Ex Parte Hung

Board of Patent Appeals and Interferences

Dec 11, 2008

11203800 (B.P.A.I. Dec. 11, 2008)

UNITED STATES PATENT AND TRADEMARK OFFICE
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BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
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Ex parte DAVID HUNG
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Appeal 2008-5398
Application 11/203,800
Technology Center 1600
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Decided: December 11, 2008
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Before DONALD E. ADAMS, ERIC GRIMES, and JEFFREY N.
FREDMAN, Administrative Patent Judges.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
of treating a patient having premalignant or malignant breast duct epithelial
cells. The Examiner has rejected the claims as obvious. We have
jurisdiction under 35 U.S.C. § 6(b). We affirm.
Appeal 2008-5398
Application 11/203,800

STATEMENT OF THE CASE
The Specification discloses that “[s]ome genes that have lower
expression in breast cancer than normal tissue are silenced by
hypermethylation of promoter sequences of the gene” (Spec. ¶ 3). The
Specification also discloses “a method of treating a patient having a breast
duct comprising atypical or malignant breast duct epithelial cells
comprising, delivering intraductally to the breast duct” an inhibitor of DNA
methylation (id. at ¶ 7) such as 5-aza-2-deoxycytidine (id. at ¶ 10).
Claims 12, 14, and 21 are on appeal. Claim 12 is representative and
reads as follows:
Claim 12: A method for inhibiting DNA methylation of breast cancer
genes in a patient having premalignant or malignant breast duct epithelial
cells in a breast duct, the method comprising:
delivering a composition into the breast duct of the patient, said
composition comprising 5-aza-2-deoxycytidine and a biocompatible solution
suitable as a vehicle for delivering 5-aza-2-deoxycytidine into the breast
duct of the patient;
thereby inhibiting DNA methylation of breast cancer-related genes
within said premalignant or malignant breast duct epithelial cells.

OBVIOUSNESS
The Issue
The Examiner has rejected claims 12, 14, and 21 under 35 U.S.C.
103(a) as obvious in view of Sukumar,1 Kimchi,2 and Ferguson.3 The
claims have not been argued separately and therefore stand or fall together.
37 C.F.R. § 41.37(c)(1)(vii).

1Sukumar, US 5,763,415, Jun. 9, 1998.
2Kimchi, US 6,255,293 B1, Jul. 3, 2001.
3Ferguson et al., J. Biol. Chem. 272(51):32260-32266 (1997).
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Application 11/203,800

The Examiner’s position is that Sukumar provides “broad teachings of
the beneficial effects of administration of anti-cancer agents directly to
epithelial cells of the breast duct” (i.e., via ductal cannulation) (Answer 10)
and that the ordinary skilled artisan “would have been motivated to use
5-aza-dC [5-aza-2’-deoxycytidine] with the administration methods of
Sukumar et al because both Kimchi and Ferguson et al teach 5-aza-dC to be
a well known and efficacious inhibitor of DNA methylase with utility in the
treatment of cancer” (id. at 6, emphasis omitted)
Appellant contends that the Examiner erred in finding that there is a
“suggestion or motivation, either in the references themselves or in the
knowledge generally available to one ordinary skill in the art, to modify the
reference or to combine the reference teachings” to arrive at the claimed
invention (Appeal Br. 9,4 emphasis omitted).
The issue presented is: Does the evidence support the Examiner’s
conclusion that one of skill in the art would have been motivated to use the
5-aza-dC of the Kimchi and Ferguson references in the breast cannulation
treatment method disclosed by Sukumar?
Findings of Fact
1. Sukumar discloses a method for treating the cancer of the ductal
epithelium of a mammary gland by contacting the ductal epithelium with an
agent that destroys the epithelium (Sukumar, col. 2, ll. 23-26).

4 The pages of the Appeal Brief are all numbered “18” – our references are
based on the page headed “Amended Appeal Brief” being page 1 and
following pages numbered consecutively.
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Application 11/203,800

2. Sukumar discloses that contacting the ductal epithelium with the
destructive agent is preferably accomplished by ductal cannulation (id. at
col. 4, ll. 35-39).
3. Sukumar discloses that suitable agents include any cytotoxic
agents known in the art, including doxorubicin and taxol (id. at col. 5, l. 51
through col. 6, l. 9).
4. Doxorubicin and taxol are well-known compounds used to treat
cancer. See In re Jolles, 628 F.2d 1322 (CCPA 1980) (“[D]aunorubicin and
doxorubicin . . . are well recognized in the art as valuable for use in cancer
chemotherapy” (footnotes omitted)); Florida State Univ. v. American
Bioscience Inc., 333 F.3d 1330, 1332 (Fed. Cir. 2003) (“Over the last several
decades, taxol has received considerable attantion in the scientific and
medical communities as an anti-cancer drug.”).
5. Sukumar discloses that the agent “need not, and preferably does
not, specifically target cancerous cells” (id. at col. 4, ll. 47-48).
6. Kimchi discloses that “DAP-kinase is a positive mediator of
apoptosis, recently identified as a tumor suppressor gene” (Kimchi, col. 1, ll.
31-32).
7. Kimchi discloses a
therapeutic method of preventing or limiting the spread of
metastases by treatment of a patient with a therapeutically
effective amount of a demethylating agent, such as 5-aza-2'-
deoxycytidine, so as to prevent methylation of … the DAP-
kinase gene, or to demethylate genes which have lost their
ability to express the DAP product due to methylation of the
gene, thereby restoring the biological metastasis-preventing
activity of the endogenous … DAP-kinase gene.
(Id. at col. 3, ll. 15-24.)
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8. Kimchi discloses that a screening test for methylation of the DAP-
kinase gene in primary human malignancies showed that two of three breast
cancers showed methylation of the gene (id. at Example 2 and Table 1).
9. Ferguson discloses that the “cytosine analog 5-aza-2'-
deoxycytidine is a potent inhibitor of DNA methyltransferase” (MTase)
(Ferguson 32260).
10. Ferguson discloses an analysis of the effect of 5-aza-dC on six
breast cancer cell lines: “two that are unmethylated at the ER [estrogen
receptor] gene and actively express the ER gene, … and four that are
hypermethylated at the ER gene and lack ER gene expression” (id. at
32262). The results showed that “ER-negative breast cancer cells are more
sensitive and undergo apoptosis in response to 5-aza-dC” (id.).
11. Ferguson discloses that 5-aza-dC may be “efficacious in the
treatment of ER-negative breast cancers and other tumors with high DNA
MTase levels” (id. at 32266).
Principles of Law
“The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results.”
KSR Int’l Co. v. Teleflex Inc., 127 S. Ct. 1727, 1739 (2007). “[W]hen the
question is whether a patent claiming the combination of elements of prior
art is obvious,” the relevant question is “whether the improvement is more
than the predictable use of prior art elements according to their established
functions.” Id. at 1740.
“A reference may be said to teach away when a person of ordinary
skill, upon reading the reference, would be discouraged from following the
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path set out in the reference, or would be led in a direction divergent from
the path that was taken by the applicant. The degree of teaching away will
of course depend on the particular facts; in general, a reference will teach
away if it suggests that the line of development flowing from the reference’s
disclosure is unlikely to be productive of the result sought by the applicant.”
In re Gurley, 27 F.3d 551, 553 (Fed. Cir. 1994).
“[I]n a section 103 inquiry, ‘the fact that a specific [embodiment] is
taught to be preferred is not controlling, since all disclosures of the prior art,
including unpreferred embodiments, must be considered.’” Merck & Co.
Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 807 (Fed. Cir. 1989)
(quoting In re Lamberti, 545 F.2d 747, 750 (CCPA 1976)).
Analysis
Claim 12 is directed to a method for inhibiting DNA methylation of
breast cancer genes in a patient having premalignant or malignant breast
duct epithelial cells by delivering 5-aza-2-deoxycytidine, a DNA
methylation inhibitor, into the breast duct of a patient. Sukumar discloses a
method of treating breast cancer by delivering agents, including cancer
treating agents, to the breast duct epithelium by breast duct cannulation.
Kimchi and Ferguson suggest that breast cancer may be treated by the
administration of the DNA methylation inhibitor 5-aza-2-deoxycytidine.5
Given that both elements of the invention – direct administration of a
treatment agent to the breast duct to treat breast cancer and the use of 5-aza-
dC to treat breast cancer – were known in the art, it would have been

5 Appellant does not dispute that the “5-aza-2'-deoxycytidine” of Kimchi and
Ferguson is equivalent to the “5-aza-2-deoxycytidine” recited in claim 12.
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obvious to one of ordinary skill in the art to administer 5-aza-dC to treat
breast cancer by delivering it to the breast duct. Such a combination is
merely the use of known elements which would reasonably be expected to
yield predictable results as discussed in KSR.
Appellant argues that Sukumar teaches away from combining the
references because Sukumar teaches that preferably the cytotoxic agents are
not cancer specific agents (Appeal Br. 13).
This argument is not persuasive because, in accordance with the test
set out in In re Gurley, a person of ordinary skill in the art would not have
been “led in a direction divergent from the path that was taken by”
Appellant. Although Sukumar indicates that preferred embodiments are
drawn to the use of agents having general cytotoxic activity, the compounds
taught by Sukumar to be useful in the disclosed method include compounds
that are well-known anticancer drugs; thus, Sukumar includes administration
of cancer-specific agents in the disclosed method. As discussed above, the
mode of administration taught in Sukumar as directly targeting the
malignant or premalignant ductal epithelial cells from which the majority of
breast cancers originate combined with the suggestion of 5-aza-dC
methylation inhibitors to treat breast cancer would have suggested to one of
skill in the art the administration of methylase inhibitors intraductally to treat
breast cancer.
Conclusions of Law
The evidence supports the Examiner’s conclusion that one of skill in
the art would have been motivated to use the 5-aza-dC of the Kimchi and
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Ferguson references in the breast cannulation treatment method disclosed by
Sukumar.
SUMMARY
We affirm the rejection of claims 12, 14, and 21 under 35 U.S.C.
§ 103(a) as being obvious in view of Sukumar, Kimchi, and Ferguson.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).

AFFIRMED
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