Patent EP0035265A2 successfully refreshed from Google Patents.
EP0035265A2
Expired / Lapsed
EP
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Agent for tumor localization and therapy with labeled antibodies and antibody fragments
Assignee: Goldenberg Milton David
•
Filing: 1981-03-02
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Granted: —
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Expires: 2001-03-02
Abstract
Abstract Methods are provided for using radiolabeled antibodies and antibody fragments specific to tumor-associated markers for detection, localization and therapy of tumors. Mixtures of labeled antibodies and/or antibody fragments with varied specificity or multivalent hybrid fragments permit detection and localization of more than one tumor type. Antibodies, antibody fragments and injectable compositions for use in the methods of the invention are also provided.
Inventors
- 👤 Milton David Goldenberg
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-11-08 06:22
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; A61P; A61P35/00; A61K2121/00; A61K2123/00; A61K38/00
Claims Analysis
Total Claims: 146
Claim 1
Independent Claim
171 words
In a method for determining the location of a tumor which produces or is associated with carcinoembryonic antigen (CEA), which comprises injecting a subject parenterally with an antibody specific to CEA and radiolabeled with a pharmacologically inert radioisotope capable of detection using a photoscanning device and subsequently scanning the subject with said device to determine the location of the resultant uptake of said labeled antibody by said tumor; the improvement which comprises concurrently injecting said subject with normal immunoglobulin from the same or different species as that used to prepare said specific antibody, said normal immunoglobulin being radiolabeled with a different radioisotope of the same element used to label the specific antibody and emitting at an energy capable of independent detection using said photoscanning device, the level of activity of the labeled normal immunoglobulin being used to determine the distribution of background activity due to non-targeted specific antibody, said distribution being subtracted from the total activity of specific antibody whereby the activity of substantially only the targeted tumor-associated antibody is determined.
Claim 2
Dependent Claim
171 words
In a method for determining the location of a tumor which produces or is associated with carcinoembryonic antigen (CEA), which comprises injecting a subject parenterally with an antibody specific to CEA and radiolabeled with a pharmacologically inert radioisotope capable of detection using a photoscanning device and subsequently scanning the subject with said device to determine the location of the resultant uptake of said labeled antibody by said tumor; the improvement which comprises concurrently injecting said subject with normal immunoglobulin from the same or different species as that used to prepare said specific antibody, said normal immunoglobulin being radiolabeled with a different radioisotope of the same element used to label the specific antibody and emitting at an energy capable of independent detection using said photoscanning device, the level of activity of the labeled normal immunoglobulin being used to determine the distribution of background activity due to non-targeted specific antibody, said distribution being subtracted from the total activity of specific antibody whereby the activity of substantially only the targeted tumor-associated antibody is determined.
Claim 3
Dependent Claim
42 words
The method of claim 1, wherein the specific anti-CEA antibody is labeled with one of , and the normal immunoglobulin is labeled with the other of Iodine-131 and Iodine-123; Indium-111 and Indium-113m; Gallium-67 and Gallium-68; Ruthenium-97 and Ruthenium-103; or Mercury-197 and Mercury-203.
Claim 4
Dependent Claim
31 words
The method of claim 1, wherein the specific anti-CEA antibody is labeled with one of Iodine-131 or Iodine-123 and the normal immunoglobulin is labeled with the other of Iodine-131 or Iodine-123.
Claim 5
Dependent Claim
32 words
The method of claim 1, wherein the amount of radiolabel introduced into the specific anti-CEA antibody is sufficient to reduce the CEA specific immunoreactivity of said antibody by from 5 to 33%.
Claim 6
Dependent Claim
15 words
The method of claim 4, wherein said immunoreactivity is reduced by from 10 to 25%.
Claim 7
Dependent Claim
30 words
The method of claim 4, wherein the specific anti-CEA antibody is radiolabeled with Iodine-131 or Iodine-123, an average of at least 2.5 atoms of iodine per antibody molecule being introduced.
Claim 8
Dependent Claim
24 words
The method of claim 6, wherein an average of at least 5 atoms of iodine per antibody molecule are introduced by direct chemical substitution.
Claim 9
Dependent Claim
119 words
In a method for determining the location of a tumor which produces or is associated with carcinoembryonic antigen, which comprises injecting a subject parenterally with an antibody specific to CEA and radiolabeled with a pharmacologically inert radioisotope capable of detection using a photoscanning device and subsequently scanning the subject with said device to determine the location of the resultant uptake of said labeled antibody by said tumor; the improvement which comprises using as said anti-CEA antibody a substantially monospecific antibody having a CEA-specific immunoreactivity prior to labeling of at least 70% and a cross-reactivity to other antigens of less than 15%, said antibody being radiolabeled to an extent sufficient to reduce its CEA-specific immunoreactivity by from 5 to 33%.
Claim 10
Dependent Claim
119 words
In a method for determining the location of a tumor which produces or is associated with carcinoembryonic antigen, which comprises injecting a subject parenterally with an antibody specific to CEA and radiolabeled with a pharmacologically inert radioisotope capable of detection using a photoscanning device and subsequently scanning the subject with said device to determine the location of the resultant uptake of said labeled antibody by said tumor; the improvement which comprises using as said anti-CEA antibody a substantially monospecific antibody having a CEA-specific immunoreactivity prior to labeling of at least 70% and a cross-reactivity to other antigens of less than 15%, said antibody being radiolabeled to an extent sufficient to reduce its CEA-specific immunoreactivity by from 5 to 33%.
Claim 11
Dependent Claim
15 words
The method of claim 8, wherein said substantially monospecific antibody is a monoclonal anti-CEA antibody.
Claim 12
Dependent Claim
28 words
The method of claim 8, wherein said substantially monospecific antibody has a CEA-specific immunoreactivity prior to labeling of at least 80% and a cross-reactivity of less than 10%.
Claim 13
Dependent Claim
27 words
The method of claim 9, wherein said monoclonal antibody has a CEA-specific immunoreactivity prior to labeling of at least 90% and a cross-reactivity of less than 10%.
Claim 14
Dependent Claim
43 words
The method of claim 8, wherein said substantially monospecific anti-CEA antibody is radiolabeled with one 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, Tellurium-121m, Tellurium-122m, Tellurium-125m, Thulium-165, Thulium-167, Thulium-168, Technetium-99m and Fluorine-18.
Claim 15
Dependent Claim
31 words
The method of claim 8, wherein said substantially monospecific anti-CEA antibody is radiolabeled with Iodine-131 or Iodine-123, an average of at least 5 atoms of iodine per antibody molecule being introduced.
Claim 16
Dependent Claim
30 words
The method of claim 10, wherein said monoclonal anti-CEA antibody is radiolabeled with Iodine-131 or Iodine-123, an average of at least 5 atoms of iodine per antibody molecule being introduced.
Claim 17
Dependent Claim
106 words
The method of claim 8, which further comprises concurrently injecting said subject with normal immunoglobulin from the same or different species as that used to prepare said specific antibody, said normal immunoglobulin being radiolabeled with a different radioisotope of the same element used to label the specifi: nd emitting at an energy capable of independent detection using said photoscanning device, the level of activity of the labeled normal immunoglobulin being used to determine the distribution of background aptivity due to non-targeted specific antibody, said distribution being subtracted from the total activity of specific antibody whereby the activity of substantially only the targeted, tumor-associated antibody is determined.
Claim 18
Dependent Claim
31 words
The method of claim 15, wherein said substantially monospecific antibody is labeled with one of 1-131 and 1-123, and said normal immunoglobulin is labeled with the other of I-131 and I-123.
Claim 19
Dependent Claim
57 words
Substantially monospecific anti-CEA antibody having a CEA-specific immunoreactivity prior to labeling of at least 70% and a cross-reactivity to other antigens of less than 15%, said antibody being radiolabeled with a pharmacologically inert radioisotope capable of detection using a photoscanning device, the extent of radiolabeling being sufficient to reduce said CEA-specific immunoreactivity by from 5 to 33%.
Claim 20
Dependent Claim
57 words
Substantially monospecific anti-CEA antibody having a CEA-specific immunoreactivity prior to labeling of at least 70% and a cross-reactivity to other antigens of less than 15%, said antibody being radiolabeled with a pharmacologically inert radioisotope capable of detection using a photoscanning device, the extent of radiolabeling being sufficient to reduce said CEA-specific immunoreactivity by from 5 to 33%.
Claim 21
Dependent Claim
42 words
The antibody of claim 17,-wherein said substantially monospecific anti-CEA antibody is radiolabeled with one of Iodine-131, Iodine-123, Iodine-126, Iodine-133, Bromine-77, Indium-111, Indium-113m, Gallium-67, Gallium-68, Rhthenium-95, Ruthenium-97, Ruthenium-103, Ruthenium-105, Mercury-197, Mercury-203, Rhenium-99m, Rhenium-105, Rhenium-101, Tellurium-121m, Tellurium-122m, Tellurium-125m, Thulium-165, Thulium-167, Thulium-168, Technetium-99m and Fluorine-18.
Claim 22
Dependent Claim
26 words
The antibody of claim 17, wherein said radioisotope is Iodine-131 or Iodine-123, an average of at least 2.5 atoms of iodine per antibody molecule being introduced.
Claim 23
Dependent Claim
21 words
The antibody of claim 17, wherein said CEA-specific immunoreactivity is at least 80% and said cross- reactivity is less than 10%.
Claim 24
Dependent Claim
25 words
The antibody of claim 20, wherein said radioisotope is Iodine-131 or Iodine-123, an average of at least 5 atoms of iodine per antibody being introduced.
Claim 25
Dependent Claim
11 words
The antibody of claim 17, which is a monoclonal anti-CEA antibody.
Claim 26
Dependent Claim
25 words
The antibody of claim 22, wherein said radioisotope is Iodine-131 or Iodine-123, an average of at least 5 atoms of iodine per antibody being introduced.
Claim 27
Dependent Claim
82 words
An injectable composition which comprises (a) an antibody specific to carcinoembryonic antigen and radiolabeled with a pharmaceutically inert radioisotope capable of detection using a photoscanning device; (b) normal immunoglobulin from the same or different species as that used to prepare said specific antibody, said normal immunoglobulin being radiolabeled with a different isotope of the same element used to label the specific antibody and emitting at an energy capable of independent detection using said photoscanning device; and (c) a pharmaceutically acceptable injection vehicle.
Claim 28
Dependent Claim
82 words
An injectable composition which comprises (a) an antibody specific to carcinoembryonic antigen and radiolabeled with a pharmaceutically inert radioisotope capable of detection using a photoscanning device; (b) normal immunoglobulin from the same or different species as that used to prepare said specific antibody, said normal immunoglobulin being radiolabeled with a different isotope of the same element used to label the specific antibody and emitting at an energy capable of independent detection using said photoscanning device; and (c) a pharmaceutically acceptable injection vehicle.
Claim 29
Dependent Claim
41 words
The composition of claim 24, wherein the specific anti-CEA antibody is labeled with one of, and the normal immunoglobulin is labeled with the other of Iodine-131 and Iodine-123; Indium-111 and Indium-113m; Gallium-67 and Gallium-68; Ruthenium-97 and Ruthenium-103; or Mercury-197 and Mercury-203.
Claim 30
Dependent Claim
31 words
The composition of claim 24, wherein the specific anti-CEA antibody is labeled with one of Iodine-131 or Iodine-123 and the normal immunoglobulin is labeled with the other of Iodine-131 or Iodine-123.
Claim 31
Dependent Claim
70 words
An injectable composition which comprises: (a) substantially monospecific anti-CEA antibody having a CEA-specific immunoreactivity prior to labeling of at least 70% and a cross-reactivity to other antigens of less than 15%, said antibody being radiolabeled with a pharmacologically inert radioisotope capable of detection using a photoscanning device, the extent of radiolabeling being sufficient to reduce said CEA-specific immunoreactivity by from 5 to 33%; and (b) a pharmaceutically acceptable injection vehicle.
Claim 32
Dependent Claim
70 words
An injectable composition which comprises: (a) substantially monospecific anti-CEA antibody having a CEA-specific immunoreactivity prior to labeling of at least 70% and a cross-reactivity to other antigens of less than 15%, said antibody being radiolabeled with a pharmacologically inert radioisotope capable of detection using a photoscanning device, the extent of radiolabeling being sufficient to reduce said CEA-specific immunoreactivity by from 5 to 33%; and (b) a pharmaceutically acceptable injection vehicle.
Claim 33
Dependent Claim
21 words
The composition of claim 27, wherein said CEA-specific immunoreactivity is at least 80% and said cross- reactivity is less than 10%.
Claim 34
Dependent Claim
25 words
The composition of claim 28, wherein said radioisotope is Iodine-131 or Iodine-123, an average of at least 5 atoms of iodine per antibody being introduced.
Claim 35
Dependent Claim
13 words
The composition of claim 27, wherein said antibody is a monoclonal anti-CEA antibody.
Claim 36
Dependent Claim
25 words
The composition of claim 30, wherein said radioisotope is Iodine-131 or Iodine-123, an average of at least 5 atoms of iodine per antibody being introduced.
Claim 37
Independent Claim
44 words
A method of tumor radiotherapy, which comprises parenterally injecting into a subject having a tumor which produces or is associated with carcinoembryonic antigen (CEA) a tumor-reducing amount of an antibody which is specific to CEA and radiolabeled with a pharmacologically inert, radiotherapeutically effective radioisotope.
Claim 38
Independent Claim
44 words
A method of tumor radiotherapy, which comprises parenterally injecting into a subject having a tumor which produces or is associated with carcinoembryonic antigen (CEA) a tumor-reducing amount of an antibody which is specific to CEA and radiolabeled with a pharmacologically inert, radiotherapeutically effective radioisotope.
Claim 39
Dependent Claim
34 words
The method of claim 32, wherein said antibody is substantially monospecific to CEA, having a CEA-specific immunoreactivity prior to labeling of at least 70% and a cross-reactivity to other antigens of less than 15%.
Claim 40
Dependent Claim
13 words
The method of claim 33, wherein said antibody is a monoclonal anti-CEA antibody.
Claim 41
Dependent Claim
21 words
The method of claim 32, wherein said radioisotope is 1-131 and said amount is from 25 to 250 mCi per administration.
Claim 42
Independent Claim
103 words
A method of tumor radiotherapy, which comprises parenterally injecting into a subject having a tumor which produces or is associated with carcinoembryonic antigen (CEA) a radiotherapeutically effective amount of an antibody which is specific to CEA and radiolabeled with a pharmacologically inert radioisotope capable of detection with a photoscanning device, said labeled antibody further containing in chemical combination at least one addend containing at least five atoms of boron with at least a natural abundance of Boron-10 isotope; wherein the location of said tumor is determined using said photoscanning device, and a beam of thermal neutrons is then directed at said tumor location.
Claim 43
Independent Claim
103 words
A method of tumor radiotherapy, which comprises parenterally injecting into a subject having a tumor which produces or is associated with carcinoembryonic antigen (CEA) a radiotherapeutically effective amount of an antibody which is specific to CEA and radiolabeled with a pharmacologically inert radioisotope capable of detection with a photoscanning device, said labeled antibody further containing in chemical combination at least one addend containing at least five atoms of boron with at least a natural abundance of Boron-10 isotope; wherein the location of said tumor is determined using said photoscanning device, and a beam of thermal neutrons is then directed at said tumor location.
Claim 44
Dependent Claim
50 words
An antibody which is specific to carcinoembryonic antigen, said antibody being radiolabeled with a pharmacologically inert radioisotope detection with a photoscanning device, said labeled antibody further containing in chemical combination at least one addend containing at least five atoms of boron with at least a natural abundance of Boron-10 isotope.
Claim 45
Dependent Claim
50 words
An antibody which is specific to carcinoembryonic antigen, said antibody being radiolabeled with a pharmacologically inert radioisotope detection with a photoscanning device, said labeled antibody further containing in chemical combination at least one addend containing at least five atoms of boron with at least a natural abundance of Boron-10 isotope.
Claim 46
Dependent Claim
65 words
An injectable composition, which comprises: (a) an antibody which is specific to carcinoembryonic 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 at least one addend containing at least five atoms of boron with at least a natural abundance of Boron-10 isotope; and (b) a pharmaceutically acceptable injection vehicle.
Claim 47
Dependent Claim
65 words
An injectable composition, which comprises: (a) an antibody which is specific to carcinoembryonic 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 at least one addend containing at least five atoms of boron with at least a natural abundance of Boron-10 isotope; and (b) a pharmaceutically acceptable injection vehicle.
Claim 48
Dependent Claim
56 words
The injectable composition of claim 38, which further comprises normal immunoglobulin from the same or different species as that used to prepare said specific antibody, said normal immunoglobulin being radiolabeled with a different isotope of the same element used to label the specific antibody and emitting an energy capable of independent detection using said photoscanning device.
Claim 49
Independent Claim
69 words
A method for detecting and localizing a tumor which produces or is associated with an intracellular marker substance, which comprises injecting a subject parenterally with an antibody specific to said marker substance and radiolabeled with a pharmacologically inert radioisotope capable of detection using a photoscanning device, and subsequently scanning with said device to detect and locate the site or sites of uptake of said labeled antibody by said tumor.
Claim 50
Independent Claim
69 words
A method for detecting and localizing a tumor which produces or is associated with an intracellular marker substance, which comprises injecting a subject parenterally with an antibody specific to said marker substance and radiolabeled with a pharmacologically inert radioisotope capable of detection using a photoscanning device, and subsequently scanning with said device to detect and locate the site or sites of uptake of said labeled antibody by said tumor.
Claim 51
Dependent Claim
35 words
The method of claim 40, wherein said marker-specific antibody is a substantially monospecific antibody having a marker-specific immunoreactivity prior to labeling of at least 70% and a cross-reactivity to non-tumor-associated antigens of less than 15%.
Claim 52
Dependent Claim
14 words
The method of claim 41, wherein said substantially monospecific antibody is a monoclonal antibody.
Claim 53
Dependent Claim
24 words
The method of claim 41, wherein said antibody is radiolabeled to an extent sufficient to reduce its marker-specific immunoreactivity by from 5 to 33%.
Claim 54
Dependent Claim
41 words
The method of claim 43, wherein said substantially monospecific antibody is radiolabeled with Iodine-131 or Iodine-123, an average of at least 5 atoms of iodine per antibody molecule being introduced by direct substitution of iodine for hydrogen on the antibody molecule.
Claim 55
Dependent Claim
38 words
The method of claim 40, wherein said radioisotope is one 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, Tellurium-121m, Tellurium-122m, Tellurium-125m, Thulium-165, Thulium-167, Thulium-168, Technetium-99m and Fluorine-18.
Claim 56
Dependent Claim
13 words
The method of claim 40, wherein said marker substance is an oncofetal antigen.
Claim 57
Dependent Claim
13 words
The method of claim 40, wherein said marker substance is a placental antigen.
Claim 58
Dependent Claim
17 words
The method of claim 40, wherein said marker substance is an oncogenic or tumor vi ed antigen.
Claim 59
Dependent Claim
25 words
The method of claim 40, wherein said marker substance is a tissue- or organ-associated antigen, an ectopic hormone or a normal antigen or variant thereof.
Claim 60
Dependent Claim
11 words
The method of claim 40, wherein said marker substance is alpha-fetoprotein(AFP).
Claim 61
Dependent Claim
14 words
The method of claim 40, wherein said marker substance is human chorionic gonadotropin (HCG).
Claim 62
Dependent Claim
13 words
The method of claim 40, wherein said marker substance is colon-specific antigen-p (CSAp).
Claim 63
Dependent Claim
90 words
The method of claim 40, wherein said marker substance is one of prostatic acid phosphatase, pancreatic oncofetal antigen, placental alkaline phosphatase, pregnancy beta l -globulin, parathormone, calcitonin, tissue polypeptide antigen, T-antigen, beta 2 -microglobulin, galactyosyl transferase-II (GT-II), gp-52 viral associated antigen, ovarian cystadenocarcinoma-associated antigen (OCAA), ovarian tumor-specific antigen (OCA), cervical cancer antigens (CA-58 CCA, TA-4), basic fetoprotein (BFP), terminal deoxynucleotidyl transferase (TdT), cytoplasmic melanoma-associated antigens, human astrocytoma-associated antigen (HAAA), common glioma antigen (CGA), glioembryonic antigen (GEA), glial fibrillary acidic protein (GFA), common meningioma antigen (CMA) and tumor angiogenesis factor (TAF).
Claim 64
Dependent Claim
89 words
The method of claim 40, 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 65
Dependent Claim
26 words
The method of claim 54, wherein said reference substance is at least one of technetium-99m-labeled normal huqan immunoglobulin, technetium-99m-labeled human serum albumin, technetium-99m-sulfur colloid and technetium-99m-pertechnetate.
Claim 66
Dependent Claim
45 words
The method of claim 54, wherein said reference substance is normal immunoglobulin from the same or different species as that used to prepare said specific antibody, said normal immunoglobulin being radiolabeled with a different isotope of the same element used to label the specific antibody.
Claim 67
Dependent Claim
18 words
The method of claim 56, wherein said radiolabeled normal immunoglobulin is injected concurrently with said radiolabeled marker-specific antibody.
Claim 68
Dependent Claim
51 words
The method of claim 56, wherein the specific antibody is labeled with one of a pair of radioisotopes and the normal immunoglobulin is labeled with the other of the pair, said pair being one of Iodine-131 and Iodine-123; Indium-111 and Indium-113m; Gallium-67 and Gallium-68; Ruthenium-97 and Ruthenium-103; or Mercury-197 and Mercury-203.
Claim 69
Dependent Claim
123 words
An injectable composition, which comprises (a) a substantially monospecific antibody having a specific immunoreactivity of at least 70% to an intracellular marker substance produced by or associated with a tumor and a cross-reactivity to non-tumor associated antigens of less than 15%; said antibody being radiolabeled with one of Iodine-131 and Iodine-123 by direct substitution of iodine for hydrogen on the antibody molecule to an extent sufficient to reduce its specific immunoreactivity by from 5 to 33%; (b) normal immu.noglobulin from the same or different species as that used to prepare said specific antibody, said normal immunoglobulin being radiolabeled with the other of Iodine-131 and Iodine-123 by direct substitution of iodine for hydrogen on the immunoglobulin molecule; and (c) a pharmaceutically acceptable injection vehicle.
Claim 70
Dependent Claim
123 words
An injectable composition, which comprises (a) a substantially monospecific antibody having a specific immunoreactivity of at least 70% to an intracellular marker substance produced by or associated with a tumor and a cross-reactivity to non-tumor associated antigens of less than 15%; said antibody being radiolabeled with one of Iodine-131 and Iodine-123 by direct substitution of iodine for hydrogen on the antibody molecule to an extent sufficient to reduce its specific immunoreactivity by from 5 to 33%; (b) normal immu.noglobulin from the same or different species as that used to prepare said specific antibody, said normal immunoglobulin being radiolabeled with the other of Iodine-131 and Iodine-123 by direct substitution of iodine for hydrogen on the immunoglobulin molecule; and (c) a pharmaceutically acceptable injection vehicle.
Claim 71
Dependent Claim
13 words
The composition of claim 59, wherein said monospecific antibody is a monoclonal antibody.
Claim 72
Dependent Claim
52 words
The composition of claim 60, wherein said monoclonal antibody is raised in a monkey, and antibody- producing monkey lymph or spleen cells are fused with human or mouse myeloma cells to produce hybrid cells which are isolated, cloned and selected for their ability to produce monoclonal antibodies specific to said marker substance.
Claim 73
Dependent Claim
16 words
The composition of claim 59, wherein said marker substance is one of AFP, HCG and CSAp.
Claim 74
Dependent Claim
90 words
The composition of claim 59, wherein said marker substance is one of prostatic acid phosphatase, pancreatic oncofetal antigen, placental alkaline phosphatase, pregnancy beta l -globulin, parathormone, calcitonin, tissue polypeptide antigen, T-antigen, beta 2 - microglobulin, galactyosyl transferase-II (GT-II), gp-52 viral-associated antigen, ovarian cystadenocarcinoma-associated antigen (OCAA), ovarian tumor-specific antigen (OCA), cervical cancer antigens (CA-58, CCA, TA-4), basic fetoprotein (BFP), terminal deoxynucleotidyl transferase (TdT), cytoplasmic melanoma-associated antigens, human astrocytoma-associated antigen (HAAA), common glioma antigen (CGA), glioembryonic antigen (GEA), glial fibrillary acidic protein (GFA), common meningioma antigen (CMA) and tumor angiogenesis factor (TAF).
Claim 75
Dependent Claim
61 words
An antibody which is specific to an intracellular marker substance produced by or associated with a tumor, said antibody being radiolabeled with a pharmacologically inert radioisotope capable of detection with a photoscanning device, said labeled antibody further containing in chemical combination at least one addend containing at least five atoms of boron with at least a natural abundance of Boron-10 isotope.
Claim 76
Dependent Claim
61 words
An antibody which is specific to an intracellular marker substance produced by or associated with a tumor, said antibody being radiolabeled with a pharmacologically inert radioisotope capable of detection with a photoscanning device, said labeled antibody further containing in chemical combination at least one addend containing at least five atoms of boron with at least a natural abundance of Boron-10 isotope.
Claim 77
Dependent Claim
74 words
An injectable composition, which comprises (a) an antibody which is specific to an intracellular marker substance produced by or associated with a tumor, said antibody being radiolabeled with a pharmacologically inert radioisotope capable of detection with a photoscanning device, said labeled antibody further containing in chemical combination at least one addend containing at least five atoms of boron with at least a natural abundance of Boron-10 isotope; and (b) a pharmaceutically acceptable injection vehicle.
Claim 78
Dependent Claim
74 words
An injectable composition, which comprises (a) an antibody which is specific to an intracellular marker substance produced by or associated with a tumor, said antibody being radiolabeled with a pharmacologically inert radioisotope capable of detection with a photoscanning device, said labeled antibody further containing in chemical combination at least one addend containing at least five atoms of boron with at least a natural abundance of Boron-10 isotope; and (b) a pharmaceutically acceptable injection vehicle.
Claim 79
Dependent Claim
56 words
The injectable composition of claim 65, which further comprises normal immunoglobulin from the same or different species as that used to prepare said specific antibody, said normal immunoglobulin being radiolabeled with a different isotope of the same element used to label the specific antibody and emitting an energy capable of independent detection using said photoscanning device.
Claim 80
Independent Claim
49 words
A method of tumor radiotherapy, which comprises parenterally injecting into a subject having a tumor which produces or is associated with an intracellular marker substance an effective tumor reducing amount of an antibody which is specific to said marker substance and radiolabeled with a pharmacologically inert, radiotherapeutically effective radioisotope.
Claim 81
Independent Claim
49 words
A method of tumor radiotherapy, which comprises parenterally injecting into a subject having a tumor which produces or is associated with an intracellular marker substance an effective tumor reducing amount of an antibody which is specific to said marker substance and radiolabeled with a pharmacologically inert, radiotherapeutically effective radioisotope.
Claim 82
Dependent Claim
21 words
The method of claim 67, wherein said radioisotope is I-131 and said amount is from 25 to 250 mCi per administration.
Claim 83
Independent Claim
106 words
A method of tumor radiotherapy, which comprises parenterally injecting into a subject having a tumor which produces or is associated with an intracellular marker substance a radiotherapeutically effective amount of an antibody which is specific to said marker substance and radiolabeled with a pharmacologically inert radioisotope capable of detection with a photoscanning device, said labeled antibody further containing in chemical combination at least one addend containing at least five atoms of boron with at least a natural abundance of Boron-10 isotope; wherein the location of said tumor is determined using said photoscanning device, and a beam of thermal neutrons is then directed at said tumor location.
Claim 84
Independent Claim
106 words
A method of tumor radiotherapy, which comprises parenterally injecting into a subject having a tumor which produces or is associated with an intracellular marker substance a radiotherapeutically effective amount of an antibody which is specific to said marker substance and radiolabeled with a pharmacologically inert radioisotope capable of detection with a photoscanning device, said labeled antibody further containing in chemical combination at least one addend containing at least five atoms of boron with at least a natural abundance of Boron-10 isotope; wherein the location of said tumor is determined using said photoscanning device, and a beam of thermal neutrons is then directed at said tumor location.
Claim 85
Independent Claim
82 words
A method for detecting and localizing a tumor which produces or is associated with a cytoplasmic, intracellular or cell-surface marker substance, which comprises injecting a subject parenterally with at least one marker-specific fragment obtained by cleavage of an antibody specific to said marker substance and radiolabeled with a pharmacologically inert radioisotope capable of detection using a photoscanning device, and subsequently scanning with said device to detect and locate the site or sites of uptake of said labeled antibody fragment by said tumor.
Claim 86
Independent Claim
82 words
A method for detecting and localizing a tumor which produces or is associated with a cytoplasmic, intracellular or cell-surface marker substance, which comprises injecting a subject parenterally with at least one marker-specific fragment obtained by cleavage of an antibody specific to said marker substance and radiolabeled with a pharmacologically inert radioisotope capable of detection using a photoscanning device, and subsequently scanning with said device to detect and locate the site or sites of uptake of said labeled antibody fragment by said tumor.
Claim 87
Dependent Claim
13 words
The method of claim 70, wherein said marker substance is an oncofetal antigen.
Claim 88
Dependent Claim
13 words
The method of claim 70, wherein said marker substance is a placental antigen.
Claim 89
Dependent Claim
16 words
The method of claim 70, wherein said marker substance is an oncogenic or tumor virus-associated antigen.
Claim 90
Dependent Claim
25 words
The method of claim 70, wherein said marker substance is a tissue- or organ-associated antigen, an ectopic hormone or a normal antigen or variant thereof.
Claim 91
Dependent Claim
13 words
The method of claim 70, wherein said marker substance is carcinoembryonic antigen (CEA).
Claim 92
Independent Claim
12 words
The method of calim 70, wherein said marker substance is alpha-fetoprotein (AFP).
Claim 93
Independent Claim
12 words
The method of calim 70, wherein said marker substance is alpha-fetoprotein (AFP).
Claim 94
Dependent Claim
18 words
The method of claim 70, wherein said marker substance is human chorionic gonadotropin (HCG) or the beta-subunit thereof.
Claim 95
Dependent Claim
13 words
The method of claim 70, wherein said marker substance is colon-specific antigen-p (CSAp).
Claim 96
Dependent Claim
95 words
The method of claim 70, wherein said marker substance is one of prostatic acid phosphatase, pancreatic oncofetal antigen, placental alkaline phosphatase, pregnancy beta l -globulin, parathormone, calcitonin, tissue polypeptide antigen, T-antigen, beta 2 - microglobulin, mammary tumor-associated glycoproteins (MTGP), galactyosyl transferase-II (GT-II), gp-52 viral-associated antigen, ovarian cystadenocarcinoma-associated antigen (OCAA), ovarian tumor-specific antigen (OCA), cervical cancer antigens (CA-58., CCA, TA-4), basic fetoprotein (BFP), terminal deoxynucleotidyl transferase (TdT), cytoplasmic melanoma-associated antigens, human astrocytoma-associated antigen (HAAA), common glioma antigen (CGA), glioembryonic antigen (GEA), glial fibrillary acidic protein (GFA), common meningioma antigen (CMA), ferritin, and tumor angiogenesis factor (TAF).
Claim 97
Dependent Claim
30 words
The method of claim 70, wherein said marker-specific fragment is at least one of the Fab, Fab' and F(ab l ) 2 fragments obtained by cleavage of said specific antibody.
Claim 98
Dependent Claim
38 words
The method of claim 70, wherein said radioisotope is one 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, Tellurium-121m, Tellurium-122m, Tellurium-125m, Thulium-165, Thulium-167, Thulium-168, Technetium-99m and Fluorine-18.
Claim 99
Dependent Claim
12 words
The method of claim 70, wherein said radioisotope is Iodine-131 or Iodine-123.
Claim 100
Dependent Claim
34 words
The method of claim 70, wherein the amount of radiolabel introduced by direct chemical substitution into said marker-specific antibody fragment is sufficient to reduce its specific marker substance immunoreactivity by from 5 to 33%.
Claim 101
Dependent Claim
38 words
The method of claim 70, wherein said marker-specific antibody fragment is substantially monospecific for the marker substance, having a crossreactivity with other antigens of less than 15% and an immunoreactivity for the marker substance of more than 50%.
Claim 102
Dependent Claim
28 words
The method of claim 70, wherein the specific antibody cleaved to produce said marker-specific fragment is a monoclonal antibody having a marker substance specificity of at least 90%.
Claim 103
Dependent Claim
29 words
The method of claim 70, wherein said fragment is labeled with a radioisotope of iodine, an average of at least 2.5 atoms of iodine per fragment molecule being introduced.
Claim 104
Dependent Claim
22 words
The method of claim 70, wherein said tumor is located in the brain and said fragment is injected intravenously, intraarterially or intrathecally.
Claim 105
Dependent Claim
11 words
The method of claim 87, wherein the fragment is injected intravenously.
Claim 106
Dependent Claim
92 words
The method of claim 70, wherein prior to photoscanning, a second substance is injected into the subject, said second substance being radiolabeled with a radioisotope emitting at a different energy from the antibody fragment label and capable of independent detection by said photoscanning device, the level of activity of said second substance being used to determine the background activity due to non-targeted specific antibody fragment, said background activity being subtracted from the total activity of the specific antibody fragment, whereby the activity of substantially only the targeted, tumor-associated antibody fragment is determined.
Claim 107
Dependent Claim
26 words
The method of claim 89, wherein said second substance is at least one of technetium-99m-labeled normal human immunoglobulin, technetium-99m-labeled human serum albumin, techetium-99m-sulfur colloid and technetium-99m-pertechnetate.
Claim 108
Dependent Claim
34 words
The method of claim 89, wherein said second substance is the corresponding fragment obtained by analogous cleavage of normal immunoglobulin from the same or different species as that used to prepare said specific antibody.
Claim 109
Independent Claim
28 words
The method of clai, 91, wherein said corresponding fragment is labeled with a different isotope of the same element used to label the fragment of said specific antibody.
Claim 110
Independent Claim
28 words
The method of clai, 91, wherein said corresponding fragment is labeled with a different isotope of the same element used to label the fragment of said specific antibody.
Claim 111
Dependent Claim
54 words
The method of claim 92, wherein the specific antibody fragment is labeled with one of a pair of radioisotopes, and the corresponding normal immunoglobulin fragment is labeled with the other of the pair, said pair being one of Iodine-131 and Iodine-123; Indium-111 and Indium-113m; Gallium-67 and Gallium-68; Ruthenium-97 and Ruthenium-103; or Mercury-197 and Mercury-203.
Claim 112
Dependent Claim
96 words
The method of claim 91, which further comprises the steps of storing the photoscanning data in a computer, equalizing the activity level of said second substance with that of said marker-specific fragment in at least one non-target area and calculating a background level value for the marker-specific fragment for each data point; subtracting the resultant background value from the total marker-specific fragment activity, pixel-by-pixel, to generate a value for the activity of targeted marker-specific fragment for each data point; and using the resultant generated values for targeted marker-specific fragment activity to generate a related output signal.
Claim 113
Independent Claim
136 words
A method for detecting and localizing at least one type of tumor which either produces or is associated with at least one cytoplasmic, intracellular or cell-surface marker substance which comprises injecting a subject parenterally with at least two marker-specific fragments, at least one fragment being a marker-specific fragment obtained by cleavage of a first antibody specific to a first tumor associated marker and at least one other fragment being a marker-specific fragment obtained by cleavage of a second antibody specific to a second tumor-associated marker, each of said at least two fragments being radiolabeled with a pharmacologically inert radioisotope capable of detection using a photoscanning device, and subsequently scanning with said device to detect and locate the site or sites of uptake of at least one of said labeled fragments by said at least one tumor.
Claim 114
Independent Claim
136 words
A method for detecting and localizing at least one type of tumor which either produces or is associated with at least one cytoplasmic, intracellular or cell-surface marker substance which comprises injecting a subject parenterally with at least two marker-specific fragments, at least one fragment being a marker-specific fragment obtained by cleavage of a first antibody specific to a first tumor associated marker and at least one other fragment being a marker-specific fragment obtained by cleavage of a second antibody specific to a second tumor-associated marker, each of said at least two fragments being radiolabeled with a pharmacologically inert radioisotope capable of detection using a photoscanning device, and subsequently scanning with said device to detect and locate the site or sites of uptake of at least one of said labeled fragments by said at least one tumor.
Claim 115
Dependent Claim
30 words
The method of claim 95, wherein said at least two marker-specific fragments are obtained by cleavage of at least two of anti-CEA antibody, anti-AFP antibody, anti-HCG antibody and anti-CSAp antibody.
Claim 116
Dependent Claim
19 words
The method of claim 95, wherein each of said at least two fragments is labeled with a different radioisotope.
Claim 117
Dependent Claim
95 words
The method of claim 95, wherein prior to photoscanning, at least one reference substance is injected into the subject, said reference substance being radiolabeled with a radioisotope emitting at a different energy from either antibody fragment label and capable of independnet detection by said photoscanning device, the level of activity of said reference substance being used to determine the background activity due to each non-targeted specific antibody fragment, said background activity being subtracted from the total activity of each specific antibody fragment, whereby the activity of substantially only each targeted, tumor-associated antibody fragment is determined.
Claim 118
Dependent Claim
26 words
The method of claim 98, 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 technetium-99m-pertechnetate..
Claim 119
Dependent Claim
118 words
The method of claim 98, wherein each of said at least two fragments is labeled with a different radioisotope; the fragments obtained by analogous cleavage of normal immunoglobulin from the same or different species as those used to prepare each said specific antibody and corresponding to each of said at least two fragments are used as reference substances; each reference fragment is labeled with a different isotope of the same element used to label the corresponding fragment of said specific antibody; and the activity of the reference fragment corresponding to each of said at least two fragments is used to determine the background activity and the targeted fragment activity for the specific antibody fragment to which it corresponds.
Claim 120
Independent Claim
124 words
A method for detecting and localizing at least one type of tumor which produces or is associated with at least one cytoplasmic, intracellular or cell-surface marker substance, which comprises injecting a subject parenterally with a multivalent hybrid containing in chemical combination at least one marker-specific fragment obtained by cleavage of an antibody specific to a first tumor-associated marker and at least a second, different marker-specific fragment obtained by cleavage of an antibody specific to the same or different tumor-associated marker, said hybrid being radiolabeled with a pharmacologically inert radioisotope capable of detection using a photoscanning device, and subsequently scanning with said device to detect and locate the site or sites of uptake of said labeled hybrid by said at least one type of tumor.
Claim 121
Independent Claim
124 words
A method for detecting and localizing at least one type of tumor which produces or is associated with at least one cytoplasmic, intracellular or cell-surface marker substance, which comprises injecting a subject parenterally with a multivalent hybrid containing in chemical combination at least one marker-specific fragment obtained by cleavage of an antibody specific to a first tumor-associated marker and at least a second, different marker-specific fragment obtained by cleavage of an antibody specific to the same or different tumor-associated marker, said hybrid being radiolabeled with a pharmacologically inert radioisotope capable of detection using a photoscanning device, and subsequently scanning with said device to detect and locate the site or sites of uptake of said labeled hybrid by said at least one type of tumor.
Claim 122
Dependent Claim
46 words
The method of claim 101, wherein said hybrid is an F(ab l ) 2 fragment obtained by cleavage and recombination of a mixture of F(ab l ) 2 fragments, a portion of which are specific to said first marker, the remainder being said second, different fragments.
Claim 123
Dependent Claim
39 words
The method of claim 101, wherein one arm in said hybrid is a CEA-specific Fab' fragment obtained by cleavage of anti-CEA antibody and a second arm in said hybrid is a CSAp-specific fragment obtained by cleavage of anti-CSAp antibody.
Claim 124
Dependent Claim
30 words
The method of claim 101, wherein said hybrid contains a marker-specific Fab' arm obtained by cleavage of at least one of anti-CEA antibody, anti-AFP antibody, anti-HCG antibody and anti-CSAp antibody.
Claim 125
Dependent Claim
29 words
The method of claim 101, wherein said hybrid contains marker-specific Fab' arms obtained by cleavage of at least two of anti-CEA antibody, anti-AFP antibody, anti-HCG antibody and anti-CSAp antibody.
Claim 126
Dependent Claim
86 words
The method of claim 101, wherein prior to photoscanning, a second substance is injected into the subject, said second substance being radiolabeled with a radioisotope emitting at a different energy from the hybrid label and capable of independent detection by said photoscanning device, the level of activity of said second substance being used to determine the background activity due to non-targeted hybrid, said background activity being subtracted from the total activity of the hybrid, whereby the activity of substantially only the targeted, tumor-associated hybrid is determined.
Claim 127
Dependent Claim
26 words
The method of claim 106, wherein said second substance is at least one of technetium-99m-labeled normal human immunoglobulin, technetium-99m-labeled human serum albumin, technetium-99m-sulfur colloid and technetium-99m-pertechnetate.
Claim 128
Dependent Claim
95 words
The method of claim 106, wherein said second substance is a second hybrid containing in chemical combination a fragment corresponding to said at least one marker-specific fragment and obtained by analogous cleavage of normal immunoglobulin from the same or different species as that used to prepare said antibody specific to a first tumor-associated marker and at least a second fragment corresponding to said different marker-specific fragment and obtained by analogous cleavage of normal immunoglobulin from the same or different species as that used to prepare said antibody specific to the same or different tumor-associated marker.
Claim 129
Dependent Claim
25 words
The method of claim 108, wherein said second hybrid is labeled with a different isotope of the same element used to label the multivalent hybrid.
Claim 130
Dependent Claim
30 words
The method of claim 109, wherein the multivalent hybrid is labeled with one of Iodine-131 or Iodine-123 and the second hybrid is labeled with the other of Iodine-131 or Iodine-123.
Claim 131
Independent Claim
59 words
A method of tumor radiotherapy, which comprises parenterally injecting into a subject having a tumor which produces or is associated with a cytoplasmic, intracellular or cell-surface marker substance an effective tumor reducing amount of at least one marker-specific fragment obtained by cleavage of an antibody specific to said marker substance and radiolabeled with a pharmaceutically inert, radiotherapeutically effective radioisotope.
Claim 132
Independent Claim
59 words
A method of tumor radiotherapy, which comprises parenterally injecting into a subject having a tumor which produces or is associated with a cytoplasmic, intracellular or cell-surface marker substance an effective tumor reducing amount of at least one marker-specific fragment obtained by cleavage of an antibody specific to said marker substance and radiolabeled with a pharmaceutically inert, radiotherapeutically effective radioisotope.
Claim 133
Independent Claim
97 words
A method of tumor radiotherapy, which comprises parenterally injecting into a subject having at least one type of tumor which produces or is associated with at least one cytoplasmic, intracellular or cell-surface marker substance an effective tumor reducing amount of a multivalent hybrid containing in chemical combination at least one marker-specific fragment obtained by cleavage of an antibody specific to a first tumor-associated marker and at least a second, different marker-specific fragment obtained by cleavage of an antibody specific to the same or different tumor-associated marker, said hybrid being radiolabeled with a pharmacologically inert, radiotherapeutically effective radioisotope.
Claim 134
Independent Claim
97 words
A method of tumor radiotherapy, which comprises parenterally injecting into a subject having at least one type of tumor which produces or is associated with at least one cytoplasmic, intracellular or cell-surface marker substance an effective tumor reducing amount of a multivalent hybrid containing in chemical combination at least one marker-specific fragment obtained by cleavage of an antibody specific to a first tumor-associated marker and at least a second, different marker-specific fragment obtained by cleavage of an antibody specific to the same or different tumor-associated marker, said hybrid being radiolabeled with a pharmacologically inert, radiotherapeutically effective radioisotope.
Claim 135
Dependent Claim
91 words
The method of claim 112, wherein said multivalent hybrid is prepared by the steps of pepsin-catalyzed cleavage of anti-CEA antibody to produce an F(ab') 2 fragment and reductive cleavage thereof to form CEA-specific Fab' fragments, pepsin-catalyzed cleavage of anti-CSAp antibody to produce an F(ab') 2 fragment and reductive cleavage thereof to form CSAp-specific Fab' fragments, and oxidative coupling of a mixture of said CEA-specific Fab' fragments and said CSAp-specific Fab' fragments to form F(ab') 2 fragments, at least a portion of which are multivalent hybrids specific to both CEA and CSAp.
Claim 136
Dependent Claim
27 words
The method of claim 113, wherein said multivalent hybrid is purified by sequential affinity chromatography through a column containing bound CEA and a column containing bound CSAp.
Claim 137
Dependent Claim
57 words
An injectable composition, which comprises: (a) at least one marker-specific fragment obtained by cleavage of an antibody specific to a cytoplasmic, intracellular or cell-surface marker substance which is produced or associated with a tumor, said fragment being radiolabeled with a pharmacologically inert radioisotope capable of detection using a photoscanning device; and (b) a pharmaceutically acceptable injection vehicle.
Claim 138
Dependent Claim
57 words
An injectable composition, which comprises: (a) at least one marker-specific fragment obtained by cleavage of an antibody specific to a cytoplasmic, intracellular or cell-surface marker substance which is produced or associated with a tumor, said fragment being radiolabeled with a pharmacologically inert radioisotope capable of detection using a photoscanning device; and (b) a pharmaceutically acceptable injection vehicle.
Claim 139
Dependent Claim
43 words
The composition of claim 115, which further comprises at least a second marker-specific fragment obtained by cleavage of a second antibody specific to a second tumor-associated marker, said fragment being radiolabeled with a pharmacologically inert radioisotope capable of detection using a photoscanning device.
Claim 140
Dependent Claim
70 words
The injectable composition of claim 115, which further comprises a reference fragment which is the corresponding fragment obtained by analogous cleavage of normal immunoglobulin from the same or different species as that used to prepare said specific antibody, said reference fragment being radiolabeled with a different isotope of the same element used to label said marker-specific fragment and emitting at an energy capable of independent detection using said photoscanning device.
Claim 141
Dependent Claim
76 words
An injectable composition which comprises: (a) a multivalent hybrid containing in chemical combination at least one marker-specific fragment obtained by cleavage of an antibody specific to a first tumor-associated marker and at least a second different marker-specific fragment obtained by cleavage of an antibody specific to the same or different tumor associated marker, said hybrid being radiolabeled with a pharmacologically inert radioisotope capable of detection using a photoscanning device; and (b) a pharmaceutically acceptable injection vehicle.
Claim 142
Dependent Claim
76 words
An injectable composition which comprises: (a) a multivalent hybrid containing in chemical combination at least one marker-specific fragment obtained by cleavage of an antibody specific to a first tumor-associated marker and at least a second different marker-specific fragment obtained by cleavage of an antibody specific to the same or different tumor associated marker, said hybrid being radiolabeled with a pharmacologically inert radioisotope capable of detection using a photoscanning device; and (b) a pharmaceutically acceptable injection vehicle.
Claim 143
Dependent Claim
69 words
The injection composition of claim 118, which further comprises a reference fragment from normal immunoglobulin from the same or different species as that used to prepare said hybrid and obtained by analogous cleavage of said normal immunoglobulin, said reference fragment being radiolabeled with a different isotope of the same element used to label said multivalent hybrid and emitting at an energy capable of independent detection using said photoscanning device.
Claim 144
Independent Claim
117 words
A method of tumor radiotherapy, which comprises parenterally injecting into a subject having a tumor which produces or is associated with a cytoplasmic, intracellular or cell-surface marker substance an effective tumor reducing amount of at least one marker-specific fragment obtained by cleavage of an antibody specific to said marker substance and radiolabeled with a pharmacologically inert radioisotope capable of detection with a photoscanning device, said labeled fragment further containing in chemical combination at least one addend containing at least five atoms of boron with at least a natural abundance of Boron-10 isotope; wherein the location of said tumor is determined using said photoscanning device, and a beam of thermal neutrons is then directed at said tumor location.
Claim 145
Independent Claim
117 words
A method of tumor radiotherapy, which comprises parenterally injecting into a subject having a tumor which produces or is associated with a cytoplasmic, intracellular or cell-surface marker substance an effective tumor reducing amount of at least one marker-specific fragment obtained by cleavage of an antibody specific to said marker substance and radiolabeled with a pharmacologically inert radioisotope capable of detection with a photoscanning device, said labeled fragment further containing in chemical combination at least one addend containing at least five atoms of boron with at least a natural abundance of Boron-10 isotope; wherein the location of said tumor is determined using said photoscanning device, and a beam of thermal neutrons is then directed at said tumor location.
Claim 146
Dependent Claim
35 words
The injectable composition of claim 115, wherein said marker-specific fragment further contains in chemical combination at least one addend containing at least five atoms of boron with at least the natural abundance of Boron-10 isotope.
References Cited (Backward Citations)
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