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US4867962A Expired / Lapsed US ⏱️ 0.0 years remaining

Functionally specific antibodies

Assignee: Poniard Pharmaceuticals Inc
•
Filing: 1988-02-26
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Granted: 1989-09-19
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Expires: 2008-02-26
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Abstract

Abstract Diagnostic or therapeutic agents are attached to two or more antibody species having non-overlapping patterns of cross-reactivity to increase the relative amount of the active agent(s) delivered to desired target cells compared to non-target cells. The agents may be attached to monoclonal antibodies which bind to cancer cells so that a higher percentage of the active agent(s) localize on the target cells compared to each type of cross-reactive normal tissue.

Inventors

  • 👤 Paul G. Abrams

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-10-23 15:14
CPC Classifications
A; A61; A61K; A61K51/00; A61K51/02; A61K51/04; A61K51/08; A61K51/10; A61K51/1045; A61K51/1054; A61K47/00; A61K47/50; A61K47/51; A61K47/68; A61K47/6801; A61K47/6803; A61K47/6811; A61K47/6817; A61K51/1093; C; C07; C07K; C07K16/00; C07K16/18; C07K16/28; C07K16/30; C07K16/3023; A61K2123/00; A61K38/00

Claims Analysis

Total Claims: 43
Claim 1
Independent Claim 68 words
A method of delivering one or more diagnostic or therapeutic agents to a target site within a mammalian or human host, comprising administering to said host two or more different antibody species each having one of said agents attached thereto, wherein each of said antibody species is reactive with a different epitope of the target site and wherein the patterns of cross-reactivity for each antibody species are non-overlapping.
Claim 2
Independent Claim 68 words
A method of delivering one or more diagnostic or therapeutic agents to a target site within a mammalian or human host, comprising administering to said host two or more different antibody species each having one of said agents attached thereto, wherein each of said antibody species is reactive with a different epitope of the target site and wherein the patterns of cross-reactivity for each antibody species are non-overlapping.
Claim 3
Dependent Claim 13 words
The method of claim 1 wherein the target site is a cancer site.
Claim 4
Independent Claim 36 words
The method of claims 1, 8, 11, 4, 5, 12, 15, or 7 wherein one antibody species is monoclonal antibody NR-LU-10 or a fragment thereof, and a second antibody species is NR-LU-11 or a fragment thereof.
Claim 5
Dependent Claim 18 words
The method of claim 1 wherein an identical therapeutic agent is attached to each of the antibody species.
Claim 6
Dependent Claim 18 words
The method of claim 4 wherein the therapeutic agent is 188 Re in the form of a chelate.
Claim 7
Dependent Claim 19 words
The method of claim 1 wherein each of the antibody species is a monoclonal antibody or a fragment thereof.
Claim 8
Dependent Claim 22 words
The method of claim 6 wherein each antibody species is a monoclonal antibody, or a fragment thereof, which binds to cancer cells.
Claim 9
Dependent Claim 18 words
The method of claim 1 wherein an identical diagnostic agent is attached to each of the antibody species.
Claim 10
Dependent Claim 14 words
The method of claim 8 wherein the diagnostic agent is a diagnostically effective radionuclide.
Claim 11
Dependent Claim 30 words
The method of claim 9 wherein the diagnostic agent is selected from the group consisting of 99m Tc, 131 I, 111 In, and 123 I, 76 Br, and 18 F.
Claim 12
Dependent Claim 18 words
The method of claim 10 wherein the diagnostic agent is 99m Tc in the form of a chelate.
Claim 13
Dependent Claim 17 words
The method of claim 1 wherein different therapeutic agents are attached to each of the antibody species.
Claim 14
Dependent Claim 34 words
The method of claim 12 wherein the target site is a cancer site, a sensitizing drug is attached to one antibody species, and a therapeutically effective radionuclide is attached to a second antibody species.
Claim 15
Dependent Claim 33 words
The method of claim 12 wherein the target site is a cancer site, a sensitizing drug is attached to one antibody species, and an anti-cancer drug is attached to a second antibody species.
Claim 16
Dependent Claim 18 words
The method of claim 14 wherein the sensitizing drug is buthionine sulfoximine and the anti-cancer drug is doxorubicin.
Claim 17
Dependent Claim 29 words
The method of claim 1, 4, or 12 wherein each therapeutic agent is selected from the group consisting of therapeutically effective radionuclides, drugs, toxins, sensitizers, and biological response modifiers.
Claim 18
Dependent Claim 44 words
The method of claim 16 wherein the radionuclide is selected from the group consisting of 188 Re, 186 Re, 203 Pb, 212 Pb, 212 Bi, 109 Pd, 64 Cu, 67 Cu, 131 I, 211 At, 97 Ru, 105 Rh, 198 Au, and 199 Ag.
Claim 19
Dependent Claim 32 words
The method of claim 16 wherein the toxin is selected from the group consisting of ricin, abrin, diphtheria toxin, Pseudomonas exotoxin A, ribosomal inactivating proteins, mycotoxins, trichothecenes, and therapeutically effective fragments thereof.
Claim 20
Dependent Claim 20 words
The method of claim 16 wherein said target site is a cancer site and the drug is an anti-cancer drug.
Claim 21
Dependent Claim 12 words
The method of claim 19 wherein the drug is an anti-cancer antibiotic.
Claim 22
Dependent Claim 10 words
The method of claim 20 wherein the drug is doxorubicin.
Claim 23
Independent Claim 104 words
A method of producing additive accumulation of two or more immunoconjugates on a target tissue within a human or mammalian host while minimizing additive accumulation of the immunoconjugates on non-target tissues, comprising: a) administering a first immunoconjugate comprising a first antibody species to the host; administering one or more additional immunoconjugates each comprising a different antibody species to the host, wherein each of the antibody species reacts with a different epitope of the target tissue and the different antibody species have non-overlapping patterns of cross-reactivity wherein each of said first and additional immunoconjugates comprise a therapeutic or diagnostic agent attached to an antibody species.
Claim 24
Independent Claim 104 words
A method of producing additive accumulation of two or more immunoconjugates on a target tissue within a human or mammalian host while minimizing additive accumulation of the immunoconjugates on non-target tissues, comprising: a) administering a first immunoconjugate comprising a first antibody species to the host; administering one or more additional immunoconjugates each comprising a different antibody species to the host, wherein each of the antibody species reacts with a different epitope of the target tissue and the different antibody species have non-overlapping patterns of cross-reactivity wherein each of said first and additional immunoconjugates comprise a therapeutic or diagnostic agent attached to an antibody species.
Claim 25
Dependent Claim 17 words
The method of claim 22 wherein each immunoconjugate comprises a diagnostic agent attached to an antibody species.
Claim 26
Dependent Claim 14 words
The method of claim 23 wherein the diagnostic agent is a diagnostically effective radionuclide.
Claim 27
Dependent Claim 29 words
The method of claim 24 wherein the diagnostic agent is selected from the group consisting of 99m Tc, 131 I, 111 In, 123 I, 76 Br, and 18 F.
Claim 28
Dependent Claim 15 words
The method of claim 22, 23, or 29 wherein the target tissue comprises cancer cells.
Claim 29
Dependent Claim 23 words
The method of claim 26 wherein each antibody species is a monoclonal antibody, or a fragment thereof, which binds to the cancer cells.
Claim 30
Dependent Claim 28 words
The method of claim 27 wherein one antibody species is monoclonal antibody NR-LU-10 or a fragment thereof, and a second antibody species is NR-LU-11 or a fragment thereof.
Claim 31
Dependent Claim 17 words
The method of claim 22 wherein each immunoconjugate comprises a therapeutic agent attached to an antibody species.
Claim 32
Dependent Claim 17 words
The method of claim 29 wherein different therapeutic agents are attached to each of the antibody species.
Claim 33
Dependent Claim 28 words
The method of claim 29 or 30 wherein each therapeutic agent is selected from the group consisting of therapeutically effective radionuclides, drugs, sensitizers, toxins, and biological response modifiers.
Claim 34
Dependent Claim 42 words
The method of claim 31 wherein each radionuclide is selected from the group consisting of 188 Re, 186 Re, 203 Pb, 212 Pb, 212 Bi, 109 Pd, 64 Cu, 131 I, 211 At, 97 Ru, 105 Rh, 198 Au, and 199 Ag.
Claim 35
Dependent Claim 32 words
The method of claim 31 wherein each toxin is selected from the group consisting of ricin, abrin, diphtheria toxin, Pseudomonas exotoxin A, ribosomal inactivating proteins, mycotoxins, trichothecenes, and therapeutically effective fragments thereof.
Claim 36
Dependent Claim 19 words
The method of claim 31 wherein said target tissue comprises cancer cells and each drug is an anti-cancer drug.
Claim 37
Dependent Claim 35 words
The method of claim 31 wherein the target tissue comprises cancer cells, a sensitizer is attached to one antibody species, and a therapeutically effective radionuclide or anti-cancer drug is attached to a second antibody species.
Claim 38
Independent Claim 91 words
A method of administering two or more different therapeutic agents to a human or mammalian host to eradicate target cells, wherein each therapeutic agent is administered at its maximum tolerated dose to the host, while minimizing toxicity toward non-target tissues, comprising attaching each different therapeutic agent to a different antibody species, wherein each, antibody species, reacts with a different epitope of the target cells, and wherein the patterns of cross-reactivity for each antibody species are non-overlapping, and administering each of the resulting immunoconjugates at the maximum tolerated dose to the host.
Claim 39
Independent Claim 91 words
A method of administering two or more different therapeutic agents to a human or mammalian host to eradicate target cells, wherein each therapeutic agent is administered at its maximum tolerated dose to the host, while minimizing toxicity toward non-target tissues, comprising attaching each different therapeutic agent to a different antibody species, wherein each, antibody species, reacts with a different epitope of the target cells, and wherein the patterns of cross-reactivity for each antibody species are non-overlapping, and administering each of the resulting immunoconjugates at the maximum tolerated dose to the host.
Claim 40
Dependent Claim 25 words
The method of claim 36 wherein each therapeutic agent is selected from the group consisting of therapeutically effective radionuclides, drugs, toxins, and biological response modifiers.
Claim 41
Dependent Claim 12 words
The method of claim 36 wherein the target cells are cancer cells.
Claim 42
Dependent Claim 25 words
The method of claim 38 wherein each of the antibody species is a monoclonal antibody, or a fragment thereof, which binds to the cancer cells.
Claim 43
Dependent Claim 28 words
The method of claim 29 wherein one antibody species is monoclonal antibody NR-LU-10 or a fragment thereof, and a second antibody species is NR-LU-11 or a fragment thereof.

References Cited (Backward Citations)

US4478815A Cited
US4624846A Cited

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