Appeal No. 1999-0339
Application 07/903,588
The examiner has premised his conclusion with respect to the obviousness of
claim 1 on the teachings of Bièche.
To that end, we find that Bièche discloses studies wherein a c-met proto-
oncogene probe (pmetH) which detects met gene sequences on chromosome 7q31, is
used to analyze tumor and blood leukocyte DNA samples in patients with primary
breast cancers. Bièche, p. 139, col. 1, para. 1, p. 140, cols. 1-2. The pmetH probe
recognizes TaqI restriction fragment length polymorphisms (RFLP) of 7.5 kb (L
fragment) and 4.0 kb (S fragment) in tumor and lymphocyte DNA of patients with
primary breast cancer. Bièche, p. 140, cols. 1-2. Bièche found that of 245 patients, 81
were homozygous for the L fragment (LL genotype), 43 were homozygous for the S
fragment (SS) and 121 were heterozygous (LS). Bièche, p. 140, col. 2, para. 1. Bièche
analyzed blood leukocyte and tumor DNA from those patients who are heterozygous
(LS) with the pmetH probe and found a loss of heterozygosity of the c-met proto-
oncogene in 49 of the 121 (40.5%) patients. Id., para. 2; see also Figure 1. In follow-
up studies, Bièche found that the loss of heterozygosity was associated with
“significantly higher risk of relapse (55% vs 21%) and of death (41% vs 15%)” and
“reduced metastasis-free (p+ 0.00022) and overall (p+0.0036) survival” compared with
patients who did not have the DNA deletion. Bièche, p. 142, col. 1., para. 2 and p. 141,
sentence bridging cols. 1-2. Bièche noted that the “frequency of [the] c-met deletion
may be underestimated because of cellular heterogeneity of tumour biopsy material.”
Bièche, p. 142, col. 1, para. 2.
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