Drug – bio-affecting and body treating compositions – In vivo diagnosis or in vivo testing – Testing efficacy or toxicity of a compound or composition
Reexamination Certificate
1996-08-26
2004-08-03
Shukla, Ram R. (Department: 1632)
Drug, bio-affecting and body treating compositions
In vivo diagnosis or in vivo testing
Testing efficacy or toxicity of a compound or composition
C424S093210, C424S278100, C800S014000
Reexamination Certificate
active
06770260
ABSTRACT:
TECHNICAL FIELD
The invention is in the field of hematopoietic cell reconstitution.
BACKGROUND ART
Animals including man tend to deplete rapidly non-autologous peripheral hematopoietic cells. This is true even if the animals are immunocompromised. This phenomenon has hindered the use of allogeneic cell transfusions in immunocompromised humans. Animal model systems have been proposed to study the human hematopoietic and immunologic system. However, they are not adequately reflective of the full complement of the immune system due to the lack or decreased amount of xenogeneic peripheral hematopoietic cells.
The most frequently used animal models of the human immune system utilize severe combined immune deficiency (SCID) mice that have been injected with human peripheral blood cells or bone marrow cells; or that have been humanized by co-implantation of human fetal thymus and liver (Thy/Liv) or by implantation of human fetal bone marrow fragments. Mosier et al. (1988) Nature, 335:256; Kamel-Reid and Dick (1988) Science, 242:1706; McCune et al. (1988) Science, 241:1632; Namikawa et al. (1990) J. Exp. Med., 172:1055; Kyoizumi et al. (1992) Blood, 79:1704; Kyoizumi (1993) Blood, 81:1497; and Namikawa et al. (1993) Blood, 82:2526. Injection of human bone marrow followed by a regimen of cytokine injections has been shown to allow substantial prolongation of survival of human myeloid progenitors. Lapidot et al. (1992) Science, 255:1137. The SCID-hu Thy/Liv grafts produce phenotypically normal human T cells in the periphery for prolonged periods, allowing mechanisms of tolerance induction and T cell repertoire to be studied. Krowka et al. (1991) J. Immunol., 146:3751; Vandekerckhove et al. (1991) J. Immunol., 146:4173; Vandekerckhove et al. (1992) J. Exp. Med., 175:1033; Vandekerckhove et al. (1992) J. Exp. Med., 176:1619; and Baccala et al. (1993) J. Exp. Med., 177:1481.
SCID-hu mice are also valuable for the study of human hematopoietic stem cell development and human immunodeficiency virus (HIV) pathogenesis. Peault et al. (1991) J. Exp. Med., 174:1283; Baum et al. (1992) Proc. Natl. Acad. Sci. USA, 89:2804; McCune et al. (1990) Science, 247:564; Bonyhadi et al. (1993) Nature, 363:728; Aldrovandi et al. (1993) Nature, 363:732; and copending co-owned U.S. patent application Ser. No. 07/882,937.
The potential use of SCID-hu mice is limited, however, by the low engraftment of human cells. The current models would be greatly improved by providing a means to allow human hematopoietic cells to survive and circulate freely in the periphery of immunocompromised mice. Moreover, methods useful in increasing engraftment of human cells in SCID-hu mice have direct application in a variety of human disorders.
The mononuclear phagocyte systems of the spleen and liver are important sites of phagocytosis of both opsonized and non-opsonized particles as well as in the early phases of bacterial infection. Lockwood (1983) Clin. Hematol. 12:449. Specific elimination of macrophages in the spleen and liver can be effected by injection of liposome-encapsulated dichloromethylene diphosphonate (C1
2
MDP). Van Rooijen et al. (1984) Cell Tissue Res., 238:355; and Van Rooijen and Claasen, In vivo Elimination of Macrophages in Spleen and Liver, Using Liposome-Encapsulated Drugs: Methods and Applications (John Wiley and Sons, Chichester, 1988). Injection of free Cl
2
MDP does not result in significant macrophage depletion because small, charged molecules like Cl
2
MDP are not subject to endocytosis by macrophages as liposomes are. Gregoriadis et al., Targeting of Drugs (Plenum Press, New York, 1982). Nor does the injection of liposome-encapsulated phosphate-buffered saline (PBS) reduce macrophage levels as neither the liposomes nor the PBS are toxic to the macrophage. However, a single intravenous injection of liposome-encapsulated Cl
2
MDP results in the disappearance of splenic red pulp and marginal zone macrophages with recovery of these subpopulations occurring 1-2 weeks and greater than one month respectively. Van Rooijen et al. (1989) J. Leuk. Biol., 45:97. The Cl
2
MDP-induced macrophage depletion can be sustained for prolonged periods (at least one month) with sequential intravenous injections. Kraal et al. (1993) Int. Arch. Allergy Immunol., 100:115.
It has now been found that the macrophages in the mononuclear phagocytic system play an important role in clearance of non-autologous hematopoietic cells and elimination of endogenous macrophages results in the ability of non-autologous hematopoietic cells to circulate and survive in the periphery of host animals.
SUMMARY OF THE INVENTION
Methods are provided for preventing depletion of peripheral non-autologous hematopoietic cells in animals including humans by substantially ablating the endogenous macrophage population. Animal models of peripheral non-autologous hematopoietic cells and the full complement of the human hematopoietic system are provided.
REFERENCES:
Alamondi et al Nature 363: 732, 1993.*
Baum, et al PNAS 89: 2804, 1992.*
Bernsen et al J. Clin Invest, 88: 540, 1988.*
Bernsen et al Blood 77(8): 1717, 1991.*
Pinto et al J. Leukocyte Brief 49: 579, 1991.*
Immunology, Kaby, pp. 488-494, 1992, W.H. Freeman and Company, NY, Sep. 25, 1997.*
Phyrenia et al, Orkansival Immunology, 5(12): 1509, 1993, Sep. 25, 1997.*
Sykes et al. “Bone Marrow transplantation as a means of inducing tolerance,” Seminars in Immunology, vol. 2: 401-417, 1990.*
Smith et al. “New Approaches to Transplantation Tolerance,” vol. 23 (4): 2157-2161, 1991.*
Mosier et al., “Transfer of a functional human immune system to mice with severe combined immunodeficiency”Nature(1988) 335:256-259.
Kamel-Reid et al., “Engraftment of immune-deficient mice with human hematopoietic stem cells”Science(1988) 242:1706-1709.
McCune et al., “The SCID-hu mouse: murine model for the analysis of human hematolymphoid differentiation and function”Science(1988) 241:1632-1639.
Namikawa et al., “Long-term human hematopoiesis in the SCID-hu mouse”J. Exp. Med.(1990) 172:1055-1063.
Kyoizumi et al., “Implantation and maintenance of functional human bone marrow in SCID-hu mice”Blood(1992) 79:1704-1711.
Lapidot et al., “Cytokine stimulation of multilineage hematopoiesis from immature human cells engrafted in SCID mice”Science(1992) 255:1137-1141.
Krowka et al., “Human T cells in the SCID-hu mouse are phenotypically normal and functionally competent”J. Immunol.(1991) 146:3751-3756.
Vanderkerckhove et al., “Clonal analysis of the peripheral T cell compartment of the SCID-hu mouse”J. Immunol.(1991) 146:4173-4179.
Vanderkerckhove et al., “Human hematopoietic cells and thymic epithelial cells induce tolerance via different mechanisms in the SCID-hu mouse thymus”J. Exp. Med.(1992) 175:1033-1043.
Péault et al., “Lymphoid reconstitution of the human fetal thymus in SCID mice with CD34+precursor cells”J. Exp. Med.(1991) 174:1283-1286.
Baum et al., “Isolation of a candidate human hematopoietic stem-cell population”Proc. Natl. Acad. Sci. USA(1992) 89:2804-2808.
McCune et al., “Suppression of HIV infection in AZT-treated SCID-hu mice”Science(1990) 247:564-566.
Lockwood, “Immunological functions of the spleen”Clin. Haematol.(1983) 12:449-465.
Van Rooijen et al., “Elimination of phagocytic cells in the spleen after intraveneous injection of liposome-encapsulated dichloromethylene diphosphonate”Cell Tiss. Res.(1984) 238:355-358.
Gregoriadis et al., eds.,Targeting of Drugs, Plenum Press, New York (1982). A title page and table of contents is enclosed herewith.
Van Rooijen et al., “Macrophage subset repopulation in the spleen: Differential kinetics after liposome-mediated elimination”J. Leuk. Biol.(1989) 45:97-104.
Oi et al., “Fluorescent phycobiliprotein conjugates for analyses of cells and molecules”J. Cell Biol.(1982) 93:981-986.
Boorsma et al., “Periodate or glutaraldehyde for preparing peroxidase conjugates?”J. Immunol. Met.(1979) 30:245-255.
Eikelenboom, “Characterization of non-lymphoid cells in the white pulp of the mouse spleen: An in vivo and in vitro study”Cell Tiss. Res.(1978) 195:445-460.
Delemarre et al.
Chen Ben
Fraser Chris
Weissman Irv
Fish & Neave
Novartis AG
Shukla Ram R.
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