Compositions for the treatment of cancer, and methods for...

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai

Reexamination Certificate

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C530S350000

Reexamination Certificate

active

08053406

ABSTRACT:
A composition comprising leukotoxin proteins isolated from a bacterium is provided. In this composition, greater than 85% of the leukotoxin proteins are chemically modified at a basic amino acid residue, and the proteins induce cell death in myeloid leukocytes, while remaining substantially non-toxic to lymphoid leukocytes, lymphocytes, and red blood cells. Also provided is a method of selectively inducing cell death in myeloid leukocytes. The method comprises contacting the myeloid leukocytes with a composition comprising leukotoxin proteins. These leukotoxin proteins may be isolated from the NJ4500 strain of Actinobacillus actinomycetemcomitans. A method of purifying leukotoxin protein from the NJ4500 strain of Actinobacillus actinomycetemcomitans is also provided, as well as an assay that allows for the rapid determination of the activity of a given drug against leukemic cells either taken from a patient or derived from a cell line. The assay is performed in the presence of whole blood or serum.

REFERENCES:
patent: WO 97/16531 (1997-05-01), None
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DiRienzo et al., “Monoclonal antibodies to leukotoxin ofActinobacillus actinomycetemcomitans”, Infection and Immunity, 47(1):31-36, 1985.
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Lally et al., “RTX toxins recognize a β2 integrin on the surface of human target cells”, The Journal of Biological Chemistry, 272(48):30463-30469, 1997.
Linhartová et al., “RTX proteins: a highly diverse family secreted by a common mechanism”, FEMS Microbiol Rev, 1-37, 2010 (E pub ahead of print).
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Taichman et al., Biochemical and morphological characterization of the killing of human monocytes by a leukotoxin derived fromActinobacillus actinomycetemcomitans, Infection and Immunity, 28(1):258-268, 1980.
Thumbikat et al., “Biological effects of two genetically defined leukotoxin mutants ofMannheimia haemolytica”, Microbial Pathogenesis 34:217-226; 2003.
Spitznagel et al., “Regulation of leukotoxin in leukotoxic and nonleukotoxic strains ofActinobacillus actinomycetemcomitans”, Infection and Immunity, 59(4):1394-1401, 1991.

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