Najib Babul et al.

Patent Trials and Appeals Board

Sep 5, 2019

13229505 - (D) (P.T.A.B. Sep. 5, 2019)

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.
13/229,505 09/09/2011 Najib BABUL RELM-15US2C 9720
26875 7590 09/05/2019
WOOD, HERRON & EVANS, LLP
2700 CAREW TOWER
441 VINE STREET
CINCINNATI, OH 45202
EXAMINER
BARSKY, JARED
ART UNIT PAPER NUMBER
1628
NOTIFICATION DATE DELIVERY MODE
09/05/2019 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):
usptodock@whe-law.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
________________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
________________

Ex parte NAJIB BABUL and ASHISH KUMAR REHNI1
________________

Appeal 2018–001362
Application 13/229,505
Technology Center 1600
________________

Before RICHARD M. LEBOVITZ, ERICA A. FRANKLIN, and
JOHN G. NEW, Administrative Patent Judges.

NEW, Administrative Patent Judge.

DECISION ON APPEAL

1 Appellants identify Relmada Therapeutics, Inc., as the real party-in-
interest. App. Br. 1.
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SUMMARY
Appellants file this appeal under 35 U.S.C. § 134(a) from the
Examiner’s Final Rejection of claims 1, 19–21, 56–60, 70, 80, 81, 112, 116,
and 211. Specifically, claims 1, 20, and 70 stand rejected as unpatentable
under 35 U.S.C. § 102(b) as being anticipated by Oshlack et al. (US
2002/0010127 A1, January 24, 2002) (“Oshlack”).2
Claims 116 and 127 stand rejected as unpatentable under 35 U.S.C.
§ 103(a) as being obvious over Oshlack.
Claims 1, 19, 21, 56–60, 80, 81, and 112 stand rejected as
unpatentable under 35 U.S.C. § 103(a) as being obvious over Oshlack and
Butler et al. (US 2004/0132802 A1, July 8, 2004) (“Butler”).
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.

NATURE OF THE CLAIMED INVENTION
Appellants’ invention is directed to oral, therapeutically effective
pharmaceutical compositions of buprenorphine and its pharmaceutically
acceptable salts and the use thereof, including delayed onset and controlled
release dosage forms, delayed onset, rapid release dosage forms and delayed
onset, extended release dosage forms of oral buprenorphine. Abstract.

2 The Final Action lists the following claims as rejected: 1, 6, 7, 19–21, 55–
60, 70, 80, 81, 112, 116, 117, 127, and 211. Final Act. 2. Appellants state
that, inter alia, claims 6, 7, 55, 117, and 127 are canceled. See App. Br. 1.
We consequently address only those claims listed supra.
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REPRESENTATIVE CLAIM
Claim 1, the only surviving independent claim on appeal, is
representative of the claims on appeal and recites:
1. An oral dosage form for a human comprising: (i) a
therapeutically effective amount of buprenorphine, a pharmaceutically
acceptable salt thereof, or a mixture of these, and (ii) a controlled
release material, wherein the oral dosage form is formulated to provide
release of buprenorphine substantially only distal to the stomach
following oral administration.

App. Br. Claims App’x. 1.

ISSUES AND ANALYSES
We adopt the Examiner’s findings, reasoning, and that the rejected
claims are anticipated by, and/or obvious over the prior art cited by the
Examiner. We address the arguments raised by Appellants in the following
analyses.

A. Rejection of claims 1, 20, and 70 under 35 U.S.C. § 102(b)
Issue 1
Appellants argue that the Examiner erred by allegedly ignoring the
structural requirements that the claimed dosage form is an “oral dosage
form” and that the recited controlled release material (“CRM”) and
formulation of the claimed dosage form are selected to result in release of
buprenorphine “substantially only distal to the stomach following oral
administration.” App. Br. 7.

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Analysis
The Examiner finds that Oshlack discloses controlled release dosage
formulations and methods of using such formulations comprising opioid
agonists and opioid antagonists for administration to a human. Final Act. 6
(citing Oshlack ¶ 7). The Examiner finds that Oshlack discloses, in a
preferred embodiment, the bimodally-acting opioid agonist buprenorphine,
and opioid antagonists such as naltrexone and naloxone, as well as
pharmaceutically acceptable salts and mixtures thereof. Id. at 6–7 (citing
Oshlack ¶ 18).
The Examiner also finds that the formulations disclosed by Oshlack
can be in a controlled release oral dosage form, and that such formulations
are effective in providing analgesia for at least 8 hours when administered to
human patients. Final Act. 7 (citing Oshlack ¶ 104, Abstr.).
The Examiner finds that, with respect to the limitation reciting
“delayed onset,” Oshlack discloses that the term “controlled release dosage”
means a form which provides a longer period of pharmacological response
than is ordinarily provided after the administration of the rapid release
dosage forms. Final Act. 7 (citing Oshlack ¶ 23). The Examiner interprets
this to mean that, in a “delayed onset,” at least part of the composition is
delayed in taking effect. Id.
Appellants argue that claim 1 recites, and requires: (1) “An oral
dosage form;” (2) a combination of buprenorphine and a CRM; and (3) that
the buprenorphine/CRM combination is formulated to provide release of
buprenorphine substantially only distal to the stomach following oral
administration. App. Br. 8.
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With respect to limitation (1), Appellants point to their Specification
as expressly defining oral dosage forms as those which can be administered
“through the mouth for rapid deposit of the dosage form into the stomach or
alimentary canal.” App. Br. 9 (quoting Spec. ¶ 256). Appellants
acknowledge that the Specification discloses multiple structures (e.g., tablets
and capsules) which satisfy the “oral dosage form” limitation, but argue that
the limitation is nevertheless a structural one, and not, as the Examiner
suggests, merely “an intended route of administration that is undertaken if a
step were required of the claims.” Id. (citing Spec. ¶ 256; Advisory Act.,
filed February 1, 2017, at 2). Appellants further contend that, regardless of
whether it is administered orally, by another route, or not administered at all,
a dosage form is one that can be administered“through the mouth for rapid
deposit of the dosage form into the stomach or alimentary canal.” Id.
According to Appellants, this capacity depends on the structure of the
dosage form, and not how it is used or intended to be used. Id.
With respect to element (3) of claim 1, Appellants argue that their
Specification expressly discloses numerous formulations of buprenorphine
and a CRM that provide release of buprenorphine substantially only distal to
the stomach following oral administration. App. Br. 9 (citing, e.g., Spec. ¶¶
1032–1159). Appellants contend that, at the time the Final Action was
issued, the words of claim 1 requiring this third element recited that the
claimed dosage form “provid[es] delayed onset of [buprenorphine] release.”
Id. Appellants assert that the Examiner interpreted that element to be
satisfied so long as: “at least part of the composition is delayed in taking
effect,” and also found that element to be element satisfied by dosage forms
disclosed by Oshlack on the grounds that if an opioid agonist were
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formulated in at least some controlled release dosage forms disclosed, then
“a longer period of pharmacological response … than is ordinarily provided
after the administration of the rapid release dosage forms” could occur.
App. Br. 9–10 (quoting Final Act. 6–7).
Appellants assert, however, that the plain and ordinary meaning of
“onset” refers to the start or beginning of a phenomenon, and not to its
duration. Id. at 10. In the context of claim 1, argue Appellants, “delayed
onset of [BUP] release" plainly refers to the start or beginning of release of
buprenorphine from the claimed dosage form, not the duration of time for
which such release continues, nor (as the Examiner interpreted it) to the
duration of pharmacological effect following from such release. Id.
Appellants argue that, to clarify this distinction, they amended the claim
term “delayed onset of buprenorphine release” to “is formulated to provide
release of buprenorphine substantially only distal to the stomach following
oral administration.” Id. (citing Appellant Argument after Final Act., filed
January 23, 2017, at 6).
We are not persuaded by Appellants’ arguments. Claim 1 recites, in
relevant part, : “wherein the oral dosage form is formulated to provide
release of buprenorphine substantially only distal to the stomach following
oral administration.”
Oshlack is expressly directed to: “a controlled release oral dosage
form comprising opioid agonist and opioid antagonist, wherein the dosage
form releases the opioid agonist and the antagonist in a controlled-release
manner.” Oshlack ¶ 9. Oshlack also teaches that: “In certain preferred
embodiments, the opioid agonist is a bimodally-acting opioid agonist
selected from, e.g., morphine, codeine, fentanyl analogs, pentazocine,
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buprenorphine, methadone, enkephalins, dynorphins, endorphins, and
similarly acting opioid alkaloids and opioid peptides.” Oshlack ¶ 17
(emphasis added); see also, e.g., ¶¶ 34, 35, 37.
Oshlack further teaches that, in certain embodiments:
The dosage forms comprising an opioid agonist and opioid
antagonist may optionally be coated with one or more materials
suitable for the regulation of the opioid agonist release or for the
protection of the formulation. In one embodiment, coatings are
provided to permit either pH-dependent or pH-independent
release, e.g., when exposed to gastrointestinal fluid. A pH-
dependent coating serves to release the opioid in desired areas
of the gastrointestinal (GI) tract, e.g., the stomach or small
intestine, such that an absorption profile is provided which is
capable of providing at least about eight hours and preferably
about twelve hours to up to about twenty-four hours of analgesia
to a patient. When a pH-independent coating is desired, the
coating is designed to achieve optimal release of the opioid
regardless of pH-changes in the environmental fluid, e.g., the GI
tract. It is also possible to formulate compositions which release
a portion of the dose in one desired area of the GI tract, e.g., the
stomach, and release the remainder of the dose in another area of
the GI tract, e.g., the small intestine.

Oshlack ¶ 108 (emphases added). Oshlack thus expressly discloses an
embodiment of an oral dosage form in which the bimodally-active opioid, in
this case buprenorphine: “is formulated to provide release of buprenorphine
substantially only distal to the stomach following oral administration,”
because the small intestine is inarguably distal to the stomach. See App. Br.
6; see also Ans. 12. We do not, therefore, find Appellants’ arguments
persuasive.

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Issue 2
Pointing to the Advisory Action, Appellants argue that the Examiner
erred in finding that a suppository formulation of buprenorphine would be
expected to release buprenorphine “substantially only distal to the stomach.”
App. Br. 10 (citing Adv. Act. 3).

Analysis
Claim 1 reads: “substantially only distal to the stomach following oral
administration. App. Br. 10. Appellants contend that if buprenorphine were
combined with a CRM in a suppository formulation of the type disclosed in
Oshlack, buprenorphine would indeed be released within the colon if the
suppository were administered rectally. Id. at 10–11. Appellants point out,
however, that the fact that colonic release of buprenorphine would be
achieved following rectal administration of the suppository form does not
mean that colonic (or other post-gastric) release would be obtained if the
suppository formulation were administered orally. Id. at 11.
Appellants next argue that Oshlack does not disclose any suppository
formulation of buprenorphine. App. Br. 11. Appellants contend that, in the
Advisory Action, the Examiner points to a section of Oshlack at which
suppository formulations for rectal administration are generically described.
Id. Appellants contend that suppository formulations are simply one among
many type of controlled-release formulations disclosed in Oshlack. Id.
We are not persuaded. Regardless of whether or not Oshlack teaches
a formulation of buprenorphine and a CRM in suppository form, as we have
explained supra, Oshlack expressly discloses oral dosages of buprenorphine
and a CRM that is “formulated to provide release of buprenorphine
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substantially only distal to the stomach following oral administration.” See
Ans. 14; see also Reply Br. 3 and Oshlack ¶¶ 9 and 108. Appellants’
arguments concerning whether the suppository formulations disclosed by
Oshlack meet the requirements of the limitations claim 1 are consequently
irrelevant.

Issue 3
Appellants argue that the Examiner erred because Oshlack discloses
no information which alters the knowledge in the contemporaneous art that
buprenorphine was unsuitable for oral administration to humans. App. Br.
13.

Analysis
Appellants first point to the Declaration of Dr. Charles E. Inturrisi,
filed December 17, 2015 (the “Inturrisi Declaration”). App. Br. 12.
According to Appellants, Dr. Inturrisi states his opinion that, as a person
highly skilled in the art, buprenorphine was unsuitable for oral
administration to humans, as of the filing date of Appellants’ application.
Id. Appellants contend that the Inturrisi Declaration therefore establishes
that, as of Appellants’ filing date, a person of ordinary skill in the art would
have understood that buprenorphine could not be effectively administered to
humans in an oral dosage form. Id. at 13.
Appellants also criticize three references cited by the Examiner in the
Advisory Action, D. Volker at al., Oral Buprenorphine is Anti-Inflammatory
and Modulates the Pathogenesis of Streptococcal Cell Wall Polymer-
Induced Arthritis in the Lew/SSN Rat, 34 LAB. ANIMALS 423–29 (2000)
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(“Volker”), Bartholomaeus et al. (US 2002/0176888 A1, November 28,
2002) (“Bartholomaeus”), and Wright, IV et al. (US 2003/0044458 A1,
March 6, 2003) (“Wright”). App. Br. 13–14. According to Appellants, none
of these references–each of which teaches buprenorphine prophetically and
without data, with the exception of Volker’s data pertaining to rats, rather
than humans–would have provided a skilled artisan any reason to question,
doubt, or disbelieve what the Inturrisi Declaration allegedly established. Id.
at 14.
We are not persuaded. Dr. Inturrisi attests that:
As of March 9, 2009, buprenorphine was known by [persons of
ordinary skill in the art] to be inappropriate for administration by
the oral route (i.e., administration dosage forms such as capsules
and tablets through the mouth for rapid deposit into the stomach
or alimentary canal), even though buprenorphine was known by
[persons of ordinary skill in the art] to be appropriate for
administration by absorption through oral cavity surfaces (e.g.,
by the lingual, sub lingual, oro-mucosal, transmucosal, or buccal
routes)

and that: “As of March 9, 2009, I was unaware of any commercially-
available preparation of buprenorphine intended for administration to
humans by the oral route.” Inturrisi Decl. 9, 10. Dr. Inturrisi further opines
that:
The Oshlack Patent does not disclose that buprenorphine can be
effectively administered by the oral route. The Oshlack Patent
discloses no information that I believe would cause a [person of
ordinary skill in the art] to ignore (or even reconsider) the known
impracticality of administering buprenorphine by an oral route
prior to March 9, 2009.

Id. at 15.
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Although we accord Dr. Inturrisi’s expert opinion due weight, we find
that the evidence presented of whether a person of ordinary skill in the art at
the time of invention would have known that oral administration of
buprenorphine was not as efficient as other methods is not relevant to an
analysis of anticipation under Section 102. “[A]nticipation requires that the
four corners of a single, prior art document describe every element of the
claimed invention, either expressly or inherently, such that a person of
ordinary skill in the art could practice the invention without undue
experimentation.” Advanced Display Sys., Inc. v. Kent State Univ., 212
F.3d 1272, 1282 (Fed. Cir. 2000) (citing Atlas Powder Co. v. Ireco Inc., 190
F.3d 1342, 1347 (Fed. Cir. 1999); see also In re Paulsen, 30 F.3d 1475,
1479 (Fed. Cir. 1994)).
As we have explained, Appellants have failed to persuade us that the
Examiner erred in finding that Oshlack discloses all of the limitations recited
in the claims. Appellants have not also provided evidence that, following
Oshlack’s disclosure, the claimed oral dosage form could be made without
undue experimentation. We consequently affirm the Examiner’s rejection of
claims 1, 20, and 70 on this ground.

B. Rejection of claims 116 and 127 under 35 U.S.C. § 103(a)
Issue
Claim 116 is representative and recites:
116. The oral dosage form of claim 1, further comprising
naloxone, a pharmaceutically acceptable salt thereof, or a
mixture thereof, said dosage form having a mass ratio of
naloxone base relative to buprenorphine base which is at least
50% less than the mass ratio of naloxone base relative to
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buprenorphine base contained in the commercially marketed
sublingual preparation containing buprenorphine and naloxone.

App. Br., Claim App’x 3. Appellants argue that the Examiner erred:
“[b]ecause claim 1 is non-obvious over [Oshlack], claims 116 and 127 are
equally non-obvious.” App. Br. 16.
Analysis
Appellants contend that, in the anticipation rejection of claim 1 over
Oshlack, the Examiner contends that a person of ordinary skill in the art
would make an oral dosage form including buprenorphine because Oshlack
includes buprenorphine in a list of known opioid analgesics, and lists oral
dosage forms among a number of types of dosage forms which can be made.
App. Br. 16–17. Appellants argue, however, that the Inturrisi Declaration
establishes that a person of ordinary skill in the art would not consider
buprenorphine to be administrable to humans in an oral dosage form. Id. at
17. Appellants assert that the Examiner erred by ignoring the Inturrisi
Declaration and relying instead on the listing of buprenorphine in a list of
preferred opioids in Oshlack, as well as in the teachings of Volker,
Bartholomaeus, and Wright, that, Appellants allege, provide no teaching to
the contrary. Id.
As we have explained supra, the Inturrisi Declaration is not relevant
to our anticipation analysis under Section 102. However, in an obvious
analysis under Section 103, the knowledge and reasonable expectation of
success of a person of ordinary skill in the art is a relevant factor of our
analysis. See In re Keller, 642 F.2d 413, 425 (C.C.P.A. 1981) (holding that:
“[t]he test for obviousness…. is what the combined teachings of the
references would have suggested to those of ordinary skill in the art”). As
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we have noted, Oshlack is directed to: “a controlled release oral dosage form
comprising opioid agonist and opioid antagonist, wherein the dosage form
releases the opioid agonist and the antagonist in a controlled-release
manner,” and names buprenorphine as a preferred opioid in embodiments of
such oral dosages. See, e.g., Oshlack ¶¶ 9, 17, 34, 35, 37. However,
Oshlack does not provide any working examples of buprenorphine in such
an oral dosage form.
As we have related, Dr. Inturrisi opines that: “As of March 9, 2009, I
was unaware of any commercially-available preparation of buprenorphine
intended for administration to humans by the oral route,” and that:
“buprenorphine was known by [persons of ordinary skill in the art] to be
inappropriate for administration by the oral route (i.e., administration dosage
forms such as capsules and tablets through the mouth for rapid deposit into
the stomach or alimentary canal).” See Inturrisi Decl. ¶¶ 9–10.
In support of his opinion, Dr. Inturrisi points first to D.S. Walter and
C.E. Inturrisi, Absorption, Distribution, Metabolism, and Excretion of
Buprenorphine in Animals and Humans, In: BUPRENORPHINE: COMBATTING
DRUG ABUSE WITH A UNIQUE OPIOID, 113–25 (Cowan and Lewis, eds.)
(1995) (“Walter”). Inturrisi Decl. ¶ 11. Walter teaches that: “Although
these data suggest that ... it is possible to overcome a marked first-pass
metabolic effect by giving large oral doses of buprenorphine, this approach
was seen as commercially impractical, and an oral dosage form of
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buprenorphine was not developed.” See Inturrisi Decl. ¶ 12 (quoting Walter
127).
Dr. Inturrisi next points to J.W. Lewis et al., Buprenorphine –
Background to Its Development as a Treatment for Opiate
Dependence, In: BUPRENORPHINE: AN ALTERNATIVE TREATMENT FOR OPIOID
DEPENDENCE, 121 Natl. Inst. Drug Abuse Res. Monogr. 5–11 (J.D. Blaine,
ed.) (1992) (“Lewis”). See Inturrisi Decl. ¶ 13. According to Dr. Inturrisi,
Lewis teaches that: “orally administered buprenorphine was extensively
metabolized by the intestine and liver during its absorptions. The low oral
bioavailability makes this route of administration impractical and costly.”
Id. (quoting Lewis 7).
In rebuttal, the Examiner cites Volker, Bartholomaeus, and Wright.
Volker teaches that: “[u]se of oral administration of buprenorphine
injectable in ‘jello’ has been reported by Pekow (1992)” and that: “that oral
administration of buprenorphine is an effective method of pain management
in the pathogenesis of SCW-induced arthritis in Lew/SSN rats.” Volker 427,
Abstr.
Bartholomaeus is directed to: “a controlled-release oral dosage
formulation of a salt-forming active ingredient, wherein the active ingredient
is present as at least two different salts in a solid aggregation state, ….” See
Bartholomaeus Abstr. Bartholomaeus further teaches:
A controlled-release oral dosage formulation …, wherein the
analgesic is selected from the group consisting of brifentanil,
carfentanil, fentatienil, lofentanil, ocfentanil, trefentanil,
codeine, dextropropoxyphene, dihydrocodeine, diphenoxylate,
meptazinol, nalbuphine, pethidine, meperidine, tilidine,
tramadol, viminol, butorphanol, dextromoramide, dezocine,
diacetylmorphine, heroin, hydrocodone, hydromorphone,
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ketobemidone, levomethadone, levomethadyl, levorphanol,
morphine, nalorphine, oxycodone, pentazocine, piritramide,
alfentanil, buprenorphine, etorphine, fentanyl, remifentanil and
sufentanil.

Bartholomaeus claim 8 (emphasis added); see also ¶ 15.
Wright teaches: “an oral dosage form comprising a first composition
and a second composition. The first composition comprises an effective
amount of a therapeutic agent and the second composition comprises an
effective amount of an adverse-effect agent.” Wright Abstr. Specifically,
Wright teaches that:
In certain embodiments, the opioid agonist is selected from the
group consisting of hydrocodone, morphine, hydromorphone,
oxycodone, codeine, levorphanol, meperidine, methadone,
oxymorphone, buprenorphine, fentanyl and derivatives thereof,
dipipanone, heroin, tramadol, etorphine, dihydroetorphine,
butorphanol, levorphanol, pharmaceutically acceptable salts
thereof, and mixtures thereof. In one embodiment the opioid
agonist is oxycodone or hydrocodone.

Wright ¶ 37 (emphasis added); see also claim 20.
Balancing the evidence, we find that the Examiner has the better
position. Although the references cited by the Inturrisi Declaration teach
that oral administration of buprenorphine is less than optimal, and requires
larger dosages, they do not state that oral administration of buprenorphine is
inoperable or harmful. See Merck & Co., Inc. v. Biocraft Labs., Inc., 874
F.2d 804, 807 (Fed. Cir. 1989) (holding that: “‘all disclosures of the prior
art, including unpreferred embodiments, must be considered’” (quoting In re
Lamberti, 545 F.2d 747, 750 (CCPA 1976)). The claims do not require that
the claimed method be commercially viable, or even commercially practical.
Dr. Inturrisi acknowledges in his declaration that “these data suggest … it is
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possible to overcome a marked first-pass metabolic by giving large oral
dosages.” Inturrisi Decl. ¶ 12.
In addition to this, the claims require “the oral dosage form is
formulated to provide release of buprenorphine substantially only distal to
the stomach,” a limitation described by Oshlack. Dr. Inturrisi did not
address practicality of administering buprenorphine when release is so
limited. Specifically, Dr. Inturrisi did not disclose whether the oral
administration discussed in his declaration involved the same type of
formulation which is claimed and disclosed by Oshlack.
Additionally, and as we have explained supra, Oshlack expressly
anticipates claim 1, the sole independent claim on appeal. Volker,
Bartholomaeus, and Wright were all published more recently than the
references relied upon by the Inturrisi Declaration, and are all directed to
oral dosages of buprenorphine. Volker, in particular, expressly teaches the
administration of oral dosages of buprenorphine in rats as a model system
for modelling opioid analgesia.
We conclude that the balance of the evidence favors the Examiner’s
position that a person of ordinary skill in the art, at the time of Appellants’
invention, would have understood that buprenorphine can be administered in
an oral dosage formulated “to provide release of [buprenorphine]
substantially only distal to the stomach following oral administration.” See
In re Amer. Acad. Sci. Tech. Center, 367 F.3d 1359, 1370 (Fed. Cir. 2004)
(holding that: “[T]he Board is entitled to give such weight to declarations as
it deems appropriate”). We consequently affirm the Examiner’s rejection of
claims 116 and 127.

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C. Rejection of claims 1, 19, 21, 56–60, 80–81, and 112 under 35 U.S.C.
§ 103(a)

Issue
Appellants argue that the Examiner erred by failing to articulate any
rational reason for combining Oshlack and Butler in the manner recited in
the rejected claims. App. Br. 20.

Analysis
Appellants’ arguments address claim 1, stating that the remaining
claims stand or fall with that claim. App. Br. 20. Appellants assert that
there is no reason why a person of ordinary skill in the art would combine
buprenorphine (as taught by Oshlack) with an oral dosage form from Butler
that provides release of the active agent distal to the stomach, nor that such a
dosage form would be useful to orally administer buprenorphine to a human.
App. Br. 20–21.
Appellants repeat their arguments with respect to Oshlack provided
supra. App. Br. 23. Appellants acknowledge that Butler discloses a variety
of controlled release formulations for statin drugs, including oral dosage
forms, and that at least some of the formulations disclosed in Butler would
likely release a statin drug substantially only distal to the stomach following
oral administration. Id. However, Appellants argue, there is no teaching or
suggestion, either in Butler or in Oshlack to include buprenorphine (rather
than a statin) in any of Butler’s formulations, because, as the Inturrisi
Declaration avers, buprenorphine was understood in the art to be not
effectively administrable as an oral dosage. Id. Appellants contend that a
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skilled artisan, understanding the teachings of Oshlack, would have had no
reason to look to the formulations of Butler to overcome the alleged
ineffectiveness of oral administration of BUP. Id. Nor, Appellants argue
would there have been any reason for a person of ordinary skill to believe
that including buprenorphine in any of the formulations disclosed in Butler
would overcome that alleged problem. Id.
We are not persuaded by Appellants’ arguments. As we have
explained supra, Oshlack anticipates claim 1 and, consequently, claim 1 is
also obvious over Oshlack. See In re McDaniel, 293 F.3d 1379, 1385 (Fed.
Cir. 2002) (holding that “[i]t is well settled that anticipation is the epitome of
obviousness”). Furthermore, we have also explained why, after according
due weight to Appellants’ Inturrisi Declaration, we conclude that its
probative value is outweighed by the teachings of Oshlack and the rebuttal
references (Volker, Bartholomaeus, and Wright) cited by the Examiner.
We consequently affirm the Examiner’s rejections of the claims on
this ground.

DECISION.
The Examiner’s rejection of claims 1, 20, and 70 as unpatentable
under 35 U.S.C. 102(b) is affirmed.
The Examiner’s rejection of claims 1, 19, 21, 56–60, 80–81, 116, 112,
and 211 as unpatentable under 35 U.S.C. 103(a) 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)(1)(iv).

AFFIRMED