What is claimed is:
1. At least one isolated mammalian anti-dual integrin antibody, comprising at least one variable region comprising SEQ ID NO:7 or 8.
2. An dual integrin antibody according to claim 1, wherein said antibody binds dual integrin with an affinity of at least one selected from at least 109 M, at least 1010 M, at least 1011 M, or at least 1012 M.
3. An dual integrin antibody according to claim 1, wherein said antibody substantially neutralizes at least one activity of at least one dual integrin protein.
4. An isolated nucleic acid encoding at least one isolated mammalian anti-dual integrin antibody having at least one variable region comprising SEQ ID NO:7 or 8.
5. An isolated nucleic acid vector comprising an isolated nucleic acid according to claim 4.
6. A prokaryotic or eukaryotic host cell comprising an isolated nucleic acid according to claim 5.
7. A host cell according to claim 6, wherein said host cell is at least one selected from COS-1, COS-7, HEK293, BHK21, CHO, BSC-1, Hep G2, 653, SP20, 293, HeLa, myeloma, or lymphoma cells, or any derivative, immortalized or transformed cell thereof.
8. A method for producing at least one anti-dual integrin antibody, comprising translating a nucleic acid according to claim 4 under conditions in vitro, in vivo or in situ, such that the dual integrin antibody is expressed in detectable or recoverable amounts.
9. A composition comprising at least one isolated mammalian anti-dual integrin antibody having at least one variable region comprising SEQ ID NO:7 or 8, and at least one pharmaceutically acceptable carrier or diluent.
10. A composition according to claim 9, further comprising at least one composition comprising an effective amount of at least one compound or protein selected from at least one of a detectable label or reporter, a TNF antagonist, an antirheumatic, a muscle relaxant, a narcotic, a non-steroid anti-inflammatory drug (NSAID), an analgesic, an anesthetic, a sedative, a local anethetic, a neuromuscular blocker, an antimicrobial, an antipsoriatic, a corticosteriod, an anabolic steroid, an erythropoietin, an immunization, an immunoglobulin, an immunosuppressive, a growth hormone, a hormone replacement drug, a radiopharmaceutical, an antidepressant, an antipsychotic, a stimulant, an asthma medication, a beta agonist, an inhaled steroid, an epinephrine or analog, a cytokine, or a cytokine antagonist.
11. An anti-idiotype antibody or fragment that specifically binds at least one isolated mammalian anti-dual integrin antibody having at least one variable region comprising SEQ ID NO:7 or 8.
12. A method for diagnosing or treating a dual integrin related condition in a cell, tissue, organ or animal, comprising
(a) contacting or administering a composition comprising an effective amount of at least one isolated mammalian anti-dual integrin antibody having at least one variable region comprising SEQ ID NO:7 or 8, with, or to, said cell, tissue, organ or animal.
13. A method according to claim 12, wherein said effective amount is 0.001-50 mgkilogram of said cells, tissue, organ or animal.
14. A method according to claim 12, wherein said contacting or said administrating is by at least one mode selected from parenteral, subcutaneous, intramuscular, intravenous, intrarticular, intrabronchial, intraabdominal, intracapsular, intracartilaginous, intracavitary, intracelial, intracelebellar, intracerebroventricular, intracolic, intracervical, intragastric, intrahepatic, intramyocardial, intraosteal, intrapelvic, intrapericardiac, intraperitoneal, intrapleural, intraprostatic, intrapulmonary, intrarectal, intrarenal, intraretinal, intraspinal, intrasynovial, intrathoracic, intrauterine, intravesical, bolus, vaginal, rectal, buccal, sublingual, intranasal, or transdermal.
15. A method according to claim 12, further comprising administering, prior, concurrently or after said (a) contacting or administering, at least one composition comprising an effective amount of at least one compound or protein selected from at least one of a detectable label or reporter, a TNF antagonist, an antirheumatic, a muscle relaxant, a narcotic, a non-steroid anti-inflammatory drug (NSAID), an analgesic, an anesthetic, a sedative, a local anethetic, a neuromuscular blocker, an antimicrobial, an antipsoriatic, a corticosteriod, an anabolic steroid, an erythropoietin, an immunization, an immunoglobulin, an immunosuppressive, a growth hormone, a hormone replacement drug, a radiopharmaceutical, an antidepressant, an antipsychotic, a stimulant, an asthma medication, a beta agonist, an inhaled steroid, an epinephrine or analog, a cytokine, or a cytokine antagonist.
16. A medical device, comprising at least one isolated mammalian anti-dual integrin antibody having at least one variable region comprising SEQ ID NO:7 or 8, wherein said device is suitable to contacting or administerting said at least one anti-dual integrin antibody by at least one mode selected from parenteral, subcutaneous, intramuscular, intravenous, intrarticular, intrabronchial, intraabdominal, intracapsular, intracartilaginous, intracavitary, intracelial, intracelebellar, intracerebroventricular, intracolic, intracervical, intragastric, intrahepatic, intramyocardial, intraosteal, intrapelvic, intrapericardiac, intraperitoneal, intrapleural, intraprostatic, intrapulmonary, intrarectal, intrarenal, intraretinal, intraspinal, intrasynovial, intrathoracic, intrauterine, intravesical, bolus, vaginal, rectal, buccal, sublingual, intranasal, or transdermal.
17. An article of manufacture for human pharmaceutical or diagnostic use, comprising packaging material and a container comprising a solution or a lyophilized form of at least one isolated mammalian anti-dual integrin antibody having at least one variable region comprising SEQ ID NO:7 or 8.
18. The article of manufacture of claim 17, wherein said container is a component of a parenteral, subcutaneous, intramuscular, intravenous, intrarticular, intrabronchial, intraabdominal, intracapsular, intracartilaginous, intracavitary, intracelial, intracelebellar, intracerebroventricular, intracolic, intracervical, intragastric, intrahepatic, intramyocardial, intraosteal, intrapelvic, intrapericardiac, intraperitoneal, intrapleural, intraprostatic, intrapulmonary, intrarectal, intrarenal, intraretinal, intraspinal, intrasynovial, intrathoracic, intrauterine, intravesical, bolus, vaginal, rectal, buccal, sublingual, intranasal, or transdermal delivery device or system.
19. A method for producing at least one isolated mammalian anti-dual integrin antibody having at least one variable region comprising SEQ ID NO:7 or 8, comprising providing a host cell or transgenic animal or transgenic plant or plant cell capable of expressing in recoverable amounts said antibody.
20. At least one anti-dual integrin antibody produced by a method according to claim 19.
21. At least one isolated mammalian anti-dual integrin antibody, comprising either (i) all of the heavy chain complementarity determining regions (CDR) amino acid sequences of SEQ ID NOS: 1, 2, and 3; or (ii) all of the light chain CDR amino acids sequences of SEQ ID NOS:4, 5, and 6.
22. An dual integrin antibody according to claim 21, wherein said antibody binds dual integrin with an affinity of at least one selected from at least 109 M, at least 1010 M, at least 1011 M, or at least 1012 M.
23. An dual integrin antibody according to claim 21, wherein said antibody substantially neutralizes at least one activity of at least one dual integrin protein.
24. An isolated nucleic acid encoding at least one isolated mammalian anti-dual integrin antibody either (i) all of the heavy chain CDR amino acid sequences of SEQ ID NOS: 1, 2, and 3; or (ii) all of the light chain CDR amino acids sequences of SEQ ID NOS:4, 5, and 6.
25. An isolated nucleic acid vector comprising an isolated nucleic acid according to claim 4.
26. A prokaryotic or eukaryotic host cell comprising an isolated nucleic acid according to claim 25.
27. A host cell according to claim 26, wherein said host cell is at least one selected from COS-1, COS-7, HEK293, BHK21, CHO, BSC-1, Hep G2, 653, SP20, 293, HeLa, myeloma, or lymphoma cells, or any derivative, immortalized or transformed cell thereof.
28. A method for producing at least one anti-dual integrin antibody, comprising translating a nucleic acid according to claim 24 under conditions in vitro, in vivo or in situ, such that the dual integrin antibody is expressed in detectable or recoverable amounts.
29. A composition comprising at least one isolated mammalian anti-dual integrin antibody having either (i) all of the heavy chain CDR amino acid sequences of SEQ ID NOS: 1,2 and 3; or (ii) all of the light chain CDR amino acids sequences of SEQ ID NOS: 4, 5, and 6, and at least one pharmaceutically acceptable carrier or diluent.
30. A composition according to claim 29, further comprising at least one composition comprising an effective amount of at least one compound or protein selected from at least one of a detectable label or reporter, a INF antagonist, an antirheumatic, a muscle relaxant, a narcotic, a non-steroid anti-inflammatory drug (NSAID), an analgesic, an anesthetic, a sedative, a local anethetic, a neuromuscular blocker, an antimicrobial, an antipsoriatic, a corticosteriod, an anabolic steroid, an erythropoietin, an immunization, an immunoglobulin, an immunosuppressive, a growth hormone, a hormone replacement drug, a radiopharmaceutical, an antidepressant, an antipsychotic, a stimulant, an asthma medication, a beta agonist, an inhaled steroid, an epinephrine or analog, a cytokine, or a cytokine antagonist.
31. An anti-idiotype antibody or fragment that specifically binds at least one isolated mammalian anti-dual integrin antibody having either (i) all of the heavy chain CDR amino acid sequences of SEQ ID NOS:1, 2, and 3; or (ii) all of the light chain CDR amino acids sequences of SEQ ID NOS:4, 5, and 6.
32. A method for diagnosing or treating a dual integrin related condition in a cell, tissue, organ or animal, comprising
(a) contacting or administering a composition comprising an effective amount of at least one isolated mammalian anti-dual integrin antibody having either (i) all of the heavy chain CDR amino acid sequences of SEQ ID NOS:1, 2, and 3; or (ii) all of the light chain CDR amino acids sequences of SEQ ID NOS:4, 5, and 6, with, or to, said cell, tissue, organ or animal.
33. A method according to claim 32, wherein said effective amount is 0.001-50 mgkilogram of said cells, tissue, organ or animal.
34. A method according to claim 32, wherein said contacting or said administrating is by at least one mode selected from parenteral, subcutaneous, intramuscular, intravenous, intrarticular, intrabronchial, intraabdominal, intracapsular, intracartilaginous, intracavitary, intracelial, intracelebellar, intracerebroventricular, intracolic, intracervical, intragastric, intrahepatic, intramyocardial, intraosteal, intrapelvic, intrapericardiac, intraperitoneal, intrapleural, intraprostatic, intrapulmonary, intrarectal, intrarenal, intraretinal, intraspinal, intrasynovial, intrathoracic, intrauterine, intravesical, bolus, vaginal, rectal, buccal, sublingual, intranasal, or transdermal.
35. A method according to claim 32, further comprising administering, prior, concurrently or after said (a) contacting or administering, at least one composition comprising an effective amount of at least one compound or protein selected from at least one of a detectable label or reporter, a TNF antagonist, an antirheumatic, a muscle relaxant, a narcotic, a non-steroid anti-inflammatory drug (NSAID), an analgesic, an anesthetic, a sedative, a local anethetic, a neuromuscular blocker, an antimicrobial, an antipsoriatic, a corticosteriod, an anabolic steroid, an erythropoietin, an immunization, an immunoglobulin, an immunosuppressive, a growth hormone, a hormone replacement drug, a radiopharmaceutical, an antidepressant, an antipsychotic, a stimulant, an asthma medication, a beta agonist, an inhaled steroid, an epinephrine or analog, a cytokine, or a cytokine antagonist.
36. A medical device, comprising at least one isolated mammalian anti-dual integrin antibody having either (i) all of the heavy chain CDR amino acid sequences of SEQ ID NOS: 1, 2, and 3; or (ii) all of the light chain CDR amino acids sequences of SEQ ID NOS:4, 5, and 6, wherein said device is suitable to contacting or administerting said at least one anti-dual integrin antibody by at least one mode selected from parenteral, subcutaneous, intramuscular, intravenous, intrarticular, intrabronchial, intraabdominal, intracapsular, intracartilaginous, intracavitary, intracelial, intracelebellar, intracerebroventricular, intracolic, intracervical, intragastric, intrahepatic, intramyocardial, intraosteal, intrapelvic, intrapericardiac, intraperitoneal, intrapleural, intraprostatic, intrapulmonary, intrarectal, intrarenal, intraretinal, intraspinal, intrasynovial, intrathoracic, intrauterine, intravesical, bolus, vaginal, rectal, buccal, sublingual, intranasal, or transdermal.
37. An article of manufacture for human pharmaceutical or diagnostic use, comprising packaging material and a container comprising a solution or a lyophilized form of at least one isolated mammalian anti-dual integrin antibody having either (i) all of the heavy chain CDR amino acid sequences of SEQ ID NOS:1, 2, and 3; or (ii) all of the light chain CDR amino acids sequences of SEQ ID NOS:4, 5, and 6.
38. The article of manufacture of claim 37, wherein said container is a component of a parenteral, subcutaneous, intramuscular, intravenous, intrarticular, intrabronchial, intraabdominal, intracapsular, intracartilaginous, intracavitary, intracelial, intracelebellar, intracerebroventricular, intracolic, intracervical, intragastric, intrahepatic, intramyocardial, intraosteal, intrapelvic, intrapericardiac, intraperitoneal, intrapleural, intraprostatic, intrapulmonary, intrarectal, intrarenal, intraretinal, intraspinal, intrasynovial, intrathoracic, intrauterine, intravesical, bolus, vaginal, rectal, buccal, sublingual, intranasal, or transdermal delivery device or system.
39. A method for producing at least one isolated mammalian anti-dual integrin antibody having either (i) all of the heavy chain CDR amino acid sequences of SEQ ID NOS:1, 2, and 3; or (ii) all of the light chain CDR amino acids sequences of SEQ ID NOS:4, 5, and 6, comprising providing a host cell or transgenic animal or transgenic plant or plant cell capable of expressing in recoverable amounts said antibody.
40. At least one anti-dual integrin antibody produced by a method according to claim 39.
41. At least one isolated mammalian anti-dual integrin antibody, comprising at least one heavy chain or light chain CDR having the amino acid sequence of at least one of SEQ ID NOS: 1, 2, 3, 4, 5, or 6.
42. An dual integrin antibody according to claim 41, wherein said antibody binds dual integrin with an affinity of at least one selected from at least 109 M, at least 1010 M, at least 1011 M, or at least 1012 M.
43. An dual integrin antibody according to claim 41, wherein said antibody substantially neutralizes at least one activity of at least one dual integrin protein.
44. An isolated nucleic acid encoding at least one isolated mammalian anti-dual integrin antibody having at least one heavy chain or light chain CDR having the amino acid sequence of at least one of SEQ ID NOS: 1, 2, 3, 4, 5, or 6.
45. An isolated nucleic acid vector comprising an isolated nucleic acid according to claim 44.
46. A prokaryotic or eukaryotic host cell comprising an isolated nucleic acid according to claim 45.
47. A host cell according to claim 46, wherein said host cell is at least one selected from COS-1, COS-7, HEK293, BHK21, CHO, BSC-1, Hep G2, 653, SP20, 293, HeLa, myeloma, or lymphoma cells, or any derivative, immortalized or transformed cell thereof.
48. A method for producing at least one anti-dual integrin antibody, comprising translating a nucleic acid according to claim 44 under conditions in vitro, in vivo or in situ, such that the dual integrin antibody is expressed in detectable or recoverable amounts.
49. A composition comprising at least one isolated mammalian anti-dual integrin antibody having at least one heavy chain or light chain CDR having the amino acid sequence of at least one of SEQ ID NOS: 1, 2, 3, 4, 5, or 6, and at least one pharmaceutically acceptable carrier or diluent.
50. A composition according to claim 49, further comprising at least one composition comprising an effective amount of at least one compound or protein selected from at least one of a detectable label or reporter, a INF antagonist, an antirheumatic, a muscle relaxant, a narcotic, a non-steroid anti-inflammatory drug (NSAID), an analgesic, an anesthetic, a sedative, a local anethetic, a neuromuscular blocker, an antimicrobial, an antipsoriatic, a corticosteriod, an anabolic steroid, an erythropoietin, an immunization, an immunoglobulin, an immunosuppressive, a growth hormone, a hormone replacement drug, a radiopharmaceutical, an antidepressant, an antipsychotic, a stimulant, an asthma medication, a beta agonist, an inhaled steroid, an epinephrine or analog, a cytokine, or a cytokine antagonist.
51. An anti-idiotype antibody or fragment that specifically binds at least one isolated mammalian anti-dual integrin antibody having at least one heavy chain or light chain CDR having the amino acid sequence of at least one of SEQ ID NOS: 1, 2, 3, 4, 5, or 6.
52. A method for diagnosing or treating a dual integrin related condition in a cell, tissue, organ or animal, comprising
(a) contacting or administering a composition comprising an effective amount of at least one isolated mammalian anti-dual integrin antibody having at least one heavy chain or light chain CDR having the amino acid sequence of at least one of SEQ ID NOS: 1, 2, 3, 4, 5, or 6, with, or to, said cell, tissue, organ or animal.
53. A method according to claim 52, wherein said effective amount is 0.001-50 mgkilogram of said cells, tissue, organ or animal.
54. A method according to claim 52, wherein said contacting or said administrating is by at least one mode selected from parenteral, subcutaneous, intramuscular, intravenous, intrarticular, intrabronchial, intraabdominal, intracapsular, intracartilaginous, intracavitary, intracelial, intracelebellar, intracerebroventricular, intracolic, intracervical, intragastric, intrahepatic, intramyocardial, intraosteal, intrapelvic, intrapericardiac, intraperitoneal, intrapleural, intraprostatic, intrapulmonary, intrarectal, intrarenal, intraretinal, intraspinal, intrasynovial, intrathoracic, intrauterine, intravesical, bolus, vaginal, rectal, buccal, sublingual, intranasal, or transdermal.
55. A method according to claim 52, further comprising administering, prior, concurrently or after said (a) contacting or administering, at least one composition comprising an effective amount of at least one compound or protein selected from at least one of a detectable label or reporter, a TNF antagonist, an antirheumatic, a muscle relaxant, a narcotic, a non-steroid anti-inflammatory drug (NSAID), an analgesic, an anesthetic, a sedative, a local anethetic, a neuromuscular blocker, an antimicrobial, an antipsoriatic, a corticosteriod, an anabolic steroid, an erythropoietin, an immunization, an immunoglobulin, an immunosuppressive, a growth hormone, a hormone replacement drug, a radiopharmaceutical, an antidepressant, an antipsychotic, a stimulant, an asthma medication, a beta agonist, an inhaled steroid, an epinephrine or analog, a cytokine, or a cytokine antagonist.
56. A medical device, comprising at least one isolated mammalian anti-dual integrin antibody having at least one heavy chain or light chain CDR having the amino acid sequence of at least one of SEQ ID NOS: 1, 2, 3, 4, 5, or 6, wherein said device is suitable to contacting or administerting said at least one anti-dual integrin antibody by at least one mode selected from parenteral, subcutaneous, intramuscular, intravenous, intrarticular, intrabronchial, intraabdominal, intracapsular, intracartilaginous, intracavitary, intracelial, intracelebellar, intracerebroventricular, intracolic, intracervical, intragastric, intrahepatic, intramyocardial, intraosteal, intrapelvic, intrapericardiac, intraperitoneal, intrapleural, intraprostatic, intrapulmonary, intrarectal, intrarenal, intraretinal, intraspinal, intrasynovial, intrathoracic, intrauterine, intravesical, bolus, vaginal, rectal, buccal, sublingual, intranasal, or transdermal.
57. An article of manufacture for human pharmaceutical or diagnostic use, comprising packaging material and a container comprising a solution or a lyophilized form of at least one isolated mammalian anti-dual integrin antibody having at least one heavy chain or light chain CDR having the amino acid sequence of at least one of SEQ ID NOS: 1, 2, 3, 4, 5, or 6.
58. The article of manufacture of claim 57, wherein said container is a component of a parenteral, subcutaneous, intramuscular, intravenous, intrarticular, intrabronchial, intraabdominal, intracapsular, intracartilaginous, intracavitary, intracelial, intracelebellar, intracerebroventricular, intracolic, intracervical, intragastric, intrahepatic, intramyocardial, intraosteal, intrapelvic, intrapericardiac, intraperitoneal, intrapleural, intraprostatic, intrapulmonary, intrarectal, intrarenal, intraretinal, intraspinal, intrasynovial, intrathoracic, intrauterine, intravesical, bolus, vaginal, rectal, buccal, sublingual, intranasal, or transdermal delivery device or system.
59. A method for producing at least one isolated mammalian anti-dual integrin antibody having at least one heavy chain or light chain CDR having the amino acid sequence of at least one of SEQ ID NOS: 1, 2, 3, 4, 5, or 6, comprising providing a host cell or transgenic animal or transgenic plant or plant cell capable of expressing in recoverable amounts said antibody.
60. At least one anti-dual integrin antibody produced by a method according to claim 59.
61. At least one isolated mammalian anti-dual integrin antibody that binds to the same region of a dual integrin protein as an antibody comprising at least one heavy chain or light chain CDR having the amino acid sequence of at least one of SEQ ID NOS: 1, 2, 3, 4, 5, or 6.
62. An dual integrin antibody according to claim 61, wherein said antibody binds dual integrin with an affinity of at least one selected from at least 109 M, at least 1010 M, at least 10M, or at least 1012 M.
63. An dual integrin antibody according to claim 61, wherein said antibody substantially neutralizes at least one activity of at least one dual integrin protein.
64. An isolated nucleic acid encoding at least one isolated mammalian anti-dual integrin antibody that binds to the same region of a dual integrin protein as an antibody comprising at least one heavy chain or light chain CDR having the amino acid sequence of at least one of SEQ ID NOS: 1, 2, 3, 4, 5, or 6.
65. An isolated nucleic acid vector comprising an isolated nucleic acid according to claim 64.
66. A prokaryotic or eukaryotic host cell comprising an isolated nucleic acid according to claim 65.
67. A host cell according to claim 66, wherein said host cell is at least one selected from COS-1, COS-7, HEK293, BHK21, CHO, BSC-1, Hep G2, 653, SP20, 293, HeLa, myeloma, or lymphoma cells, or any derivative, immortalized or transformed cell thereof.
68. A method for producing at least one anti-dual integrin antibody, comprising translating a nucleic acid according to claim 64 under conditions in vitro, in vivo or in situ, such that the dual integrin antibody is expressed in detectable or recoverable amounts.
69. A composition comprising at least one isolated mammalian anti-dual integrin antibody that binds to the same region of a dual integrin protein as an antibody comprising at least one heavy chain or light chain CDR having the amino acid sequence of at least one of SEQ ID NOS: 1, 2, 3, 4, 5, or 6, and at least one pharmaceutically acceptable carrier or diluent.
70. A composition according to claim 69, further comprising at least one composition comprising an effective amount of at least one compound or protein selected from at least one of a detectable label or reporter, a TNF antagonist, an antirheumatic, a muscle relaxant, a narcotic, a non-steroid anti-inflammatory drug (NSAID), an analgesic, an anesthetic, a sedative, a local anethetic, a neuromuscular blocker, an antimicrobial, an antipsoriatic, a corticosteriod, an anabolic steroid, an erythropoietin, an immunization, an immunoglobulin, an immunosuppressive, a growth hormone, a hormone replacement drug, a radiopharmaceutical, an antidepressant, an antipsychotic, a stimulant, an asthma medication, a beta agonist, an inhaled steroid, an epinephrine or analog, a cytokine, or a cytokine antagonist.
71. An anti-idiotype antibody or fragment that specifically binds at least one isolated mammalian anti-dual integrin antibody that binds to the same region of a dual integrin protein as an antibody comprising at least one heavy chain or light chain CDR having the amino acid sequence of at least one of SEQ ID NOS: 1, 2, 3, 4, 5, or 6.
72. A method for diagnosing or treating a dual integrin related condition in a cell, tissue, organ or animal, comprising
(a) contacting or administering a composition comprising an effective amount of at least one isolated mammalian anti-dual integrin antibody that binds to the same region of a dual integrin protein as an antibody comprising at least one heavy chain or light chain CDR having the amino acid sequence of at least one of SEQ ID NOS: 1, 2, 3, 4, 5, or 6, with, or to, said cell, tissue, organ or animal.
73. A method according to claim 72, wherein said effective amount is 0.001-50 mgkilogram of said cells, tissue, organ or animal.
74. A method according to claim 72, wherein said contacting or said administrating is by at least one mode selected from parenteral, subcutaneous, intramuscular, intravenous, intrarticular, intrabronchial, intraabdominal, intracapsular, intracartilaginous, intracavitary, intracelial, intracelebellar, intracerebroventricular, intracolic, intracervical, intragastric, intrahepatic, intramyocardial, intraosteal, intrapelvic, intrapericardiac, intraperitoneal, intrapleural, intraprostatic, intrapulmonary, intrarectal, intrarenal, intraretinal, intraspinal, intrasynovial, intrathoracic, intrauterine, intravesical, bolus, vaginal, rectal, buccal, sublingual, intranasal, or transdermal.
75. A method according to claim 72, further comprising administering, prior, concurrently or after said (a) contacting or administering, at least one composition comprising an effective amount of at least one compound or protein selected from at least one of a detectable label or reporter, a TNF antagonist, an antirheumatic, a muscle relaxant, a narcotic, a non-steroid anti-inflammatory drug (NSAID), an analgesic, an anesthetic, a sedative, a local anethetic, a neuromuscular blocker, an antimicrobial, an antipsoriatic, a corticosteriod, an anabolic steroid, an erythropoietin, an immunization, an immunoglobulin, an immunosuppressive, a growth hormone, a hormone replacement drug, a radiopharmaceutical, an antidepressant, an antipsychotic, a stimulant, an asthma medication, a beta agonist, an inhaled steroid, an epinephrine or analog, a cytokine, or a cytokine antagonist.
76. A medical device, comprising at least one isolated mammalian anti-dual integrin antibody that binds to the same region of a dual integrin protein as an antibody comprising at least one heavy chain or light chain CDR having the amino acid sequence of at least one of SEQ ID NOS: 1, 2, 3, 4, 5, or 6, wherein said device is suitable to contacting or administerting said at least one anti-dual integrin antibody by at least one mode selected from parenteral, subcutaneous, intramuscular, intravenous, intrarticular, intrabronchial, intraabdominal, intracapsular, intracartilaginous, intracavitary, intracelial, intracelebellar, intracerebroventricular, intracolic, intracervical, intragastric, intrahepatic, intramyocardial, intraosteal, intrapelvic, intrapericardiac, intraperitoneal, intrapleural, intraprostatic, intrapulmonary, intrarectal, intrarenal, intraretinal, intraspinal, intrasynovial, intrathoracic, intrauterine, intravesical, bolus, vaginal, rectal, buccal, sublingual, intranasal, or transdermal.
77. An article of manufacture for human pharmaceutical or diagnostic use, comprising packaging material and a container comprising a solution or a lyophilized form of at least one isolated mammalian anti-dual integrin antibody that binds to the same region of a dual integrin protein as an antibody comprising at least one heavy chain or light chain CDR having the amino acid sequence of at least one of SEQ ID NOS: 1, 2, 3, 4, 5, or 6.
78. The article of manufacture of claim 77, wherein said container is a component of a parenteral, subcutaneous, intramuscular, intravenous, intrarticular, intrabronchial, intraabdominal, intracapsular, intracartilaginous, intracavitary, intracelial, in tracelebellar, intracerebroventricular, intracolic, intracervical, intragastric, intrahepatic, intramyocardial, intraosteal, intrapelvic, intrapericardiac, intraperitoneal, intrapleural, intraprostatic, intrapulmonary, intrarectal, intrarenal, intraretinal, intraspinal, intrasynovial, intrathoracic, intrauterine, intravesical, bolus, vaginal, rectal, buccal, sublingual, intranasal, or transdermal delivery device or system.
79. A method for producing at least one isolated mammalian anti-dual integrin antibody that binds to the same region of a dual integrin protein as an antibody comprising at least one heavy chain or light chain CDR having the amino acid sequence of at least one of SEQ ID NOS: 1, 2, 3, 4, 5, or 6, comprising providing a host cell or transgenic animal or transgenic plant or plant cell capable of expressing in recoverable amounts said antibody.
80. At least one anti-dual integrin antibody produced by a method according to claim 79.
81. At least one isolated mammalian anti-dual integrin antibody, comprising at least one human CDR, wherein said antibody specifically binds at least one epitope comprising at least 1-3, to the entire amino acid sequence of SEQ ID NO: 9.
82. An dual integrin antibody according to claim 81, wherein said antibody binds dual integrin with an affinity of at least one selected from at least 109 M, at least 1010 M, at least 10 11 M, or at least 1012 M.
83. An dual integrin antibody according to claim 81, wherein said antibody substantially neutralizes at least one activity of at least one dual integrin protein.
84. An isolated nucleic acid encoding at least one isolated mammalian anti-dual integrin antibody having at least one human CDR, wherein said antibody specifically binds at least one epitope comprising at least 1-3, to the entire amino acid sequence of SEQ ID NO: 9.
85. An isolated nucleic acid vector comprising an isolated nucleic acid according to claim 84.
86. A prokaryotic or eukaryotic host cell comprising an isolated nucleic acid according to claim 85.
87. A host cell according to claim 86, wherein said host cell is at least one selected from COS-1, COS-7, HEK293, BHK21, CHO, BSC-1, Hep G2, 653, SP20, 293, HeLa, myeloma, or lymphoma cells, or any derivative, immortalized or transformed cell thereof.
88. A method for producing at least one anti-dual integrin antibody, comprising translating a nucleic acid according to claim 84 under conditions in vitro, in vivo or in situ, such that the dual integrin antibody is expressed in detectable or recoverable amounts.
89. A composition comprising at least one isolated mammalian anti-dual integrin antibody having at least one human CDR, wherein said antibody specifically binds at least one epitope comprising at least 1-3, to the entire amino acid sequence of SEQ ID NO: 9, and at least one pharmaceutically acceptable carrier or diluent.
90. A composition according to claim 89, further comprising at least one composition comprising an effective amount of at least one compound or protein selected from at least one of a detectable label or reporter, a INF antagonist, an antirheumatic, a muscle relaxant, a narcotic, a non-steroid anti-inflammatory drug (NSAID), an analgesic, an anesthetic, a sedative, a local anethetic, a neuromuscular blocker, an antimicrobial, an antipsoriatic, a corticosteriod, an anabolic steroid, an erythropoietin, an immunization, an immunoglobulin, an immunosuppressive, a growth hormone, a hormone replacement drug, a radiopharmaceutical, an antidepressant, an antipsychotic, a stimulant, an asthma medication, a beta agonist, an inhaled steroid, an epinephrine or analog, a cytokine, or a cytokine antagonist.
91. An anti-idiotype antibody or fragment that specifically binds at least one isolated mammalian anti-dual integrin antibody having at least one human CDR, wherein said antibody specifically binds at least one epitope comprising at least 1-3, to the entire amino acid sequence of SEQ ID NO: 9.
92. A method for diagnosing or treating a dual integrin related condition in a cell, tissue, organ or animal, comprising
(a) contacting or administering a composition comprising an effective amount of at least one isolated mammalian anti-dual integrin antibody having at least one human CDR, wherein said antibody specifically binds at least one epitope comprising at least 1-3, to the entire amino acid sequence of SEQ ID NO: 9, with, or to, said cell, tissue, organ or animal.
93. A method according to claim 92, wherein said effective amount is 0.001-50 mgkilogram of said cells, tissue, organ or animal.
94. A method according to claim 92, wherein said contacting or said administrating is by at least one mode selected from parenteral, subcutaneous, intramuscular, intravenous, intrarticular, intrabronchial, intraabdominal, intracapsular, intracartilaginous, intracavitary, intracelial, intracelebellar, intracerebroventricular, intracolic, intracervical, intragastric, intrahepatic, intramyocardial, intraosteal, intrapelvic, intrapericardiac, intraperitoneal, intrapleural, intraprostatic, intrapulmonary, intrarectal, intrarenal, intraretinal, intraspinal, intrasynovial, intrathoracic, intrauterine, intravesical, bolus, vaginal, rectal, buccal, sublingual, intranasal, or transdermal.
95. A method according to claim 92, further comprising administering, prior, concurrently or after said (a) contacting or administering, at least one composition comprising an effective amount of at least one compound or protein selected from at least one of a detectable label or reporter, a TNF antagonist, an antirheumatic, a muscle relaxant, a narcotic, a non-steroid anti-inflammatory drug (NSAID), an analgesic, an anesthetic, a sedative, a local anethetic, a neuromuscular blocker, an antimicrobial, an antipsoriatic, a corticosteriod, an anabolic steroid, an erythropoietin, an immunization, an immunoglobulin, an immunosuppressive, a growth hormone, a hormone replacement drug, a radiopharmaceutical, an antidepressant, an antipsychotic, a stimulant, an asthma medication, a beta agonist, an inhaled steroid, an epinephrine or analog, a cytokine, or a cytokine antagonist.
96. A medical device, comprising at least one isolated mammalian anti-dual integrin antibody having at least one human CDR, wherein said antibody specifically binds at least one epitope comprising at least 1-3, to the entire amino acid sequence of SEQ ID NO: 9, wherein said device is suitable to contacting or administerting said at least one anti-dual integrin antibody by at least one mode selected from parenteral, subcutaneous, intramuscular, intravenous, intrarticular, intrabronchial, intraabdominal, intracapsular, intracartilaginous, intracavitary, intracelial, intracelebellar, intracerebroventricular, intracolic, intracervical, intragastric, intrahepatic, intramyocardial, intraosteal, intrapelvic, intrapericardiac, intraperitoneal, intrapleural, intraprostatic, intrapulmonary, intrarectal, intrarenal, intraretinal, intraspinal, intrasynovial, intrathoracic, intrauterine, intravesical, bolus, vaginal, rectal, buccal, sublingual, intranasal, or transdermal.
97. An article of manufacture for human pharmaceutical or diagnostic use, comprising packaging material and a container comprising a solution or a lyophilized form of at least one isolated mammalian anti-dual integrin antibody having at least one human CDR, wherein said antibody specifically binds at least one epitope comprising at least 1-3, to the entire amino acid sequence of SEQ ID NO: 9.
98. The article of manufacture of claim 97, wherein said container is a component of a parenteral, subcutaneous, intramuscular, intravenous, intrarticular, intrabronchial, intraabdominal, intracapsular, intracartilaginous, intracavitary, intracelial, intracelebellar, intracerebroventricular, intracolic, intracervical, intragastric, intrahepatic, intramyocardial, intraosteal, intrapelvic, intrapericardiac, intraperitoneal, intrapleural, intraprostatic, intrapulmonary, intrarectal, intrarenal, intraretinal, intraspinal, intrasynovial, intrathoracic, intrauterine, intravesical, bolus, vaginal, rectal, buccal, sublingual, intranasal, or transdermal delivery device or system.
99. A method for producing at least one isolated mammalian anti-dual integrin antibody having at least one human CDR, wherein said antibody specifically binds at least one epitope comprising at least 1-3, to the entire amino acid sequence of SEQ ID NO: 9, comprising providing a host cell or transgenic animal or transgenic plant or plant cell capable of expressing in recoverable amounts said antibody.
100. At least one anti-dual integrin antibody produced by a method according to claim 99.
101. Any invention described herein.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. Aldehyde ALD of the formula (I\u2032):
where
R1 and R2 are either
each independently a monovalent hydrocarbon radical having 1 to 12 carbon atoms
or
together are a divalent hydrocarbon radical having 4 to 12 carbon atoms which is part of an optionally substituted carbocyclic ring having 5 to 8 carbon atoms;
R3 is a hydrogen atom or an alkyl group or an arylalkyl group or an alkoxycarbonyl group; and
R4\u2032 and R5\u2032 are either
each independently a methyl group or a monovalent aliphatic, cycloaliphatic or arylaliphatic radical which has 2 to 20 carbon atoms and optionally has hydroxyl groups or aldehyde groups and optionally contains heteroatoms in the form of ether oxygen or tertiary amine nitrogen, with the proviso that R4\u2032 has at least one hydroxyl group, and that R4\u2032 and R5\u2032 together have at least two hydroxyl groups,
or
together are a divalent aliphatic radical which has at least two hydroxyl groups and 4 to 20 carbon atoms, and is part of an optionally substituted heterocyclic ring having 5 to 8 ring atoms, this ring optionally containing further heteroatoms in the form of ether oxygen or tertiary amine nitrogen and optionally having aldehyde groups.
2. Aldehyde according to claim 1, wherein R1 and R2 are each a methyl group.
3. Aldehyde according to claim 1, wherein R3 is a hydrogen atom.
4. Aldehyde according to claim 1, wherein R4\u2032 and R5\u2032 are each a 2-hydroxyethyl group or a 2-hydroxypropyl group.
5. Aldehyde according to claim 1, wherein the aldehyde ALD is an aldehyde ALD2 of the formula (I\u2033)
where
R4\u2033 and R5\u2033 are either
each independently a methyl group or a monovalent aliphatic, cycloaliphatic or arylaliphatic radical which has 2 to 20 carbon atoms and optionally has hydroxyl groups or aldehyde groups, and which optionally contains heteroatoms in the form of ether oxygen or tertiary amine nitrogen, with the proviso that R4\u2033 has at least two hydroxyl groups, and that R5\u2033 does not have a hydroxyl group;
or
together are a divalent aliphatic radical which has a hydroxyl group and 4 to 20 carbon atoms, and is part of an optionally substituted heterocyclic ring having 5 to 8 ring atoms, this ring optionally containing further heteroatoms in the form of ether oxygen or tertiary amine nitrogen and optionally having aldehyde groups.
6. Aldehyde of the formula (V)
where
R1 and R2 are either
each independently a monovalent hydrocarbon radical having 1 to 12 carbon atoms
or
together are a divalent hydrocarbon radical having 4 to 12 carbon atoms which is part of an optionally substituted carbocyclic ring having 5 to 8 carbon atoms;
R3 is a hydrogen atom or an alkyl group or an arylalkyl group or an alkoxycarbonyl group;
R6 is a divalent aliphatic, cycloaliphatic or arylaliphatic radical which has 2 to 20 carbon atoms and optionally has hydroxyl groups, and which optionally contains heteroatoms in the form of ether oxygen or tertiary amine nitrogen;
R7 and R8 are either
each independently a methyl group or a monovalent aliphatic, cycloaliphatic or arylaliphatic radical which has 2 to 20 carbon atoms and optionally has hydroxyl groups, and which optionally contains heteroatoms in the form of ether oxygen or tertiary amine nitrogen;
or
together are a divalent aliphatic radical which has at least one hydroxyl group and 4 to 20 carbon atoms, which, together with N\u2014R6\u2014N, forms a heterocyclic ring having 5 to 8 ring atoms, this ring optionally containing further heteroatoms in the form of ether oxygen or tertiary amine nitrogen,
with the proviso that at least one of the R6, R7 and R8 radicals has at least one hydroxyl group.
7. Aldehyde according to claim 1, wherein the aldehyde ALD is an aldehyde of the formula (VI\u2032):
8. Aldehyde of the formula (VII\u2032)
where
R9 is a hydrogen atom or an alkyl, cycloalkyl or arylalkyl radical having 1 to 20 carbon atoms, and the aldehyde of the formula (VII) is obtainable by protonation or alkylation from an aldehyde ALD of the formula (I\u2032) according to claim 1.
9. Process for preparing an aldehyde according to claim 1, wherein an aldehyde Y1 of the formula (II):
an aldehyde Y2 of the formula (III):
and a secondary aliphatic amine C which has at least two hydroxyl groups and is of the formula (\u2032IV):
are reacted with elimination of water to give an aldehyde ALD of the formula (I\u2032).
10. Process for preparing an aldehyde, wherein at least one primary aliphatic amine C\u2032 which has at least one hydroxyl group and is of the formula (IV\u2032):
H2N\u2014R4\u2003\u2003(IV\u2032)
is reacted with an aldehyde Y1 of the formula (II):
and an aldehyde Y2 of the formula (III):
in a molar ratio of 1:2:2 with elimination of water to give an aldehyde of the formula (VI):
where
R1 and R2 are either
each independently a monovalent hydrocarbon radical having 1 to 12 carbon atoms
or
together are a divalent hydrocarbon radical having 4 to 12 carbon atoms which is part of an optionally substituted carbocyclic ring having 5 to 8 carbon atoms;
R3 is a hydrogen atom or an alkyl group or an arylalkyl group or an alkoxycarbonyl group;
R4 is a methyl group or a monovalent aliphatic, cycloaliphatic or arylaliphatic radical which has 2 to 20 carbon atoms and optionally has hydroxyl groups or aldehyde groups and optionally contains heteroatoms in the form of ether oxygen or tertiary amine nitrogen, with the proviso that R4 has at least one hydroxyl group.
11. Process for preparing an aldehyde, wherein an aldehyde Y1 of the formula (II):
an aldehyde Y2 of the formula (III):
and a secondary aliphatic amine C which has at least one hydroxyl group and is of the formula (IV):
are reacted with elimination of water to give an aldehyde ALD of the formula (I):
where
R1 and R2 are either
each independently a monovalent hydrocarbon radical having 1 to 12 carbon atoms
or
together are a divalent hydrocarbon radical having 4 to 12 carbon atoms which is part of an optionally substituted carbocyclic ring having 5 to 8 carbon atoms:
R3 is a hydrogen atom or an alkyl group or an arylalkyl group or an alkoxycarbonyl group:
R4 and R5 are either
each independently a methyl group or a monovalent aliphatic, cycloaliphatic or arylaliphatic radical which has 2 to 20 carbon atoms and optionally has hydroxyl groups or aldehyde groups and optionally contains heteroatoms in the form of ether oxygen or tertiary amine nitrogen, with the proviso that R4 has at least one hydroxyl group,
or
together are a divalent aliphatic radical which has at least one hydroxyl group and 4 to 12 carbon atoms, and is part of an optionally substituted heterocyclic ring having 5 to 8 ring atoms, this ring optionally containing further heteroatoms in the form of ether oxygen or tertiary amine nitrogen, and optionally having aldehyde groups; and the amine C is an amine C1 which has at least two hydroxyl groups, and which is selected from the group consisting of diethanolamine, dipropanolamine, diisopropanolamine, 3-(2-hydroxyethylamino)-1-propanol and 3-(2-hydroxypropylamino)-1-propanol, N-methyl-2,3-dihydroxypropylamine, 3,4-dihydroxypyrrolidine, 2,5-bis(hydroxymethyl)-pyrrolidine, 2,6-bis(hydroxymethyl)piperidine, 3,4- or 3,5-dihydroxy-piperidine, 2-(2,3-dihydroxy-propyl)pyrrolidine and 2-(2,3-dihydroxypropyl)-piperidine, and the reaction products of ammonia with two molecules which each have an epoxy group.
12. Process according to claim 9, wherein the amine C is a secondary amine C2 which has at least two hydroxyl groups and which is selected from the group consisting of alkoxylates of primary amines.
13. Process according to claim 10, wherein the amine C\u2032 is selected from the group consisting of aminoalkoxylates, 2-amino-ethanol, 3-amino-1-propanol, 1-amino-2-propanol, 2-amino-1-butanol, 3-(2-hydroxy-ethoxy)propylamine, 2-(2-aminoethoxy)ethanol, 4-(2-aminoethyl)-2-hydroxyethylbenzene, and 3-aminomethyl-3,5,5-trimethylcyclo-hexanol.
14. A method for preparing a composition, the method comprising:
adding an aldehyde ALD of the formula (I\u2032) according to claim 1 to a composition based on isocyanates or epoxy resins; wherein the composition is a member selected from the group consisting of adhesives, sealants, potting compositions, coatings, floor coverings, paints, coating materials, primers and foams.
15. Polyol which has at least one aldehyde group and is obtainable from the polyalkoxylation of an aldehyde ALD of the formula (I):
where
R1 and R2 are either
each independently a monovalent hydrocarbon radical having 1 to 12 carbon atoms
or
together are a divalent hydrocarbon radical having 4 to 12 carbon atoms which is part of an optionally substituted carbocyclic ring having 5 to 8 carbon atoms;
R3 is a hydrogen atom or an alkyl group or an arylalkyl group or an alkoxycarbonyl group:
R4 and R5 are either
each independently a methyl group or a monovalent aliphatic, cycloaliphatic or arylaliphatic radical which has 2 to 20 carbon atoms and optionally has hydroxyl groups or aldehyde groups and optionally contains heteroatoms in the form of ether oxygen or tertiary amine nitrogen, with the proviso that R4 has at least one hydroxyl group,
or
together are a divalent aliphatic radical which has at least one hydroxyl group and 4 to 12 carbon atoms, and is part of an optionally substituted heterocyclic ring having 5 to 8 ring atoms, this rinu optionally containing further heteroatoms in the form of ether oxygen or tertiary amine nitrogen, and optionally having aldehyde groups.
16. Curable composition comprising at least one polyisocyanate and at least one aldehyde ALD of the formula (I):
where
R1 and R2 are either
each independently a monovalent hydrocarbon radical having 1 to 12 carbon atoms
or
together are a divalent hydrocarbon radical having 4 to 12 carbon atoms which is part of an optionally substituted carbocyclic ring having 5 to 8 carbon atoms;
R3 is a hydrogen atom or an alkyl group or an arylalkyl group or an alkoxycarbonyl group:
R4 and R5 are either
each independently a methyl group or a monovalent aliphatic, cycloaliphatic or arylaliphatic radical which has 2 to 20 carbon atoms and optionally has hydroxyl groups or aldehyde groups and optionally contains heteroatoms in the form of ether oxygen or tertiary amine nitrogen, with the proviso that R4 has at least one hydroxyl group,
or
together are a divalent aliphatic radical which has at least one hydroxyl group and 4 to 12 carbon atoms, and is part of an optionally substituted heterocyclic ring having 5 to 8 ring atoms, this ring optionally containing further heteroatoms in the form of ether oxygen or tertiary amine nitrogen, and optionally having aldehyde groups.
17. Curable composition comprising at least one polyisocyanate and at least one aldehyde ALD1 of the formula (I\u2032) according to claim 1.
18. Curable composition according to claim 17, wherein it is a one-component composition, and in that it comprises at least one polyisocyanate whose isocyanate groups are present in the form of blocked isocyanate groups.
19. Curable composition according to claim 17, wherein it is a two-component composition consisting of a component K1 and a component K2, which component K1 comprises at least one polyisocyanate P.
20. Curable composition according to claim 19, wherein the polyisocyanate P is a polyisocyanate PI in the form of a monomeric di- or triisocyanate or of an oligomer of a monomeric diisocyanate or of a derivative of a monomeric diisocyanate.
21. Curable composition according to claim 19, wherein the polyisocyanate P is a polyurethane polymer PUP which has isocyanate groups and is obtainable by the reaction of at least one polyol with at least one polyisocyanate.
22. Curable composition according to claim 19, wherein component K2 comprises water.
23. Cured composition obtained by the reaction of a curable composition according to claim 16 and water.
24. Process for bonding a substrate S1 to a substrate S2, which comprises the steps of
i) applying a curable composition according to claim 16 to a substrate S1;
ii) contacting the applied composition with a substrate S2 within the open time of the composition;
or
i\u2032) applying a composition according to claim 16 to a substrate S1 and to a substrate S2;
ii\u2032) contacting the applied compositions with one another within the open time of the composition;
the substrate S2 consisting of the same material as, or a different material than, the substrate S1.
25. Process for sealing, which comprises the step of
i\u2033) applying a curable composition according to claim 16 between a substrate S1 and a substrate S2, such that the composition is in contact with the substrate S1 and the substrate S2;
the substrate S2 consisting of the same material as, or a different material than, the substrate S1.
26. Process for coating a substrate S1, which comprises the step of
i\u2032\u2033) applying a curable composition according to claim 16 to a substrate S1 within the open time of the composition.
27. Process according to claim 24, characterized in that the substrate S1 andor the substrate S2 is an inorganic substrate such as glass, glass ceramic, concrete, mortar, brick, tile, gypsum or natural stone such as granite or marble; a metal or an alloy, such as aluminium, steel, nonferrous metal, galvanized metal; an organic substrate such as wood, a plastic such as PVC, polycarbonate, PMMA, polyethylene, polypropylene, polyester, epoxy resin; a coated substrate such as powder-coated metal or alloy; or a paint or a coating.
28. Article which has been bonded by a process according to claim 24.
29. Article according to claim 28, wherein the article is a built structure, or an industrial good or a consumer good, or a mode of transport, or an installable component on a mode of transport, or an article in the furniture, textile or packaging industry.