Ex Parte Bhagwat et al

Patent Trials and Appeals Board

Jul 8, 2019

14111627 - (D) (P.T.A.B. Jul. 8, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
14/111,627 12/13/2013 Sachin Subhash Bhagwat
58478 7590 07/08/2019
BIO INTELLECTUAL PROPERTY SERVICES (BIO IPS) LLC
8509 KERNON CT.
LORTON, VA 22079
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
WH-76 5056
EXAMINER
PEEBLES, KATHERINE
ART UNIT PAPER NUMBER
1617
MAIL DATE DELIVERY MODE
07/08/2019 PAPER
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.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte SACHIN SUBHASH BHAGWAT, MOHAMMAD ALAM JAFRI,
and MARESH VITHALBHAI PATEL
Appeal2019-000838
Application 14/111,627
Technology Center 1600
Before ULRIKE W. JENKS, TIMOTHY G. MAJORS, and
MICHAEL A. VALEK, Administrative Patent Judges.
VALEK, Administrative Patent Judge.
DECISION ON APPEAL
Appellants 1 submit this appeal under 35 U.S.C. § 134(a) involving
claims to a pharmaceutical composition comprising 2 grams of cefepime and
2 grams oftazobactam. We have jurisdiction under 35 U.S.C. § 6(b).
We REVERSE.
STATEMENT OF THE CASE
In the Specification, Appellants state, "[s]urprisingly, it has been
found that a pharmaceutical composition comprising [an] effective amount
1 Appellants identify the real party in interest as W ockhardt Limited
Company. App. Br. 3. Herein we refer to the Final Office Action mailed
Nov. 22, 2017 ("Final Act."), Appeal Brief filed May 16, 2018 ("App. Br.")
and Examiner's Answer mailed Sept. 6, 2018 ("Ans."), and Reply Brief filed
Nov. 6, 2018 ("Reply Br.").
Appeal2019-000838
Application 14/111,627
of an antibacterial agent and tazobactam or a pharmaceutically acceptable
salt thereof, in a specific ratio of tazobactam to the antibacterial agent in the
composition, exhibits unexpectedly improved antibacterial efficacy, even
against highly resistant ESBL [i.e., extended spectrum B-lactams] producing
gram negative pathogens." Spec. 3.
Claims 35, 49, and 50 are on appeal and can be found in the Claims
Appendix of the Appeal Brief. Claim 3 5 is the only independent claim and
representative of the claims on appeal. It reads as follows:
35. A pharmaceutical composition comprising active
ingredients consisting of (a) cefepime or a pharmaceutically
acceptable salt thereof; and (b) tazobactam or a pharmaceutically
acceptable salt thereof, wherein the composition comprises 2
grams of cefepime and 2 grams of tazobactam, and is capable of
treating bacterial infection in a subject.
App. Br. 99.
Appellants seek review of Examiner's rejection of claims 35, 49, and
50 under 35 U.S.C. § 103 as unpatentable over Prezelj 2 in view of Zhang. 3
App. Br. 5.
The issue is: Does the preponderance of evidence of record support
Examiner's conclusion that the cited prior art renders obvious the claimed
method?
Analysis
Examiner finds that Prezelj "discloses laboratory experiments that
demonstrate compositions [ of cefepime and tazobactam] ... are markedly
2 Andrej Prezelj et al., US 2010/0029604 Al, published Feb. 4, 2010
("Prezelj").
3 Zhefeng Zhang, CN 1565456, published Jan. 19, 2005 (English translation
added to file Mar. 1, 2016) ("Zhang").
2
Appeal2019-000838
Application 14/111,627
more effective than compositions comprising the antibiotic alone." Final
Act. 3--4. Examiner notes that "Prezelj does not disclose examples where
the compositions have been scaled up for use in humans," but relies on
Zhang' s disclosure of an embodiment in which "the final amount of
cefepime is 1 g and the final amount of tazobactam sodium is 1 g in the
ready-to-use product." Id. at 4. Examiner determines that this embodiment
would provide "a reasonable starting point in optimizing the dose of each
ingredient for treating specific bacterial infections." Id. From there,
Examiner finds it would be obvious to optimize the dose up to the claimed
"2 grams of cefepime and 2 grams of tazobactam" because "[ o ]ne of
ordinary skill in the art would recognize that increasing the dose will
increase the efficacy of any given drug." Id. at 3, 5. According to
Examiner, "[a]bsent evidence to the contrary, the examiner considers
arriving at the doses specified in the claims to be a matter of routine
optimization." Id.
Appellants dispute Examiner's findings. Among other things,
Appellants contend there is evidence of surprising and unexpected results
that demonstrates that the claimed dosage is not obvious. See App. Br. 54--
59. Appellants point to the declarations of Mahesh Patel dated February 15,
201 7 ("First Patel Declaration") and September 26, 2017 ("Second Patel
Declaration"), which they argue demonstrate that a composition "comprising
2 grams of cefepime and 2 grams of tazobactam exhibited greater than
expected antibacterial activity." Id. at 54. In particular, Appellants urge that
the data in "Table 4"4 of the Second Patel Declaration show that the claimed
4 The table labelled as "Table 4" in Appellants' Brief appears to be Table 3
of the Second Patel Declaration.
3
Appeal2019-000838
Application 14/111,627
dosage is "superior by nearly 30% to the activity of both a combination
comprising 1 gram of cefepime and 1 gram of tazobactam and a combination
comprising 4 grams of cefepime and 4 grams of tazobactam." Id. at 59.
According to Appellants, this demonstrates "there is no linear relationship
between dosage and bactericidal activity for the combinations tested,"
thereby rebutting Examiner's determination that the claimed dosage is
merely an obvious optimization of the dosage taught in Zhang. See id. at 64.
Upon considering the evidence cited by the Examiner, and the
evidence of unexpected results presented by Appellant, we determine that
the preponderance of the evidence of record does not support the Examiner's
conclusion of obviousness. As discussed below, Appellants' evidence of
unexpected results is sufficient to outweigh the evidence of obviousness.
We begin by noting that we are not persuaded by Appellants'
arguments that Prezelj and Zhang disclose too many possible combinations
to render the claimed combination obvious. See, e.g., App. Br. 9-37 and
41--48; Reply Br. 6, 11-12, 18, 22-25, 32-54, and 59-60. Both references
specifically teach that the combination of cefepime and tazobactam exhibit
greater antibacterial activity than cefepime alone. See Prezelj ,r 165; Zhang
6 (Table 3). In addition, Zhang discloses a number of specific
pharmaceutical "embodiment[ s]" that combine cefepime and tazobactam.
See Zhang 9-13 (Embodiments 9-14, 18, and 30-35). Appellants'
mathematical calculation of other "combinations" they say are also taught by
Prezelj and Zhang does not change the fact that these references specifically
teach the combination of cefepime and tazobactam as well as a rationale
(increased activity) for combining the two. See Merck & Co., Inc. v.
Biocraft Labs., Inc., 874 F.2d 804, 807 (Fed. Cir. 1989) (explaining that a
4
Appeal2019-000838
Application 14/111,627
reference's disclosure of "a multitude of effective combinations does not
render any particular formulation less obvious.").
What distinguishes Appellants' claims from the express teachings of
Prezelj and Zhang is the claimed dosage, i.e., "2 grams of cefepime and 2
grams of tazobactam." Prezelj does not disclose any particular
pharmaceutical dosage. And the closest dosage taught in Zhang is that in
Embodiment 33, which equates to 1 gram of cefepime salt and 1 gram of
tazobactam salt per "powder injection[]." 5 Zhang 12.
Examiner has not identified any teaching of a composition comprising
either cefepime or tazobactam in an amount greater than 1 gram in the
record before us. Rather, Examiner finds it would be obvious to optimize up
from the dosage in Zhang Embodiment 33 to the claimed dosage because
"one of ordinary skill in the art would recognize that increasing the dose will
increase the efficacy" and "expect that the optimal ratio and dose of each
agent would vary depending upon the identity of the bacteria being treated,
particularly in view of Prezelj, table 4, pages 12-13, which shows some
variability in MIC depending upon the genus, species, and strain being
tested." Final Act. 5.
While that may be sufficient to meet Examiner's initial burden to
demonstrate a prima facie case, Appellants have produced evidence that
rebuts Examiner's dosage optimization finding. Specifically, the Second
Patel Declaration includes data from "in vitro pharmacokinetic modeling
(IVPM)" showing that the claimed 2 gram/2 gram dose provided a higher
bactericidal activity in a particular multi-drug resistant bacterial strain than
5 Zhang's other embodiments comprising the combination of cefepime and
tazobactam include a smaller amount of tazobactam.
5
Appeal2019-000838
Application 14/111,627
both the lower (1 gram/I gram) dose taught in Zhang as well as a higher (4
gram/4 gram) dose of cefepime and tazobactam. Second Patel Deel. 1-3.
According to the declaration, this data evidences that "there is no linear
relationship between dosage and bactericidal activity for the combinations
tested." Id. at 19. In this regard, the Second Patel Declaration directly
responds to and rebuts Examiner's finding that "increasing the dose will
increase the efficacy." See Final Act. 5.
Examiner determined that Appellants' IVPM data could not "suffice
to overcome a rejection under 35 USC I03(a)" because IVPM is an in vitro
technique and therefore merely an "educated guess of what would happen in
vivo." Final Act. 7-9; Ans. 13. We disagree. Appellants have identified
multiple scientific references to support their position that IVPM is a
"scientifically well-established system for studying comparative
antibacterial activities of multiple-dose regimens." See Reply 7-8 (citing
App. Br. 19-20, 54--56, and 74--77). Examiner does not respond to these
references. Indeed, Examiner offers no evidence in support of the
conclusion that IVPM data is so unreliable that it is necessarily insufficient
as rebuttal evidence. It may be that an evidence-supported rationale could
be advanced to show that Appellants' evidence of a non-linear relationship
between dosage and activity is insufficient, e.g., because that finding is
unreliable or expected in light of the prior art, but Examiner has not
articulated such here. See MPEP 2145 ( explaining that if evidence of
unexpected results is "deemed insufficient to rebut the prima facie case ...
Office personnel should specifically set forth the facts and reasoning that
justify this conclusion" and not "summarily dismiss it as not compelling or
insufficient").
6
Appeal2019-000838
Application 14/111,627
Therefore, based on the record before us, we agree with Appellants
that the Second Patel Declaration evidences that the claimed dosage
provides unexpected results over those taught in the prior art. Considering
"the entire merits of the matter" in light of this rebuttal evidence, we
determine that the preponderance of the evidence does not support
Examiner's obviousness rejection. See In re Hedges, 783 F.2d 1038, 1039
(Fed. Cir. 1986). Accordingly, we reverse.
SUMMARY
We reverse the rejection of claims 35, 49, and 50 under 35 U.S.C.
§ 103 as unpatentable over Prezelj in view of Zhang.
REVERSED
7