Ex Parte Donde et al

Board of Patent Appeals and Interferences

May 17, 2010

10916243 (B.P.A.I. May. 17, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte YARIV DONDE,
ROBERT M. BURK and MICHAEL E. GARST
__________

Appeal 2009-012378
Application 10/916,243
Technology Center 1600
__________

Decided: May 18, 2010
__________

Before LORA M. GREEN, MELANIE L. McCOLLUM, and
STEPHEN WALSH, Administrative Patent Judges.

GREEN, Administrative Patent Judge.

DECISION ON APPEAL
This is a decision on appeal under 35 U.S.C. § 134 from the
Examiner’s rejection of claims 1-23, 25, 26, 28, and 29. We have
jurisdiction under 35 U.S.C. § 6(b).
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STATEMENT OF THE CASE
The claims are directed to a compound of specified formula, a method
of administering the compound for the prevention or treatment of glaucoma
or ocular hypertension, and a liquid comprising the compound. Claim 1 is
representative of the claims on appeal, and reads as follows:
1. A compound having a formula

or a pharmaceutically acceptable salt or a prodrug thereof,
wherein
a dashed line represents the presence or absence of a bond;
A is -(CH2)6-, or cis -CH2-CH=CH-(CH2)3-, wherein 1 or 2 carbons may be
substituted with S or O;
B is hydrogen, -CH3, or =CH2;
J is -OH or =O;
D is -(CH2)n-, -X(CH2)n, or -(CH2)nX-, wherein n is from 0 to 3 and X is S or
O;
and
E is thienyl or benzothienyl, or substituted thienyl or benzothienyl having
substituents comprising from 1 to 6 non-hydrogen atoms each.

We reverse.

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Application 10/916,243

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ISSUE
Has the Examiner established by a preponderance of the evidence of
record that the combination of Burk and Patani suggests modifying the
compounds taught by Burk to arrive at the claimed compound?

FINDINGS OF FACT
FF1 The Examiner rejects claims 1-23, 25, 26, 28, and 29 under 35 U.S.C.
§ 103(a) as being rendered obvious by the combination of Burk1 and Patani.2
(Ans. 4.)
FF2 Burk teaches compounds of the formula:

(Burk, col. 3, ll. 25-35.)
FF3 The Examiner finds that Burk teaches the compound:

1 Burk, US Patent No. 6,124,344, issued Sep. 26, 2000.
2 Patani, et. al, Bioisosterism: A Rational Approach in Drug Design, Chem
Rev, pp. 3147-3176 (1996).
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and its use in the treatment of hypertension. (Ans. 4.)
FF4 The Examiner notes that “while Burk show[s] the effects of varying
the X substituent, the hydroxyl group on the omega chain, and the
carboxylic acid group on the alpha chain, Burk does not preclude the person
of ordinary skill in the art to try reasonable bioisosteric replacements on the
other functional groups of the molecule, namely the[ ] hydroxyl groups on
the cyclopentane ring.” (Id. at 6.)
FF5 The Examiner notes that “Burk does not teach a carbon in place of the
oxygen in the cyclopentane ring substituent ortho to the chain containing the
thienyl group.” (Id. at 4.)
FF6 The Examiner relies on Patani for its teaching “that methyl and
hydroxyl are bioisosteres of each other.” (Id. at 5.)
FF7 Specifically, the Examiner relies on Figure 14 and Table 12 at page
3153 of Patani that show thymidylate synthase enzyme inhibition activity for
benzo(f)quinazalin-4(2H)-ones. (Ans. 7.) The compounds having a methyl
group had an IC50 of 0.178, and the compound that had a hydroxyl group
had an IC50 of 0.48. (Id.)
FF8 According to the Examiner, the data presented “shows that inserting a
methyl or a hydroxyl group in the X position gives compounds that possess
the same utility, namely inhibiting thymidylate synthase enzyme.” (Id.) The
Examiner acknowledges that the data does not deal with prostaglandins, but
concludes that “one of ordinary skill in the art would infer that hydroxyl and
methyl are bioisosteres of each other and that the groups could be swapped
in other molecules with a reasonable expectation that another molecule with
the same utility would be generated.” (Id.)
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PRINCIPLES OF LAW
While the analysis under 35 U.S.C. § 103 allows flexibility in
determining whether a claimed invention would have been obvious, KSR
Int’l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007), it still requires showing
that “there was an apparent reason to combine the known elements in the
fashion claimed by the patent at issue.” Id. “We must still be careful not to
allow hindsight reconstruction of references to reach the claimed invention
without any explanation as to how or why the references would be combined
to produce the claimed invention.” Innogenetics, N.V. v. Abbott Labs., 512
F.3d 1363, 1374 n.3 (Fed. Cir. 2008).
In order to make a prima facie case of obviousness based on the
structural similarity between the claimed compound and the compound
disclosed by the prior art, not only must the structural similarity exist, but
the prior art must also provide reason or motivation to make the claimed
compound. See In re Dillon, 919 F. 2d 688, 692 (Fed. Cir. 1990) (en banc),
In re Mayne, 104 F. 3d 1339, 1341 (Fed. Cir. 1997); In re Payne, 606 F.2d
303, 313 (CCPA 1979); see also In re Grabiak, 769 F.2d 729, 731-32 (Fed.
Cir. 1985 (noting that in addition similarity in structures between the prior
art compound and the claimed compound, a prima facie case of obviousness
also requires a showing of “adequate support in the prior art” for the change
in structure). Therefore, in order to establish a prima facie case of
obviousness, there need be “a showing that the ‘prior art would have
suggested making the specific molecular modifications necessary to achieve
the claimed invention.’” Takeda Chemical Industries, Ltd. v. Alphapharm
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Pty., Ltd., 492 F.3d 1350, 1356 (Fed. Cir. 2007), quoting In re Deuel, 51
F.3d 1552, 1558 (Fed. Cir. 1995). The court in Takeda noted that the “test
for prima facie obviousness for chemical compounds is consistent with the
legal principles enunciated in KSR,” Takeda, 492 F.3d at 1356, and thus, “in
cases involving new chemical compounds, it remains necessary to identify
some reason that would have led a chemist to modify a known compound in
a particular manner to establish prima facie obviousness of a new claimed
compound.” Id. at 1357.

ANALYSIS
Appellants argue that there are a nearly infinite number of
substitutions that could be made to the structure of Burk. (App. Br. 20.)
Appellants assert that there must be something in the prior art that suggests
the modification, and that nothing in the combination of references as set
forth by the Examiner suggests the modification of replacing the oxygen in
the cyclopentane ring substituent ortho to the chain containing the thienyl
group with a carbon. (Id. at 20-21.)
We agree with Appellants. As acknowledged by the Examiner, while
Burk shows the effects of varying the X substituent, the hydroxyl group on
the omega chain, and the carboxylic acid group on the alpha chain (FF4),
Burk does not suggest replacing the oxygen in the cyclopentane ring
substituent ortho to the chain containing the thienyl group with any group,
much less than the claimed carbon group. If we were to adopt the
Examiner’s reasoning, any substitution of any group for a known bioisostere
would be prima facie obvious, whether there is any suggestion in the art to
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make the modification or not. But that is not the state of the law, because as
noted by the Court of Appeals for the Federal Court, in order to establish a
prima facie case of obviousness, there must be a reason in the prior art that
would have suggested making the specific molecular modifications
necessary to achieve the claimed invention. Takeda 492 F.3d at 1356.

CONCLUSION OF LAW
We conclude that the Examiner has not established by a
preponderance of the evidence of record that the combination of Burk and
Patani suggests modifying the compounds taught by Burk to arrive at the
claimed compounds.
We are therefore compelled to reverse the rejection of claims 1-23,
25, 26, 28, and 29 under 35 U.S.C. § 103(a) as being rendered obvious by
the combination of Burk and Patani.

REVERSED

alw

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