US4444744A
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Tumor localization and therapy with labeled antibodies to cell surface antigens
Assignee: Individual
•
Filing: 1982-09-03
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Granted: 1984-04-24
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Expires: 2002-09-03
Abstract
Abstract Improved methods are provided for using radiolabeled antibodies to tumor cell surface antigens to locate, diagnose and stage tumors having such antigens on their cell surfaces by external photoscanning, whereby significantly increased resolution, convenience and/or efficiency of operation may be achieved. A method is provided for using highly specific radiolabeled antibodies to cell surface antigens for tumor therapy. Radiolabeled antibodies and injectable compositions containing them are provided for use in the method of the invention.
Inventors
- 👤 Milton D. Goldenberg
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 20:38
CPC Classifications
C; C07; C07K; C07K16/00; C07K16/18; C07K16/28; C07K16/30; C07K16/3007; A; A61; A61K; A61K51/00; A61K51/02; A61K51/04; A61K51/08; A61K51/10; A61K51/1045; A61K51/1048; A61K2121/00; A61K2123/00; A61K38/00; Y; Y10; Y10S; Y10S436/00; Y10S436/804; Y10S436/811; Y10S436/813
Claims Analysis
Total Claims: 33
Claim 1
Independent Claim
183 words
A method for detecting and localizing a tumor having on its cell surface a tumor-associated or tumorspecific antigen, which comprises injecting a human subject parenterally with an antibody specific to said antigen and radiolabeled with a pharmacologically inert radioisotope capable of detection using a photoscanning device, and with indifferent immunoglobulin from the same or different species as that used to prepare said specific antibody, said indifferent immunoglobulin being radiolabeled with a different pharmacologically inert radioisotope emitting at an energy capable of independent detection using said photoscanning device, the radiolabeling being so effected that the kinetics and distribution of the radiolabeled specific antibody and indifferent immunoglobulin in said subject are substantially the same during the time period required for scanning; and scanning the subject with said photoscanning device, the level of activity of the labeled indifferent immunoglobulin being used to determine the distribution of background activity due to non-targeted specific antibody, said background activity being subtracted from the total activity of specific antibody, whereby the activity of substantially only the targeted tumor-localized specific antibody is determined and said tumor is thereby detected and localized.
Claim 2
Independent Claim
183 words
A method for detecting and localizing a tumor having on its cell surface a tumor-associated or tumorspecific antigen, which comprises injecting a human subject parenterally with an antibody specific to said antigen and radiolabeled with a pharmacologically inert radioisotope capable of detection using a photoscanning device, and with indifferent immunoglobulin from the same or different species as that used to prepare said specific antibody, said indifferent immunoglobulin being radiolabeled with a different pharmacologically inert radioisotope emitting at an energy capable of independent detection using said photoscanning device, the radiolabeling being so effected that the kinetics and distribution of the radiolabeled specific antibody and indifferent immunoglobulin in said subject are substantially the same during the time period required for scanning; and scanning the subject with said photoscanning device, the level of activity of the labeled indifferent immunoglobulin being used to determine the distribution of background activity due to non-targeted specific antibody, said background activity being subtracted from the total activity of specific antibody, whereby the activity of substantially only the targeted tumor-localized specific antibody is determined and said tumor is thereby detected and localized.
Claim 3
Dependent Claim
160 words
The method of claim 1, wherein said cell surface antigen is carcinoembryonic antigen, a gastrointestinal cancer cell surface antigen, a lung cancer cell surface antigen, a brain tumor cell surface antigen, a glioma cell surface antigen, a breast cancer cell surface antigen, an esophageal cancer cell surface antigen, a common epithelial cancer cell surface antigen, a common sarcoma cell surface antigen, an osteosarcoma cell surface antigen, a fibrosarcoma cell surface antigen, a melanoma cell surface antigen, a gastric cancer cell surface antigen, a pancreatic cancer cell surface antigen, a colorectal cancer cell surface antigen, a urinary bladder cancer cell surface antigen, a prostatic cancer cell surface antigen, a renal cancer cell surface antigen, an ovarian cancer cell surface antigen, a testicular cancer cell surface antigen, an endometrial cancer cell surface antigen, a cervical cancer cell surface antigen, a Hodgkin's disease cell surface antigen, a lymphoma cell surface antigen, a leukemic cell surface antigen or a trophoblastic tumor cell surface antigen.
Claim 4
Dependent Claim
51 words
The method of claim 1, wherein the specific antibody is radiolabeled with one of, and the indifferent immunoglobulin is labeled with another of Iodine-131, Iodine-123, Iodine-126, Iodine-133, Bromine-77, Indium-111, Indium-113m, Gallium-67, Gallium-68, Ruthenium-95, Ruthenium-97, Ruthenium-103, Ruthenium-105, Mercury-197, Mercury-203, Rhenium-99m, Rhenium-105, Rhenium-101, Scandium-47, Tellurium-121m, Tellurium-122m, Tellurium-125m, Thulium-165, Thulium-167, Thulium-168, Technetium-99m or Fluorine-18.
Claim 5
Dependent Claim
25 words
The method of claim 1, wherein the indifferent immunoglobulin is radiolabeled with a different radioisotope of the same element used to label the specific antibody.
Claim 6
Dependent Claim
38 words
The method of claim 1, wherein the specific antibody is a substantially monospecific antibody having a specific immunoreactivity to said antigen prior to labeling of at least 70% and a cross-reactivity to non-tumor-associated antigens of less than 15%.
Claim 7
Dependent Claim
14 words
The method of claim 5, wherein said substantially monospecific antibody is a monoclonal antibody.
Claim 8
Dependent Claim
25 words
The method of claim 5, wherein said antibody is radiolabeled to an extent sufficient to reduce its specific immunoreactivity to said antigen by about 5-33%.
Claim 9
Dependent Claim
31 words
The method of claim 1, wherein the specific antibody is radiolabeled with one of I-131, Tc-99m or In-111 and the indifferent immunoglobulin is radiolabeled with another of I-131, Tc-99m or In-111.
Claim 10
Dependent Claim
19 words
The method of claim 1, wherein tumor localization is effected within 48 hours of injection of the Iabeled immunoglobulins.
Claim 11
Dependent Claim
14 words
The method of claim 9, wherein localization is effected within 24 hours of injection.
Claim 12
Independent Claim
78 words
A method of tumor radiotherapy, which comprises parenterally injecting into a human subject having a tumor which produces or is associated with a tumor cell surface antigen a tumor-reducing amount of an antibody which is specific to said antigen and radiolabeled with a pharmacologically inert, radiotherapeutically effective radioisotope; wherein said antibody is substantially monospecific to said antigen, having a specific immunoreactivity prior to labeling of at least 70% and a crossreactivity to other antigens of less than 15%.
Claim 13
Independent Claim
78 words
A method of tumor radiotherapy, which comprises parenterally injecting into a human subject having a tumor which produces or is associated with a tumor cell surface antigen a tumor-reducing amount of an antibody which is specific to said antigen and radiolabeled with a pharmacologically inert, radiotherapeutically effective radioisotope; wherein said antibody is substantially monospecific to said antigen, having a specific immunoreactivity prior to labeling of at least 70% and a crossreactivity to other antigens of less than 15%.
Claim 14
Dependent Claim
160 words
The method of claim 11, wherein said cell surface antigen is carcinoembryonic antigen, a gastrointestinal cancer cell surface antigen, a lung cancer cell surface antigen, a brain tumor cell surface antigen, a glioma cell surface antigen, a breast cancer cell surface antigen, an esophageal cancer cell surface antigen, a common epithelial cancer cell surface antigen, a common sarcoma cell surface antigen, an osteosarcoma cell surface antigen, a fibrosarcoma cell surface antigen, a melanoma cell surface antigen, a gastric cancer cell surface antigen, a pancreatic cancer cell surface antigen, a colorectal cancer cell surface antigen, a urinary bladder cancer cell surface antigen, a prostatic cancer cell surface antigen, a renal cancer cell surface antigen, an ovarian cancer cell surface antigen, a testicular cancer cell surface antigen, an endometrial cancer cell surface antigen, a cervical cancer cell surface antigen, a Hodgkin's disease cell surface antigen, a lymphoma cell surface antigen, a leukemic cell surface antigen or a trophoblastic tumor cell surface antigen.
Claim 15
Dependent Claim
12 words
The method of claim 11, wherein said radioisotope is I-131 or Sc-47.
Claim 16
Dependent Claim
28 words
The method of claim 11, wherein the amount of labeled antibody administered in each treatment session carries 25-250 mCi of I-131 radioactivity per 70 kg patient. body weight.
Claim 17
Dependent Claim
31 words
The method of claim 11, wherein the radiolabeled antibody is administered in a plurality of divided doses carrying 20-120 mCi of I-131 radioactivity per 70 kg patient body weight per dose.
Claim 18
Independent Claim
120 words
A method of tumor radiotherapy, which comprises the steps of parenterally injecting into a human subject having a tumor which produces or is associated with a tumor cell surface antigen a radiotherapeutically effective amount of an antibody which is specific to said antigen and radiolabeled with a pharmacologically inert radioisotope capable of detection with a photoscanning device, said labeled antibody further comtaining in chemical combination an addend containing at least five atoms of boron with at least a natural abundance of Boron-10 isotope; locating said tumor by scanning the subject with said photoscanning device to determine the location of the resultant uptake of said labeled antibody by said tumor; and directing a beam of thermal neutrons at said tumor location.
Claim 19
Independent Claim
120 words
A method of tumor radiotherapy, which comprises the steps of parenterally injecting into a human subject having a tumor which produces or is associated with a tumor cell surface antigen a radiotherapeutically effective amount of an antibody which is specific to said antigen and radiolabeled with a pharmacologically inert radioisotope capable of detection with a photoscanning device, said labeled antibody further comtaining in chemical combination an addend containing at least five atoms of boron with at least a natural abundance of Boron-10 isotope; locating said tumor by scanning the subject with said photoscanning device to determine the location of the resultant uptake of said labeled antibody by said tumor; and directing a beam of thermal neutrons at said tumor location.
Claim 20
Dependent Claim
89 words
The method of claim 16, wherein prior to photoscanning, a reference substance is injected into the subject, said reference substance being radiolabeled with a radioisotope emitting at a different energy from the marker-specific antibody label and capable of independent detection by said photoscanning device, the level of activity of said reference substance being used to determine the background activity due to non-targeted specific antibody, said background activity being subtracted from the total activity of the specific antibody, whereby the activity of substantially only the targeted, tumor-associated antibody is determined.
Claim 21
Dependent Claim
26 words
The method of claim 17, wherein said reference substance is at least one of technetium-99m-labeled normal human immunoglobulin, technetium-99m-labeled human serum albumin, technetium-99m-sulfur colloid and technetium99m-pertechnetate.
Claim 22
Dependent Claim
62 words
The method of claim 17, wherein said reference substance is indifferent immunoglobulin from the same or different species as that used to prepare said specific antibody, said indifferent immunoglobulin being radiolabeled in a manner such that the kinetics and distribution of the radiolabeled specific antibody and indifferent immunoglobulin in said subject are substantially the same during the time period required for scanning.
Claim 23
Dependent Claim
18 words
The method of claim 19, wherein said radiolabeled indifferent immunoglobulin is injected concurrently with said radiolabeled marker-specific antibody.
Claim 24
Dependent Claim
58 words
A radiolabeled, boron-conjugated antibody which is specific to a tumor-associated or tumor-specific tumor cell surface antigen, said antibody being radiolabeled with a pharmacologically inert radioisotope capable of detection with a photoscanning device, said labeled antibody further containing in chemical combination an addend containing at least five atoms of boron with at least a natural abundance of Boron-10 isotope.
Claim 25
Dependent Claim
58 words
A radiolabeled, boron-conjugated antibody which is specific to a tumor-associated or tumor-specific tumor cell surface antigen, said antibody being radiolabeled with a pharmacologically inert radioisotope capable of detection with a photoscanning device, said labeled antibody further containing in chemical combination an addend containing at least five atoms of boron with at least a natural abundance of Boron-10 isotope.
Claim 26
Dependent Claim
158 words
The antibody of claim 21, which is specific to carcinoembryonic antigen, a gastrointestinal cancer cell surface antigen, a lung cancer cell surface antigen, a brain tumor cell surface antigen, a glioma cell surface antigen, a breast cancer cell surface antigen, an esophageal cancer cell surface antigen, a common epithelial cancer cell surface antigen, a common sarcoma cell surface antigen, an osteosarcoma cell surface antigen, a fibrosarcoma cell surface antigen, a melanoma cell surface antigen, a gastric cancer cell surface antigen, a pancreatic cancer cell surface antigen, a colorectal cancer cell surface antigen, a urinary bladder cancer cell surface antigen, a prostatic cancer cell surface antigen, a renal cancer cell surface antigen, an ovarian cancer cell surface antigen, a testicular cancer cell surface antigen, an endometrial cancer cell surface antigen, a cervical cancer cell surface antigen, a Hodgkin's disease cell surface antigen, a lymphoma cell surface antigen, a leukemic cell surface antigen or a trophoblastic tumor cell surface antigen.
Claim 27
Dependent Claim
118 words
An injectable composition, comprising (a) an antibody specific to a tumor-associated or tumor-specific tumor cell surface antigen and radiolabeled with a pharmacologically inert radioisotope capable of detection using a photoscanning device; (b) indifferent immunoglobulin from the same or different species as that used to prepare said specific antibody, said indifferent immunoglobulin being radiolabeled with a different pharmacologically inert radioisotope emitting at an energy capable of independent detection using said photoscanning device; and (c) a pharmaceutically acceptable injection vehicle; wherein the radiolabeling is so effected that the kinetics and distribution of the radiolabeled specific antibody and indifferent immunoglobulin will be substantially the same in a human subject during a period of time following injection sufficient for localization and detection.
Claim 28
Dependent Claim
118 words
An injectable composition, comprising (a) an antibody specific to a tumor-associated or tumor-specific tumor cell surface antigen and radiolabeled with a pharmacologically inert radioisotope capable of detection using a photoscanning device; (b) indifferent immunoglobulin from the same or different species as that used to prepare said specific antibody, said indifferent immunoglobulin being radiolabeled with a different pharmacologically inert radioisotope emitting at an energy capable of independent detection using said photoscanning device; and (c) a pharmaceutically acceptable injection vehicle; wherein the radiolabeling is so effected that the kinetics and distribution of the radiolabeled specific antibody and indifferent immunoglobulin will be substantially the same in a human subject during a period of time following injection sufficient for localization and detection.
Claim 29
Dependent Claim
160 words
The composition of claim 23, wherein said cell surface antigen is carcinoembryonic antigen, a gastrointestinal cancer cell surface antigen, a lung cancer cell surface antigen, a brain tumor cell surface antigen, a glioma cell surface antigen, a breast cancer cell surface antigen, an esophageal cancer cell surface antigen,, a common epithelial cancer cell surface antigen, a common sarcoma cell surface antigen, an osteosarcoma cell surface antigen, a fibrosarcoma cell surface antigen, a melanoma cell surface antigen, a gastric cancer cell surface antigen, a pancreatic cancer cell surface antigen, a colorectal cancer cell surface antigen, a urinary bladder cancer cell surface antigen, a prostatic cancer cell surface antigen, a renal cancer cell surface antigen, an ovarian cancer cell surface antigen, a testicular cancer cell surface antigen, an endometrial cancer cell surface antigen, a cervical cancer cell surface antigen, a Hodgkin's disease cell surface antigen, a lymphoma cell surface antigen, a leukemic cell surface antigen or a trophoblastic tumor cell surface antigen.
Claim 30
Dependent Claim
51 words
The composition of claim 23, wherein the specific antibody is radiolabeled with one of, and the indifferent immunoglobulin is labeled with another of Iodine-131, Iodine-123, Iodine-126, Iodine-133, Bromine-77, Indium-111, Indium-113m, Gallium-67, Gallium-68, Ruthenium-95, Ruthenium-97, Ruthenium-103, Ruthenium-105, Mercury-197, Mercury-203, Rhenium-99m, Rhenium-105, Rhenium-101, Scandium-47, Tellurium-121m, Tellurium-122m, Tellurium-125m, Thulium-165, Thulium-167, Thulium-168, Technetium-99m or Fluorine-18.
Claim 31
Dependent Claim
25 words
The composition of claim 23, wherein the indifferent immunoglobulin is radiolabeled with a different radioisotope of the same element used to label the specific antibody.
Claim 32
Dependent Claim
31 words
The composition of claim 23, wherein the specific antibody is labeled with one of I-131, Tc-99m or In-111 and the indifferent immunoglobulin is labeled with another of I-131, Tc-99m or In-111.
Claim 33
Dependent Claim
20 words
The composition of claim 23, wherein the specific antibody is a monoclonal antibody and the indifferent immunoglobulin is myeloma protein.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1987-04-24 | 1987-10-24 | 1988-04-24 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1991-04-24 | 1991-10-24 | 1992-04-24 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1995-04-24 | 1995-10-24 | 1996-04-24 | $7700.00 | Window Closed / Lapsed |