EP0294703A2
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EP
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Bifunctional antibody constructs and method for selectively destroying cell populations
Assignee: Dana Farber Cancer Institute Inc
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Filing: 1988-06-01
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Granted: —
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Expires: 2008-06-01
Abstract
Abstract A bifunctional heterodimeric antibody conjugate comprising (a) an anti-target cell antibody component joined to (b) an anti-lymphocyte antibody component wherein the anti-lymphocyte antibody component is specific for activated lymphocytes. A bifunctional antibody/cell surface-binding molecule conjugate comprising (a) a molecular component other than an antibody, capable of binding to target cell surface molecules and (b) an anti-lymphocyte antibody component wherein the anti-lymphocyte antibody component is specific for activated lymphocytes. A bifunctional hybrid antibody comprising (a) an anti-target cell binding site component and (b) an anti-lymphocyte binding site component, wherein the anti-lymphocyte binding site component is specific for activated lymphocytes. A method for selectively destroying target cell populations comprising: (1) binding the component (a) of one or more of the above described bifunctional antibody constructs to target cells; (2) activating lymphocytes; and (3) binding the activated lymphocytes to the component (b) of the bifunctional antibody construct; wherein said steps (1), (2) and (3) can be conducted simultaneously or in any order, provided that step (2) is always conducted simultaneously with or prior to step (3).
Inventors
- 👤 Stuart F. Schlossman
- 👤 Charles F. Scott, Jr.
- 👤 John M. Lambert
- 👤 Walter A Blattler
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-10-23 19:26
CPC Classifications
C; C07; C07K; C07K16/00; C07K16/46; C07K16/468; A; A61; A61K; A61K47/00; A61K47/50; A61K47/51; A61K47/68; A61K47/6835; A61K47/6875; A61K47/6879; A61P; A61P35/00; A61K38/00
Claims Analysis
Total Claims: 60
Claim 1
Independent Claim
29 words
A bifunctional heterodimeric antibody conjugate comprising (a) an anti-target cell antibody component joined to (b) an anti-lymphocyte antibody component wherein the anti-lymphocyte antibody component is specific for activated lymphocytes.
Claim 2
Dependent Claim
29 words
A bifunctional heterodimeric antibody conjugate comprising (a) an anti-target cell antibody component joined to (b) an anti-lymphocyte antibody component wherein the anti-lymphocyte antibody component is specific for activated lymphocytes.
Claim 3
Dependent Claim
18 words
The bifunctional heterodimeric antibody conjugate of Claim 1, wherein said anti-lymphocyte antibody component (b) is an anti-T11₃ antibody.
Claim 4
Dependent Claim
18 words
The bifunctional heterodimeric antibody conjugate of Claim 1, wherein said anti-lymphocyte antibody component (b) is an anti-T11₂ antibody.
Claim 5
Dependent Claim
69 words
The bifunctional heterodimeric antibody conjugate of Claim 1, wherein said anti-target cell antibody component (a) is one member selected from the group consisting of an anti-tumor cell antibody, an antibody to a virus infected cell, an antibody to a parasite infected cell, an antibody to an autoimmune cell, an antibody to activated cells that cause graft rejection and an antibody to activated cells that cause graft vs. host disease.
Claim 6
Dependent Claim
69 words
The bifunctional heterodimeric antibody conjugate of Claim 2, wherein said anti-target cell antibody component (a) is one member selected from the group consisting of an anti-tumor cell antibody, an antibody to a virus infected cell, an antibody to a parasite infected cell, an antibody of an autoimmune cell, an antibody to activated cells that cause graft rejection and an antibody to activated cells that cause graft vs. host disease.
Claim 7
Dependent Claim
27 words
The bifunctional heterodimeric antibody conjugate of Claim 1, wherein said antibody components (a) and (b) of the heterodimeric antibody conjugate are joined by cross-linked complimentary reactive groups.
Claim 8
Dependent Claim
39 words
A bifunctional antibody/cell surface-binding molecule conjugate comprising (a) a molecular component, other than an antibody, capable of binding to target cell surface molecules and (b) an anti-lymphocyte antibody component wherein the anti-lymphocyte antibody component is specific for activated lymphocytes.
Claim 9
Dependent Claim
39 words
A bifunctional antibody/cell surface-binding molecule conjugate comprising (a) a molecular component, other than an antibody, capable of binding to target cell surface molecules and (b) an anti-lymphocyte antibody component wherein the anti-lymphocyte antibody component is specific for activated lymphocytes.
Claim 10
Dependent Claim
19 words
The bifunctional antibody/cell surface-binding molecule conjugate of Claim 7, wherein said anti-lymphocyte antibody component (b) is an anti-T11₃ antibody.
Claim 11
Dependent Claim
19 words
The bifunctional antibody/cell surface-binding molecule conjugate of Claim 7, wherein said anti-lymphocyte antibody component (b) is an anti-T11₂ antibody.
Claim 12
Dependent Claim
66 words
The bifunctional antibody/cell surface-binding molecule conjugate of Claim 7, wherein said molecular component (a) is capable of binding to one member selected from the group consisting of tumor cell surface molecules, virus infected cell surface molecules, parasite infected cell surface molecules, autoimmune cell surface molecules, surface molecules of activated cells that cause graft rejection and surface molecules of activated cells that cause graft vs. host disease.
Claim 13
Dependent Claim
66 words
The bifunctional antibody/cell surface-binding molecule conjugate of Claim 8, wherein said molecular component (a) is capable of binding to one member selected from the group consisting of tumor cell surface molecules, virus infected cell surface molecules, parasite infected cell surface molecules, autoimmune cell surface molecules, surface molecules of activated cells that cause graft rejection and surface molecules of activated cells that cause graft vs. host disease.
Claim 14
Dependent Claim
25 words
The bifunctional antibody/cell surface-binding molecule conjugate of Claim 7, wherein said components (a) and (b) of the conjugate are joined by cross-linked complementary reactive groups.
Claim 15
Dependent Claim
31 words
The bifunctional antibody/cell surface-binding molecule conjugate of Claim 7 or 8, wherein said molecular component (a) is one member selected from the group consisting of hormones, lymphokines, and colony stimulating factors.
Claim 16
Dependent Claim
30 words
A bifunctional hybrid antibody comprising (a) an anti-target cell binding site component and (b) an anti-lymphocyte binding site component, wherein the anti-lymphocyte binding site component is specific for activated lymphocytes.
Claim 17
Dependent Claim
30 words
A bifunctional hybrid antibody comprising (a) an anti-target cell binding site component and (b) an anti-lymphocyte binding site component, wherein the anti-lymphocyte binding site component is specific for activated lymphocytes.
Claim 18
Dependent Claim
17 words
The bifunctional hybrid antibody of Claim 14, wherein said anti-lymphocyte binding site (b) is specific for T11₃.
Claim 19
Dependent Claim
17 words
The bifunctional hybrid antibody of Claim 14, wherein said anti-lymphocyte binding site (b) is specific for T11₂.
Claim 20
Dependent Claim
50 words
The bifunctional hybrid antibody of Claim 14, wherein said anti-target cell binding site (a) is specific for one member selected from the group consisting of tumor cells, virus infected cells, parasite infected cells, autoimmune cells, activated cells that cause graft rejection and activated cells that cause graft vs. host disease.
Claim 21
Dependent Claim
50 words
The bifunctional hybrid antibody of Claim 15, wherein said anti-target cell binding site (a) is specific for one member selected from the group consisting of tumor cells, virus infected cells, parasite infected cells, autoimmune cells, activated cells that cause graft rejection and activated cells that cause graft vs. host disease.
Claim 22
Independent Claim
104 words
A method for selectively destroying target cell populations using a bifunctional heterodimeric antibody conjugate which comprises (a) an anti-target cell antibody component joined to (b) an anti-lymphocyte antibody component, wherein said anti-lymphocyte antibody component is specific for activated lymphocytes, said method comprising: (1) binding the bifunctional heterodimeric antibody conjugate through the component (a) to target cells; (2) activating lymphocytes; and (3) binding the activated lymphocytes to the component (b) of the bifunctional heterodimeric antibody conjugate; wherein said steps (1), (2) and (3) can be conducted simultaneously or in any order, provided that step (2) is always conducted simultaneously with or prior to step (3).
Claim 23
Independent Claim
104 words
A method for selectively destroying target cell populations using a bifunctional heterodimeric antibody conjugate which comprises (a) an anti-target cell antibody component joined to (b) an anti-lymphocyte antibody component, wherein said anti-lymphocyte antibody component is specific for activated lymphocytes, said method comprising: (1) binding the bifunctional heterodimeric antibody conjugate through the component (a) to target cells; (2) activating lymphocytes; and (3) binding the activated lymphocytes to the component (b) of the bifunctional heterodimeric antibody conjugate; wherein said steps (1), (2) and (3) can be conducted simultaneously or in any order, provided that step (2) is always conducted simultaneously with or prior to step (3).
Claim 24
Dependent Claim
16 words
The method of Claim 19, wherein the method comprises destroying the target cells in vitro .
Claim 25
Dependent Claim
16 words
The method of Claim 19, wherein the method comprises destroying the target cells in vivo .
Claim 26
Dependent Claim
18 words
The method of Claim 21, wherein the method comprises activating the lymphocytes in vivo or ex vivo .
Claim 27
Dependent Claim
30 words
The method of Claim 19, 20, 21 or 22, wherein the method comprises activating said lymphocytes with one member selected from the group consisting of antibodies, mitogens, antigens, and lymphokines.
Claim 28
Dependent Claim
17 words
The method of Claim 23, wherein the method comprises activating the lymphocytes with one or more antibodies.
Claim 29
Dependent Claim
27 words
The method of Claim 24, wherein the method comprises activating the lymphocytes with one or more antibodies selected from the group consisting of anti-T11₂, anti-T3, and anti-2H1.
Claim 30
Dependent Claim
20 words
The method of Claim 22, wherein the method comprises activating the lymphocytes with a mixture of anti-T11₂ and anti-T11₃ antibodies.
Claim 31
Dependent Claim
35 words
The method of Claim 22, wherein said anti-lymphocyte antibody component (b) of said bifunctional heterodimeric antibody conjugate is an anti-T11₃ antibody and said method comprises activating said lymphocytes in vivo or ex vivo with anti-T11₂.
Claim 32
Dependent Claim
21 words
The method of Claim 19, wherein said anti-lymphocyte antibody component (b) of said bifunctional heterodimeric antibody conjugate is an anti-T11₂ component.
Claim 33
Dependent Claim
78 words
The method of Claim 19, 20, 21, 22, 26, 27, or 28, wherein said anti-target cell component (a) of said bifunctional heterodimeric antibody conjugate is one member selected from the group consisting of an anti-tumor cell antibody, an antibody to a virus infected cell, an antibody to a parasite infected cell, an antibody to an autoimmune cell, an antibody to activated cells that cause graft rejection and an antibody to activated cells that cause graft vs. host disease.
Claim 34
Independent Claim
28 words
The method of Claim19, 20, 21 or 22, wherein said antibody components (a) and (b) of the bifunctional heterodimeric antibody conjugate are joined by cross-liked complimentary reactive groups.
Claim 35
Independent Claim
116 words
A method for selectively destroying target cell populations using a bifunctional antibody/cell surface-binding molecule conjugate which comprises (a) a molecular component other than an antibody capable of binding to target cell surface molecules and (b) an anti-lymphocyte antibody component wherein the anti-lyumphocyte antibody component is specific for activated lymphocytes, said method comprising: (1) binding the bifunctional antibody/cell surface-binding molecule conjugate through the component (a) to target cells; (2) activating lymphocytes; and (3) binding the activated lymphocytes to the component (b) of the bifunctional antibody/cell surface-binding molecule conjugate; wherein said steps (1), (2) and (3) can be conducted simultaneously or in any order, provided that step (2) is always conducted simultaneously with or prior to step (3).
Claim 36
Independent Claim
116 words
A method for selectively destroying target cell populations using a bifunctional antibody/cell surface-binding molecule conjugate which comprises (a) a molecular component other than an antibody capable of binding to target cell surface molecules and (b) an anti-lymphocyte antibody component wherein the anti-lyumphocyte antibody component is specific for activated lymphocytes, said method comprising: (1) binding the bifunctional antibody/cell surface-binding molecule conjugate through the component (a) to target cells; (2) activating lymphocytes; and (3) binding the activated lymphocytes to the component (b) of the bifunctional antibody/cell surface-binding molecule conjugate; wherein said steps (1), (2) and (3) can be conducted simultaneously or in any order, provided that step (2) is always conducted simultaneously with or prior to step (3).
Claim 37
Dependent Claim
16 words
The method of Claim 31, wherein the method comprises destroying the target cells in vitro .
Claim 38
Dependent Claim
16 words
The method of Claim 31, wherein the method comprises destroying the target cells in vivo .
Claim 39
Dependent Claim
18 words
The method of Claim 33, wherein the method comprises activating the lymphocytes in vivo or ex vivo .
Claim 40
Dependent Claim
30 words
The method of Claim 31, 32, 33, or 34, wherein the method comprises activating said lymphocytes with one member selected from the group consisting of antibodies, mitogens, antigens, and lymphokines.
Claim 41
Dependent Claim
17 words
The method of Claim 35, wherein the method comprises activating the lymphocytes with one or more antibodies.
Claim 42
Dependent Claim
27 words
The method of Claim 36, wherein the method comprises activating the lymphocytes with one or more antibodies selected from the group consisting of anti-T11₂, anti-T3, and anti-2H1.
Claim 43
Dependent Claim
20 words
The method of Claim 34, wherein the method comprises activating the lymphocytes with a mixture of anti-T11₂ and anti-T11₃ antibodies.
Claim 44
Dependent Claim
36 words
The method of Claim 34, wherein said anti-lymphocyte antibody component (b) of said bifunctional antibody/cell surface-binding molecule conjugate is an anti-T11₃ antibody and said method comprises activating said lymphocytes in vivo or ex vivo with anti-T11₂.
Claim 45
Dependent Claim
22 words
The method of Claim 31, wherein said anti-lymphocyte antibody component (b) of said bifunctional antibody/cell surface-binding molecule conjugate is an anti-T11₂ antibody.
Claim 46
Dependent Claim
76 words
The method of Claim 31, 32, 33, 34, 38, 39, or 40, wherein said molecular component (a) of said bifunctional antibody/cell surface-binding molecule conjugate is capable of binding to one member selected from the group consisting of tumor cell surface molecules, virus infected cell surface molecules, parasite infected cell surface molecules, autoimmune cell surface molecules, surface molecules of activated cells that cause graft rejection and surface molecules of activated cells that cause graft vs. host disease.
Claim 47
Dependent Claim
32 words
The method of Claim 31, wherein said molecular component (a) of said bifunctional antibody/cell surface-binding molecule conjugate is one member selected from the group consisting of hormones, lymphokines, and colony stimulating factors.
Claim 48
Dependent Claim
29 words
The method of Claim 31, 32, 33 or 34, wherein said components (a) and (b) of said bifunctional antibody/cell surface-binding molecule conjugate are joined by cross-linked complimentary reactive groups.
Claim 49
Independent Claim
103 words
A method for selectively destroying target cell populations using a bifunctional hybrid antibody which comprises (a) an anti-target cell binding site component and (b) an anti-lymphocyte binding site component, wherein the anti-lymphocyte binding site component is specific for activated lymphocytes, said method comprising: (1) binding the bifunctional hybrid antibody through the component (a) to target cells; (2) activating lymphocytes; and (3) binding the activated lymphocytes to the component (b) of the bifunctional hybrid antibody; wherein said steps (1), (2) and (3) can be conducted simultaneously or in any order, provided that step (2) is always conducted simultaneously with or prior to step (3).
Claim 50
Independent Claim
103 words
A method for selectively destroying target cell populations using a bifunctional hybrid antibody which comprises (a) an anti-target cell binding site component and (b) an anti-lymphocyte binding site component, wherein the anti-lymphocyte binding site component is specific for activated lymphocytes, said method comprising: (1) binding the bifunctional hybrid antibody through the component (a) to target cells; (2) activating lymphocytes; and (3) binding the activated lymphocytes to the component (b) of the bifunctional hybrid antibody; wherein said steps (1), (2) and (3) can be conducted simultaneously or in any order, provided that step (2) is always conducted simultaneously with or prior to step (3).
Claim 51
Dependent Claim
16 words
The method of Claim 44, wherein the method comprises destroying the target cells in vitro .
Claim 52
Dependent Claim
16 words
The method of Claim 44, wherein the method comprises destroying the target cells in vivo .
Claim 53
Dependent Claim
18 words
The method of Claim 46, wherein the method comprises activating the lymphocytes in vivo or ex vivo .
Claim 54
Dependent Claim
30 words
The method of Claim 44, 45, 46, or 47, wherein the method comprises activating said lymphocytes with one member selected from the group consisting of antibodies, mitogens, antigens, and lymphokines.
Claim 55
Dependent Claim
17 words
The method of Claim 48, wherein the method comprises activating the lymphocytes with one or more antibodies.
Claim 56
Dependent Claim
27 words
The method of Claim 49, wherein the method comprises activating the lymphocytes with one or more antibodies selected from the group consisting of anti-T11₂, anti-T3, and anti-2H1.
Claim 57
Dependent Claim
27 words
The method of Claim 47, wherein the method comprises activating the lymphocytes with a mixture of (i) a binding site specific for T11₃ and (ii) anti-T11₂ antibody.
Claim 58
Dependent Claim
36 words
The method of Claim 47, wherein the component (b) of said bifunctional hybrid antibody is a binding site specific for T11₃ and said method comprises activating said lymphocytes in vivo or ex vivo with anti-T11₂ antibody.
Claim 59
Dependent Claim
21 words
The method of Claim 44, wherein the component (b) of said bifunctional hybrid antibody is a binding site specific for T11₂.
Claim 60
Dependent Claim
61 words
The method of Claim 44, 45, 46, 47, 51, 52 or 53 wherein said anti-target cell binding site component (a) of said bifunctional hybrid antibody is specific for one member selected from the group consisting of tumor cells, virus infected cells, parasite infected cells, autoimmune cells, activated cells that cause graft rejection and activated cells that cause graft vs. host disease.
References Cited (Backward Citations)
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