Human eosinophil-derived basic protein

The present invention provides a human eosinophil-derived basic protein (EBPH) and polynucleotides which identify and encode EBPH. The invention also provides genetically engineered expression vectors and host cells comprising the nucleic acid sequences encoding EBPH and a method for producing EBPH. The invention also provides for use of EBPH and agonists, antibodies or antagonists specifically binding EBPH, in the prevention and treatment of diseases associated with expression of EBPH. Additionally, the invention provides for the use of antisense molecules to polynucleotides encoding EBPH for the treatment of diseases associated with the expression of EBPH. The invention also provides diagnostic assays which utilize the polynucleotide, or fragments or the complement thereof, and antibodies specifically binding EBPH.

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Claims

1. An isolated and purified polynucleotide sequence encoding the eosinophil-derived basic protein of SEQ ID NO:1.

2. A hybridization probe consisting of the polynucleotide sequence of claim 1.

3. An isolated and purified polynucleotide sequence consisting of SEQ ID NO:2.

4. A polynucleotide sequence which is complementary to SEQ ID NO:2.

5. A hybridization probe consisting of the polynucleotide sequence of claim 4.

6. An expression vector containing the polynucleotide sequence of claim 1.

7. A host cell containing the vector of claim 6.

8. A method for producing a polypeptide comprising the amino acid sequence of SEQ ID NO:1, the method comprising the steps of:

a) culturing the host cell of claim 7 under conditions suitable for the expression of the polypeptide; and
b) recovering the polypeptide from the host cell culture.
Referenced Cited
Other references
  • Gleich et al., "The eosinophil as a mediator of damage to respiratory epithelium: A model for bronchial hyperreactivity," J. Allergy Clin. Immun., 81(5) (1):776-781 (1988). Frigas et al., "Elevated Levels of the Eosinophil Granule Major Basic Protein in the Sputum of Patients with Bronchial Asthma," Mayo Clin. Proc., 56:345-353 (1981). Filley et al., "Identification By Immunofluorescence of Eosinophil, Granule, Major Basic Protein in Lung Tissues of Patients with Bronchial Asthma", Lancet, 2:11-16 (Jul. 3, 1982). Sarmiento et al., "IL-3, IL-5, and Granulocyte-Macrophage Colony-Stimulating Factor Potentiate Basophil Mediator Release Stimulated by Eosinophil Granule Major Basic Protein," J. Immunol., 155:2211-2221 (1995). Moy et al., Identification of an IgA inhibitor of neutrophil chemotaxis and its membrane target for the metabolic burst, J. Immunol., 145:2626-2632 (1990). Rohrbach et al., "Activation of Platelets by Eosinophil Granule Proteins" J. Exp. Med., 145:1271-1274 (1990). Kita et al., "Eosinophil Major Basic Protein Induces Degranulation and IL-8 Production by Human Eosinophilsl," The Journal of Immunology, 154:4749-4758 (1995). Popken-Harris et al., "Expression, Purification, and Characterization of the Recombinant Proform of Eosinophil Granule Major Basci Protein," J. Immunol., 155:1472-1480 (1995). Oxvig, et al., "Localization of disulfide bridges and free sulfyhydryl groups in human eosinophil granule major basic protein," FEBS Lett., 341:213-217 (1994). Abu-Ghazaleh, "Interaction of Eosinophil Granule Major Basic Protein with Synthetic Lipid Bilayers: A Mechanism for Toxicity," J. Membrane Biol., 128:153-164 (1992). Wagner, "Pregnancy-Associated Major Basic Protein: Deposition of Protein and Expression of mRNA at the Maternal-Fetal Junction in Early and Late Gestation," Placenta, 15:625-640 (1994). Maddox, "Localization of a Molecule Immunochemically Similar to Eosinophil Major Basic Protein in Human Placenta," J. Exp. Med., 160:29-41 (1984). Oxvig, "Circulating Human Pregnancy-Associated Plasma Protein-A Is Disulfide-bridged to the Proform of Eosinophil Major Basic Protein," The Journal of Biological Chemistry, 268(17):12243-12246 (1993). Oxvig, "Identification of Angiotensinogen and Complement C3dg ans Novel Proteins Binding the Proform of Eosinophil Major Basic Protein in Human Pregnancy Serum and Plasma," The Journal of Biological Chemistry, 270(23):13645-13651 (1995). Brambati et al., "Low Material Serum levels of pregnancy associated plasma protein A (PAPP-A) in the first trimester in association with abnormal fetal karyotype," British Journal of Obstetrics and Gynecology, 100:324-326 (Apr. 1993). Tewksbury et al., "Immunochemical Comparison of High Molecular Weight Angiotensinogen from Amniotic Fluid, Plasma of Men, and Plasma of Pregnant Women," J. Exp. Med., 168:1493-1498 (1988). Barker et al., "Acidic Precursor Revealed in Human Eosinophil Granule Major Basic Protein cDNA," J. Exp. Med., 168:1493-1498 (Sep. 1988) (GI 34476). Aoki et al., "Comparison of the amino acid and nucleotide sequences between human and two guinea pig major basic proteins," FEBS Letters, 282(1): 56-60 (GI 220291 & GI 544241) (1994).
Patent History
Patent number: 5728820
Type: Grant
Filed: Oct 23, 1996
Date of Patent: Mar 17, 1998
Assignee: Incyte Pharmaceuticals, Inc. (Palo Alto, CA)
Inventor: Ingrid E. Akerblom (Redwood City, CA)
Primary Examiner: David Saunders
Assistant Examiner: F. Pierre VanderVegt
Attorney: Lucy J. Billings
Application Number: 8/740,036