In Re Huai-Hung Kao

United States Court of Appeals
for the Federal Circuit
__________________________

IN RE HUAI-HUNG KAO, ANAND R. BAICHWAL,
TROY MCCALL, AND DAVID LEE
__________________________

2010-1307
__________________________

Appeal from the United States Patent and Trademark
Office, Board of Patent Appeals and Interferences in
application Serial No. 11/680,432.
__________________________

IN RE HUAI-HUNG KAO, ANAND R. BAICHWAL,
TROY MCCALL, AND DAVID LEE
__________________________

2010-1308
__________________________

Appeal from the United States Patent and Trademark
Office, Board of Patent Appeals and Interferences in
application Serial No. 12/167,859.
__________________________

IN RE HARRY AHDIEH
__________________________

2010-1309
__________________________
2 IN RE KAO, IN RE KAO, IN RE AHDIEH

Appeal from the United States Patent and Trademark
Office, Board of Patent Appeals and Interferences in
application Serial No. 11/766,740.
__________________________

Decided: May 13, 2011
__________________________

JEFFREY I. D. LEWIS, Patterson, Belknap Webb & Ty-
ler, LLP, of New York, New York, argued for appellants.
With him on the briefs were MELISSA MANDRGOC, and
CATHERINE A. WILLIAMS; and GUY DONATIELLO, Endo
Pharmaceuticals, Inc., of Chadds Ford, Pennsylvania; and
JOSEPH MAHONEY, Mayer Brown LLP, of Chicago, Illinois.

FRANCES M. LYNCH, Associate Solicitor, Office of the
Solicitors, United States Patent and Trademark Office, of
Alexandria, Virginia, argued for appellee in both 2010-
1307 and 2010-1308. BENJAMIN D.M. WOOD, Associate
Solicitor, argued for appellee in 2010-1309. With them on
the briefs was RAYMOND T. CHEN, Solicitor.
__________________________

Before RADER, Chief Judge, LINN and MOORE, Circuit
Judges.
LINN, Circuit Judge.

Endo Pharmaceuticals, Inc. (“Endo”) is the assignee of
three patent applications related to controlled-release
tablets containing the opioid narcotic oxymorphone. The
Board of Patent Appeals and Interferences (“the Board”),
in separate appeals, affirmed the rejection of the claims of
each application as obvious, and Endo has separately
appealed each decision to this court.

The Board affirmed the rejection of all pending claims
of United States Patent Application No. 11/680,432 (“the
’432 Application”), United States Patent Application No.
IN RE KAO, IN RE KAO, IN RE AHDIEH 3
12/167,859 (“the ’859 Application”), and United States
Patent Application No. 11/766,740 (“the ’740 Application”)
principally over a prior art international patent applica-
tion that is involved in each appeal. Endo timely ap-
pealed each decision of the Board, and this court has
jurisdiction under 28 U.S.C. § 1295(a)(4)(A).

Because the Board based its conclusion of obviousness
regarding the ’432 Application on factual findings lacking
in substantial evidence, this court vacates and remands.
Because the Board’s conclusions regarding the obvious-
ness of the ’859 and ’740 Applications were supported by
substantial evidence, this court affirms the Board’s deci-
sions regarding those two applications.

BACKGROUND

I. The ’432 Application

The claimed invention of the ’432 Application relates
to drug formulations containing opioids, a type of narcotic
frequently used to manage chronic pain. To provide
consistent pain relief, a minimum level of the opioid must
be maintained in the blood. Opioids, however, are typi-
cally available in immediate release formulations that
quickly release the entire dose of the opioid into the body.
Moreover, some opioids are rapidly metabolized by the
liver (a phenomenon known as the “first-pass effect”)
resulting in the drug having a low “bioavailability.” When
a drug has low bioavailability this means that only a
small amount of the drug is systemically available
throughout the body. Because of these drawbacks, imme-
diate release opioid formulations must be administered
frequently (e.g., every 4-6 hours) to maintain continuous
pain relief. But frequent administration of opioids can
result in a variety of side effects, ranging from disturbed
sleep to altered mental states.
4 IN RE KAO, IN RE KAO, IN RE AHDIEH

To overcome the difficulties associated with immedi-
ate release formulations, the ’432 Application discloses
controlled release formulations containing the opioid
oxymorphone, and capable of relieving pain for between
twelve and twenty-four hours.

Independent claims 1 and 20, as well as dependent
claims 2-3 and 5-19, are pending in the ’432 Application.
Because the ’432 Application was filed under the Acceler-
ated Examination Program of the United States Patent
and Trademark Office (“the Office”), Endo was limited to
arguing the patentability of independent claims 1 and 20.
Claim 1 reads as follows (relevant terms emphasized):

1. An analgesically effective controlled release
pharmaceutical composition with a twelve hour
dosing interval in the form of a tablet, comprising
oxymorphone or a pharmaceutically acceptable
salt thereof as the sole active ingredient in the
tablet and a controlled release delivery system
comprising at least one pharmaceutical excipient,
wherein upon placement of the composition in an
in vitro dissolution test comprising USP Paddle
Method at 50 rpm in 500 ml media having a pH of
1.2 to 6.8 at 37º C, about 15% to about 50%, by
weight, of the oxymorphone or salt thereof is re-
leased from the tablet at about 1 hour in the test.

Claim 20 is similar to claim 1 but recites that “about
45% to about 80%, by weight, of the oxymorphone or salt
thereof is released from the composition at about four
hours in the test, and at least about 80%, by weight, of the
oxymorphone or salt thereof is released from the composi-
tion at about 10 hours in the test.”

The examiner rejected claims 1 and 20 as obvious in
view of Patent Cooperation Treaty Publication No. WO
01/08661 to Maloney (“Maloney”), both alone and in
IN RE KAO, IN RE KAO, IN RE AHDIEH 5
combination with United States Patent No. 5,047,248 to
Calanchi et al. As is relevant here, the examiner found
that, with the exception of the claimed dissolution rate,
Maloney disclosed controlled release opioid formulations
that taught the recited limitations. The examiner stated
that the burden fell on Endo to show why Maloney failed
to satisfy the claimed dissolution rate because, in her
view, the controlled release system described by Maloney
satisfied the other limitations of the claims.

In response, Endo submitted declarations explaining
that because Maloney only disclosed a dissolution profile
for a controlled release formulation containing oxycodone,
an opioid with markedly different bioavailability than
oxymorphone, it provided little guidance on the appropri-
ate design of a controlled release oxymorphone formula-
tion. The declarations further explained that controlled
release oxymorphone formulations exhibit an unexpected
result: Over time the formulations cause multiple peaks
in oxymorphone blood concentration, which help prevent
patients from building a tolerance to the opioid. Endo
also included evidence that Opana® ER, a commercial
embodiment of the invention, had experienced significant
commercial success. The examiner concluded that the
declarations were insufficient to show that Maloney did
not suggest the claimed range of dissolution profiles. The
examiner also found that the evidence of unexpected
results and commercial success offered by Endo was not
commensurate with the scope of the claims, because that
evidence largely related to Opana® ER and the claims
encompassed a large number of other formulations, for
which no secondary considerations were shown.

On appeal, the Board affirmed the examiner’s rejec-
tion, relying exclusively on Maloney and in particular on
the controlled release formulation denominated “Formula
6.” The Board recognized that Maloney disclosed that
Formula 6 contains oxycodone instead of oxymorphone as
6 IN RE KAO, IN RE KAO, IN RE AHDIEH

recited in the claims. The Board also recognized that
Maloney disclosed dissolution data for Formula 6 meas-
ured by the USP Basket Method, not the claimed USP
Paddle Method. Nevertheless, the Board concluded that
Formula 6 rendered the claims obvious. The Board
determined that it would have been obvious to one of skill
in the art to replace the oxycodone in Formula 6 with
oxymorphone because Maloney generally identifies oxy-
morphone as a preferred opioid for use in his invention.
Regarding the claimed dissolution rate, the Board found
that a declaration submitted by Endo in response to the
first office action suggested that the dissolution rate as
measured by the Basket Method was 1.3 times faster than
the rate as measured by the Paddle Method. Applying
this correlation to the dissolution data for the Formula 6
oxycodone disclosed in Maloney, the Board found that
Formula 6 satisfied the claimed dissolution profile. The
Board then appeared to reason that if one were to substi-
tute oxymorphone for oxycodone in Maloney’s Formula 6,
the result would be an oxymorphone controlled release
pill with a dissolution profile within the range of pending
claim 1.

The Board then turned to the evidence of secondary
considerations. It assumed that the evidence of commer-
cial success and unexpected results presented by Endo
was sufficient to overcome a prima facie case of obvious-
ness with respect to the commercial embodiment but, like
the examiner, concluded that the evidence was not com-
mensurate with the scope of the claims and, therefore,
failed to overcome the rejections.

II. The ’859 Application

The ’859 Application discloses a method of relieving
pain using oxymorphone in a controlled release delivery
IN RE KAO, IN RE KAO, IN RE AHDIEH 7
system to overcome the difficulties associated with imme-
diate release formulations of opioids.

Claims 8-27 are pending and on appeal. Because the
’859 Application was filed under the Accelerated Exami-
nation Program, Endo was limited to arguing the pat-
entability of the independent claims and only argued
independent claims 8 and 21 before the Board. Thus, the
claims of the ’859 Application stand or fall with independ-
ent claims 8 and 21.

Claim 8 of the ’859 Application is directed to a method
for treating pain by administering oxymorphone in a
controlled release formulation that (1) provides at least 12
hours of sustained pain relief and (2) results in a “Cmax”
(maximum concentration) at least about 50% higher when
administered to fed versus fasting patients. Claim 8
reads as follows (relevant terms emphasized):

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 con-
trolled release delivery system with a release rate
profile designed to provide an adequate blood
plasma level over at least 12 hours to provide sus-
tained pain relief over this same period, the sys-
tem comprising a filler and a hydrophilic material,
wherein oxymorphone is the sole active ingredi-
ent; 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.
8 IN RE KAO, IN RE KAO, IN RE AHDIEH

Claim 21 additionally requires, among other limita-
tions, that the controlled release formulation include a
hydrophobic material. Claim 21 reads as follows (relevant
terms emphasized):

21. A method for treating pain in a human sub-
ject in need of acute or chronic pain relief, com-
prising 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 con-
trolled release delivery system with a release rate
profile designed to provide an adequate blood
plasma level over at least 12 hours to provide sus-
tained pain relief over this same period, the sys-
tem 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 ingredi-
ent; 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.

The examiner rejected claims 8 and 21 as obvious in
view of, among other references, Maloney. The examiner
found that Maloney “teaches oral sustained release
preparations of opioid analgesics” with the use of oxymor-
phone as a preferred opioid.
IN RE KAO, IN RE KAO, IN RE AHDIEH 9
On appeal, the Board affirmed the examiner’s rejec-
tion, relying exclusively on Maloney. The Board found
that Maloney discloses a controlled release formulation
with an opioid in amounts of 5-100 mg and that oxymor-
phone is a preferred opioid. The Board found that Ma-
loney further teaches using calcium sulfate (a cross
linking agent), lactose (a filler), and hydrogenated vegeta-
ble oil (a hydrophobic material) in his formulation. Based
on these disclosures, the Board determined that it would
have been obvious to a person of ordinary skill in the art
to formulate the claimed oral dosage form and to adminis-
ter the form to the subject as claimed in the ’859 Applica-
tion.

The Board then turned to the evidence of secondary
considerations. Just as it did with the ’432 Application, it
assumed that the evidence of commercial success and
unexpected results presented by Endo was sufficient to
overcome a prima facie case of obviousness with respect to
the commercial embodiment but agreed with the exam-
iner that the evidence was not commensurate with the
scope of the claims and, therefore, failed to overcome the
rejections.

III. The ’740 Application

The ’740 Application was likewise filed under the Ac-
celerated Examination Program; so only the independent
claims 21, 25, and 30 are potentially at issue. For reasons
that will become clear below, we limit our discussion to
claim 21.

Independent claim 21 reads:

21. A method of providing extended pain relief to
patients in need thereof, comprising:
10 IN RE KAO, IN RE KAO, IN RE AHDIEH

providing information that the average bioavail-
ability of oxymorphone in an oral extended release
formulation designed to have a 12 hour dosing cy-
cle is increased by at least about 26% for subjects
with renal impairment compared to that for
healthy subjects, and

providing a therapeutically effective amount of
such an extended release oral dosage form of oxy-
morphone or its pharmaceutically acceptable salt
thereof.

’740 Application.

The Office rejected claim 21 as obvious over three dif-
ferent combinations. We need focus on only one: Maloney
in view of United States Patent Publication No.
2002/0032581 (“Reitberg”). The examiner found that
“Maloney teaches a controlled-release dosage form com-
prising oxymorphone,” that Reitberg teaches a clinical
evaluation kit for measuring the effectiveness of treat-
ment of a specific individual comprising a medication and
instructions, and that it would have been obvious to
combine the two. Ahdieh argued to the Board that it
would not have been obvious to a person of ordinary skill
to combine the two references because the correlation
between renal impairment and bioavailability of con-
trolled release oxymorphone was not previously known,
and because, in any case, evidence of commercial success
and unexpected results compel a determination of nonob-
viousness.

DISCUSSION

A claimed invention is unpatentable “if the differences
between the subject matter sought to be patented and the
prior art are such that the subject matter as a whole
would have been obvious at the time the invention was
IN RE KAO, IN RE KAO, IN RE AHDIEH 11
made to a person having ordinary skill in the art.” 35
U.S.C. § 103(a). Whether an invention is obvious is a
question of law based on underlying facts. In re Kotzab,
217 F.3d 1365, 1369 (Fed. Cir. 2000). This court reviews
the Board’s ultimate determination of obviousness de
novo and the Board’s fact findings for substantial evi-
dence. In re Gartside, 203 F.3d 1305, 1316 (Fed. Cir.
2000). “Substantial evidence is such relevant evidence as
a reasonable mind might accept as adequate to support a
conclusion.” In re Kumar, 418 F.3d 1361, 1366-67 (Fed.
Cir. 2005) (quotation omitted).

I. The ’432 Application

A. Obviousness

Endo contends that the examiner failed to present a
prima facie case of obviousness because there is no evi-
dence that substituting oxymorphone for oxycodone in
Maloney’s Formula 6 would result in a formulation that
satisfies the claimed dissolution profile. Endo claims that
the Board improperly relied on speculation and hindsight
to conclude otherwise.

The Office argues that the Board correctly concluded
that replacing oxycodone with oxymorphone in Formula 6
would result in the claimed invention. The Office asserts
that Maloney provides ample reason for one of skill in the
art to alter Formula 6 as suggested by the Board and
teaches that Formula 6 can relieve pain for twelve hours.
It claims that the Board reasonably concluded that there
is a correlation between the claimed dissolution test (the
USP Paddle Method) and the test disclosed by Maloney
(the USP Basket Method), and applying this correlation
demonstrates that Formula 6 has the claimed dissolution
profile.
12 IN RE KAO, IN RE KAO, IN RE AHDIEH

Before turning to the merits of Endo’s appeal, we first
consider the Office’s contention that only claim 1, and not
claim 20, is properly before us on appeal. The Office
contends that Endo did not present separate arguments
concerning claim 20 to the Board, and that claim 20
therefore stands or falls with claim 1. Endo responds by
pointing to various portions of the record where it con-
tends it separately argued the patentability of claim 20.

We agree with the Office that Endo waived the right
to have the Board separately consider claim 20. Under 37
C.F.R. § 41.37(c)(1)(vii), “the failure of appellant to sepa-
rately argue claims which appellant has grouped together
shall constitute a waiver of any argument that the Board
must consider the patentability of any grouped claim
separately.” The portions of the record cited by Endo
merely mention claim 20 and lack any type of separate,
substantive argument concerning the claim as required by
37 C.F.R. § 41.37(c)(1)(vii). See also In re McDaniel, 293
F.3d 1379, 1383 (Fed. Cir. 2002) (“[T]he Board is free to
select a single claim from each group of claims subject to a
common ground of rejection as representative of all claims
in that group and to decide the appeal of that rejection
based solely on the selected representative claim” in the
absence of a clear statement asserting separate pat-
entability of the claims.).

On the merits, this court agrees with Endo that the
Board relied on erroneous reasoning in making the fac-
tual determinations that underlie its conclusion that
claim 1 is obvious, and that its factual findings are there-
fore unsupported by substantial evidence. However,
because the evidence of record may yet satisfy the re-
quired substantial evidence standard, the Board’s deter-
mination will be vacated and remanded.

An examiner bears the initial burden of presenting a
prima facie case of obviousness. See In re Glaug, 283 F.3d
IN RE KAO, IN RE KAO, IN RE AHDIEH 13
1335, 1338 (Fed. Cir. 2002). Once the examiner estab-
lishes a prima facie case of obviousness, the burden shifts
to the applicant to rebut that case. “The prima facie case
is a procedural tool, and requires that the examiner
initially produce evidence sufficient to support a ruling of
obviousness; thereafter the burden shifts to the applicant
to come forward with evidence or argument in rebuttal.”
In re Kumar, 418 F.3d at 1366. However, once the appli-
cant has come forward with rebuttal evidence, the exam-
iner must consider the totality of the evidence to
determine whether the obviousness rejection should
stand. “When rebuttal evidence is provided, the prima
facie case dissolves, and the decision is made on the
entirety of the evidence.” Id.

The Board first observed that Maloney discloses spe-
cific controlled release formulations of oxycodone, that
Maloney states that oxymorphone can also be used in a
controlled release formulation, and that it is indeed a
preferred compound. Based on these observations, the
Board concluded that it would have been obvious to
substitute oxymorphone in Maloney’s Formula 6 (that
being one of the controlled release oxycodone formulations
disclosed in Maloney). The Board then observed that
while Maloney does not disclose the dissolution rate of
Formula 6 as measured by the Paddle Method, it does
disclose that rate as measured by the Basket Method. To
support that observation, the Board relied upon the
Second Chang declaration to find a correlation between
Paddle Method and Basket Method measurements for
Opana® ER after one hour of dissolution. Applying that
correlation to the Basket Method measurements of the
oxycodone Formula 6 disclosed in Maloney, the Board
concluded that oxycodone Formula 6 fell within the disso-
lution rate range of claim 1. On the basis of these factual
determinations, the Board concluded that “the product
made obvious by Maloney [i.e. Formula 6 with an oxy-
morphone substitute] would have a dissolution rate
14 IN RE KAO, IN RE KAO, IN RE AHDIEH

between 15% and 50% after one hour when measured by
the USP Paddle Method.”

Accepting that it would be obvious to substitute oxy-
morphone in Maloney’s Formula 6, the Board’s reasoning
nonetheless does not pass the substantial evidence
threshold as to whether such a substitution would indeed
fall within the dissolution profile of pending claim 1. As
an initial matter, it should be clear that it makes no
difference, a priori, to the question of obviousness whether
the hypothetical person of ordinary skill in the art would
have understood the claimed dissolution profile in terms
of a Paddle-Method or a Basket-Method test range, just as
it would make no difference whether the hypothetical
person of skill in the art preferred to think in English or
Metric units. The claimed subject matter is not presumed
to change as a function of how one elects to measure it.
The reason this “correlation” appears to matter on the
Board’s formulation of the present case is that there is a
lack of direct factual support in the record for the view
that the claimed range of dissolution rates actually over-
laps with the dissolution rate disclosed in Maloney, a
premise upon which the Board’s reasoning is founded.
Thus, while it matters not whether the hypothetical
skilled artisan would have appreciated the “correlation” at
issue here, it matters greatly whether anything the
skilled artisan would be prompted by the prior art to do is
in fact within the scope of the pending claim.

The declaration relied upon by the Board does not
provide substantial evidence for its finding of a correla-
tion between the Basket and Paddle Methods. The Board
relied on four data points from an exhibit correlating the
dissolution rates of Opana® ER, when tested by both
methods, and Maloney’s Formula 6, tested only by the
Basket Method, and concluded, without any reasoning,
that because the Basket Method dissolution in the first
hour for Opana® ER was 1.3 times faster than the disso-
IN RE KAO, IN RE KAO, IN RE AHDIEH 15
lution rate of the Paddle Method for Opana® ER, this
correlation would also hold for Maloney’s Formula 6.
Moreover, the declarant responsible for the exhibit ex-
pressly stated that there is no general correlation between
the Basket and Paddle Methods and cited prior art litera-
ture that supported this conclusion. The Board has not
provided any reason, apart from its own statement to the
contrary, to question this conclusion. The Board’s own
conjecture does not supply the requisite substantial
evidence to support the rejections, i.e., “such evidence as a
reasonable mind might accept as adequate to support a
conclusion.” Consol. Edison Co. v. Nat’l Labor Relations
Bd., 305 U.S. 197, 229 (1938). For these reasons, the
Board’s reliance on its own conjecture regarding whether
a direct substitution of oxymorphone in Formula 6 would
satisfy the claimed range of dissolution rates is improper.

While the Board did not base its factual conclusions
regarding the correlation of the two ranges on substantial
evidence, the importance, or lack thereof, of the claimed
range to the alleged nonobviousness of the invention is a
question we leave for the Board to consider on remand.
See, e.g., Ormco Corp. v. Align Technology, Inc., 463 F.3d
1299, 1311 (Fed. Cir. 2006) (explaining that overlap
between claimed range and prior art gives rise to a pre-
sumption of obviousness; where claimed range and prior
art value are insubstantially different, prima facie obvi-
ousness rejection is proper).

The Board’s decision is vacated and remanded so that
the Board can consider whether, under the proper analy-
sis, the evidence of record is sufficient to maintain an
obviousness rejection. As the Supreme Court has ex-
plained:

When there is. . . market pressure to solve a prob-
lem and there are a finite number of identified,
predictable solutions, a person of ordinary skill in
16 IN RE KAO, IN RE KAO, IN RE AHDIEH

the art has good reason to pursue the known op-
tions within his or her technical grasp. If this
leads to the anticipated success, it is likely the
product not of innovation but of ordinary skill and
common sense.

KSR Intern. Co. v. Teleflex Inc., 550 U.S. 398, 402-403
(2007). Thus, while the Board should neither rely upon
conclusory reasoning nor its own conjecture in assessing
the weight of evidence, the Board may, or may not, still
find that the evidence supports the examiner’s rejection.

B. Secondary Considerations

Endo argues that it submitted evidence of unexpected
results and commercial success sufficient to rebut a prima
facie showing of obviousness. The Office contends that
the Board correctly discounted the secondary considera-
tions evidence submitted by Endo because the evidence
was not commensurate with the scope of the claims. Endo
is correct that the Board erred by failing to give the
evidence of secondary considerations its due weight. But
there were nonetheless other defects in at least the pres-
entation of this evidence.

To start, when secondary considerations are present,
though they are not always dispositive, it is error not to
consider them. See Stratoflex v. Aeroquip Corp., 713 F.2d
1530, 1538 (Fed. Cir. 1983) (“[E]vidence rising out of the
so-called ‘secondary considerations’ must always when
present be considered en route to a determination of
obviousness.”); Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348,
1372 (Fed. Cir. 2007) (“Although secondary considerations
must be taken into account, they do not necessarily con-
trol the obviousness conclusion.”).

Evidence of secondary considerations must be rea-
sonably commensurate with the scope of the claims. See
IN RE KAO, IN RE KAO, IN RE AHDIEH 17
In re Tiffin, 448 F.2d 791, 792 (CCPA 1971); In re Hiniker,
150 F.3d 1362, 1369 (Fed. Cir. 1998). This does not mean
that an applicant is required to test every embodiment
within the scope of his or her claims. If an applicant
demonstrates that an embodiment has an unexpected
result and provides an adequate basis to support the
conclusion that other embodiments falling within the
claim will behave in the same manner, this will generally
establish that the evidence is commensurate with scope of
the claims. See In re Greenfield, 571 F.2d 1185, 1189
(CCPA 1978) (concluding that evidence of secondary
considerations was not commensurate with the scope of
the claims where that evidence related to a single com-
pound and there was no adequate basis to conclude that
other compounds included within the scope of the claims
would exhibit the same behavior); In re Cescon, 474 F.2d
1331, 1334 (CCPA 1973) (concluding that, although not
every compound within the scope of the claims was tested,
the evidence of secondary considerations was sufficient
where evidence showed a correlation and there was no
factual basis to expect the compounds to behave differ-
ently in different environments).

But there is a more fundamental requirement that
must be met before secondary considerations can carry
the day. “For objective evidence of secondary considera-
tions to be accorded substantial weight, its proponent
must establish a nexus between the evidence and the
merits of the claimed invention.” Wyers v. Master Lock
Co., 616 F.3d 1231, 1246 (Fed. Cir. 2010) (quotation
omitted). Where the offered secondary consideration
actually results from something other than what is both
claimed and novel in the claim, there is no nexus to the
merits of the claimed invention. Tokai Corp. v. Easton
Enters., Inc., 632 F.3d 1358, 1369 (Fed. Cir. 2011) (“If
commercial success is due to an element in the prior art,
no nexus exists.”); Ormco Corp., 463 F.3d at 1312 (“[I]f the
feature that creates the commercial success was known in
18 IN RE KAO, IN RE KAO, IN RE AHDIEH

the prior art, the success is not pertinent.”); In re Wood-
ruff, 919 F.2d 1575, 1578 (Fed. Cir. 1990) (“The law is
replete with cases in which the difference between the
claimed invention and the prior art is some range or other
variable within the claims . . . . [and] in such a situation,
the applicant must show that the particular range is
critical, generally by showing that the claimed range
achieves unexpected results relative to the prior art
range.” (citations omitted)).

1. Unexpected Results

The Board acknowledged applicant’s evidence that,
unlike immediate release formulations, ingesting a par-
ticular disclosed controlled-release formulation resulted in
unexpected multiple peaks in oxymorphone blood concen-
tration. Despite assuming that this evidence was suffi-
cient to overcome the prima facie case of obviousness for
that formulation, the Board disregarded this evidence
because, in its view, the evidence was not commensurate
with the scope of the claims.

The Board noted that the ’432 Application disclosed
that a particular controlled release formulation caused
unexpected multiple peaks in oxymorphone blood concen-
tration, while immediate release formulations did not. In
light of this, the Board concluded that this unexpected
property must be caused by some component of that
particular disclosed controlled-release formulation. This
is unsupported by the record. The only evidence of record
indicates that the unexpected in vivo characteristics of
oxymorphone controlled release compositions did not
result from properties unique to any specific commercial
embodiment. Endo supplied a declaration from one of its
experts stating that, after reviewing clinical studies and
scientific literature, it appeared that extended release
formulations of oxymorphone—not limited to formulations
IN RE KAO, IN RE KAO, IN RE AHDIEH 19
with any specific excipient—cause multiple peaks in
oxymorphone blood concentration. The Board did not
challenge this conclusion. Because the Board ignored the
evidence of record and relied instead upon its own conjec-
ture, its treatment of Endo’s argument regarding unex-
pected results was improper.

On remand, the Board, in considering the evidence of
unexpected results, should determine whether there is a
nexus between the unexpected in vivo concentration
profile and aspects of the claimed invention not already
present in the prior art. More specifically, for the unex-
pected in vivo concentration profile of the applicant’s
product to have substantial weight, there must be a nexus
to some aspect of the claim not already in the prior art,
such as the claimed range of dissolution rates, as against
other unclaimed prior-art dissolution rates.

2. Commercial Success

The Board also discounted Endo’s evidence of com-
mercial success of Opana® ER on the grounds that it was
not commensurate with the scope of the claims. But an
applicant “need not sell every conceivable embodiment of
the claims in order to rely upon evidence of commercial
success, so long as what was sold was within the scope of
the claims.” In re DBC, 545 F.3d 1373, 1384 (Fed. Cir.
2008). See also Applied Materials, Inc. v. Advanced
Semiconductor Materials Am. Inc., 98 F.3d 1563, 1570
(Fed. Cir. 1996) (“[A] patentee need not show that all
possible embodiments within the claims were successfully
commercialized in order to rely on the success in the
marketplace of the embodiment that was commercial-
ized.”). As this court recently explained, “[i]t seems
unlikely that a company would sell a product containing
multiple, redundant embodiments of the patented inven-
tion . . . . Under the [Office’s] logic, there would never be
20 IN RE KAO, IN RE KAO, IN RE AHDIEH

commercial success evidence for a claim that covers more
than one embodiment.” In re Glatt Air Techniques, Inc.,
630 F.3d. 1026, 1030 (Fed. Cir 2011). The Board’s refusal
to credit the applicant’s evidence of commercial success
because it was not proven across the entire claimed range
of dissolution rates was improper.

Nonetheless, the record is nearly silent on whether
the commercial success was caused by the merits of the
invention as distinct from the prior art. In short, if it is
not established that the claimed and novel range for a
controlled release oxymorphone formulation causes com-
mercial success where the prior art range would not, then
it will be difficult to show the required nexus. Applicants’
expert opined that the unexpected in vivo concentration
was likely responsible for the commercial success of the
embodying product. Applicants’ expert further opined
that the amelioration of analgesic tolerance to which
Applicants attribute commercial success “is precisely the
practical impact [he] would expect from the biphasic and
triphasic pK behavior” of the commercial embodiment.
But if the same behavior would be observed in any oxy-
morphone controlled release formulation, then there is no
necessary nexus between the commercial success and the
claimed formulation. On remand, the Board, in consider-
ing the commercial success argument, should make a
factual determination as to whether the commercial
success of the embodying product resulted from the merits
of the claimed invention as opposed to the prior art or
other extrinsic factors.

II. The ’859 Application

A. Obviousness

Endo advances three main arguments in challenging
the Board’s finding of obviousness. First, Endo argues
IN RE KAO, IN RE KAO, IN RE AHDIEH 21
that Maloney fails to disclose the claimed food effects.
Second, Endo argues that Maloney fails to disclose the 12-
hour effectiveness of the claimed controlled release formu-
lation of oxymorphone. Third, Endo argues that Maloney
fails to disclose the claimed combination that includes a
hydrophobic material. We address each argument in
turn.

1. Food Effects Limitation

Endo argues that Maloney does not expressly disclose
the “food effect” limitation: “wherein the oxymorphone
Cmax is at least about 50% higher when the dosage form
is administered to the subject under fed versus fasted
conditions.” Endo asserts that the Board erroneously
relied on the teaching in the specification of the ’859
Application that the claimed “food effect” was a property
of oxymorphone and that Maloney inherently disclosed
the limitation. Endo argues that an obviousness rejection
can only be based on what is known by those of skill in
the art at the time of the invention, and there is no evi-
dence in the record that anyone recognized the claimed
food effect at that time.

The Office responds that substantial evidence sup-
ports the Board’s finding of inherency. The Office further
responds that the Board’s reliance upon the specification
of the ’859 Application to support this conclusion is en-
tirely proper. Further, the Office responds that inherency
is indeed a part of the obviousness inquiry.

This court agrees with the Office. Substantial evi-
dence supports the Board’s finding, based upon the speci-
fication, which confirms that the claimed “food effect” is
an inherent property of oxymorphone itself, present both
in controlled release and immediate release formulations
of that drug. See In re Kubin, 561 F.3d 1351, 1357 (Fed.
22 IN RE KAO, IN RE KAO, IN RE AHDIEH

Cir. 2009) (stating “[e]ven if no prior art of record explic-
itly discusses the [limitation], [applicant’s] application
itself instructs that [the limitation] is not an additional
requirement imposed by the claims on the [claimed inven-
tion], but rather a property necessarily present in [the
claimed invention]”); see also King Pharmaceuticals, Inc.
v. Eon Labs, Inc., 616 F.3d 1267, 1275-76 (Fed. Cir. 2010)
(stating that “merely discovering and claiming a new
benefit of an old process cannot render the process again
patentable” (citations omitted)). This is not a case where
the Board relied on an unknown property of prior art for a
teaching. Rather, Maloney’s express teachings render the
claimed controlled release oxymorphone formulation
obvious, and the claimed “food effect” adds nothing of
patentable consequence.

2. 12-Hour Effectiveness Limitation

Endo argues that Maloney does not expressly disclose
the recited 12-hour effectiveness limitation. Endo asserts
that it provided evidence that one of skill in the art would
not have expected that oxymorphone could be substituted
for oxycodone because (1) oxymorphone has a much lower
bioavailability than oxycodone and (2) oxymorphone is
subject to the “first-pass effect.”

The Office responds that the Board found that Ma-
loney expressly teaches using oxymorphone in the dis-
closed formulations. Although Endo’s experts essentially
stated their view that Maloney did not enable the dis-
closed oxymorphone formulation, their statements were
based on various “concerns” that fall short of establishing
that the Maloney reference was non-enabling. See In re
Merck & Co., Inc., 800 F.2d 1091, 1097 (Fed. Cir. 1986)
(concluding that obviousness does not require absolute
predictability, only a reasonable expectation that the
beneficial result will be achieved).
IN RE KAO, IN RE KAO, IN RE AHDIEH 23
This court agrees with the Office. Substantial evi-
dence supports the Board’s finding. The Board found that
Maloney teaches a controlled release opioid formulation
comprising an opioid compound in amounts of 5-100 mg.
Maloney further discloses that oxymorphone is a pre-
ferred opioid compound. Finally, Maloney discloses that
its dosage form provides a dissolution rate of 60%-80%
active agent released after 12 hours. Based on these
findings, the Board reasonably concluded 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. Notwithstanding the “concerns” expressed by
Endo’s experts, Endo has failed to provide record evidence
showing that Maloney’s disclosure fails to provide a
reasonable expectation of obtaining the plasma levels of
oxymorphone suggested by Maloney and required by
claims 8 and 21. See Merck, 800 F.2d at 1097. Substan-
tial evidence supports the Board’s conclusion that the
oxymorphone formulation disclosed in Maloney would
satisfy the claimed 12-hour effectiveness limitation.

3. Hydrophobic Limitation

Endo argues that Maloney fails to teach a controlled
release formulation including both a hydrophilic and a
hydrophobic material. According to Endo, although
Maloney discloses an example using a hydrophobic lubri-
cant, the example describes this hydrophobic material as
“optional” and it is used as a lubricant, not as part of the
release formulation.

The Office responds that substantial evidence sup-
ports the Board’s finding that Maloney teaches the use of
hydrophilic polymers with lubricants, such as hydrogen-
ated vegetable oil, a hydrophobic material. Claim 21
simply requires the inclusion of a hydrophobic material,
irrespective of its function. That Kao’s alleged purpose for
incorporating a hydrophobic material into the claimed
24 IN RE KAO, IN RE KAO, IN RE AHDIEH

formulation differs from Maloney’s is irrelevant when
Kao’s alleged purpose is not a limitation of claim 21.

This court again agrees with the Office. Substantial
evidence supports the Board’s finding that Maloney
teaches a controlled release formulation using both hy-
drophobic and hydrophilic materials, as required by claim
21. Kao’s argument is wholly without merit because
Maloney expressly recites adding hydrogenated vegetable
oil to the formulation, which Kao’s own specification
states is a hydrophobic material.

B. Secondary Considerations

Endo argues that it presented sufficient evidence of
secondary considerations to overcome the Board’s finding
of obviousness. Endo’s evidence of secondary considera-
tions and the Board’s response are identical between each
of the three patent applications related to controlled-
release tablets containing the drug oxymorphone and are
addressed more fully above. Here, as with the ’432 Appli-
cation, the Board erred by failing to consider Endo’s
evidence of secondary considerations. Unlike the ’432
Application, however, the Board, in this appeal, presented
a strong showing of obviousness. Indeed, the only claim
element not expressly disclosed in the prior art was the
previously-unknown, yet inherent, food-effect property.
As stated above, merely discovering and claiming a new
benefit of an old process cannot render the process again
patentable. Endo’s evidence of secondary considerations
was insufficient to overcome this strong showing of pri-
mary considerations that rendered the claims at issue
invalid. See, e.g., Leapfrog Enters., Inc. v. Fisher-Price,
Inc., 485 F.3d 1157, 1162 (Fed. Cir. 2007).
IN RE KAO, IN RE KAO, IN RE AHDIEH 25

II. The ’740 Application

The Board determined that Ahdieh failed to sepa-
rately argue the patentability of claims 25 and 30 of the
’740 Application, and so it determined the patentability of
all claims based on claim 21. Ahdieh cites three state-
ments in his brief to the Board as showing a separate
patentability argument regarding claims 25 and 30.
Reply Br. of Ahdieh at 20 n.7. Far from showing distinct
arguments for each claim, these fragments show that
Ahdieh argued all the claims together. Because Ahdieh
failed to argue to the Office that claim 25 is separately
patentable, and fails to argue here that claim 30 is sepa-
rately patentable, the only relevant claim before this
court in this appeal is independent claim 21.

A. Obviousness

It is undisputed that Maloney discloses a method of
providing extended pain relief by the provision of a thera-
peutically effective amount of controlled release oxymor-
phone. Ahdieh’s asserted novel contribution is “providing
information” about a previously undiscovered correlation
between renal failure and bioavailability. Ahdieh argues
that the Board and the examiner erred in holding his
claim obvious because there was not substantial evidence
that the correlation was known in the prior art.

This court squarely rejected a similar argument in
King Pharmaceuticals. There, the claim at issue recited
“a method of increasing the oral bioavailability of metax-
alone” by “administering to the patient a therapeutically
effective amount of metaxalone in a pharmaceutical
composition with food,” and “informing” the patient that
taking metaxalone with food will increase the drug’s
bioavailability. King Pharms., 616 F.3d at 1270-71. This
court stated that the relevant question in determining
26 IN RE KAO, IN RE KAO, IN RE AHDIEH

whether the method claims were patentable was “whether
the additional instructional limitation of claim 21 has a
‘new and unobvious functional relationship’ with the
known method of administering metaxalone with food.”
Id. at 1279 (citing In re Ngai, 367 F.3d 1336, 1338 (Fed.
Cir. 2004)). We held that there was no functional rela-
tionship between the informing step and the administer-
ing step, because “[i]nforming a patient about the benefits
of a drug in no way transforms the process of taking the
drug with food,” and therefore the claim was invalid as
anticipated by the prior art. Id.

This case is not meaningfully distinct. Though the
correlation between the renal impairment and bioavail-
ability was not known, informing someone of the correla-
tion cannot confer patentability absent a functional
relationship between the informing and administering
steps. In re Ngai, 367 F.3d at 1338; see also General Elec.
Co. v. Jewel Incandescent Lamp Co., 326 U.S. 242, 249
(1945) (“It is not invention to perceive that the product
which others had discovered had qualities they failed to
detect.”). Just as in King Pharmaceuticals, the informing
step does not “transform[] the process of taking the drug.”
616 F.3d at 1279. This is because there is no requirement
in the claim that the dosage be adjusted in response to the
informing step. Indeed, because there is no indication of
who is to be informed or to whom the drug is to be admin-
istered, the claim would presumably cover a situation
where a doctor informs patient A of the correlation and
administers a therapeutically effective dose of controlled
release oxymorphone to patient B. Because there is no
functional relationship between the two steps in the
method, and because the administration of controlled
release oxymorphone is squarely present in the prior art,
Ahdieh’s claim must fail. We agree with our predecessor
court that to allow such a claim would effectively “remove
from the public that which is in the public domain by
virtue of its inclusion in, or obviousness from, the prior
IN RE KAO, IN RE KAO, IN RE AHDIEH 27
art.” In re Wiseman, 596 F.2d 1019, 1023 (CCPA 1979);
see also In re Ngai, 367 F.3d at 1339 (noting that allowing
claims where the printed matter was the only novel
contribution would allow “anyone [to] continue patenting
a product indefinitely provided that they add a new
instruction sheet to the product”).

Endo attempts to limit King Pharmaceuticals to the
anticipation context, and distinguish it because the “in-
forming” step was itself in the prior art, unlike the “pro-
viding information” step here. The King Pharmaceuticals
analysis is not so limited. Claim 5 of United States
Patent Number 6,683,102 was rejected as obvious in King
Pharmaceuticals, though it depended upon a claim that
was rejected for anticipation under the above reasoning.
616 F.3d at 1280-81. Moreover, it is simply not true that
the correlation in King Pharmaceuticals was itself known
in the prior art. See id. at 1278 (“Eon tacitly concedes
that the district court never expressly found the ‘inform-
ing’ limitation disclosed in the prior art.”).

Endo also argues that the “providing information”
step and the administration step are functionally related
because the step of “providing a therapeutically effective
amount” “of necessity, requires adjusting the dosage as
appropriate in accordance with the information provided
in the prior step in light of the patient’s renal condition.”
Br. of Appellant at 29. However, nothing in the claim
requires that the dosage be adjusted in response to the
providing of the information. Indeed, there is nothing in
the claim even referencing the actual condition of the
patient’s renal system, which would presumably be the
basis of any adjustment. Endo invites this court to import
from the specification into the claim the limitation that
the dosage be adjusted as a result of the informing step.
This court declines Endo’s invitation. The claim calls
merely for informing someone of the noted correlation,
and administering an effective dose of controlled release
28 IN RE KAO, IN RE KAO, IN RE AHDIEH

oxymorphone to someone. There is no functional relation-
ship between the two steps.

B. Secondary Considerations

Endo argues that the commercial success and unex-
pected results of Endo’s Opana® ER product overcome the
showing of obviousness. There is no dispute that Opana®
ER is an embodiment of the claimed invention.

The Board assumed that the secondary considerations
would be enough to overcome a prima facie case of obvi-
ousness but held that because Opana® ER was a single
embodiment of the broad claim, the secondary considera-
tions were not commensurate with the scope of the claim.

As discussed above, the Board’s application of so strict
a commensurateness requirement was improper. How-
ever, here, this error was harmless because there was no
nexus between the secondary considerations presented
and the claimed invention. See Tokai, 632 F.3d at 1369.

The only limitation not expressly recited in the prior
art of record is the informing step. Endo does not contend
that the evidence of unexpected results in the form of the
multiple peaks is at all related to the informing step of
the claim. Likewise, there is no indication that Opana®
ER’s commercial success is attributable to the informing
step, particularly because, as discussed above, the claim
does not require that the informing step have any appre-
ciable effect on the administration of the drug.

Because here Endo has not provided any evidence of
secondary considerations with a nexus to the novel com-
ponents of claim 21, the secondary considerations do not
compel a holding of nonobviousness.
IN RE KAO, IN RE KAO, IN RE AHDIEH 29

CONCLUSION

For the foregoing reasons, this court vacates the deci-
sion of the Board in Appeal No. 2010-1307 regarding the
’432 Application and remands for further proceedings
consistent with this opinion, and affirms the decisions of
the Board in Appeal No. 2010-1308 regarding the ’859
Application and in Appeal No. 2010-1309 regarding the
’740 Application.

VACATED AND REMANDED AS TO THE ’432
APPLICATION

AFFIRMED AS TO THE ’859 AND ’740
APPLICATIONS

COSTS

Each party shall bear its own costs.