Methods of facilitating vascular growth

Details Methods of facilitating vascular growth Methods of facilitating vascular growth

1999-11-12

2001-10-23

Carlson, Karen Cochrane (Department: 1653)

Chemistry: molecular biology and microbiology

Measuring or testing process involving enzymes or...

Involving antigen-antibody binding, specific binding protein...

Reexamination Certificate

active

06306612

ABSTRACT:

FIELD OF THE INVENTION
The present invention concerns methods of facilitating vascular growth in a subject, such as a subject at risk for ischemic reperfusion injury, or a newborn afflicted with bronchopulmonary displaysia. Methods of identifying compounds useful for the aforesaid treatments are also disclosed.
BACKGROUND OF THE INVENTION
U.S. Pat. No. 5,641,867 to D. Stern et al. (assigned to Columbia University) describes purified endoethelial monocyte activating polypeptide (EMAP) II, antibodies that specifically bind to EMAP II, and methods of treating tumors by administering EMAP II to an afflicted subject.
U. Knies et al.,
Proc. Natl. Acad. Sci. USA
95, 12322-12327 (October 1998), describes the regulation of endothelial monocyte-activating polypepetide II release by apoptosis.
SUMMARY OF THE INVENTION
A first aspect of the invention is a method of facilitating vascular growth in a subject, such as in an organ or tissue of the subject, in need of such treatment. The method comprises inhibiting EMAP II activity in the of the subject (e.g., in the aforesaid organ or tissue) by an amount effective to stimulate vascular growth.
A second aspect of the present invention is a pharmaceutical formulation comprising: an active compound selected from the group consisting of compounds that specifically bind to EMAP II, compounds that inhibit the expression of EMAP II, and EMAP II receptor antagonists; and a pharmaceutically acceptable carrier.
A third aspect of the present invention is a method of screening for compounds useful for facilitating vascular growth in a subject in need thereof. The method comprises: contacting a test compound (e.g., a protein or peptide)to a probe molecule, the probe molecule selected from the group consisting of EMAP II and fragments thereof; and then detecting the presence or absence of binding of the test compound to the probe molecule, the presence of binding indicating the compound may be useful for facilitating vascular growth in a subject.
A fourth aspect of the present invention is a method of screening for compounds useful for facilitating vascular growth in a subject, comprising: contacting a test compound (e.g., an oligonucleotide) to probe molecule, the probe molecule selected from the group consisting of DNA encoding EMAP II, RNA encoding EMAP II, and fragments thereof; and then detecting the presence or absence of binding of the test compound to the probe molecule, the presence of binding indicating the compound may be useful for facilitating vascular growth in the subject.
A fifth aspect of the present invention is a method of screening for compounds useful for facilitating vascular growth in a subject, comprising: determining in vitro whether a test compound inhibits expression of EMAP II; the inhibition of expression of EMAP II indicating the compound may be useful for facilitating vascular growth in a subject.
The present invention is explained in greater detail in the specification set forth below.


REFERENCES:
patent: 5641867 (1997-06-01), Stern et al.
patent: 5885798 (1999-03-01), Bandman et al.
Kao et al.; Endothelial Monocyte-activating Polypeptide II,The Journal of Biological Chemistry, 267 (28): 20239-20247 (1992).
Schwarz et al.; EMAP II: A modulator of neovascularization in the developing lung,Am. J. Physiol., 276:L365-L375 (1999).
Knies et al.; Regulation of Endothelial Monocyte-Activating Polypeptide II Release by Apoptosis,Proc. Natl. Acad. Sci. USA, 95:12322-12327 (1998).
International Search Report for PCT US99/26743; mailed Feb. 23, 2000.

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