US5034223A
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Methods for improved targeting of antibody, antibody fragments, hormones and other targeting agents, and conjugates thereof
Assignee: Poniard Pharmaceuticals Inc
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Filing: 1987-10-09
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Granted: 1991-07-23
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Expires: 2007-10-09
Abstract
Abstract Methods for improved targeting of antibody, antibody fragments, peptides hormones, steroid hormones and conjugates thereof are disclosed. Enhanced delivery to target cells of antibodies or fragments thereof or other receptor-mediated delivery system, such as peptide, specific for a population of cells of a mammal comprises steps of administering to said mammal an adequate dosage of blocking antibodies or fragments thereof or other receptor-mediated delivery system, such as peptide, and administering to said mammal an effective dosage of said antibodies or fragments thereof or other receptor-mediated delivery system, such as peptide, specific for said population of cells. In the preferred embodiment, the specific antibodies are monoclonal antibodies directed toward tumor-associated antigen in man.
Inventors
- 👤 Paul G. Abrams
- 👤 Robert W. Schroff
- 👤 Alton C. Morgan, Jr.
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-29 05:59
CPC Classifications
C; C07; C07K; C07K16/00; C07K16/18; C07K16/28; C07K16/30; C07K16/3053; A; A61; A61K; A61K47/00; A61K47/50; A61K47/51; A61K47/68; A61K47/6835; A61K47/6851; A61K47/6865; A61K38/00; Y; Y10; Y10S; Y10S424/00; Y10S424/809
Claims Analysis
Total Claims: 35
Claim 1
Independent Claim
100 words
A method of enhancing delivery to solid tumor target cells within a mammal of conjugated specific antibodies or fragments thereof pharmaceutically active and specific for said target cells, comprising the steps of: administering to said mammal an adequate dosage of blocking antibodies or fragments thereof, said blocking antibodies being capable of blocking the binding of the conjugated specific antibodies or fragments thereof to non-target tissue(s) through antigen recognition; and then administering to said mammal a diagnostically or therapeutically effective dosage of said conjugated specific antibodies or fragments thereof, said conjugated specific antibodies being specific for said solid tumor target cells.
Claim 2
Independent Claim
100 words
A method of enhancing delivery to solid tumor target cells within a mammal of conjugated specific antibodies or fragments thereof pharmaceutically active and specific for said target cells, comprising the steps of: administering to said mammal an adequate dosage of blocking antibodies or fragments thereof, said blocking antibodies being capable of blocking the binding of the conjugated specific antibodies or fragments thereof to non-target tissue(s) through antigen recognition; and then administering to said mammal a diagnostically or therapeutically effective dosage of said conjugated specific antibodies or fragments thereof, said conjugated specific antibodies being specific for said solid tumor target cells.
Claim 3
Dependent Claim
21 words
The method of claim 1 wherein said blocking antibodies or fragments thereof are capable of cross-reactive, epitope-specific binding to non-target cells.
Claim 4
Dependent Claim
25 words
The method of claim 1 wherein said antibody fragments are selected from the group consisting of F(ab)', F(ab)' 2 , Fab, Fv, and mixtures thereof.
Claim 5
Dependent Claim
17 words
The method of claim 1 wherein said solid tumor target cells are characterized by having tumor-associated antigen.
Claim 6
Dependent Claim
13 words
The method of claim 1 wherein any of the antibodies are monoclonal antibodies.
Claim 7
Dependent Claim
13 words
The method of claim 1 wherein any of the antibodies are polyclonal antibodies.
Claim 8
Dependent Claim
24 words
The method of claim 1 wherein the conjugated specific antibodies comprise antibodies or fragments thereof specific for said target cells conjugated to a cytotoxin.
Claim 9
Dependent Claim
24 words
The method of claim 1 wherein the conjugated specific antibodies comprise antibodies or fragments thereof specific for said target cells conjugated to a radionuclide.
Claim 10
Dependent Claim
19 words
The method of claim 1 wherein the effective dosage of conjugated specific antibodies or fragments thereof is diagnostically effective.
Claim 11
Dependent Claim
19 words
The method of claim 1 wherein the effective dosage of conjugated specific antibodies or fragments thereof is therapeutically effective.
Claim 12
Dependent Claim
11 words
The method of claim 1 wherein the mammal is a human.
Claim 13
Independent Claim
107 words
A method of enhancing the localization at a solid tumor target site of conjugated specific antibodies or fragments thereof specific for an antigen contained on the target site and also on a non-target tissue or organ within a mammal, comprising the steps of: perfusing said non-target tissue or organ with an adequate dosage of blocking antibodies or fragments thereof, said blocking antibodies being capable of blocking the binding of the conjugated specific antibodies or fragments thereof to non-target tissue(s) or organ through antigen recognition; and administering to the mammal a diagnostically or therapeutically effective dosage of said conjugated specific antibodies or fragments thereof specific for said antigen.
Claim 14
Independent Claim
107 words
A method of enhancing the localization at a solid tumor target site of conjugated specific antibodies or fragments thereof specific for an antigen contained on the target site and also on a non-target tissue or organ within a mammal, comprising the steps of: perfusing said non-target tissue or organ with an adequate dosage of blocking antibodies or fragments thereof, said blocking antibodies being capable of blocking the binding of the conjugated specific antibodies or fragments thereof to non-target tissue(s) or organ through antigen recognition; and administering to the mammal a diagnostically or therapeutically effective dosage of said conjugated specific antibodies or fragments thereof specific for said antigen.
Claim 15
Dependent Claim
24 words
The method of claim 12 wherein said blocking antibodies or fragments thereof are capable of cross-reactive, epitope-specific binding to the non-target tissue or organ.
Claim 16
Dependent Claim
25 words
The method of claim 12 wherein said antibody fragments are selected from the group consisting of F(ab)', F(ab)' 2 , Fab, Fv, and mixtures thereof.
Claim 17
Dependent Claim
16 words
The method of claim 12 wherein said tissue or organ is characterized by having tumor-associated antigen.
Claim 18
Dependent Claim
11 words
The method of claim 12 wherein the antibodies are monoclonal antibodies.
Claim 19
Dependent Claim
11 words
The method of claim 12 wherein the antibodies are polyclonal antibodies.
Claim 20
Dependent Claim
21 words
The method of claim 12 wherein the conjugated specific antibodies comprise antibodies or fragments thereof conjugated to a cytotoxin or drug.
Claim 21
Dependent Claim
19 words
The method of claim 12 wherein the conjugated specific antibodies comprise antibodies or fragments thereof conjugated to a radionuclide.
Claim 22
Dependent Claim
23 words
The method of claim 12 wherein the blocking antibodies or fragments thereof and the conjugated specific antibodies or fragments thereof are administered simultaneously.
Claim 23
Dependent Claim
23 words
The method of claim 12 wherein the blocking antibodies or fragments thereof are administered prior to the conjugated specific antibodies or fragments thereof.
Claim 24
Dependent Claim
20 words
The method of claim 12 wherein the effective dosage of said conjugated specific antibodies or fragments thereof is diagnostically effective.
Claim 25
Dependent Claim
20 words
The method of claim 12 wherein the effective dosage of said conjugated specific antibodies or fragments thereof is therapeutically effective.
Claim 26
Dependent Claim
11 words
The method of claim 12 wherein the mammal is a human.
Claim 27
Independent Claim
65 words
A method of targeting melanoma in humans, comprising the steps of: administering to said human an adequate dosage of unlabeled specific antibody or fragment thereof that binds to a melanoma-associated antigen; and then administering to said human a diagnostically or therapeutically effective dose of labeled specific antibody or fragment thereof that binds to the same epitope of the melanoma-associated antigen as the unlabeled specific antibody.
Claim 28
Independent Claim
65 words
A method of targeting melanoma in humans, comprising the steps of: administering to said human an adequate dosage of unlabeled specific antibody or fragment thereof that binds to a melanoma-associated antigen; and then administering to said human a diagnostically or therapeutically effective dose of labeled specific antibody or fragment thereof that binds to the same epitope of the melanoma-associated antigen as the unlabeled specific antibody.
Claim 29
Dependent Claim
22 words
The method of claim 25 wherein the antibody or fragment thereof that binds to a melanoma-associated antigen recognizes the 250 Kd. glycoprotein/proteoglycan.
Claim 30
Dependent Claim
35 words
The method of claim 25 wherein the antigen-binding region of the antibody or fragment thereof is selected from the group consisting of antigen-binding regions of antibodies 9.2.27 and NR-ML-05, and their clones, chimaeras and derivatives.
Claim 31
Dependent Claim
22 words
The method of claim 25 wherein the antigen-binding region of the antibody or fragment thereof recognizes the G D3 glycolipid melanoma-associated antigen.
Claim 32
Dependent Claim
19 words
The method of claim 25 wherein the antigen-binding region of antibody or fragment thereof recognizes the P97 melamona-associated antigen.
Claim 33
Independent Claim
93 words
A method of enhancing delivery to solid tumor target cells within a mammal of conjugated specific antibodies or fragments thereof pharmaceutically active and specific for said target cells, comprising the steps of: administering to said mammal an adequate dosage of blocking antibodies or fragments thereof, wherein said blocking antibodies are the unconjugated form of the conjugated specific antibodies or fragments thereof; and then administering to said mammal a diagnostically or therapeutically effective dosage of said conjugated specific antibodies or fragments thereof, said conjugated specific antibodies being specific for said solid tumor target cells.
Claim 34
Independent Claim
93 words
A method of enhancing delivery to solid tumor target cells within a mammal of conjugated specific antibodies or fragments thereof pharmaceutically active and specific for said target cells, comprising the steps of: administering to said mammal an adequate dosage of blocking antibodies or fragments thereof, wherein said blocking antibodies are the unconjugated form of the conjugated specific antibodies or fragments thereof; and then administering to said mammal a diagnostically or therapeutically effective dosage of said conjugated specific antibodies or fragments thereof, said conjugated specific antibodies being specific for said solid tumor target cells.
Claim 35
Dependent Claim
24 words
The method of claim 30 wherein the conjugated specific antibodies comprise antibodies or fragments thereof specific for said target cells conjugated to a radionuclide.
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