Ex Parte Beier et al

Patent Trial and Appeal Board

Jan 23, 2017

12991524 (P.T.A.B. Jan. 23, 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.
12/991,524 11/08/2010 Norbert Beier MERCK-3776 9585
23599 7590 01/25/2017
MILLEN, WHITE, ZELANO & BRANIGAN, P.C.
2200 CLARENDON BLVD.
SUITE 1400
ARLINGTON, VA 22201
EXAMINER
DECK, JASON A
ART UNIT PAPER NUMBER
1627
NOTIFICATION DATE DELIVERY MODE
01/25/2017 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
following e-mail address(es):
docketing@mwzb.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte NORBERT BEIER, WOLFGANG SCHOLZ, ULRICH BETZ, and
MARIAN BRAENDLE
Appeal 2016-000194
Application 12/991,5241
Technology Center 1600
Before JEFFREY N. FREDMAN, ELIZABETH A. LaVIER, and
TIMOTHY G. MAJORS, Administrative Patent Judges.
LaVIER, Administrative Patent Judge.
DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellants seek review of the
Examiner’s rejections of claims 8, 14—16, 18, 20, 22—24, 26, and 28. We
have jurisdiction under 35 U.S.C. § 6(b). For the reasons set forth below, we
AFFIRM.
BACKGROUND
The Specification describes “the use of 2-Methyl-4,5-di-
(methylsulfonyl)-benzoyl-guanidine, or derivatives thereof, for the
1 Appellants state the real party in interest is Merck Patent GmbH. Appeal Br.
1.
Appeal 2016-000194
Application 12/991,524
enhancement of insulin sensitivity and the preservation or increase of P-cell
compensation,” as well as “for the prophylaxis and therapy of Type II
diabetes mellitus, the Metabolic syndrome, diabetic nephropathy and/or
neuropathy.” Spec. 1,11. 6—11. Claim 8 is illustrative:
8. A method for the treatment of a disease that is associated
with P-cell dysfunction, comprising administering to a patient
an effective amount of 2-methyl-4,5-di(methylsulfonyl)-
benzoyl-guanidine, and/or a physiologically acceptable salt
and/or solvate thereof, such that the P-cell dysfunction in the
patient is decreased.
Appeal Br. 17 (Claims Appendix).
REJECTION MAINTAINED ON APPEAL
Claims 8, 14—16, 18, 20, 22—24, 26, and 28 stand rejected under 35
U.S.C. § 103(a) as unpatentable over Gericke,2 Tracey,3 Patti,4 and Siffert.5
Ans. 2—3.
FINDINGS OF FACT
The Examiner’s findings, which we adopt as our own, are set forth on
pages 6—10 of the Final Rejection. We highlight the following for context.
2-Methyl-4,5-di-(methylsulfonyl)-benzoyl-guanidine, also known as
“rimeporide,” was known in the art at the time of the claimed invention. See
2 Gericke et al., US 6,673,968 Bl, issued Jan. 6, 2004.
3 Tracey et al., US 2003/0212104 Al, published Nov. 13, 2003.
4 Patti et al., Coordinated Reduction of Genes of Oxidative Metabolism in
Humans with Insulin Resistance and Diabetes: Potential Role of PGC1 and
NRF1, 100 PNAS 8466 (2003).
5 Siffert & Diising, Na+/H+ Exchange in Hypertension and in Diabetes
Mellitus — Facts and Hypotheses, 91 Basic Res. Cardiol. 179 (1996).
2
Appeal 2016-000194
Application 12/991,524
Gericke 1:6—13; see also Appeal Br. 3—\\ Final Action 7. Rimeporide is part
of a class of compounds, sulfonylbenzolguanidines, useful as therapeutic
agents. See Gericke 1:18—47. As is especially relevant to the Examiner’s
findings, Gericke includes “diabetes and late complications of diabetes”
among the conditions that can be treated with this class of compounds.
Gericke 1:41—42; see also Final Action 7.
As the Examiner notes, Gericke “does not specifically teach the
treatment of a disease that is associated with P-cell dysfunction.” Final
Action 7. However, the Examiner finds that Tracey describes treatment of
insulin resistance (which was known to be associated with P-cell dysfunction
(see Patti Abstract)) and type II diabetes using NHE-16 inhibitors that are
“highly homologous” to the compounds of Gericke. Final Action 7—8
(citing Tracey Abstract, 1193). Also, the Examiner cites Patti as disclosing
that insulin resistance “precedes and predicts the development of type II
diabetes mellitus,” which is “characterized by insulin resistance and
pancreatic P-cell dysfunction.” Id. at 8 (citing Patti Abstract, 8466).
Finally, the Examiner relies on Siffert as teaching that NHE-1 “plays a
pivotal role in a variety of cardiovascular pathologies,” including diabetic
nephropathy, a complication that may be suffered by 30-40% of patients
with type I or type II diabetes. Id. (citing Siffert 180, 186).
The Examiner finds that one of ordinary skill in the art would have
been motivated to combine the references because Gericke teaches that
rimeporide “is useful for the treatment of diabetes, in general, and it would
have been obvious to one of ordinary skill in the art to apply the general
6 Sodium-hydrogen exchanger type (or isoform) 1. See Final Action 7—8.
3
Appeal 2016-000194
Application 12/991,524
teaching of the treatment of diabetes to the two specific subtypes of diabetes,
including type II diabetes.” Final Action 9. The other cited references
provide, inter alia, the connections between type II diabetes and insulin
resistance with P-cell dysfunction. See id. at 9.
DISCUSSION
Appellants argue the pending claims in three groups.7
A. Claims 8, 14—16, 18, 20, and 24
Appellants’ central argument is that the prior art references do not
teach or suggest that rimeporide “would decrease beta-cell dysfunction
and/or preserve or increase P-cell compensation.” Appeal Br. 5; see also id.
at 3 (emphasizing the “functional interaction between the particular drug and
the particular condition of beta-cells”), 8—11. In support, Appellants
maintain that Gericke’s “generic” recitation of various applications of
rimeporide (including diabetes) do not amount to a disclosure of “any
particular use.” Id. at 4 (discussing Gericke 1:14—47); see also id. at 8.
Further, Appellants assert that “different types of diabetes can be treated
using different functional means,” such that “[f]or example, a suggestion in a
reference that a compound may be useful to treat type II diabetes does not
necessarily suggest a method wherein type II diabetes is treated in a way
7 Appellants do not include claims 26 and 28 in any of these groups, or
otherwise address them specifically. However, claims 26 and 28 appear in
Appellants’ list of Claims on Appeal (see Appeal Br. 2) and the Claims
Appendix (see id. at 17—18). Claim 26 depends from claim 8; claim 28
depends from claim 24. See id. Accordingly, we treat claims 26 and 28 as
standing or falling with claims 8 and 24.
4
Appeal 2016-000194
Application 12/991,524
‘such that the P-cell dysfunction in the patient is decreased.’” Id. at 5—6.
Indeed, according to Appellants, “Gericke and Tracey teach the effect of
NHE-1 inhibition . . . which is based on treating insulin resistance” {id. at 8)
and that the prior art in fact “teaches away from an enhanced NHE-1 activity
as a target for P-cell dysfunction therapy, and thus away from the claimed
invention” {id. at 11). Accordingly, Appellants assert that Gericke and
Tracey focus on improving the insulin sensitivity of cells in peripheral
tissues/organs, rather than on combatting dysfunction of P-cells in the
pancreas. See id. at 8—9. Siffert further supports this lack of “connection
between NHE-1 inhibition and the ability to decrease P-cell dysfunction” in
the cited art, Appellants maintain, as “Siffert lacks any example that shows
an enhanced NHE-1 activity in patients with type II diabetes mellitus.” Id.
at 12.
These arguments are not persuasive. As the Examiner explains, “[t]he
metric is whether or not the prior art would have made the administration of
the instantly claimed composition to the instantly claimed patient population
obvious, which it does, and the P-cell modulation mechanism would have
followed.” Ans. 9. Appellants’ distinctions among the types and stages of
diabetes, functional mechanisms, and treatment targets {see, e.g., Appeal Br.
5—6, 8—10; Reply Br. 3 4) do not undercut this basic point. Although P-cell
dysfunction does not characterize all stages or types of diabetes,8 P-cell
dysfunction was known to characterize, in particular, type II diabetes. This
is sufficient to support the Examiner’s rejection, in which Gericke’s express
8 The articles included by Appellants in the Evidence Appendix, which we
have considered, amply demonstrate this point.
5
Appeal 2016-000194
Application 12/991,524
inclusion of “diabetes” among various therapeutic uses for rimeporide is
supported by explanation of the link between type II diabetes and P-cell
dysfunction in Tracey and Patti, as discussed above. Cf. KSR Int’l Co. v.
Teleflex Inc., 550 U.S. 398, 421 (2007) (observing that the ordinarily skilled
artisan is “a person of ordinary creativity, not an automaton”). As for
Siffert, Appellants’ discussion (see Appeal Br. 12—14; see also Reply Br. 6—
7) is directed largely to points for which the Examiner does not rely on
Siffert. For this reason, the Examiner correctly observes that “[o]ne cannot
show nonobviousness by attacking references individually where the
rejections are based on combinations of references.” Ans. 21 (citing In re
Keller, 642 F.2d 413 (CCPA 1981); In re Merck & Co., 800 F.2d 1091 (Fed.
Cir. 1986)).
Appellants also argue that the Examiner’s rejection misapplies the
doctrine of inherency.9 Appeal Br. 8; see also Reply Br. 4—5. In the context
of obviousness, a disclosure is inherent if it is “sufficient to show that the
9 Appellants suggest inherency is limited to circumstances in which “a
reference discloses an actual embodiment which meets all of the explicit
steps of a method claim.” Appeal Br. 7. This conception of inherency is
under-inclusive, and, as the Examiner points out (see Ans. 13), is more
descriptive of anticipation than obviousness. In re Rijckaert, 9 F.3d 1531
(Fed. Cir. 1993), on which Appellants rely (see Appeal Br. 7) distinguishes
between optimal and inherent conditions, emphasizing that what “may” result
is not sufficient for inherency. Rijckaert, 9 F.3d at 1534 (quoting Oelrich, 666
F.2d at 581—82). Rijckaert reaffirms the proposition that “[ojbviousness
cannot be predicated on what is unknown,” id. (quoting In re Spormann, 363
F.2d 444, 448 (CCPA 1966)), but cannot be interpreted as restrictively as
Appellants suggest. In any event, the Examiner’s rejection is not “predicated
on what [was] unknown,” for the reasons discussed above.
6
Appeal 2016-000194
Application 12/991,524
natural result flowing from the operation as taught would result in the
performance of the questioned function.” PAR Pharm., Inc. v. TWI Pharms.,
Inc., 773 F.3d 1186, 1195 (Fed. Cir. 2014) (quoting In re Oelrich, 666 F.2d
578, 581 (CCPA 1981)). Thus it has long been recognized that “the
application of an old process to a new and analogous purpose does not
involve invention, even if the new result had not before been contemplated.”
Id. (quoting Ansonia Brass & Copper Co. v. Elec. Supply Co., 144 U.S. 11,
18 (1892)). Here, as the Examiner puts it, “it would have been obvious to
administer rimeporide to patients with type II diabetes regardless of the
instantly claimed inherent properties, and the inherent mechanism of action
would have then necessarily followed.” Ans. 12—13. “[EJfficacy is inherent
in carrying out the claim steps.” In re Montgomery, 677 F.3d 1375, 1381
(Fed. Cir. 2012). We discern no error in the Examiner’s inherency analysis.
Having reviewed all of Appellants’ arguments as presented in the
Appeal Brief and further discussed in the Reply Brief, we are unpersuaded
that the Examiner erred in rejecting claims 8, 14—16, 18, 20, and 24, for the
reasons of record and as further explained herein.
B. Claim 14
Claim 14 depends from claim 8, and further recites “wherein the
method is for treating Type II diabetes mellitus.” Appeal Br. 17 (Claims
Appendix). Referencing their previously-stated arguments, Appellants
maintain that “none of the cited references teach the treatment specifically of
type II diabetes with rimeporide.” Id. at 14. This line of reasoning is
unpersuasive for the same reasons as discussed above with respect to claims
7
Appeal 2016-000194
Application 12/991,524
8, 14—16, 18, 20, and 24, as the combination of references is sufficiently
specific with respect to type II diabetes.
C. Claims 22 and 23
Claim 22 depends from claim 8, and further recites “wherein the
pancreatic P-cell compensation in the patient is preserved to at least 70% of
baseline prior to usage.” Appeal Br. 17 (Claims Appendix). Claim 23
depends on claim 22, and further recites administration of rimeporide “for a
period of at least 4 weeks.” Id. Appellants argue that “[n]one of the prior
art documents teach or suggest the administration of rimeporide for a period
of 4 weeks with the result of decreasing P-cell dysfunction in the patient,”
and further that “none of the cited references teach the resulting significant
advantageous effects found by appellants of preserving P-cell compensation
to 70%.” Id. at 14—15. The Examiner’s optimization analysis, Appellants
contend, fails because “the references provide no teaching regarding the
effect on beta-cell dysfunction,” and so “they obviously could not suggest
optimizing their methods” as recited in claims 22 and 23. Id. at 15.
As discussed above, we agree with the Examiner that P-cell
modulation would have been a natural consequence of what was suggested
by the combined prior art, i.e., administering rimeporide to treat diabetes.
Accordingly, we discern no error in the Examiner’s finding that “dosing is a
result determinate variable, and one of ordinary skill would have optimized
the dose and regimen of 2-methyl-4,5-di-(methylsulfonyl)-benzoyl-
guanidine for optimum efficacy in treating type II diabetes” based on the
prior art teachings. Final Action 9. Further, Appellants do not appear to
dispute (see Appeal Br. 14—15; Reply Br. 7) the Examiner’s finding (see
8
Appeal 2016-000194
Application 12/991,524
Final Action 7—8 (citing Tracey 1193)) that the prior art teaches a treatment
regimen lasting six weeks. Thus, “the skilled artisan would have found it
obvious to administer the rimeporide for greater than 4 weeks, which would
have necessarily resulted in [] P-cell compensation to 70%.” Ans. 24.
CONCLUSION
The rejection of claims 8, 14—16, 18, 20, 22—24, 26, and 28 is
affirmed.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(l)(iv).
AFFIRMED
9