Ex Parte Kim et al

Patent Trial and Appeal Board

Nov 14, 2016

10562615 (P.T.A.B. Nov. 14, 2016)

United States Patent and Trademark Office
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O.Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
10/562,615 07/27/2006 Myung-Hwa Kim 428.1145 6138
7590 11/16/2016
LUCAS & MERCANTI, LLP
30 BROAD STREET
21st FLOOR
NEW YORK, NY 10004
EXAMINER
SZNAIDMAN, MARCOS L
ART UNIT PAPER NUMBER
1628
NOTIFICATION DATE DELIVERY MODE
11/16/2016 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte MYUNG-HWA KIM, KWNAGWOO CHUN,
JAE-WON CHOL, BO-YOUNG JOE, SANG-WOO PARK,
KWANG HEE KIM, BYUNG-KYU OH, and JONG-HEE CHOL1
Appeal 2014-007893
Application 10/562,615
Technology Center 1600
Before DEMETRA J. MILLS, MELANIE L. McCOLLUM, and TAWEN
CHANG, Administrative Patent Judges.
McCOLLUM, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35U.S.C. § 134 involving claims to a tricyclic
derivative and to a composition containing it. The Examiner has rejected the
claims for obviousness and for obviousness-type double patenting. We have
jurisdiction under 35 U.S.C. § 6(b). We affirm.
1 Appellants identify the real party in interest as JE IL PHARMA­
CEUTICAL CO., LTD. (Br. 2).
Appeal 2014-007893
Application 10/562,615
STATEMENT OF THE CASE
Claims 12, 13, and 16—21 are on appeal (Br. 2). The claims have not
been argued separately and therefore stand or fall together. 37 C.F.R.
§ 41.37(c)(l)(iv). Claim 12 is representative and is set forth in Appellants’
Claims Appendix (Br. 10—11).
Claims 12, 13, and 16—21 stand rejected under 35 U.S.C. § 103(a) as
obvious over Kim '8242 in view of Patani3 and Park4 (Ans. 2).
Claims 12, 13, and 16—21 also stand rejected on the ground of
nonstatutory obviousness-type double patenting as being unpatentable over
claims 1—5 of U.S. Patent No. 7,119,229 B2 to Kim et al. (hereinafter
“Kim '229”) in view of Patani and Park (Ans. 21).5
OBVIOUSNESS
The Examiner relies on Kim '824 for teaching, in Example 12, a
compound, which the Examiner refers to as compound A, that “differs from
the instant compounds 10, 12 and 17, in the presence of a Hydrogen atom
instead of Fluorine atom in the aromatic ring” (Ans. 4).
The Examiner relies on Patani for teaching “that the substitution of
Hydrogen by Fluorine is one of the most commonly employed monovalent
isosteric replacements” (id.). In particular, the Examiner finds that Patani
“in Figure 2 . . . give[s] an example wherein replacing Hydrogen with
2 Kim et al., WO 02/100824 Al, published Dec. 19, 2002.
3 George A. Patani & Edmond J. LaVoie, Bioisosterism: A Rational
Approach in Drug Design, 96 Chem. Rev. 3147—76 (1996).
4 B. Kevin Park et al., Metabolism of Fluorine-Containing Drugs, 41 Annu.
Rev. Pharmacol. Toxicol. 443—70 (2001).
5 A second obviousness-type double patenting rejection was withdrawn by
the Examiner (Ans. 22).
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Application 10/562,615
Fluorine in an aromatic ring maintains or improves the pharmacological
properties of the compounds” {id. at 4—5).
The Examiner relies on Park for teaching:
Fluorine substitution can alter the chemical properties,
disposition, and biological activity of drugs. Many fluorinated
compounds are currently widely used in the treatment of a
disease. These include antidepressants, anti-inflammatory drugs,
antimalarial drugs, etc. The chemistry and medicinal chemistry
of fluoro-organic compounds have been extensively reviewed.
The development of new fluorinating agents has vastly increased
the potential for synthesis of novel fluorinated drugs .... The
replacement of a hydrogen atom or hydroxyl group by a fluorine
atom is a strategy widely used in drug development to alter
biological function .... In terms of drug design, fluorine
substitution can be used to alter the rate of drug metabolism and
thereby produce a drug with a longer duration of action. Such an
approach has already been used successfully for several classes
of drugs. In addition, fluorine substitution can be used to reduce
toxicity by blocking the formation of toxic metabolites and, in
particular, chemically reactive metabolites. This can be achieved
by fluorine substitution, at the appropriate site of the molecule,
with an alteration in the balance between direct detoxication and
metabolic bioactivation, provided the chemical modification
does not impair drug efficacy.
{Id. at 5.)
The Examiner concludes that it would have been obvious “to replace
any Hydrogen of the aromatic ring of compound A with a Fluorine in order
to obtain any of the instant compound[s]: 10, 12, or 17, and expect these
compounds to have . . . similar biological/pharmaceutical properties” {id. at
7).
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Application 10/562,615
Analysis
We incorporate the Examiner’s findings of fact and conclusions of
law as set forth in the Final Rejection at pages 4—8 and in the Examiner’s
Answer at pages 2—7, which are summarized above.
Appellants argue, however, that none of the cited legal authority on
structural obviousness supports a prima facie case for fluorination (Br. 4).
We are not persuaded.
We agree with Appellants that the Examiner has not provided a
specific legal authority for the proposition that it is prima facie obvious to
replace a hydrogen with a fluorine. However, Appellants have not
adequately explained why it would not have been obvious in view of the
teachings in Patani and Park.
Appellants also argue that the “Examiner’s narrow focus on the
phenyl substituent clearly indicates impermissible hindsight because the
combination of Kim ['824], Patani and Park does not teach or suggest one
skilled in the art to focus on just the phenyl substituent for possible
fluorination” {id. at 6). We are not persuaded.
According to Appellants, ‘“compound A’ has at least 24 possible sites
for fluorination” {id.). In response, the Examiner finds that this “is still a
small number of hydrogens, so the skilled in the art will envision each and
every fluorine isomer” (Ans. 12). In addition, the Examiner provides
reasoning as to why one of skill in the art may focus on phenyl substitutions
{id. at 12—14). We conclude that Appellants have not adequately explained
why the Examiner’s reasoning is incorrect.
In addition, Appellants argue that “the Examiner provides no
definitive rationale as to why Appellants’ data on toxicity is not sufficient to
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Appeal 2014-007893
Application 10/562,615
demonstrate unexpected results indicative of non-obviousness under the
Graham factors” (Br. 7). We are not persuaded.
As noted by the Examiner (Ans. 17), Appellants’ Declaration6
compares the compounds in Examples 8 and 12 of the present Specification
to compound 6 of Kim '824 (Decl. 3—4, | 8), which differ not only in
fluorination but also in the presence of a 10-methylsulfanyl group rather than
a 10-methoxy group (compare Spec. 82—83 & 86—87 to Kim '824, p. 24).7
In contrast, Example 12 of Kim '824, which is specifically relied on by the
Examiner (Ans. 4), discloses a compound that, like the compounds in
present Examples 8 and 12, has a 10-methylsulfonyl group (Kim '824,
p. 28). Thus, Appellants have not compared the present invention to the
closest prior art. As a result, it is not clear whether the “improved
toxicology profile” indicated in the Declaration (Decl. 19) is actually due to
the fluorination. Moreover, even if it is, we agree with the Examiner that
Appellants have not provided sufficient evidence indicating that improved
toxicity would have been unexpected in view of Park (Ans. 20), which
specifically teaches that “fluorine substitution can be used to reduce toxicity
by blocking the formation of toxic metabolites and, in particular, chemically
reactive metabolites” (Park 464).
6 Declaration Under 37 C.F.R. § 1.132 of Myung-Hwa Kim dated
September 20, 2011 (filed September 21, 2011).
7 The compound in present Example 8 also differs in having a 3-ethoxy
group rather than a 3-methoxy group.
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Application 10/562,615
Conclusion
The evidence supports the Examiner’s conclusion that Kim '824,
Patani, and Park suggest the derivative of representative claim 12. We
therefore affirm the obviousness rejection.
DOUBLE PATENTING
The Examiner finds that “Claims 1-5 of [Kim '229] teach similar
compounds and pharmaceutical compositions as claimed in the instant
application” (Ans. 21). In particular, the Examiner finds that these
“compounds only differ in the absence of a[] halogen (i.e. F, Cl, Br or I) in
the aromatic ring” (id.). For the reasons discussed in the obviousness
rejection, the Examiner concludes that it would have been obvious, “based
on the teachings of Patani and Park[,] ... to replace a[] hydrogen atom of
the aromatic ring of any of the compounds disclosed in [Kim '229] and
arrive at the compounds of the instant application” (id.).
Analysis
We incorporate the Examiner’s findings of fact and conclusions of
law as set forth in the Final Rejection at pages 10—11 and in the Examiner’s
Answer at page 21, which are summarized above.
Appellants argue that the “double patenting rejection should be
reversed because the current claims are not an obvious variation of the
claims of [Kim '229] for the reasons discussed above” (Br. 8). We are not
persuaded by these arguments for the reasons discussed above.
Conclusion
The evidence supports the Examiner’s conclusion that claims 1—5 of
Kim '229 in view of Patani and Park suggest the derivative of representative
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claim 12. We therefore affirm the obviousness-type double patenting
rejection.
TIME PERIOD FOR RESPONSE
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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