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US4520226A Expired / Lapsed US ⏱️ 0.0 years remaining

Treatment of graft versus host disease using a mixture of T-lymphocyte specific monoclonal antibody: ricin conjugates

Assignee: HEALTH AND HUMAN SERVICES United States, Secretary of, Department of
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Filing: 1983-01-07
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Granted: 1985-05-28
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Expires: 2003-01-07
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Abstract

Abstract A reagent and the protocol for the treatment of Graft Versus Host Disease is disclosed. Monoclonal antibodies specific for T-lymphocytes in human donor bone marrow are covalently linked to separate ricin toxin, combined in a mixture to form a treatment reagent, and combined with bone marrow removed from a human donor. The bone marrow-reagent mixture is then infused into an irradiated recipient. This protocol virtually eliminates T-lymphocyte activity, the cause of Graft Versus Host Disease.

Inventors

  • 👤 David M. Neville, Jr.
  • 👤 Richard J. Youle

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-10-23 17:15
CPC Classifications
C; C07; C07K; C07K16/00; C07K16/18; C07K16/28; A; A61; A61K; A61K38/00

Claims Analysis

Total Claims: 8
Claim 1
Independent Claim 55 words
A composition for the treatment of graft versus host disease in humans consisting essentially of a mixture of equal parts of conjugate molecules TA-1:ricin, T101:ricin, and UCHT1:ricin, said conjugate molecules consisting of ricin bonded to a monoclonal antibody, TA:1, T101 and UCHT1, respectively, said monoclonal antibody having binding specificity for a thymic lymphocyte antigenic site.
Claim 2
Dependent Claim 55 words
A composition for the treatment of graft versus host disease in humans consisting essentially of a mixture of equal parts of conjugate molecules TA-1:ricin, T101:ricin, and UCHT1:ricin, said conjugate molecules consisting of ricin bonded to a monoclonal antibody, TA:1, T101 and UCHT1, respectively, said monoclonal antibody having binding specificity for a thymic lymphocyte antigenic site.
Claim 3
Independent Claim 103 words
A method for the treatment of graft versus host disease in humans consisting essentially of covalently bonding antibodies exhibiting binding specificity for human bone marrow T-cells to ricin toxin in order to form three human T-cell specific cytotoxic hybrids; mixing said three hybrids in equal parts to form a reagent; incubating in vitro said reagent with human donor bone marrow cells obtained from a human donor in the presence of lactose, washing said bone marrow cells with PBS containing 1% HA and 15 mM lactose to remove any unbound conjugates; and injecting washed bone marrow cells incubated with said reagent into irradiated recipients.
Claim 4
Independent Claim 103 words
A method for the treatment of graft versus host disease in humans consisting essentially of covalently bonding antibodies exhibiting binding specificity for human bone marrow T-cells to ricin toxin in order to form three human T-cell specific cytotoxic hybrids; mixing said three hybrids in equal parts to form a reagent; incubating in vitro said reagent with human donor bone marrow cells obtained from a human donor in the presence of lactose, washing said bone marrow cells with PBS containing 1% HA and 15 mM lactose to remove any unbound conjugates; and injecting washed bone marrow cells incubated with said reagent into irradiated recipients.
Claim 5
Dependent Claim 17 words
The method of claim 2 wherein the human T-cell specific cytotoxic hybrids are TA-1-ricin, T101-ricin, and UCHT1-ricin.
Claim 6
Dependent Claim 20 words
The method of claim 2 in which the mixture is formed by combining equal amounts of TA-1-ricin, T101-ricin, and UCHT1-ricin.
Claim 7
Independent Claim 65 words
A method for eliminating T-cells from human bone marrow grafts consisting essentially of separately convalently bonding monoclonal antibodies TA-1, T101, and UCHT1 to ricin toxins to form three human T-cell specific cytotoxic hybrids, forming a mixture by combining equal amounts of each hybrid, and incubating under standard biological conditions said mixture with human bone marrow cells in the presence of a suitable amount of lactose.
Claim 8
Independent Claim 65 words
A method for eliminating T-cells from human bone marrow grafts consisting essentially of separately convalently bonding monoclonal antibodies TA-1, T101, and UCHT1 to ricin toxins to form three human T-cell specific cytotoxic hybrids, forming a mixture by combining equal amounts of each hybrid, and incubating under standard biological conditions said mixture with human bone marrow cells in the presence of a suitable amount of lactose.

References Cited (Backward Citations)

FR63988E Cited
US4340535A Cited
US4359457A Cited
US4356117A Cited
US4397843A Cited
US4363758A Cited
US4368149A Cited
US4414148A Cited
EP0074279A2 Cited

USPTO Annuity & Maintenance Windows

Annuity Stage Window Opens Payment Deadline Surcharge Period Until Estimated Fee Status
3.5 Years (Year 4) 1988-05-27 1988-11-26 1989-05-28 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 1992-05-27 1992-11-26 1993-05-28 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 1996-05-27 1996-11-26 1997-05-28 $7700.00 Window Closed / Lapsed

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