Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Reexamination Certificate
1999-08-18
2001-12-18
Park, Hankyel T. (Department: 1648)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
C424S184100, C424S277100, C424S278100, C514S002600, C514S885000
Reexamination Certificate
active
06331403
ABSTRACT:
FIELD OF THE INVENTION
The invention is concerned with slowing cell growth and promoting the maturation of cells. In particular, it has been discovered that modified C-reactive protein (mCRP) and mutant-mCRP can be used to slow the cell growth and promote the maturation of cells other than cancer cells and megakaryocyte progenitors.
BACKGROUND OF THE INVENTION
During injury, invasion of pathogens, or other forms of tissue damage, higher vertebrates implement a cascade of biochemical, immune and inflammatory reactions collectively termed the acute phase response. The inflammation results in an increase in blood flow and the delivery of important factors to the affected site. These factors act to limit microbial growth, reduce tissue damage, and aid in the removal of damaged tissue. The acute phase response is a primitive, nonspecific mechanism which reacts quickly prior to the development of the specific processes of humoral and cellular immunity.
C-reactive protein (CRP) has long been recognized as an important acute phase response protein, and its concentration in serum may increase as much as 1,000-fold during the acute phase response. CRP is a pentamer consisting of five identical subunits, each having a molecular weight of about 23,500. The pentameric form of CRP is sometimes referred to as “native CRP.”
In about 1983, another form of CRP was discovered which is referred to as “modified-CRP” or “mCRP.” The formation of mCRP from native CRP involves the dissociation of native CRP into its subunits which also undergo a change in conformation. As a result, mCRP expresses antigenicity which is distinct from that of native CRP (referred to as “neo-CRP antigenicity”), and antibodies are available which can distinguish mCRP from native CRP (see, e.g., U.S. Pat. No. 5,272,258 and Potempa et al.,
Mol. Immunol.,
24, 531-541 (1987)). The conversion of native CRP into mCRP is irreversible (the subunits do not reassemble into native CRP). Kresl et al.,
Int'l J. Biochem. Cell Biol.,
30, 1415-1426 (1998).
It has been reported that mCRP can influence the development of monocyte cytotoxicity, improve the accessory cell function of monocytes, potentiate aggregated IgG-induced phagocytic cell oxidative metabolism, and increase the production of interleukin-1, prostaglandin E and lipoxygenase products by monocytes. Potempa et al.,
Protides Biol. Fluids,
34, 287-290 (1987); Potempa et al.,
Inflammation,
12, 391-405 (1988); Potempa et al.,
Proc. Amer. Acad. Cancer Res.,
28, 344a (1987); Chu et al.,
Proc. Amer. Acad. Cancer Res.,
28, 344a (1987); Zeller et al.,
Fed. Proc.,
46, 1033a (1987); Chu et al.,
Proc. Amer. Acad. Cancer Res.,
29, 371a (1988). It is also known that mCRP can be used to treat viral infections, bacterial infections, endotoxic shock and cancer. See U.S. Pat. Nos. 5,283,238, 5,405,832, 5,474,904, and 5,585,349. It is further known that mCRP stimulates thrombocytopoiesis and the maturation of megakaryocytes and that it can be used to treat thrombocytopenia. See U.S. Pat. No. 5,547,931. Finally, it is known that mCRP binds immune complexes and aggregated immunoglobulin and can, therefore, be used to remove immune complexes and aggregated immunoglobulin from fluids and to quantitate immune complexes. See U.S. Pat. No. 5,593,897. It should be noted that mCRP differs from native CRP in its biological activities. See, e.g., the patents listed above.
SUMMARY OF THE INVENTION
The invention provides a method of slowing the growth of growing cells other than cancer cells and megakaryocyte progenitor cells. The method comprises contacting the growing cells with a modified C-reactive protein (mCRP) or a mutant-mCRP. The method may be performed in vitro or in vivo.
The invention also provides a method of promoting the maturation of cells other than cancer cells and megakaryocyte progenitor cells. The method comprises contacting the immature cells with an mCRP or a mutant-mCRP. The method may be performed in vitro or in vivo.
REFERENCES:
patent: 4857314 (1989-08-01), O'Connor et al.
patent: 5272258 (1993-12-01), Siegel et al.
patent: 5283238 (1994-02-01), Potempa et al.
patent: 5405832 (1995-04-01), Potempa
patent: 5474904 (1995-12-01), Potempa et al.
patent: 5547931 (1996-08-01), Potempa
patent: 5585349 (1996-12-01), Potempa
patent: 5593897 (1997-01-01), Potempa et al.
patent: 5858399 (1999-01-01), Lanza et al.
patent: 5874238 (1999-02-01), Potempa et al.
patent: 5939529 (1999-08-01), Potempa
patent: 6051415 (2000-04-01), Potempa
Bareika et al., “Changes in C-Reactive Protein Levels in Rabbit Sera Following Intraarticular Injection of Chymopapain,” 45th Annual Meeting, Orthopaedic Research Society, Feb. 1-4, 1999, Anaheim, California.
Bertolini et al.,Blood, 89(8):2679-2688 (1997).
Bray et al.,J. Immunol., 140(12):4271-4278 (1988).
Bray et al.,Clin. Immunol. Newsletter 8, pp. 137-140 (1987).
Brugger et al.,N Engl J Med, 333:283-7 (1995).
Chu et al.,Proc. Amer. Acad. Cancer Res., 29, 371a (1988).
Chu et al.,Proc. Amer. Acad. Cancer Res., 28, 344a (1987).
Ciliberto et al.,Nucleic Acids Res., 15, 5895 (1987).
Crump et al., “Bacterial Expression of Mutant Human C-Reactive Protein Subunit,” Annual Meeting of the Society for Industrial Microbiology, Research Triangle Park, North Carolina, Aug. 3-9, 1996 (abstract).
Crump et al., “Bacterial Expression of Mutant Human C-Reactive Protein Subunit” Annual Meeting of the Society for Industrial Microbiology, Research Triangle Park, North Carolina, Aug. 3-9, 1996 (presentation materials).
de Beer et al.,J. Immunol. Meth., 50:17-31 (1982).
Debili et al.,Blood, 86(7):2516-2525 (1995).
Diehl et al., “Effects of the Modified Form of C-Reactive Protein on Human Tumor Cells” Cancer Research AMFR Meeting, 1998.
Diehl et al., “Cellular effects of the modified form of C-reactive protein (mCRP) on tumor cells” 17th Int'l Cancer Congress, Rio de Janeiro, Brazil, Aug. 24-28, 1998.
Hu et al.,Biochem., 25, 7834-39 (1986).
Hu et al.,J. Biol. Chem., 263, 1500-1504 (1988).
Kabat et al., “Antiretroviral Activity of a Recombinant Modified C-Reactive Protein” Twenty-First AIDS Clinical Trials Group Meeting, Washington, D.C., Jul. 27-31, 1996.
Kilpatrick et al.,Immunol. Res., 10:43-53 (1991).
Kinoshita et al.,Biochemistry, 28:9840-9848 (1989).
Kolb-Bachofen,Immunobiol., 183:133-145 (1991).
Kresl et al.,Int'l J. Biochem. Cell Biol., 30, 1415-1426 (1998).
Kresl et al.,Tumor Biol., 20:72-87 (1999).
Lei et al.,J. Biol Chem., 260, 13377-83 (1985).
McAdams et al.,TIBTECH, 14:341-349 (1996).
McAdams et al.,TIBTECH, 14:388-396 (1996).
McKenna et al.,Blood, 86(9):3413-3420 (1995).
Motie et al.,J. Immunol., 156:4435-4441 (1996).
Motie et al.,Drug Metabolism and Disposition, 26(10):977-981 (1998).
Potempa et al.,Mol. Immunol., 20, 1165-1175 (1983).
Potempa et al.,Protides Biol. Fluids, 34, 287-290 (1986).
Potempa et al.,Mol. Immunol., 24, 531-541 (1987).
Potempa et al.,Proc. Amer. Acad. Cancer Res., 28, 344a (1987).
Potempa et al.,Inflammation, 12, 391-405 (1988).
Potempa et al., Proceedings of the International Congress on Membranes and Membrane Processes, 1:169-171 (1990).
Potempa et al.,Clinical Materials, 11:105-117 (1992).
Potempa et al.,Exper. Hematol., 24:258-264 (1996).
Potempa et al.,FASEB J., 10:1332a (1996) (Abstract #1918 and presentation materials).
Potempa et al., “In vitro studies of recombinant human modified C reactive protein, an active new agent against HIV disease” #B01 Hong Kong AIDS Conference, 1996.
Potempa et al., “Phase I/II clinical trial of recombinant human modified C reactive protein, an active new agent against HIV disease” #B02 Hong Kong AIDS Conference, 1996.
Potempa et al., “Biological activity and clinical safety of human modified C-reactive protein, an active new agent against cancer” #H41.1 Hong Kong Int'l Cancer Congress, 1996.
Rees et al.,Clin. Immunol. and Immunopathol., 48:95-107 (1988).
Samberg et al.,Cell Immunol., 116:86-98 (1988).
Samols and Hu,Protides Biol. Fluids, 34, 263-66 (1986).
Schneider et al.,FASEB J., 12:185a (1998) (abstract and presentation materials).
Stein et al.,Immun
Potempa Lawrence A.
Radosevich James A.
Park Hankyel T.
Ross P.C. Sheridan
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