Ex Parte Kao et al

Board of Patent Appeals and Interferences

Jan 11, 2010

12167859 (B.P.A.I. Jan. 11, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte HUAI-HUNG KAO, ANAND R. BAICHWAL,
TROY MCCALL, and DAVID LEE
__________

Appeal 2009-013711
Application 12/167,859
Technology Center 1600
__________

Decided: January 12, 2010
__________

Before DONALD E. ADAMS, ERIC GRIMES, and RICHARD M.
LEBOVITZ, Administrative Patent Judges.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to methods
and compositions for treating pain using controlled release formulations of
oxymorphone, which is an “opioid agonist, widely used in the treatment of
acute and chronic pain” (Spec. 1, ¶ 3). The Examiner has rejected the claims
for obviousness. We have jurisdiction under 35 U.S.C. § 6(b). We affirm.
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STATEMENT OF THE CASE
Claims 8-27 are pending and on appeal. Claims 8 and 21 are
representative and read as follows:
8. A method for treating pain in a human subject in need of acute or
chronic pain relief, comprising the steps of:
(a) Providing a solid oral dosage form comprising about 5 mg to about
80 mg oxymorphone or a pharmaceutically acceptable salt thereof in a
controlled release delivery system with a release rate profile designed to
provide an adequate blood plasma level over at least 12 hours to provide
sustained pain relief over this same period, the system comprising a filler
and a hydrophilic material, wherein oxymorphone is the sole active
ingredient; and
(b) administering the dosage form to the subject, wherein the
oxymorphone Cmax is at least about 50% higher when the dosage form is
administered to the subject under fed versus fasted conditions.

21. A method for treating pain in a human subject in need of acute or
chronic pain relief, comprising the steps of:
(a) Providing a solid oral dosage form comprising about 5 mg to about
80 mg oxymorphone or a pharmaceutically acceptable salt thereof in a
controlled release delivery system with a release rate profile designed to
provide an adequate blood plasma level over at least 12 hours to provide
sustained pain relief over this same period, the system comprising:
(i) a hydrophilic material
(ii) a hydrophobic material
(iii) a cationic cross-linking agent, and
(iv) a filler,
wherein oxymorphone is the sole active ingredient; and
(b) administering the dosage form to the subject, wherein the
oxymorphone Cmax is at least about 50% higher when the dosage form is
administered to the subject under fed versus fasted conditions.

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The claims stand rejected under 35 U.S.C. § 103(a) as follows:
• Claims 8-15 and 18-20 based on Maloney,1 by itself or combined
with Calanchi2 (Ans. 3);
• Claims 16 and 17 based on Maloney, by itself or combined with
Calanchi, and further in view of Baichwal3 (Office action mailed Jan. 12,
2009, p. 8);4 and
• Claims 21-27 based on Maloney, Calanchi, Baichwal, and Oshlack5
(Ans. 6).
OBVIOUSNESS
Issue
Appellants state that “because the application on appeal was filed
under the Accelerated Examination program, Appellant is precluded from
arguing separate patentability of dependent claims on appeal” (Appeal Br. 9,
n.3). And, because Appellants have not presented separate arguments with
respect to claims 8 and 19, all of the claims stand or fall with claims 8 and
21. 37 C.F.R. § 41.37(c)(1)(vii). The only issues presented on appeal,
therefore, relate to whether the methods of claims 8 and 21 would have been
obvious in view of the cited references.

1 Maloney, WO 01/08661 A2, Feb. 8, 2001
2 Calanchi et al., US 5,047,248, Sept. 10, 1991
3 Baichwal et al., US 5,128,143, July 7, 1992
4 This rejection was set out in the Final Rejection (mailed Jan. 12, 2009).
Although it was not repeated in the Answer, Appellants understood claims
16 and 17 to be rejected (Appeal Br. 5) and the Examiner confirmed that that
understanding was correct (Ans. 2). We therefore understand the omission
of the rejection of claims 16 and 17 from the Answer to be inadvertent and
not an indication that the rejection was withdrawn.
5 Oshlack et al., US 5,266,331, Nov. 30, 1993
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The Examiner finds that Maloney “teaches oral sustained release
preparations of opioid analgesics” and “in particular prefers oxycodone,
oxymorphone etc” (Ans. 3-4). The Examiner also finds that the “example
compositions of [Maloney] include methocel K100M, which is a hydrophilic
polymer” (id. at 4). The Examiner concludes that:
[w]hile [Maloney] does not mention the claimed amounts of
oxymorphone or the pharmacological parameters such as Cmax,
. . . the sustained release delivery system described by
[Maloney] reads on the claimed as well as the described
systems of the instant application. Therefore, the burden is on
applicants to show that the matrix system of [Maloney] does
not provide the claimed parameters with opioid analgesic
oxymorphone.
(Id. at 4-5.)
The Examiner concludes that Appellants’ evidence of unexpected
results and commercial success does not rebut the prima facie case of
obviousness because, among other things, the evidence is based on the
Opana ER® composition, which is not commensurate in scope with the
claims (id. at 17, 19).
Appellants contend that the food effect and release rate profile recited
in claims 8 and 21 are not inherently disclosed in Maloney or Calanchi, and
that skilled workers would not have known what dissolution rate would
provide an effective oxymorphone composition with a 12-hour dosing cycle.
Appellants also contend that the evidence of secondary considerations
(unexpected results and commercial success) rebuts any prima facie case of
obviousness.
The specific issues presented are:
(a) Have Appellants shown that the Examiner erred in concluding that
Maloney’s disclosure, alone or combined with Calanchi, would have made
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obvious a method of treating pain with a controlled-release oxymorphone
composition that provides 12 hours of pain relief and a Cmax that is at least
50% higher when administered under fed versus fasted conditions, as recited
in claims 8 and 21?
and
(b) Have Appellants presented evidence of secondary considerations
that outweighs the evidence in favor of obviousness?
Findings of Fact – Prima Facie Obviousness
1. Maloney discloses a “solid, oral controlled release dosage form
comprising a therapeutically effective amount of opioid compound, . . .
between about 30 and 65% of a matrix-forming polymer, . . . and between 5
and 15% of a[n] ionic exchange resin” (Maloney 8).
2. Maloney discloses that “[p]referred opioid compounds useful in
the present invention” include oxycodone hydrochloride and oxymorphone
(id. at 13).
3. Maloney discloses “formulations having from about 5 to about 100
mg oxycodone” (id. at 7).
4. Maloney discloses that matrix-forming polymers include
hydroxypropylmethylcellulose, hydroxypropyl cellulose, and hydroxyethyl
cellulose, and that a “preferred matrix-forming material is alkylcellulose-
based, more particularly hydroxyalkylcellulose-based” (id. at 9).
5. The Specification states that hydroxypropylmethylcellulose,
hydroxyethyl cellulose, and hydroxypropyl cellulose are hydrophilic
materials suitable for use in controlled release formulations (Spec. 12, ¶ 42).
6. Maloney discloses that its formulations “may include diluents,
lubricants, glidants, and additives, as known to those of ordinary skill in the
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art to improve compaction, augment swallowability, [and] decrease
gastrointestinal irritation” (Maloney 10).
7. Maloney discloses that suitable diluents include calcium sulfate
(id. at 11).
8. The Specification discloses that “suitable cationic cross-linking
agents include calcium sulfate” (Spec. 15, ¶ 52).
9. Maloney discloses that suitable diluents also include lactose,
microcrystalline cellulose, sucrose, dextrose, fructose, and sorbitol (Maloney
11).
10. The Specification discloses that “suitable inert pharmaceutical
fillers include sucrose, dextrose, lactose, microcrystalline cellulose, fructose,
xylitol, [and] sorbitol” (Spec. 14, ¶ 51).
11. Maloney discloses that suitable lubricants include “hydrogenated
vegetable oil (type 1)” (Maloney 11).
12. The Specification discloses that hydrophobic materials include
hydrogenated vegetable oils (Spec. 16, ¶ 54).
13. Maloney discloses that its dosage form provides a “dissolution
rate in vitro, when measured by the USP Basket Method . . . [of] between 5
and 25% (by weight) oxycodone released over the first hour . . . and between
about 60 and 80% (by weight) oxycodone released after twelve hours”
(Maloney 12).
14. The Specification defines Cmax as “[m]aximum observed drug
concentration” (Spec. 21, ¶ 66).
15. The Specification provides an example showing that for
oxymorphone controlled-release tablets “[l]east squares (LS) mean Cmax was
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58% higher . . . for the fed condition (Treatment B) compared to the fasted
condition (Treatment A)” (id. at 31, ¶ 97).
16. The Specification’s example also shows that for oxymorphone
immediate-release solution “LS mean Cmax was 50% higher . . . for the fed
condition (Treatment D) compared to the fasted condition (Treatment C)”
(id. at 31, ¶ 98).
Principles of Law – Prima Facie Obviousness
“The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results.”
KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007).
“[T]here must be some articulated reasoning with some rational
underpinning to support the legal conclusion of obviousness.” In re Kahn,
441 F.3d 977, 988 (Fed. Cir. 2006) (quoted with approval in KSR, 550 U.S.
at 418).
“The test for obviousness is what the combined teachings of the
references would have suggested to one of ordinary skill in the art.” In re
Young, 927 F.2d 588, 591 (Fed. Cir. 1991).
Analysis – Prima Facie Obviousness
Maloney discloses a controlled release formulation comprising an
opioid compound (FF 1) in amounts of 5-100 mg (FF 3), and discloses that
oxymorphone is a preferred opioid compound (FF 2). Maloney’s
formulation also comprises a matrix-forming polymer (FF 4), including
polymers described by the Specification as hydrophilic materials (FF 5).
Maloney also discloses that its formulation can include other
conventional pharmaceutical excipients such as calcium sulfate, lactose, and
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hydrogenated vegetable oil (FFs 6, 7, 9, 11), which the Specification
describes as a cross-linking agent, filler, and hydrophobic material,
respectively (FFs 8, 10, 12). Based on these disclosures, it would have been
obvious to a person of ordinary skill in the art to formulate a controlled-
release formulation comprising 5-80 mg of oxymorphone, a filler, and a
hydrophilic material (as recited in claim 8), or a controlled-release
formulation comprising 5-80 mg of oxymorphone, a hydrophilic material, a
hydrophobic material, a cationic cross-linking agent, and a filler (as recited
in claim 21), because Maloney expressly suggests those ingredients for its
compositions, and to administer the formulation to a human subject to treat
pain.
Claims 8 and 21 also require that the dosage form “provide[s] an
adequate blood plasma level over at least 12 hours to provide sustained pain
relief over this same period.” Appellants argue that this limitation is not
inherent in Maloney’s dosage form (Appeal Br. 12). However, Maloney
discloses that its dosage form provides a dissolution rate of 60-80% active
agent released after 12 hours (FF 13). It is reasonable to conclude that
Maloney’s active agent would still be effective after 12 hours because it is
still being released from Maloney’s dosage form at 12 hours. Appellants
have not pointed to evidence of record showing that Maloney’s dosage form
would not provide the plasma levels of oxymorphone required by claims 8
and 21.
Finally, claims 8 and 21 require that the dosage form provides a Cmax
“at least about 50% higher when the dosage form is administered to [a]
subject under fed versus fasted conditions.” Appellants argue that this
limitation is not inherent in Maloney’s dosage form (Appeal Br. 12).
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However, the Specification discloses that even an immediate release
oxymorphone solution provides a Cmax that is 50% higher when it is
administered to a subject under fed versus fasted conditions (FF 16). Since
the food effect recited in claims 8 and 21 occurs with both immediate-
release and controlled-release dosage forms of oxymorphone, it is
reasonable to conclude that it is due to the oxymorphone itself, rather than
the particular dosage form. Therefore, it is reasonable to expect that the
controlled-release oxymorphone formulation made obvious by Maloney
would show the same food effect.
In summary, Maloney would have made obvious to a person of
ordinary skill in the art methods of treating pain with a controlled-release
dosage form of oxymorphone that reasonably appear to meet all the
limitations of claims 8 and 21.
Appellants argue that it would not have been obvious to modify
Maloney’s composition to have the properties recited in claims 8 and 21
because persons skilled in the art would not know “what the appropriate
dissolution rates are in order to achieve the goal of developing a safe,
effective controlled release oxymorphone formulation with a 12 hour dosing
cycle” (Appeal Br. 12). Appellants argue that they have provided evidence
that oxymorphone is subject to an extensive first-pass effect and has a lower
bioavailability than oxycodone, and therefore Maloney’s disclosure of the
release rate of oxycodone-containing compositions would not have
suggested an appropriate release rate for oxymorphone-containing
compositions (id. at 13-14).
These arguments are not persuasive, because claims 8 and 21 do not
recite any specific dissolution rate; the claims only require that the dosage
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form has a release rate profile that provides plasma levels of oxymorphone
adequate to provide at least 12 hours of pain relief. As discussed above,
Maloney’s disclosure of a controlled release dosage form with 60-80%
dissolution after 12 hours reasonably appears to meet the limitations of
claims 8 and 21, and Appellants have not provided adequate evidence to
show that Maloney’s dosage form would not provide plasma levels of
oxymorphone adequate to provide 12-hour pain relief.
Appellants also argue that their position is supported by Ex parte
Affrime, 2008 WL 460213 (BPAI 2008) because in Affrime the “Board
reversed because the Examiner could not adequately show that
administration of the compound according to the prior art reference would
necessarily achieve the claimed PK profile” (Appeal Br. 17). Similarly,
Appellants argue that the facts of this appeal are like those of Abbott Labs. v.
Sandoz, Inc., 544 F.3d 1341 (Fed. Cir. 2008) (Appeal Br. 17-18).
These arguments are not persuasive because the claims on appeal
differ materially from the claims in Affrime or Abbott Labs. The claims in
Affrime required a particular pharmacokinetic profile, including specific
values for Cmax and Tmax. 2008 WL 460213 at *1. Claim 1 in Abbott Labs.
was directed to an extended release composition of an erythromycin
derivative that “induces statistically significantly lower mean fluctuation
index in the plasma than an immediate release composition of the
erythromycin derivative while maintaining bioavailability substantially
equivalent.” 544 F.3d at 1344. The principal opinion6 in Abbott Labs.

6 Judge Newman’s opinion was not joined in relevant part by either of the
other judges on the panel and therefore does not represent the view of the
court.
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concluded that the accused infringer had not shown that the prior art
disclosed compositions having the pharmacokinetic properties recited in the
claims because different erythromycin derivatives (e.g., azithromycin and
clarithromycin) had different chemical and biological properties and were
metabolized differently. Id. at 1352.
The facts of this case differ from those of Affrime and Abbott Labs. in
that instant claims 8 and 21 do not recite specific pharmacokinetic
parameters. The functional limitations of claims 8 and 21 require only a
dosage form that provides 12 hours of pain relief and 50% higher Cmax in fed
versus fasted subjects, and Maloney provides a reasonable basis on which to
conclude that the product suggested by the prior art meets these limitations.
Findings of Fact – Secondary Considerations
17. The Specification states that the “oxymorphone controlled release
oral solid dosage form of this invention can be made using any of several
different techniques for producing controlled release oral solid dosage forms
of opioid analgesics” (Spec. 10, ¶ 33).
18. The Specification states that, “[i]n one embodiment, a core
comprising oxymorphone or an oxymorphone salt is coated with a controlled
release film” (id. at 10, ¶ 34).
19. The Specification states that, “[i]n a second embodiment, the
oxymorphone or oxymorphone salt is dispersed in a controlled release
delivery system that comprises a hydrophilic material which upon exposure
to gastrointestinal fluid forms a gel matrix” (id.).
20. The Specification states that a “third embodiment is a
combination of the first two: a controlled release matrix coated with a
controlled release film” (id.).
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21. The Specification states that “[i]n a fourth embodiment the
oxymorphone is incorporated into an osmotic pump” (id.)
22. All of the compositions exemplified in the Specification use a
controlled release delivery system (“Formulation 1”) made from locust bean
gum, xanthan gum, dextrose, calcium sulfate dihydrate, ethylcellulose, and
alcohol (id. at 17, ¶ 57; see also 18, ¶¶ 58, 59 (describing tablets prepared
using Formulation 1)).
23. Appellants have provided evidence that the “commercial Opana
ER® 20 mg product . . . is very similar to the formulation of Example 4 of
the [instant] Application” (Declaration under 37 C.F.R. § 1.132 of Sou-Chan
Chang dated May 21, 2008, ¶ 12). Example 4 is of tablet prepared with the
Formulation 1 controlled release delivery system (Spec. 18, ¶ 59).
24. The Specification discloses a study in which fasted subjects were
given either an immediate release oxymorphone solution or a controlled
release oxymorphone composition (including the Formulation 1 controlled
release delivery system) (Spec. 22, ¶ 71).
25. The Specification discloses that the “immediate release liquid . . .
shows a classical curve, with a high and relatively narrow peak, followed by
an exponential drop in plasma concentration. However, the controlled
release oxymorphone tablets exhibit triple peaks in blood plasma
concentration.” (Id. at 23, ¶ 73.)
26. The Specification discloses a study in which fed subjects were
given either an immediate release oxymorphone solution or a controlled
release oxymorphone composition (including the Formulation 1 controlled
release delivery system) (id. at 25, ¶ 79).
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27. The Specification discloses that, “[a]s with Study 1, the
immediate release liquid . . . shows a classical curve, with a high and
relatively narrow peak, followed by an exponential drop in plasma
concentration, while the controlled release oxymorphone tablets exhibit
triple peaks in blood plasma concentration” (id. at 26, ¶ 81).
28. Appellants have provided a declaration under 37 C.F.R. § 1.132 of
David C. Yeomans (dated May 6, 2008).
29. Dr. Yeomans declares that he examined “a number of clinical
studies performed by Endo, in which its Opana® ER is orally administered to
healthy volunteers and the resultant pK [pharmacokinetics] of oxymorphone
is tracked” (Yeomans Declaration, ¶ 16).
30. Dr. Yeomans declares that “[i]n almost every case, the curves for
the extended release formulations showed a second peak and, frequently, a
third peak in concentration, resulting from the administration of a single
dose of extend[ed] release oxymorphone” (id.).
31. Dr. Yeomans declares that “this feature illustrates that
oxymorphone enters a patient’s bloodstream in a biphasic or triphasic
manner” (id. at ¶ 17).
32. Dr. Yeomans states:
In my opinion, this will likely have an ameliorating effect on
the problem of analgesic tolerance. As an expert in the field of
pain management with narcotic analgesics particularly strong
opioids, I expect that extended release formulations of
oxymorphone will display more reliable analgesia while
minimizing the need to increase the dose or decrease the dosing
interval because of this multiphasic effect.
(Id.)
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33. Dr. Yeomans declares that he “did not observe this second peak
behavior to a pharmacologically significant degree, nor did [he] ever observe
a third peak in the literature” he reviewed pertaining to pK behavior of
extended release morphine, hydromorphone, or oxycodone (id. at ¶ 19).
34. Dr. Yeomans concludes that the two- or three-peak pK curve of
extended release oxymorphone is “a surprising and unexpected feature . . .
highly likely to have a beneficial impact on the pharmacological effect of the
formulations” (id. at ¶ 20).
35. Appellants have provided a declaration under 37 C.F.R. § 1.132 of
Nancy Wysenski (dated May 28, 2008).
36. Ms. Wysenski declares that “Opana® ER . . . has displayed
unqualified commercial success” (Wysenski Declaration, ¶ 11), as shown by
“dramatic growth in the number of prescriptions written” (id. at ¶ 13), the
amount of revenues generated (id. at ¶ 16), and its acceptance in the market
(id. at ¶¶ 18-25).
Principles of Law – Secondary Considerations
“If a prima facie case is made in the first instance, and if the applicant
comes forward with reasonable rebuttal, whether buttressed by experiment,
prior art references, or argument, the entire merits of the matter are to be
reweighed.” In re Hedges, 783 F.2d 1038, 1039 (Fed. Cir. 1986).
“The evidence presented to rebut a prima facie case of obviousness
must be commensurate in scope with the claims to which it pertains.” In re
Dill, 604 F.2d 1356, 1361 (CCPA 1979).
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Analysis – Secondary Considerations
The Specification provides evidence that administering compositions
of oxymorphone that include the Formulation 1 controlled release delivery
system results in triple peaks in plasma oxymorphone concentration, while
immediate release oxymorphone solution “shows a classical curve, with a
high and relatively narrow peak, followed by an exponential drop in plasma
concentration” (FFs 24-27).
Dr. Yeomans provides evidence that the double- or triple-peak
pharmacokinetics seen in clinical studies of Opana® ER was unexpected in
view of the properties of other extended release opioids (FFs 29-33) and is
“highly likely to have a beneficial impact on the pharmacological effect” of
Opana® ER (FF 34). Ms. Wysenski provides evidence that Opana® ER has
enjoyed commercial success and acceptance in the market since its
introduction (FF 36).
We will assume that the evidence shown in the Specification and in
the Yeomans and Wysenski Declarations establishes that the controlled
release formulations addressed therein have unexpectedly superior properties
and commercial success that would overcome a prima facie conclusion of
obviousness with respect to those formulations. The issue, then, is whether
the showing of secondary considerations is commensurate in scope with the
claims on appeal.
We conclude that it is not. Claims 8 and 21 encompass treating pain
using any oxymorphone dosage form that has the recited 12-hour
effectiveness and food effect. The Specification makes clear that such
compositions can comprise any of a variety of controlled-release delivery
systems (FFs 17-21). All of the compositions relied upon by Appellants,
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however, include the Specification’s controlled-release delivery system of
Formulation 1 (FF 22) or something “very similar” to it (FF 23).
The Specification provides evidence that the two- or three-peak
pharmacokinetic behavior of extended-release oxymorphone compositions is
not due to the oxymorphone itself, because an immediate-release
oxymorphone solution showed a “classical curve” rather than multiple peaks
(FFs 25, 27). Since both the immediate-release and controlled-release
formulations contained oxymorphone, the only reasonable conclusion to be
drawn is that the different pharmacokinetic behavior of the formulations is
due to differences in the other components of the formulations. That is, the
multiple peaks seen in the studies in the Specification and in the clinical
studies examined by Dr. Yeomans must have been due to the components of
the controlled-release delivery system in those formulations.
All of the Specification’s exemplified formulations include the same
controlled-release delivery system. Opana® ER uses a controlled-release
delivery system that is very similar to the one used in the Specification’s
examples. But the claims are not limited to that controlled-release delivery
system, or even controlled-release delivery systems that are similar to it.
The claims encompass, among other things, formulations using a controlled-
release film (FF 18), different controlled-release matrices (FF 19),
controlled-release matrices coated with a controlled-release film (FF 20), or
an osmotic pump (FF 21).
The evidence shows, at best, unexpectedly superior results for one
specific controlled-release matrix. The evidence does not show that
unexpectedly superior results result from using any of the other controlled-
release delivery systems encompassed by the claims that produce the
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12-hour effectiveness and food effect recited in claims 8 and 21. The
evidence of unexpected results therefore is not commensurate with the scope
of the claims on appeal.
In addition to their arguments based on the Yeomans and Wysenski
Declarations, Appellants also argue that unexpected results are shown in the
declaration under 37 C.F.R. § 1.132 of William Fiske (Appeal Br. 19).
Specifically, Appellants argue that, as discussed in the Fiske Declaration,
“one of skill in the art would have expected that decreasing the release rate
of oxymorphone would have caused an increase in the first-pass effect of
oxymorphone, thus preventing achievement of a sustainable systemic
therapeutic concentration” but Appellants found that “a sustainable systemic
therapeutic concentration was achieved” (id.).
This argument is also unpersuasive. Maloney expressly contemplates
controlled-release formulations of oxymorphone (FFs 1-2). Prior art
references are presumed to be enabled for what they disclose, and the burden
is on Appellants to show that they are not. Amgen, Inc. v. Hoechst Marion
Roussel, Inc., 314 F.3d 1313, 1355 (Fed. Cir. 2003). Appellants have not
provided sufficient evidence to show that the prior art disclosures would not
have led skilled workers to expect that they could make an effective
controlled-release formulation of oxymorphone without undue
experimentation.
With respect to claim 21, Appellants argue that “the Examiner did not
indicate where in the prior art the limitation of the ‘cationic cross-linking
agent’ appears . . . . This alone is sufficient to overturn the Examiner’s
rejection of claim 21.” (Appeal Br. 24.) In response to this argument, the
Examiner pointed to Baichwal’s disclosure of cross-linking agents (Ans. 20-
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21), but Appellants argue that Baichwal’s cross-linking agents “are not
cationic crosslinking agents” (Reply Br. 5). Regardless of whether Baichwal
discloses cationic cross-linking agents, however, Maloney discloses that
calcium sulfate is a conventional pharmaceutical excipient (FF 7) and the
instant Specification describes calcium sulfate as a cationic cross-linking
agent (FF 8); therefore, a person of ordinary skill in the art would have
considered it obvious to include calcium sulfate (a cationic cross-linking
agent) in Maloney’s controlled-release formulation.
Conclusions of Law
Appellants have not shown that the Examiner erred in concluding that
Maloney’s disclosure would have made obvious a controlled-release
oxymorphone composition meeting the limitations of claims 8 and 21. And
Appellants have not presented evidence of secondary considerations that
outweighs the evidence in favor of obviousness.
SUMMARY
We affirm the rejections under 35 U.S.C. § 103(a) of claims 8-15 and
18-20 based on Maloney, by itself or combined with Calanchi, and of claims
21-27 based on Maloney, Calanchi, Baichwal, and Oshlack. Because
Appellants did not argue it separately, we also affirm the rejection of claims
16 and 17 under 35 U.S.C. § 103(a) based on Maloney, by itself or
combined with Calanchi, and further in view of Baichwal.
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).

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AFFIRMED

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