Appeal 2007-0582
Application 09/832,069
(id. at 42: 9-10). The damage was reported to be significant in both cell
types, treated with either reactive oxygen species (id. at 64: 22-29).
The Specification also reports that:
• “Treatment of HUVEC and HASMC with peroxynitrite resulted in
substantially decreased transcript levels in the mitochondrial encoded genes,
NADH dehydrogenase 2 (ND2) and cytochrome b (Cyt b), but not the 16S
rRNA” (id. at 43: 20 to 44: 2);
• “Reactive oxygen species treatment also resulted in a decrease in
mitochondrial protein synthesis in both cell lines” (id. at 45: 13-14), with
decreases of 12% to 70% depending on the concentration of reactive oxygen
species (id. at 46: 10-15); and
• “Peroxynitrite treatment also resulted in an overall decrease in ATP
levels and mitochondrial respiration (complex II) in HUVEC and HASMC”
(id. at 46: 17 to 47: 1), with “significant decreases in ATP” and “a
significant decrease of complex II reduction of MTT (mitochondrial
respiration)” (id. at 47: 4-7).
Thus, the Examiner is correct in stating that the Specification does not
provide “working examples of measuring the amount of mtDNA damage in
tissue using mitochondrial mRNA production,” etc. (Answer 6); i.e., the
examples do not provide formulas to convert a specific amount of, e.g.,
mitochondrial mRNA production to a specific amount of mtDNA damage.
However, the Specification provides convincing evidence of a
correlation between increased mitochondrial DNA damage and decreased
mitochondrial mRNA production, protein production, ATP levels, and
respiration. The claims do not require precise, quantitative determination of
6
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