Patent US5135915A successfully refreshed from Google Patents.
US5135915A
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US
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Method for the treatment of grafts prior to transplantation using TGF-.beta.
Assignee: Genentech Inc
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Filing: 1988-10-14
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Granted: 1992-08-04
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Expires: 2008-10-14
Abstract
Abstract A method is provided for the treatment of grafts such as tissue or organs prior to transplantation into a suitable host. The grafts are incubated, coated, or perfused with TGF-β for an effective time for the uptake of the agent into the grafts and induction of its biological effects. The thus-treated graft is then transplanted into a compatible host, preferably a human host.
Inventors
- 👤 Christine W. Czarniecki
- 👤 Michael A. Palladino
- 👤 Eli Shefter
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-30 23:25
CPC Classifications
A; A61; A61L; A61L27/00; A61L27/36; A61L27/3683; A61L27/3687; A61L27/50; A61L27/54; A61L2300/00; A61L2300/40; A61L2300/412; A61L2300/414; A61L2300/426
Claims Analysis
Total Claims: 56
Claim 1
Independent Claim
36 words
A method for the treatment of a graft prior to transplantation comprising: pre-treating the graft with a composition comprising a therapeutically effective amount of transforming growth factor-β (TGF-β); and transplanting the graft into a compatible host.
Claim 2
Independent Claim
36 words
A method for the treatment of a graft prior to transplantation comprising: pre-treating the graft with a composition comprising a therapeutically effective amount of transforming growth factor-β (TGF-β); and transplanting the graft into a compatible host.
Claim 3
Dependent Claim
10 words
The method of claim 1 wherein the graft is tissue.
Claim 4
Dependent Claim
10 words
The method of claim 1 wherein the graft is skin.
Claim 5
Dependent Claim
19 words
The method of claim 3 wherein the treatment comprises coating the lower surface of the skin with the composition.
Claim 6
Dependent Claim
11 words
The method of claim 4 wherein the composition comprises a polysaccharide.
Claim 7
Dependent Claim
11 words
The method of claim 1 wherein the graft comprises isolated cells.
Claim 8
Dependent Claim
11 words
The method of claim 6 wherein the graft comprises islet cells.
Claim 9
Dependent Claim
11 words
The method of claim 1 wherein the graft is an organ.
Claim 10
Dependent Claim
27 words
The method of claim 8 wherein the organ is selected from group consisting of heart, liver, spleen, pancreas, thyroid lobe, lung, kidney, intestine, blood vessel, and esophagus.
Claim 11
Dependent Claim
11 words
The method of claim 1 wherein the host is a mammal.
Claim 12
Dependent Claim
20 words
The method of claim 10 wherein the mammal is a human and the graft is derived from a human donor.
Claim 13
Dependent Claim
11 words
The method of claim 1 wherein the TGF-β is human TGF-β.
Claim 14
Dependent Claim
18 words
The method of claim 12 wherein the TGF-β is TGF-β 1 , TGF-β 2 or TGF-β 3 .
Claim 15
Dependent Claim
19 words
The method of claim 1 wherein the treating step takes place in vitro for at least about one minute.
Claim 16
Dependent Claim
22 words
The method of claim 1 wherein the treating step takes place in vitro for from about one minute to about 72 hours.
Claim 17
Dependent Claim
32 words
The method of claim 1 wherein the composition further comprises a therapeutically effective amount of an immunosuppressive agent that suppresses cytokine production, downregulates or suppresses self-antigen expression, or masks the MHC antigens.
Claim 18
Dependent Claim
62 words
The method of claim 16 wherein the immunosuppressive agent is a 2-amino-6-aryl-5-substituted pyrimidine, glutaraldehyde, azathioprine, bromocryptine, cyclophosphamide, antiidiotypic antibodies for major histocompatibility complex antigens, cyclosporin A, a steroid, anti-interferon-γ antibodies, anti-tumor necrosis factor-α antibodies, anti-interleukin-2 antibodies, anti-cytokine receptor antibodies, anti-tumor necrosis factor-β antibodies, anti-Ia antibodies, heterologous anti-lymphocyte globulin, pan-T antibodies, antibodies to CD4, streptokinase, streptodornase, or RNA or DNA from the host.
Claim 19
Dependent Claim
26 words
The method of claim 17 wherein the immunosuppressive agent is cyclosporin A, a glucocorticosteroid, OKT-3 monoclonal antibody, azathioprine, bromocryptine, heterologous anti-lymphocyte globulin, or a mixture thereof.
Claim 20
Dependent Claim
10 words
The method of claim 1 wherein the composition is acidic.
Claim 21
Dependent Claim
17 words
The composition of claim 19 wherein the pH of the composition is about 4 to about 6.
Claim 22
Dependent Claim
15 words
The method of claim 1 wherein the composition is a perfluorochemical emulsion of the TGF-β.
Claim 23
Dependent Claim
26 words
The method of claim 1 further comprising, after the treatment step and before the transplantation step, the step of washing the graft free of the composition.
Claim 24
Dependent Claim
16 words
The method of claim 1 wherein the therapeutically effective amount is 1 pg/ml to 1 mg/ml.
Claim 25
Dependent Claim
20 words
The method of claim 1 wherein the host undergoes a donor-specific blood transfusion or total lymphoid irradiation before the transplantation.
Claim 26
Dependent Claim
21 words
The method of claim 11 wherein the donor of the graft and the host are matched for HLA class II antigens.
Claim 27
Dependent Claim
20 words
The method of claim 25 wherein the host undergoes a donor-specific blood transfusion or total lymphoid irradiation before the transplantation.
Claim 28
Dependent Claim
39 words
The method of claim 1 further comprising the step of administering to the host after the transplantation a therapeutically effective amount of an immunosuppressive agent that suppresses cytokine production, downregulates or suppresses self-antigen expression, or masks the MHC antigens.
Claim 29
Dependent Claim
39 words
The method of claim 26 further comprising the step of administering to the host after the transplantation a therapeutically effective amount of an immunosuppressive agent that suppresses cytokine production, downregulates or suppresses self-antigen expression, or masks the MHC antigens.
Claim 30
Dependent Claim
63 words
The method of claim 27 wherein the immunosuppressive agent is TGF-β, a 2-amino-6-aryl-5-substituted pyrimidine, glutaraldehyde, azathioprine, bromocryptine, cyclophosphamide, antiidiotypic antibodies for major histocompatibility complex antigens, cyclosporin A, a steroid, anti-interferon-γ antibodies, anti-tumor necrosis factor-a antibodies, anti-interleukin-2 antibodies, anti-cytokine receptor antibodies, anti-tumor necrosis factor-β antibodies, anti-Ia antibodies, heterologous anti-lymphocyte globulin, pan-T antibodies, antibodies to CD4, streptokinase, streptodornase, or RNA or DNA from the host.
Claim 31
Dependent Claim
27 words
The method of claim 29 wherein the immunosuppressive agent is TGF-β, cyclosporin A, a glucocorticosteroid, OKT-3 monoclonal antibody, azathioprine, bromocryptine, heterologous anti-lymphocyte globulin, or a mixture thereof.
Claim 32
Dependent Claim
15 words
The method of claim 27 wherein the host is continuously infused with the immunosuppressive agent.
Claim 33
Dependent Claim
17 words
The method of claim 27 wherein pulse infusions of the immunosuppressive agent are administered to the host.
Claim 34
Dependent Claim
19 words
The method of claim 32 wherein the pulse infusions are carried out using declining doses of the immunosuppressive agent.
Claim 35
Dependent Claim
24 words
The method of claim 1 wherein the graft is transplanted into a mammalian species different from that from which the original graft was derived.
Claim 36
Dependent Claim
23 words
The method of claim 34 wherein the graft is transplanted into a human and was derived from a mammalian species other than human.
Claim 37
Dependent Claim
23 words
The method of claim 1 further comprising, after said treating step and before said transplantation step, the step of storing the treated graft.
Claim 38
Dependent Claim
23 words
A graft of living cells, tissue, bone marrow, or organs suitable for transplantation into a recipient host treated with a composition comprising TGF-β.
Claim 39
Dependent Claim
23 words
A graft of living cells, tissue, bone marrow, or organs suitable for transplantation into a recipient host treated with a composition comprising TGF-β.
Claim 40
Dependent Claim
27 words
The graft of claim 37 wherein the composition further comprises an immunosuppressive agent that suppresses cytokine production, downregulates or suppresses self-antigen expression, or masks the MHC antigens.
Claim 41
Dependent Claim
56 words
The graft of claim 38 wherein the immunosuppressive agent is a 2-amino-6-aryl-5-substituted pyrimidine, glutaraldehyde, azathioprine, bromocryptine, cyclophosphamide, antiidiotypic antibodies for major histocompatibility complex antigens, cyclosporin A, a steroid, anti-interferon-γ antibodies, anti-tumor necrosis factor-a antibodies, anti-interleukin-2 antibodies, anti-cytokine receptor antibodies, anti-tumor necrosis factor-β antibodies, anti-Ia antibodies, heterologous anti-lymphocyte globulin, pan-T antibodies, antibodies to CD4, streptokinase, or streptodornase.
Claim 42
Dependent Claim
26 words
The graft of claim 39 wherein the immunosuppressive agent is cyclosporin A, a glucocorticosteroid, OKT-3 monoclonal antibody, azathioprine, bromocryptine, heterologous anti-lymphocyte globulin, or a mixture thereof.
Claim 43
Dependent Claim
10 words
The graft of claim 38 wherein the composition is acidic.
Claim 44
Dependent Claim
26 words
The graft of claim 37 that is skin, wherein the lower surface of the skin to be applied to a host is coated with the composition.
Claim 45
Dependent Claim
11 words
The graft of claim 42 wherein the composition comprises a polysaccharide.
Claim 46
Dependent Claim
12 words
The graft of claim 37 wherein the composition is a perfluorochemical emulsion.
Claim 47
Dependent Claim
13 words
The graft of claim 37 wherein the graft is perfused with the composition.
Claim 48
Dependent Claim
11 words
The graft of claim 37 that is derived from a mammal.
Claim 49
Dependent Claim
11 words
The graft of claim 46 that is derived from a human.
Claim 50
Dependent Claim
11 words
The graft of claim 37 wherein the TGF-β is human TGF-β.
Claim 51
Dependent Claim
18 words
The graft of claim 37 wherein the TGF-β is TGF-β 1 , TGF-β 2 or TGF-β 3 .
Claim 52
Dependent Claim
8 words
A composition comprising TGF-β in a perfluorochemical emulsion.
Claim 53
Dependent Claim
8 words
A composition comprising TGF-β in a perfluorochemical emulsion.
Claim 54
Dependent Claim
12 words
The method of claim 1 wherein the TGF-β is TGF-β 1 .
Claim 55
Dependent Claim
12 words
The graft of claim 37 wherein the TGF-β is TGF-β 1 .
Claim 56
Dependent Claim
12 words
The composition of claim 50 wherein the TGF-β is TGF-β 1 .
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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) | 1995-08-04 | 1996-02-03 | 1996-08-04 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1999-08-04 | 2000-02-03 | 2000-08-04 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2003-08-04 | 2004-02-03 | 2004-08-04 | $7700.00 | Window Closed / Lapsed |