Appeal No. 2007-0057
Application No. 10/174,586
Holmgren’s disclosure regarding the thioredoxin active site is
supported by Meng,2 which states that thioredoxin (TRX) “is characterized
by two cysteine residues within the conserved active site sequence CGPC,”
which is identical to Holmgren’s Cys-Gly-Pro-Cys sequence. Meng,
page 105. Meng also teaches that “[m]any TRX-like proteins are members
of the TRX superfamily and have the CGHC [i.e., Cys-Gly-His-Cys]
sequence.” Id.
As the Examiner has pointed out, “PRO270 lacks a Cys-Gly-Pro-Cys
active site.” Examiner’s Answer, page 10. It also does not contain a Cys-
Gly-His-Cys sequence. See SEQ ID NO:32: amino acids 160-166 form the
sequence VEFFANW, which roughly matches the first part of the consensus
sequence disclosed by Holmgren (VDFXAXW) but the next four amino
acids are SNDC, not CGPC or CGHC. See also the Appeal Brief, page 13
(“Meng . . . disclosed a protein ‘thioredoxin-related transmembrane protein
2’ or ‘TMX2’ that is 100% identical to PRO270, excluding a 12 amino acid
insert absent in the TMX2 polypeptide”) and Meng, page 105 (“TMX2
protein does not have the CGPC or CGHC sequence”).
The two cysteine (Cys or C) residues in the active site carry the –SH
groups that are reversibly oxidized to form a disulfide bridge, the “simple
and elegant mechanism” of electron transfer described by Holmgren. Thus,
PRO270 lacks the specific amino acids that are known in the art to be the
basis of thioredoxin’s activity.
2 Meng et al., “Cloning and identification of a novel cDNA coding
thioredoxin-related transmembrane protein 2,” Biochem. Genetics, Vol. 41,
pp. 99-106 (2003).
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