US5716595A
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US
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Intraperative, intravascular and endoscopic tumor and lesion detection and therapy with monovalent antibody fragments
Assignee: Immunomedics Inc
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Filing: 1994-08-22
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Granted: 1998-02-10
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Expires: 2014-08-22
Abstract
Abstract Methods are provided for close-range intraoperative, endoscopic and intravascular detection and treatment of lesions, including tumors and non-malignant lesions. The methods use agents labeled with isotopic and non-isotopic agents. Also provided are methods for detection and treatment of lesions with photodynamic agents and methods of treating lesions with a protein conjugated to an agent capable of being activated to emit Anger electron or other ionizing radiation. Compositions and kits useful in the above methods are also provided.
Inventors
- 👤 David M. Goldenberg
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-28 03:12
CPC Classifications
A; A61; A61K; A61K49/00; A61K49/001; A61K49/0013; A61K49/0017; A61K49/0019; A61K49/0021; A61K49/0036; A61K47/00; A61K47/50; A61K47/51; A61K47/68; A61K47/6891; A61K47/6897; A61K47/6898; A61K49/005; A61K49/0058; A61K51/00; A61K51/02; A61K51/04; A61K51/08; A61K51/10; A61K51/1045; A61K51/1048; A61K51/1072; A61K51/1093; A61P; A61P29/00; A61P31/00; A61P31/04; A61P35/00; A61P7/00; A61P7/02; A61P9/00; A61P9/08; A61P9/10; B; B82; B82Y; B82Y5/00; A61K2121/00; A61K2123/00
Claims Analysis
Total Claims: 57
Claim 1
Independent Claim
146 words
A method for close-range tumor detection and, optionally, treatment, during an operative, intravascular or endoscopic procedure, wherein the method comprises the steps of: injecting a patient subject to such a procedure parenterally with an effective amount of a labeled monovalent antibody fragment or subfragment which specifically binds antigen produced by or associated with a tumor; conducting the procedure within 48 hours of the injection; scanning the accessed interior of the patient at close range with a detection means for detecting the presence of the labeled antibody fragment or subfragment; locating the sites of accretion of the labeled antibody fragment or subfragment by detecting elevated levels of the labeled antibody fragment or subfragment at such sites with the detection means, without the use of a clearing agent, contrast agent or subtraction agent, and optionally, treating the detected sites of accretion of said labeled antibody fragment or subfragment.
Claim 2
Independent Claim
146 words
A method for close-range tumor detection and, optionally, treatment, during an operative, intravascular or endoscopic procedure, wherein the method comprises the steps of: injecting a patient subject to such a procedure parenterally with an effective amount of a labeled monovalent antibody fragment or subfragment which specifically binds antigen produced by or associated with a tumor; conducting the procedure within 48 hours of the injection; scanning the accessed interior of the patient at close range with a detection means for detecting the presence of the labeled antibody fragment or subfragment; locating the sites of accretion of the labeled antibody fragment or subfragment by detecting elevated levels of the labeled antibody fragment or subfragment at such sites with the detection means, without the use of a clearing agent, contrast agent or subtraction agent, and optionally, treating the detected sites of accretion of said labeled antibody fragment or subfragment.
Claim 3
Dependent Claim
16 words
The method of claim 1, wherein the procedure is conducted within 24 hours of the injection.
Claim 4
Dependent Claim
16 words
The method of claim 1, wherein the procedure is conducted within 12 hours of the injection.
Claim 5
Dependent Claim
16 words
The method of claim 1, wherein the procedure is conducted within 6 hours of the injection.
Claim 6
Dependent Claim
17 words
The method of claim 1, wherein the fragment or subfragment is a monoclonal antibody fragment or subfragment.
Claim 7
Dependent Claim
15 words
The fragment of claim 5, which is an Fv, single-chain antibody, Fab or Fab' fragment.
Claim 8
Dependent Claim
16 words
The method of claim 1, wherein the label for the fragment or subfragment is a radioisotope.
Claim 9
Dependent Claim
15 words
The method of claim 7, wherein the radioisotope emits at an energy of 20-1,000 KeV.
Claim 10
Dependent Claim
10 words
The method of claim 7, wherein the radioisotope is technetium-99m.
Claim 11
Dependent Claim
13 words
The method of claim 7, wherein the radioisotope is iodine-125, iodine-131 or iodine-123.
Claim 12
Dependent Claim
10 words
The method of claim 7, wherein the radioisotope is indium-111.
Claim 13
Dependent Claim
10 words
The method of claim 7, wherein the radioisotope is gallium-67.
Claim 14
Dependent Claim
19 words
The method of claim 1, wherein the label of said labeled antibody fragment or subfragment is a non-isotopic agent.
Claim 15
Dependent Claim
13 words
The method of claim 13, wherein the non-isotopic agent is a photoactive agent.
Claim 16
Dependent Claim
13 words
The method of claim 14, wherein the photoactive agent is a fluorescent agent.
Claim 17
Dependent Claim
16 words
The method of claim 1, wherein the method further comprises treating detected sites during the procedure.
Claim 18
Dependent Claim
12 words
The method of claim 1, wherein the procedure is an operative procedure.
Claim 19
Dependent Claim
12 words
The method of claim 1, wherein the procedure is an intravascular procedure.
Claim 20
Dependent Claim
12 words
The method of claim 1, wherein the procedure is an endoscopic procedure.
Claim 21
Dependent Claim
12 words
The method of claim 1, wherein said procedure is a laparoscopic procedure.
Claim 22
Dependent Claim
23 words
The method of claim 1, further comprising treating the tumor during the procedure by brachytherapy, external beam radiation, laser therapy or surgical removal.
Claim 23
Independent Claim
103 words
A method of detection of lesions during an endoscopic, intravascular catheter or surgical procedure, wherein the method comprises the steps of: injecting a patient to undergo such a procedure with an antibody fragment or subfragment labeled with a fluorescent agent or dye, wherein the labeled antibody fragment or subfragment accretes at the lesion; permitting the labeled antibody fragment or subfragment to accrete; conducting the procedure within 48 hours of the injection; and detecting the label with a light source supplied via an endoscope or intravascular catheter or during the surgical procedure, without the use of a clearing agent, contrast agent or subtraction agent.
Claim 24
Independent Claim
103 words
A method of detection of lesions during an endoscopic, intravascular catheter or surgical procedure, wherein the method comprises the steps of: injecting a patient to undergo such a procedure with an antibody fragment or subfragment labeled with a fluorescent agent or dye, wherein the labeled antibody fragment or subfragment accretes at the lesion; permitting the labeled antibody fragment or subfragment to accrete; conducting the procedure within 48 hours of the injection; and detecting the label with a light source supplied via an endoscope or intravascular catheter or during the surgical procedure, without the use of a clearing agent, contrast agent or subtraction agent.
Claim 25
Dependent Claim
23 words
The method of claim 22, further comprising the step of removing lesions at sites of elevated label accretion with a laser or surgically.
Claim 26
Dependent Claim
21 words
The method of claim 22, further comprising the step of treating lesions at sites of elevated label accretion with ionizing radiation.
Claim 27
Dependent Claim
41 words
The method of claim 24, wherein the procedure is selected from the group consisting of endoscopic and intravascular catheter procedures, and further comprising the step of administering brachytherapy via the endoscope or catheter to lesions at sites of elevated label accretion.
Claim 28
Dependent Claim
28 words
The method of claim 22, wherein the antibody fragment is selected from the group consisting of an Fv, single-chain antibody, Fab, Fab', F(ab) 2 and F(ab') 2 fragment.
Claim 29
Dependent Claim
26 words
The method of claim 22, wherein the lesion is selected from the group consisting of a cancer, infectious or inflammatory lesion, clot, hyperplasia and atherosclerotic plaque.
Claim 30
Dependent Claim
23 words
The method of claim 22, wherein said procedure is conducted within 24 hours of the injection of said labeled antibody fragment or subfragment.
Claim 31
Dependent Claim
12 words
The method of claim 22, wherein said procedure is a laparoscopic procedure.
Claim 32
Independent Claim
131 words
A method of detection and treatment of lesions during an endoscopic or intravascular catheter procedure, wherein the method comprises the steps of: (a) injecting a patient to undergo such a procedure with an antibody fragment or subfragment labeled with an agent capable of detection, which labeled antibody fragment or subfragment preferentially accretes at the lesion; (b) permitting the labeled antibody fragment or subfragment to accrete at the lesion; (c) conducting the procedure within 48 hours of the injection of the labeled antibody fragment or subfragment; (d) detecting the agent with a detection means supplied via the endoscope or intravascular catheter, wherein the agent is detected without the use of a clearing agent, contrast agent or subtraction agent; and (e) treating the lesion by brachytherapy administered through the endoscope or intravascular catheter.
Claim 33
Independent Claim
131 words
A method of detection and treatment of lesions during an endoscopic or intravascular catheter procedure, wherein the method comprises the steps of: (a) injecting a patient to undergo such a procedure with an antibody fragment or subfragment labeled with an agent capable of detection, which labeled antibody fragment or subfragment preferentially accretes at the lesion; (b) permitting the labeled antibody fragment or subfragment to accrete at the lesion; (c) conducting the procedure within 48 hours of the injection of the labeled antibody fragment or subfragment; (d) detecting the agent with a detection means supplied via the endoscope or intravascular catheter, wherein the agent is detected without the use of a clearing agent, contrast agent or subtraction agent; and (e) treating the lesion by brachytherapy administered through the endoscope or intravascular catheter.
Claim 34
Dependent Claim
22 words
The method of claim 30, wherein the antibody fragment is an Fv, single-chain antibody, Fab, Fab', F(ab) 2 or F(ab') 2 .
Claim 35
Dependent Claim
20 words
The method of claim 30, wherein the lesion is a cancer, infectious or inflammatory lesion, clot, hyperplasia or atherosclerotic plague.
Claim 36
Dependent Claim
23 words
The method of claim 30, wherein said procedure is conducted within 24 hours of the injection of said labeled antibody fragment or subfragment.
Claim 37
Dependent Claim
12 words
The method of claim 30, wherein said procedure is a laparoscopic procedure.
Claim 38
Independent Claim
94 words
A method of treatment of lesions during a laparoscopic or intravascular catheter procedure, wherein the method comprised the steps of: injecting a patient to undergo such a procedure with an antibody fragment or subfragment labeled with a photoactive agent, wherein the antibody fragment or subfragment preferentially accretes at targeted lesions; permitting the labeled antibody fragment or subfragment to accrete; conducting the procedure within 48 hours of the injection of the labeled antibody or subfragment; and activating the photoactive agent with a light source supplied via the laparascope or intravascular catheter, thereby treating said lesions.
Claim 39
Independent Claim
94 words
A method of treatment of lesions during a laparoscopic or intravascular catheter procedure, wherein the method comprised the steps of: injecting a patient to undergo such a procedure with an antibody fragment or subfragment labeled with a photoactive agent, wherein the antibody fragment or subfragment preferentially accretes at targeted lesions; permitting the labeled antibody fragment or subfragment to accrete; conducting the procedure within 48 hours of the injection of the labeled antibody or subfragment; and activating the photoactive agent with a light source supplied via the laparascope or intravascular catheter, thereby treating said lesions.
Claim 40
Dependent Claim
20 words
The method of claim 35, wherein the lesion is a cancer, infectious or inflammatory lesion, clot, hyperplasia or atherosclerotic plaque.
Claim 41
Dependent Claim
23 words
The method of claim 35, wherein said procedure is conducted within 24 hours of the injection of said labeled antibody fragment or subfragment.
Claim 42
Independent Claim
78 words
A method of treatment of lesions, wherein the method comprises the steps of: (a) injecting a patient with composition comprising a protein conjugated to an agent capable of being activated to emit Auger electrons or other ionizing radiation, and, optionally, to an agent capable of detection, wherein the protein conjugate accretes preferentially at the targeted lesion; and (b) activating said agent capable of being activated, thereby treating said lesions, and, optionally, detecting the optional agent capable of detection.
Claim 43
Independent Claim
78 words
A method of treatment of lesions, wherein the method comprises the steps of: (a) injecting a patient with composition comprising a protein conjugated to an agent capable of being activated to emit Auger electrons or other ionizing radiation, and, optionally, to an agent capable of detection, wherein the protein conjugate accretes preferentially at the targeted lesion; and (b) activating said agent capable of being activated, thereby treating said lesions, and, optionally, detecting the optional agent capable of detection.
Claim 44
Dependent Claim
20 words
The method of claim 38, wherein the activation and optional detection is during an endoscopic, intravascular, catheter or surgical procedure.
Claim 45
Dependent Claim
12 words
The method of claim 39, wherein said procedure is a laparoscopic procedure.
Claim 46
Dependent Claim
21 words
The method of claim 38, wherein the activatable agent is a stable element capable of being activated to emit ionizing radiation.
Claim 47
Dependent Claim
21 words
The method of claim 38, wherein the activatable agent is a stable element capable of being activated to emit Auger electrons.
Claim 48
Dependent Claim
13 words
The method of claim 42, wherein the activatable agent is a halogenated compound.
Claim 49
Dependent Claim
12 words
The method of claim 43, wherein the agent is a halogenated pyrimidine.
Claim 50
Dependent Claim
13 words
The method of claim 41, wherein the stable element is iodine or indium.
Claim 51
Dependent Claim
26 words
The method of claim 38, wherein the protein is a peptide, polypeptide, growth factor, hormone, lymphokine, cytokine, receptor protein, immune modulator, enzyme, antibody or antibody fragment.
Claim 52
Dependent Claim
22 words
The method of claim 46, wherein the antibody fragment is an Fv, single-chain antibody, Fab, Fab', F(ab) 2 or F(ab') 2 .
Claim 53
Dependent Claim
15 words
The method of claim 46, wherein the antibody or antibody fragment is a monoclonal antibody.
Claim 54
Dependent Claim
12 words
The method of claim 38, wherein the activating energy is monochromatic X-rays.
Claim 55
Dependent Claim
16 words
The method of claim 49, wherein the monochromatic X-rays emit at an energy of 20-70 KeV.
Claim 56
Dependent Claim
16 words
The method of claim 50, wherein the monochromatic X-rays emit at an energy of 30-40 KeV.
Claim 57
Dependent Claim
20 words
The method of claim 38, wherein the lesion is a cancer, infectious or inflammatory lesion, clot, hyperplasia or atherosclerotic plague.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 2001-02-09 | 2001-08-11 | 2002-02-10 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2005-02-09 | 2005-08-11 | 2006-02-10 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2009-02-09 | 2009-08-11 | 2010-02-10 | $7700.00 | Window Closed / Lapsed |