Ex Parte Hu et al

Patent Trial and Appeal Board

May 5, 2017

13624488 (P.T.A.B. May. 5, 2017)

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.
13/624,488 12/24/2012 Yanmin Hu 17686.0003 7366
27890 7590 05/09/2017
STEPTOE & JOHNSON LLP
1330 CONNECTICUT AVENUE, N.W.
WASHINGTON, DC 20036
EXAMINER
PAGONAKIS, ANNA
ART UNIT PAPER NUMBER
1628
NOTIFICATION DATE DELIVERY MODE
05/09/2017 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte YANMIN HU and ANTHONY M. R. COATES
Appeal 2016-006355
Application 13/624,4881
Technology Center 1600
Before JEFFREY N. FREDMAN, RICHARD J. SMITH, and
DAVID COTTA, Administrative Patent Judges.
COTTA, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a
pharmaceutical composition. The Examiner rejected the claims on appeal
under 35 U.S.C. § 103(a) as obvious and on the ground of obviousness-type
double patenting.
We affirm-in-part.
1 According to Appellants, the real party in interest is the Helperby
Therapeutics Ltd. App. Br. 3.
Appeal 2016-006355
Application 13/624,488
STATEMENT OF THE CASE
Claims 16, 26, and 27 are on appeal and read as follows:
16. A pharmaceutical composition comprising dyclonine
hydrochloride and 4-methyl-1-(2-phenylethyl)-8-phenoxy-2,3-
dihydro-1 H-pyrrolo[3,2-c]-quinoline.
26. A pharmaceutical composition comprising dyclonine
hydrochloride and 4-methyl-1-(2-phenylethyl)-8-phenoxy-2,3-
dihydro-1 H-pyrrolo[3,2-c]-quinoline, wherein the combination
of dyclonine hydrochloride and 4-methyl-1-(2-phenylethyl)-8-
phenoxy-2,3-dihydro-1 H-pyrrolo[3,2-c]-quinoline shows a
synergistic antimicrobial activity against log phase and/or latent
microorganisms.
27. A pharmaceutical composition comprising dyclonine
hydrochloride and 4-methyl-1-(2-phenylethyl)-8-phenoxy-2,3-
dihydro-1 H-pyrrolo[3,2-c]-quinoline, wherein the combination
of dyclonine hydrochloride and 4-methyl-1-(2-phenylethyl)-8-
phenoxy-2,3-dihydro-1 H-pyrrolo[3,2-c]-quinoline shows a
synergistic activity against stationary phase S. aureus.
App. Br. 19-20 (Claims App’x).
The claims stand rejected as follows:
Claims 16, 26, and 27 under 35 U.S.C. § 103(a) as obvious over
the combination of Beck2 and Florestano.3
2 Beck et al., WO 2007/054693 Al, published May 18, 2007 (“Beck”).
3 Florestano et al., Antimicrobial Properties of Dyclonine Hydrochloride, A
New Topical Anesthetic, 45(5) J. of the American Pharmaceutical
Association 320-25 (1956) (“Florestano”).
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Application 13/624,488
Claims 16, 26, and 27 on the ground of non-statutory
obviousness-type double patenting over claims 1 and 6 of the ’187
Patent4 in view of Florestano.
OBVIOUSNESS
In finding claims 16, 26, and 27 obvious, the Examiner found that
Beck disclosed the use of 4-methyl-1-(2-phenethyl)-8-phenoxy-2,3-dihydro-
lH-pyrrolo[3,2-c]-quinoline (“HT61”) as an antimicrobial agent alone or in
combination with one or more conventional antimicrobial agents. Ans. 2.
The Examiner acknowledged that Beck did not disclose the use of HT61 in
combination with dyclonine hydrochloride. Id. The Examiner found,
however, that Florestano taught that dyclonine hydrochloride had significant
bactericidal and fungicidal activity. Id. at 3. The Examiner concluded that it
would have been obvious to administer HT61 in combination with dyclonine
hydrochloride because “each of the therapeutics have been taught in the
prior art to be successful as antimicrobial agents.” Id. at 3 (citing In re
Kerkhoven, 205 USPQ 1069 (CCPA 1980).
Appellants do not dispute that the Examiner has established a prima
facie case of obviousness, instead arguing that the claimed composition
unexpectedly exhibits synergistic anti-microbial activity. App. Br. 5—6. In
particular, Appellants contend that experimental testing using the
combination of HT61 and dyclonine hydrochloride showed unexpected
synergistic antimicrobial activity. Id.
Appellants rely on the declaration of co-inventor Anthony Coates to
support their unexpected results argument. The Coates Declaration provides
4 Beck et al., US Patent No. 8,207,187 B2, issued June 26, 2012 (“the ’187
Patent”).
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Application 13/624,488
the results of treating 19 strains of S. aureus with various concentrations of
HT61 and dyclonine hydrochloride. Coates Declaration5 3 (110), 5—9. This
testing was used to generate a fractional inhibitory concentration (“FIC”) for
each of the tested strains. Id. The FIC was calculated as: (the mean
inhibitory concentration (“MIC”) of HT61, tested alone)/(MIC of HT61,
tested in combination with dyclonine hydrochloride) + (MIC of dyclonine
hydrochloride, tested alone)/(MIC of dyclonine hydrochloride, tested with
HT61). Id. at 6. ‘“[A] combination is considered synergistic when the XFIC
is <0.5, indifferent when the XFIC is >0.5 to < 2, and antagonistic when
XFIC is >2.’” Id. at 2 (| 6) (quoting Orhan et al., Synergy Tests by E Test
and Checkerboard Methods of Antimicrobial Combinations against Brucella
melitensis, 43(1) J. Clin. Microbiol. 140-43 (2005)). The Coates
Declaration reports that “synergistic activity was seen when HT61 was
combined with dyclonine for 5 strains showing FIC index less than 0.5” and
that “14 strains showed no interaction between the two drugs.” Id. at 3 (1
10). Mr. Coates asserts that these results were unexpected. Id. at 4 flflf 11—
12).
The Coates Declaration also tested for synergy between HT61 and
dyclonine hydrochloride using “time-kill methods” in which “the dynamic
effect of a drug combination is compared to each drug alone.” Id. at 2—3 (1
7). The results of this testing were as follows:
In the stationary phase culture, HT61 at concentration of 8
jig/ml showed about 3 log kill over 8 hour period and 4 jig/ml
barely had any activity. Dyclonine exhibited stationary phase
cidal activity at the concentration from 32 pg/ml. Importantly,
when the two drugs combined at different combination
5 Declaration of Anthony RM Coates to Support Unexpected Results, dated
July 14, 2014 (“Coates Declaration”).
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Appeal 2016-006355
Application 13/624,488
regimens, significant kills were seen against the stationary
phase bacteria.
Id. at 3 (110). The Coates Declaration asserts that these results were also
unexpected. Id. at 4 flflf 11—12).
The Examiner finds Appellants’ evidence of unexpected results
unpersuasive because it is not commensurate with the scope of the claims
and because the combination of HT61 and dyclonine hydrochloride did not
exhibit synergistic effects against every strain of S. aureus tested. Ans. 7.
We find that the Examiner has the better position with respect to claim 16
and that Appellants have the better position with respect to claims 26 and 27.
As an initial matter, we agree with Appellants that the Coates
Declaration establishes that the combination of HT61 and dyclonine
hydrochloride exhibits unexpectedly synergistic antimicrobial effects with
respect to at least 5 S. aureus strains. The Examiner has not provided any
evidence or argument to the contrary. See In re Soni, 54 F.3d 746, 751 (Fed.
Cir. 1995) (“when an applicant demonstrates substantially improved results .
. . and states that the results were unexpected, this should suffice to establish
unexpected results in the absence of evidence to the contrary.”). The fact
that the combination of HT61 and dyclonine hydrochloride did not exhibit
synergistic effects with respect to certain strains of S. aureus does not negate
the unexpected and synergistic results exhibited with respect to these 5
strains. See In re Chupp, 816 F.2d 643, 646 (Fed. Cir. 1987) (finding that
unexpected properties of herbicide with respect to com and soybeans
overcame prima facie case of obviousness even though claims were not
limited to use on those plants, stating “[ejvidence that a compound is
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Application 13/624,488
unexpectedly superior in one of a spectrum of common properties . . . can be
enough to rebut a prima facie case of obviousness.”).
While the evidence of record supports the Appellants’ position that
the combination of HT61 and dyclonine hydrochloride exhibited
unexpectedly improved antimicrobial activity with respect to 5 strains of S.
aureus, in order to be probative of non-obviousness, such unexpected results
must be commensurate with the scope of the claims. In re Huai-Hung Kao,
639 F.3d 1057, 1068 (Fed. Cir. 2011) (“Evidence of secondary
considerations must be reasonably commensurate with the scope of the
claims.”). Claim 16 does not place any limitations on the amounts of HT61
and dyclonine hydrochloride present. It encompasses compositions
including, e.g., trace amounts of HT61 together with large quantities of
dyclonine hydrochloride and vice versa. The evidence of record does not
support unexpected results for all possible ratios of HT61 to dyclonine
hydrochloride. Accordingly, we affirm the Examiner’s rejection of claim
16.
Claim 26 requires that the claimed composition “shows a synergistic
antimicrobial activity against log phase and/or latent microorganisms.”
Claim 27 similarly requires that the claimed composition “shows a
synergistic activity against stationary phase S. aureus.'” Unlike claim 16,
claims 26 and 27 do not encompass all possible ratios of HT61 to dyclonine
hydrochloride. By requiring that the composition show synergistic activity,
claims 26 and 27 exclude ratios that do not exhibit synergistic activity.
Appellants’ evidence of unexpected results is, thus, reasonably
commensurate with the scope of claims 26 and 27. Viewing the record as a
whole, we find that Appellants’ evidence of unexpected results with respect
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Application 13/624,488
to claims 26 and 27 is sufficient to overcome the Examiner’s prima facie
case of obviousness. Accordingly, we reverse the Examiner’s rejection of
claims 26 and 27.
DOUBLE PATENTING
The Examiner’s double patenting rejection is similar to the
obviousness rejection. In finding claims 16, 26, and 27 obvious, the
Examiner found that claims 1 and 6 of the ’187 Patent disclosed the use of
HT61 in combination with another antimicrobial agent. Ans. 5. The
Examiner acknowledged that the claims of the ’ 187 Patent did not disclose
the use of HT61 in combination with dyclonine hydrochloride. Id. The
Examiner found, however, that Florestano taught that dyclonine
hydrochloride had significant bactericidal and fungicidal activity. Id. As
with the obviousness rejection, the Examiner concluded that it would have
been obvious to administer HT61 in combination with dyclonine
hydrochloride because “each of the therapeutics have been taught in the
prior art to be successful as antimicrobial agents.” Id. (citing In re
Kerkhoven, 205 USPQ 1069 (CCPA 1980).
Appellants contend that the Examiner’s double patenting rejection
should be reversed for the reasons advanced in connection with the
obviousness rejection. App. Br. 9. For the reasons discussed above, we
affirm the Examiner’s rejection of claim 16 and reverse the Examiner’s
rejection of claims 26 and 27 on the ground of non-statutory obviousness-
type double patenting.
SUMMARY
For the reasons provided herein, and those set forth in the Examiner’s
Answer and Final Action, we affirm the Examiner’s rejection of claim 16
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Application 13/624,488
under 35 U.S.C. § 103(a) as obvious over the combination of Beck and
Florestano and the Examiner’s rejection of claim 16 on the ground of non-
statutory obviousness-type double patenting over claims 1 and 6 of the ’ 187
Patent in view of Florestano.
For the reasons provided herein, we reverse the Examiner’s rejection
of claims 26 and 27 under 35 U.S.C. § 103(a) as obvious over the
combination of Beck and Florestano and the Examiner’s rejection of claims
26 and 27 on the ground of non-statutory obviousness-type double patenting
over claims 1 and 6 of the ’187 Patent in view of Florestano.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(1).
AFFIRMED-IN-PART
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