Ex Parte Pau et al

Board of Patent Appeals and Interferences

Sep 14, 2011

10516946 (B.P.A.I. Sep. 14, 2011)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
____________

Ex parte BERNARD PAU, ISABELLE GOURDIER, MAGUY DEL RIO,
and LAURE CRABBE
____________

Appeal 2010-008026
Application 10/516,946
Technology Center 1600
____________

Before TONI R. SCHEINER, DONALD E. ADAMS, and
JEFFREY N. FREDMAN, Administrative Patent Judges.

ADAMS, Administrative Patent Judge.

DECISION ON APPEAL
This appeal under 35 U.S.C. § 134 involves claims 1, 2, 5, 8, 10-12,
24, and 27 (App. Br. 4). “Claims 6, 7, 9, 13, and 19-23 have been
withdrawn from consideration as being directed to a non-elected invention”
(id.). We have jurisdiction under 35 U.S.C. § 6(b).
STATEMENT OF THE CASE
The claims are directed to a process for detecting resistance of a
cancer cell to oxaliplatin treatment. Claim 1 is representative and is
reproduced in the “Claims Appendix” of Appellants’ Brief (App. Br. 13).
Appeal 2010-008026
Application 10/516,946

2
Claims 1, 2, 5, 8, 10-12, 24, and 27 stand rejected under 35 U.S.C.
§ 103(a) as unpatentable over the combination of Maurer,
1
Macpherson,
2
and
Chao.
3

Claims 1, 2, 5, 8, 10-12, 24, and 27 stand rejected under 35 U.S.C.
§ 103(a) as unpatentable over the combination of Maurer, Macpherson,
Chao, and Aggarwal.
4

We reverse.

The combination of Maurer, Macpherson, and Chao:
ISSUE
Does the preponderance of evidence on this record support a
conclusion of obviousness?
FACTUAL FINDINGS
FF 1. Maurer suggests “a process comprising measuring the level of
mRNA encoding Bax by detecting expression of an effector or marker gene
expressing the pro-apoptotic Bax protein in a colorectal cancer cell” (Ans.
4).

1
Christoph A. Maurer, et al., Apoptosis Inhibiting Factor Bcl-xL Might Be
the Crucial Member of the Bcl-2 Gene Family in Colorectal Cancer, 43(12)
DIGESTIVE DISEASES AND SCIENCES 2641-2648 (1998).
2
Janet Macpherson, et al., Prior antisense mediated Bcl-xl down regulation
in colon cancer cells switches the chemotherapy response from growth
arrest to apoptosis and enhances oxaliplatin cytotoxicity, 43 PROC. NATL.
ACAD. SCI, ANNUAL MEETING 407-408, Abst. No. 2027 (2002).
3
Debra T. Chao, et al., Bcl-xL and Bcl-2 Repress a Common Pathway of Cell
Death, 182 J. EXP. MED. 821-828 (1995).
4
Sudeepta Aggarwal and Sudhir Gupta, Increased Apoptosis of T Cell
Subsets in Aging Humans: Altered Expression of Fas (CD95), Fas Ligand,
Bcl-2, and Bax, 160 J. IMMUNO. 1627-1637 (1998).
Appeal 2010-008026
Application 10/516,946

3
FF 2. The Examiner finds that Maurer fails to “specifically teach methods
comprising determining the level of expression of BAX gene in cancer cells
obtained from a patient and comparing the level with the level measured in a
corresponding control sample of cells not resistant to oxaliplatin” (id.).
FF 3. Macpherson suggests that “reduced expression of Bcl-xl in colon
cancer cells, as compared to control cells . . . results in an enhanced
apoptotic response to oxaliplatin” (id.).
FF 4. Chao suggests that “Bcl-xl and Bcl-2 function as repressors of
apoptosis by heterodimerizing with and inhibiting pro-apoptotic Bax” (id).
ANALYSIS
Based on the combined teachings of Maurer, Macpherson, and Chao
the Examiner reasons that because a reduction in the Bax inhibitor, Bcl-xl, in
cancer cells relative to control cells results in an enhanced apoptotic
response to oxaliplatin, a reduction in the expression of the Bax gene in
cancer cells relative to control cells would result in the identification of cells
that are “more resistant” to oxaliplatin (Ans. 5-6; FF 1, 3, and 4).
Accordingly, the Examiner concludes that, at the time of Appellants’
claimed invention, it would have been prima facie obvious to a person of
ordinary skill in this art to utilize the method of Maurer to measure Bax
expression in both cancer cells and control cells to determine the level of
Bax expression in the cancer cells, wherein a reduction in Bax expression,
relative to control cells, would correlate to cells that are more resistant to
oxaliplatin (Ans. 5-6). We are not persuaded.
As Appellants explain “while the Examiner’s analysis considers the
effects of knocking out Bcl-xl expression as correlating with oxaliplatin
resistance, it does not establish any direct connection between lower Bax
Appeal 2010-008026
Application 10/516,946

4
expression and oxaliplatin resistance” (Reply Br. 2). Stated differently, the
Examiner failed to provide an evidentiary foundation that supports a
conclusion that “a reduced level of expression of Bax gene alone correlates
with enhanced resistance to oxaliplatin” (id.). We agree.
CONCLUSION OF LAW
The preponderance of evidence on this record fails to support a
conclusion of obviousness. The rejection of claims 1, 2, 5, 8, 10, 12, 24, and
27 under 35 U.S.C. § 103(a) as unpatentable over the combination of
Maurer, Macpherson, and Chao is reversed.

The combination of Maurer, Macpherson, Chao, and Aggarwal:
ISSUE
Does the preponderance of evidence on this record support a
conclusion of obviousness?
FACTUAL FINDINGS
FF 5. The Examiner relies on the combination of Maurer, Macpherson, and
Chao as discussed above (Ans. 7).
FF 6. The Examiner finds that the combination of Maurer, Macpherson,
and Chao fails to suggest “a method comprising obtaining a cDNA from the
RNA of the biological sample and amplifying the cDNA using at least one
primer for amplification of BAX” (id.).
FF 7. Aggarwal suggests “a quantitative PCR method comprising
obtaining a cDNA from RNA of a biological sample and amplifying the
cDNA using at least one primer for amplification of BAX” (id.).

Appeal 2010-008026
Application 10/516,946

5
ANALYSIS
Based on the foregoing factual findings the Examiner concludes that it
would have been obvious to utilize Aggarwal’s PCR method in the method
suggested by the combination of Maurer, Macpherson, and Chao, to provide
for quantitative results (id.). Appellants contend that Aggarwal fails to make
up for the deficiencies in the combination of Maurer, Macpherson, and
Chao. We agree.
CONCLUSION OF LAW
The preponderance of evidence on this record fails to support a
conclusion of obviousness. The rejection of claims 1, 2, 5, 8, 10-12, 24, and
27 under 35 U.S.C. § 103(a) as unpatentable over the combination of
Maurer, Macpherson, Chao, and Aggarwal is reversed.

REVERSED

cdc