compound may be transmetalated in site-specific reaction with one of the following organometallic groups: HgX 2 , Hg(OAc) 2 , BX 3 , or BZ 3 , wherein X is Cl, Br, or I, and Z is alkyl or alkoxy. The stannylated or otherwise metalated compounds are subsequently radiohalogenated via a demetalation reaction. The Stannylated or otherwise metalated compounds are subsequently radiohalogenated via a demetalation reaction. The functional group is suitable for conjugation to protein and can be present or be added subsequent, but most preferably prior, to the radiohalogenation. Also compounds of the formula: R 1 --Ar--R 2 , wherein R 1 is either a radiohalogen or any one of the organometallic groups stated above, Ar is aromatic or heteroaromatic ring, and R 2 is a short-chain substituent that does not highly activate the aromatic ring an that bears a functional group suitable for conjugation to protein under conditions that preserve the biological activity of the protein. The radiohalogenated small nolecules are conjugated to proteins such as monoclonal antibodies for use in diagnosis and therapy.
Inventors
- 👤 Daniel S. Wilbur
- 👤 Alan R. Fritzberg
- 👤 David S. Jones
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-29 13:26
CPC Classifications
C; C07; C07F; C07F3/00; C07F3/10; C07F3/12; C07F7/00; C07F7/22; C07F7/2208
Claims Analysis
Total Claims: 26
Claim 1
Independent Claim
133 words
A substantially pure radiohalogenated protein produced by covalently linking a protein and a compound having the formula: *X--Ar--R wherein Ar is an aromatic or heteroaromatic ring; R is a chemical bond or a substituent containing 1 to 12 straight-chain carbon atoms that does not activate Ar to electrophilic substitution on the order produced by hydroxy or amino substitution of the ring, wherein said bond or said substituent has attached thereto a functional group suitable for covalent linkage to a protein under conditions that preserve the biological activity of the protein, said functional group selected from phenolic ester, imide ester, imidate ester, anhydride, acylsuccinimide, aldehyde, isothiocyanate, thiol, diazo, amine, hydrazine, alkyl halide and maleimide; and *X is a radioisotope of iodine, bromine, fluorine or astatine and is para- or meta-positioned relative to substituent R.
Claim 2
Dependent Claim
133 words
A substantially pure radiohalogenated protein produced by covalently linking a protein and a compound having the formula: *X--Ar--R wherein Ar is an aromatic or heteroaromatic ring; R is a chemical bond or a substituent containing 1 to 12 straight-chain carbon atoms that does not activate Ar to electrophilic substitution on the order produced by hydroxy or amino substitution of the ring, wherein said bond or said substituent has attached thereto a functional group suitable for covalent linkage to a protein under conditions that preserve the biological activity of the protein, said functional group selected from phenolic ester, imide ester, imidate ester, anhydride, acylsuccinimide, aldehyde, isothiocyanate, thiol, diazo, amine, hydrazine, alkyl halide and maleimide; and *X is a radioisotope of iodine, bromine, fluorine or astatine and is para- or meta-positioned relative to substituent R.
Claim 3
Dependent Claim
41 words
A method of imaging tumor cell location in the body of a mammal comprising the steps of introducing a diagnostically effective amount of the radiohalogenated protein of claim 1 into the body and thereafter scanning the body with scintillation detector means.
Claim 4
Dependent Claim
27 words
A method of tumor radiotherapy comprising the step of introducing a therapeutically effective amount of the radiohalogenated protein of claim 1 into the body of a mammal.
Claim 5
Dependent Claim
10 words
The radiohalogenated protein of claim 1, wherein Ar is phenyl.
Claim 6
Dependent Claim
11 words
The radiohalogenated protein of claim 4, wherein R is N-succinimidyl carboxylate.
Claim 7
Dependent Claim
10 words
The radiohalogenated protein of claim 4, wherein R is ethylmaleimide.
Claim 8
Dependent Claim
16 words
The radiohalogenated protein of claim 1 wherein said protein is a monoclonal antibody or fragment thereof.
Claim 9
Dependent Claim
41 words
A method of imaging tumor cell loction in the body of a mammal comprising the steps of introducing a diagnostically effective amount of the radiohalogenated protein of claim 7 into the body and thereafter scanning the body with scintillation detector means.
Claim 10
Dependent Claim
27 words
A method of tumor radiotherapy comprising the step of introducing a therapeutically effective amount of the radiohalogenated protein of claim 7 into the body of a mammal.
Claim 11
Dependent Claim
21 words
The radiohalogenated protein of claim 7 wherein said monoclonal antibody or fragment thereof is specifically reactive with a tumor cell-associated antigen.
Claim 12
Dependent Claim
41 words
A method of imaging tumor cell location in the body of a mammal comprising the steps of introducing a diagnostically effective amount of the radiohalogenated protein of claim 10 into the body and thereafter scanning the body with scintillation detector means.
Claim 13
Dependent Claim
27 words
A method of tumor radiotherapy comprising the step of introducing a therapeutically effective amount of the radiohalogenated protein of claim 10 into the body of a mammal.
Claim 14
Dependent Claim
164 words
A radiohalogenated protein composition comprising a nonradioactive protein and a radiohalogenated protein, wherein said radiohalogenated protein composition is produced by covalently linking protein molecules and a labeling composition comprising a nonradioactive compound and a compound having the formula: *X--Ar--R wherein Ar is an aromatic or heteroaromatic ring; R is a chemical bond or a substituent containing 1 to 12 straight-chain carbon atoms that does not activate Ar to electrophilic substitution on the order produced by hydroxy or amino substitution of the ring, wherein said bond or said substituent has attached thereto a functional group suitable for covalent linkage to a protein under conditions that preserve the biological activity of the protein, said functional group selected from phenolic ester, imide ester, imidate ester, anhydride, acylsuccinimide, aldehyde, isothiocyanate, thiol, diazo, amine, hydrazine, alkyl halide and maleimide; and *X is a radioisotope of iodine, bromine, fluorine or astatine and is para- or meta-positioned relative to substituent R; wherein said radiohalogenated protein composition has a high specific activity.
Claim 15
Dependent Claim
164 words
A radiohalogenated protein composition comprising a nonradioactive protein and a radiohalogenated protein, wherein said radiohalogenated protein composition is produced by covalently linking protein molecules and a labeling composition comprising a nonradioactive compound and a compound having the formula: *X--Ar--R wherein Ar is an aromatic or heteroaromatic ring; R is a chemical bond or a substituent containing 1 to 12 straight-chain carbon atoms that does not activate Ar to electrophilic substitution on the order produced by hydroxy or amino substitution of the ring, wherein said bond or said substituent has attached thereto a functional group suitable for covalent linkage to a protein under conditions that preserve the biological activity of the protein, said functional group selected from phenolic ester, imide ester, imidate ester, anhydride, acylsuccinimide, aldehyde, isothiocyanate, thiol, diazo, amine, hydrazine, alkyl halide and maleimide; and *X is a radioisotope of iodine, bromine, fluorine or astatine and is para- or meta-positioned relative to substituent R; wherein said radiohalogenated protein composition has a high specific activity.
Claim 16
Dependent Claim
42 words
A method of imaging tumor cell location in the body of a mammal comprising the steps of introducing a diagnostically effective amount of the radiohalogenated protein composition of claim 13 into the body and thereafter scanning the body with scintillation detector means.
Claim 17
Dependent Claim
28 words
A method of tumor radiotherapy comprising the step of introducing a therapeutically effective amount of the radiohalogenated protein composition of claim 13 into the body of a mammal.
Claim 18
Dependent Claim
11 words
The radiohalogenated protein composition of claim 13, wherein Ar is phenyl.
Claim 19
Dependent Claim
12 words
The radiohalogenated protein composition of claim 16, wherein R is N-succinimidyl carboxylate.
Claim 20
Dependent Claim
11 words
The radiohalogenated protein composition of claim 16, wherein R is ethylmaleimide.
Claim 21
Dependent Claim
17 words
The radiohalogenated protein composition of claim 13 wherein said protein is a monoclonal antibody or fragment thereof.
Claim 22
Dependent Claim
42 words
A method of imaging tumor cell location in the body of a mammal comprising the steps of introducing a diagnostically effective amount of the radiohalogenated protein composition of claim 19 into the body and thereafter scanning the body with scintillation detector means.
Claim 23
Dependent Claim
28 words
A method of tumor radiotherapy comprising the step of introducing a therapeutically effective amount of the radiohalogenated protein composition of claim 19 into the body of a mammal.
Claim 24
Dependent Claim
22 words
The radiohalogenated protein composition of claim 19 wherein said monoclonal antibody or fragment thereof is specifically reactive with a tumor cell-associated antigen.
Claim 25
Dependent Claim
42 words
A method of imaging tumor cell location in the body of a mammal comprising the steps of introducing a diagnostically effective amount of the radiohalogenated protein composition of claim 22 into the body and thereafter scanning the body with scintillation detector means.
Claim 26
Dependent Claim
28 words
A method of tumor radiotherapy comprising the step of introducing a therapeutically effective amount of the radiohalogenated protein composition of claim 22 into the body of a mammal.
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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) | 1992-12-04 | 1993-06-05 | 1993-12-05 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1996-12-04 | 1997-06-05 | 1997-12-05 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2000-12-04 | 2001-06-05 | 2001-12-05 | $7700.00 | Window Closed / Lapsed |