Patent US5256395A successfully refreshed from Google Patents.
US5256395A
Expired / Lapsed
US
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Affinity enhancement immunological reagents for in vivo detection and killing of specific target cells
Assignee: Immunotech SAS
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Filing: 1987-09-10
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Granted: 1993-10-26
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Expires: 2007-09-10
Abstract
Abstract Immunological reagents, consisting of a) antibody or fragment conjugates having both an anti-cell specificity and an anti-hapten specificity, and b) synthetic tracers containing at least two hapten sites and at least one site suitable to attach radioactive isotopes, paramagnetic ions, drugs or toxins, are provided. These reagents are capable of binding to target cells in a specific way, and the tracer localizes preferentially on the membrane of antigen-bearing cells, even in the presence of excess antibody conjugate (affinity enhancement). These reagents are usefully employed, either in vitro or in vivo, to detect tumors, metastases, or other tissue injuries, when the synthetic tracer carries radioactive or paramagnetic compounds, and to kill target cells when the synthetic tracer carries radioactive compounds or drugs or toxins.
Inventors
- 👤 Jacques Barbet
- 👤 Michel Delaage
- 👤 Jean-Marc Le Doussal
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-02 11:50
CPC Classifications
G; G01; G01N; G01N33/00; G01N33/48; A; A61; A61K; A61K51/00; A61K51/02; A61K51/04; A61K51/08; A61K51/10; A61K51/1093; A61K47/00; A61K47/50; A61K47/51; A61K47/68; A61K47/6801; A61K47/6803; A61K47/6811; A61K47/6817; A61P; A61P35/00; A61K2121/00; A61K2123/00
Claims Analysis
Total Claims: 27
Claim 1
Independent Claim
135 words
A method for delivering to predetermined antigens of desired target cells, in vivo, a detectable substance or a toxic substance capable of killing target cells, comprising: (a) administering a dual specificity antibody conjugate comprising a first monoclonal antibody or fragment conjugated to a second monoclonal antibody or fragment, said first monoclonal antibody or fragment having binding affinity for said predetermined antigen on the desired target cells, and said second monoclonal antibody or fragment having binding affinity for a predetermined hapten; (b) without administration of a clearing agent intended to remove circulating antibody conjugates, administering an affinity enhancement probe comprising at least two of said predetermined haptens, said haptens being covalently linked together in a uniquely defined chemical structure, said affinity enhancement probe further having at least one said detectable substance or toxic substance bound thereto.
Claim 2
Independent Claim
135 words
A method for delivering to predetermined antigens of desired target cells, in vivo, a detectable substance or a toxic substance capable of killing target cells, comprising: (a) administering a dual specificity antibody conjugate comprising a first monoclonal antibody or fragment conjugated to a second monoclonal antibody or fragment, said first monoclonal antibody or fragment having binding affinity for said predetermined antigen on the desired target cells, and said second monoclonal antibody or fragment having binding affinity for a predetermined hapten; (b) without administration of a clearing agent intended to remove circulating antibody conjugates, administering an affinity enhancement probe comprising at least two of said predetermined haptens, said haptens being covalently linked together in a uniquely defined chemical structure, said affinity enhancement probe further having at least one said detectable substance or toxic substance bound thereto.
Claim 3
Dependent Claim
17 words
A method in accordance with claim 1, wherein said affinity enhancement probe comprises only two predetermined haptens.
Claim 4
Dependent Claim
20 words
A method in accordance with claim 1, wherein said affinity enhancement probe comprises only one said detectable or toxic substance.
Claim 5
Dependent Claim
20 words
A method in accordance with claim 1, wherein said second monoclonal antibody or fragment is an Fab or Fab' fragment.
Claim 6
Dependent Claim
23 words
A method in accordance with claim 1, wherein said first monoclonal antibody or fragment is an F(ab') 2 , Fab' or Fab fragment.
Claim 7
Dependent Claim
23 words
A method in accordance with claim 1, wherein said affinity enhancement probe contains a chelating agent which can be labeled with metal cations.
Claim 8
Dependent Claim
15 words
A method in accordance with claim 1, wherein said predetermined antigen is a tumor-associated antigen.
Claim 9
Dependent Claim
15 words
A method in accordance with claim 1, wherein said predetermined antigen is a cell-associated antigen.
Claim 10
Dependent Claim
37 words
A method in accordance with claim 1 for delivering a radioactive isotope to predetermined antigens on the desired target cells, wherein said detectable substance or toxic substance bound to said affinity enhancement probe is a radioactive isotope.
Claim 11
Dependent Claim
35 words
A method in accordance with claim 9, wherein said affinity enhancement probe contains a phenol group and said radioactive isotope is a radioactive halogen covalently attached to the phenol group of said affinity enhancement probe.
Claim 12
Dependent Claim
47 words
A method for killing desired cells bearing predetermined antigens, in vivo, comprising: delivering, in accordance with claim 1, a toxic substance to the predetermined antigens on the desired target cells, wherein the detectable substance or toxic substance bound to said affinity enhancement probe is a toxic substance.
Claim 13
Dependent Claim
20 words
A method in accordance with claim 11, wherein said toxic substance is a radioactive isotope, a drug or a toxin.
Claim 14
Dependent Claim
18 words
A method in accordance with claim 1, wherein said haptens are linked together by means of a peptide.
Claim 15
Dependent Claim
16 words
A method in accordance with claim 13, wherein said peptide contains at least one D-amino acid.
Claim 16
Dependent Claim
95 words
A method in accordance with claim 1, wherein said step of administering a dual specificity conjugate comprises administering a mixture of two different conjugates, wherein the first monoclonal antibodies or fragments of said two different conjugates have binding affinity for different predetermined antigens on said desired target cells and the second monoclonal antibodies or fragments of said two different conjugates have binding affinity for different haptens, and wherein said haptens of said affinity enhancement probe include each of the haptens toward which the second monoclonal antibodies or fragments of said two different conjugates are specific.
Claim 17
Dependent Claim
23 words
A method in accordance with claim 15, wherein at least one of the haptens of said affinity enhancement probe includes a 2,4-dinitrophenyl group.
Claim 18
Dependent Claim
35 words
A method in accordance with claim 15, wherein one said predetermined antigen is a tumor associated antigen and the other said predetermined antigen is a different tumor associated antigen or a cell- or tissue-associated antigen.
Claim 19
Dependent Claim
58 words
A method for imaging of desired target cells bearing predetermined antigens, comprising: delivering, in accordance with claim 1, a detectable substance to the predetermined antigens of the desired target cells, wherein the detectable substance or toxic substance bound to said affinity enhancing probe is a detectable substance, and detecting the detectable substance, thereby imaging the desired target cells.
Claim 20
Dependent Claim
15 words
A method in accordance with claim 18, wherein said detectable substance is a radioactive isotope.
Claim 21
Dependent Claim
31 words
A method in accordance with claim 18, wherein said detectable substance comprises paramagnetic metal ions and said detecting step comprises detecting nuclear magnetic resonance relaxation by a magnetic resonance imaging device.
Claim 22
Dependent Claim
21 words
A method in accordance with claim 1, wherein each of said predetermined haptens on said affinity enhancement probe is the same.
Claim 23
Dependent Claim
21 words
A method in accordance with claim 21, wherein each of the haptens of said affinity enhancement probe includes a 2,4-dinitrophenyl group.
Claim 24
Dependent Claim
16 words
A method in accordance with claim 21, wherein said affinity enhancement probe has the structure: ##STR3##
Claim 25
Dependent Claim
16 words
A method in accordance with claim 21, wherein said affinity enhancement probe has the structure: ##STR4##
Claim 26
Independent Claim
173 words
A method for delivering to predetermined antigens of desired target cells, in vivo, a detectable substance or a toxic substance capable of killing target cells, comprising: (a) administering a mixture of two different dual specificity antibodies each comprising a first monoclonal antibody or fragment conjugated to a second monoclonal antibody or fragment, said first monoclonal antibodies or fragments of said two different conjugates having binding affinity for different ones of said predetermined antigens on the desired target cells, and said second monoclonal antibodies or fragments of said two different conjugates having binding affinity for different predetermined haptens; (b) without administration of a clearing agent intended to remove circulating antibody conjugates, administering an affinity enhancement probe comprising at least two different haptens which are covalently linked to one another, wherein said haptens of said affinity enhancement probe include each of the haptens toward which said second monoclonal antibodies or fragments of said two different conjugates are specific, said affinity enhancement probe further having at least one said detectable substance or toxic substance bound thereto.
Claim 27
Independent Claim
173 words
A method for delivering to predetermined antigens of desired target cells, in vivo, a detectable substance or a toxic substance capable of killing target cells, comprising: (a) administering a mixture of two different dual specificity antibodies each comprising a first monoclonal antibody or fragment conjugated to a second monoclonal antibody or fragment, said first monoclonal antibodies or fragments of said two different conjugates having binding affinity for different ones of said predetermined antigens on the desired target cells, and said second monoclonal antibodies or fragments of said two different conjugates having binding affinity for different predetermined haptens; (b) without administration of a clearing agent intended to remove circulating antibody conjugates, administering an affinity enhancement probe comprising at least two different haptens which are covalently linked to one another, wherein said haptens of said affinity enhancement probe include each of the haptens toward which said second monoclonal antibodies or fragments of said two different conjugates are specific, said affinity enhancement probe further having at least one said detectable substance or toxic substance bound thereto.
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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) | 1996-10-25 | 1997-04-26 | 1997-10-26 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2000-10-25 | 2001-04-26 | 2001-10-26 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2004-10-25 | 2005-04-26 | 2005-10-26 | $7700.00 | Window Closed / Lapsed |