Appeal No. 1999-1273
Application 08/709,916
hypochlorous acid (HOCl) and tyrosyl radical, might be a pivotal element in the
development of atherosclerotic lesions. Daugherty, page 442, column 2.
The examiner acknowledges that while Daugherty demonstrates a correlation
between the presence of myeloperoxidase enzyme and atherosclerosis, it does not
provide a direct correlation of atherosclerosis with 3-chlorotyrosine and does not suggest
the detection of 3-chlorotyrosine as a marker for atherosclerosis. Answer, page 4.
The examiner relies upon Domigan for demonstrating that neutrophil hypochlorous
acid reacts with tyrosine residues in small peptides and converts them to chlorotyrosine.
Chlorotyrosine is indicated in Domigan to be a marker for the production of hypochlorous
acid in vivo and for the involvement of myeloperoxidase in inflammatory tissue damage.
Answer, page 4; Domigan, abstract. Domigan suggests that it is likely that 3-
chlorotyrosine isomer is formed by the activity of myeloperoxidase in human neutrophils
because the hydroxyl group on the aromatic ring of tyrosine activates the ortho positions
for substitution. Domigan, page 16545.
The examiner concludes that it would have been obvious to one of ordinary
skill in the art to determine elevated levels of 3-chlorotyrosine as a screen for
atherosclerosis, since Daugherty specifically teaches that myeloperoxidase is found in
atherosclerotic lesions and is not present in normal tissue, and that the enzyme promotes
lipoprotein oxidation by pathways involving hypochlorous acid and tyrosyl radical, and
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