Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues – Glycoprotein – e.g. – mucins – proteoglycans – etc.
Reexamination Certificate
1997-04-23
2002-09-24
Nolan, Patrick J. (Department: 1644)
Chemistry: natural resins or derivatives; peptides or proteins;
Proteins, i.e., more than 100 amino acid residues
Glycoprotein, e.g., mucins, proteoglycans, etc.
C530S350000, C530S806000, C530S838000
Reexamination Certificate
active
06455678
ABSTRACT:
TECHNICAL FIELD
This invention relates to antigens expressed by hematopoietic stem cells and progenitor cells and to methods of using such antigens, especially for cell separation and purification.
BACKGROUND
The high turnover of mammalian blood cells requires a supply of hematopoietic stem cells that are able to give rise to other blood cell lineages. The immediate progeny of the hematopoietic stem cell are called progenitor cells, and are capable of giving rise to various cell types within one or more lineages, i.e. the erythroid, myeloid and lymphoid lineages. The stem cell and progenitor cell populations constitute only a small percentage of the total number of cells in bone marrow, fetal liver, etc. These populations are of immense interest because of their ability to repopulate the hematopoietic system.
A number of methods have been described in the literature for the purification or enrichment of hematopoietic stem cell and progenitor cell populations. There is significant commercial interest in these methods because hematopoietic progenitors have a number of clinical uses. Progenitor cell transplantation is currently used in conjunction with chemotherapy and radiation for the treatment of leukemia, breast cancer and other tumors. Frequently, autologous transplants are used to avoid the danger of graft rejection, but there is an increased risk of disease reappearance, due to the presence of tumor cells in the engrafting cell population. Transplantation of a more purified source of progenitor cells is therefore preferable.
There is also interest in the use of hematopoietic progenitor cells as a vehicle for gene therapy. Although not yet proven in the clinic, the longevity of hematopoietic stem cells and the dissemination of their progeny in the vasculature are desirable characteristics. A number of vectors, including several retrovirus and adenovirus based constructs, that can transfect hematopoietic stem cells have been described.
Proteins and other cell surface markers found on hematopoietic stem cell and progenitor cell populations are of great interest, as they are useful in preparing reagents for identification, separation and isolation of these populations and in the further characterization of these important cells. Although some antigens are now known that can be used in the identification and separation (positive and negative) of stem cells, such as (for example) the CD 34 antigen, which is found on stem cells but not on mature blood cells, there is a continued need for development of other antigens, particularly one that can simplify the identification and separation of desirable classes and subclasses of cells, especially hematopoietic stem cells and progenitor cells.
BACKGROUND LITERATURE
U.S. Pat. No. 5,061,620 describes a substantially homogeneous human hematopoietic stem cell composition and the manner of obtaining such composition. Stromal cell-associated hematopoiesis is described by Paul et al. (1991)
Blood
77:1723-1733. The phenotype of stem cells with rhodamine staining is discussed in Spangrude and Johnson (1990)
P.N.A.S.
87:7433-7437. Cell surface antigen expression in hematopoiesis is discussed in Strauss et al. (1983)
Blood
61:1222-1231 and Sieff et al. (1982)
Blood
60:703-713. Descriptions of pluripotential hematopoietic cells are found in McNiece et al. (1989)
Blood
74:609-612 and Moore et al. (1979)
Blood Cells
5:297-311. Characterization of a human hematopoietic progenitor cell capable of forming blast cell-containing colonies in vitro is found in Gordon et al. (1987)
J. Cell. Physiol.
130:150-156 and Brandt et al. (1988)
J. Clin. Invest.
82:1017-1027. The use of progenitor cells in transplantation is discussed in To et al. in
Progenitor Threshold in Transplantation
(ISBN 1-880854 17-1) pp. 15-20. Utilities for the cell compositions obtained using the methods and compositions of the invention are described in these publications, among others.
The use of high-gradient magnetic separation for the isolation of human hematopoietic progenitor cells is described in Thomas and Landsdorp (1992) in
Advances in Bone Marrow Purging
pp.537-544; and Kato and Radbruch (1993)
Cytometry
14:384-392. Other methods of magnetic selection for human hematopoietic progenitor cells are described in Bigas et al. (1992) in
Advances in Bone Marrow Purging
pp.545-551; Oku et al. (1992) in
Advances in Bone Marrow Purging
pp. 553-560; and Hardwick et al. (1992) in
Advances in Bone Marrow Purging
pp. 583-589. High gradient magnetic cell sorting is described in Miltenyi et al. (1990)
Cytometry
11:231-238. Molday, U.S. Pat. No. 4,452,773 describes the preparation of magnetic iron-dextran microspheres and provides a summary describing the various means of preparation of particles suitable for attachment to biological materials.
SUMMARY OF THE INVENTION
Methods and compositions are provided for the enrichment and characterization of human hematopoietic progenitor and stem cells. An antigen has been identified, referred to here as the AC133 antigen, that is present on stem cells and on progenitor cells and that can be used for the identification and/or separation of these important cells from the vast majority of cells present in a biological (or other) source of hematopoietic cells. Novel antigen compositions and reagents that react with them, such as antibodies, are provided for use in the methods of the invention and for the further investigation of hematopoietic progenitor and stem cell biology. For example, hematopoietic cells can be obtained from various sources, including fetal and adult bone marrow, cytokine mobilized peripheral blood cells, and fetal liver, and can be separated using reagents and methods of the invention.
REFERENCES:
patent: 4452773 (1984-06-01), Molday
patent: 4714680 (1987-12-01), Civin
patent: 5061620 (1991-10-01), Tsukamoto et al.
patent: 5248599 (1993-09-01), Sariyama et al.
patent: 5411863 (1995-05-01), Miltenyi
patent: 5573930 (1996-11-01), Ladner et al.
patent: 0 662 512 (1995-07-01), None
Mikayama et al. Molecular Cloning & Functional Expression of a cDNA . . . P.N.A.S. (90) 10056-10060. 1993.*
Hardwick, A., et al., “Development of a Large-Scale Immunomagnetic Separation System for Harvesting CD34-Positive Cells From Bone Marrow,” Advances in Bone Marrow Purging and Processing, pp. 583-589 (1992).
Oku, Naritoshi, et at., “Monitoring o fKinetics of CD34 Positive Cells By Immunomagnetic Beads During Peripheral Blood Stem Cell Harvest for Autotransplantation,” Advances in Bone Marrow Purging and Processing, pp. 553-560 (1992).
Bigas, A., et al., “CD34 Positive Cell Selection By Immunomagnetic Techniques,” Advances in Bone Marrow Purging and Processing, pp. 545-551 (1992).
Thomas, T.E., et al., “Purification of CD34 Positive Cells from Human Bone Marrow Using High Gradient Magnetic Separation,” Advances in Bone Marrow Purging and Processing, pp. 537-544 (1992).
Grimsley, P.G., et al., “Rapid Positive Selection of CD34 + Cells Using Magnetic Microspheres Coated with Monoclonal Antibody QBEND/10 Linked via a Cleavable Disulphide Bond,” Leukemia, vol. 7, No. 6:898-908 (1993).
Miltenyi, S., et al., “High Gradient Magnetic Cell Separation with MACS,” pp. 231-238 (1990).
McNiece, I.K., “Detection of a Human CFC with a High Proliferative Potential,” Blood, vol. 74, (No. 2) :609-612 (Aug. 1, 1989).
Gordon, M.Y., et al., “Characterisation of Stroma-Dependent Blast Colony-Forming Cells in Human Marrow,” Journal of Cellular Physiology, pp. 150-156 (1987).
Spangrude, G.J., et al., “Resting and activated subsets of mouse multipotent hematopoietic stem cells,” pp. 7433-7439 (Jun. 18, 1990).
Brandt, J., et al., “Cytokine-dependent Long-Term Culture of Highly Enriched Precursors of Hematopoietic Progenitor Cells from Human Bone Marrow,” The American Society for Clinical Investigation, Inc., pp. 932-941 (Sep. 1990).
To, L.B., et al., “Establishment of a Clinical Threshold Cell Dose: Correlation Between CFU-Gm and Duration of Aplasia,” AlphaMed Press, pp. 15-20. (1990).
Cioffi, J.A., et al., “Novell B219/OB receptor isoforms: Po
Buck David W.
Godfry Wayne G.
Miraglia Sheri
Yin Amy H.
AmCell Corporation
Cooley & Godward LLP
Ewolt Gerald R.
Nolan Patrick J.
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