Ex Parte Robinson et al

Board of Patent Appeals and Interferences

Sep 21, 2010

12020068 (B.P.A.I. Sep. 21, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
12/020,068 01/25/2008 Cynthia Y. Robinson 30481/30009A 1164
89229 7590 09/21/2010
Marshall, Gerstein & Borun LLP (Intermune)
233 South Wacker Drive
6300 Willis Tower
Chicago, IL 60606
EXAMINER
FINN, MEGHAN R
ART UNIT PAPER NUMBER
1614
MAIL DATE DELIVERY MODE
09/21/2010 PAPER
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte CYNTHIA Y. ROBINSON, JEFFERY S. LOUTIT,
and MICHELLE M. FREEMER
__________

Appeal 2010-007074
Application 12/020,068
Technology Center 1600
__________

Before CAROL A. SPIEGEL, TONI R. SCHEINER, and STEPHEN
WALSH, Administrative Patent Judges.

WALSH, Administrative Patent Judge.

DECISION ON APPEAL1
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
method of administering pirfenidone to a pulmonary fibrosis patient. The
Patent Examiner rejected the claims on the ground of obviousness. We have
jurisdiction under 35 U.S.C. § 6(b). We affirm.

1 The two-month time period for filing an appeal or commencing a civil
action, as recited in 37 C.F.R. § 1.304, or for filing a request for rehearing,
as recited in 37 C.F.R. § 41.52, begins to run from the “MAIL DATE”
(paper delivery mode) or the “NOTIFICATION DATE” (electronic delivery
mode) shown on the PTOL-90A cover letter attached to this decision.
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STATEMENT OF THE CASE
“The invention relates to methods for decreasing adverse events
associated with pirfenidone . . . therapy.” (Spec. 1:[0002].) According to
the Specification, “Phase II human investigations are ongoing or have
recently been completed for pulmonary fibrosis” (id. at 1:[0003]), and “[t]he
most common adverse reactions or events associated with pirfenidone
therapy include gastrointestinal upset, nausea, fatigue, somnolence,
dizziness, headache, and photosensitivity rash” (id. at 2:[0006]). The
invention is said to be “based on the unexpected finding that the
administration of pirfenidone at or around the time food is consumed
decreases the adverse events associated with the oral dosage form in
humans.” (Id. at 2:[0009].)
Claims 1, 3-5, 7, 11-13 and 21, which are all the pending claims, are
on appeal. A copy of the claims is provided in Appellants’ “Appendix A.”
(App. Br. 34-36.) Claim 1 is illustrative:
1. A method of administering pirfenidone to a human patient suffering
from idiopathic pulmonary fibrosis comprising

(a) orally administering to the patient (1) food and (2) a
pharmaceutical composition comprising pirfenidone, at a total daily
dose that is not a reduced dose, wherein said total daily dose is 2400
mg or 2403 mg pirfenidone,

wherein the ratio of the mean maximum plasma concentration of
pirfenidone when said pharmaceutical composition is administered to
a human subject under fed conditions (Cmax(fed)) to the mean maximum
plasma concentration of pirfenidone when said pharmaceutical
composition is administered to said human subject under fasted
conditions (Cmax(fasted)) is about 0.35 to about 0.7 and

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(b) advising the patient that taking pirfenidone with food, at a total
daily dose of 2400 or 2403 mg pirfenidone, reduces the incidence of
one or more of dizziness, somnolence, or headache.

The Examiner rejected claims 1, 3-5, 7, 11-13 and 21 under 35 U.S.C.
§ 103(a) as unpatentable over Raghu2 and Walker.3 Appellants argue claims
1, 3 and 21 separately.
OBVIOUSNESS
The Issue
The Examiner’s position is that Raghu taught administering
pirfenidone to human patients suffering from idiopathic pulmonary fibrosis,
and that Raghu disclosed reminding the patients to take the medication with
food and liquid. (Ans. 5.) The Examiner found that Raghu’s disclosed dose,
40 mg/kg/day or oral pirfenidone, would be a dose of 2400 mg for the
normal 60 kg patient, and that 60 kg was recognized as a normal patient
weight. According to the Examiner, Raghu explicitly taught informing
patients about anticipated side effects, including nausea, fatigue and
headache. The Examiner additionally found that Walker taught
administering 800 mg pirfenidone three times a day, i.e. a daily dose of
2400mg, and that Walker disclosed a nausea problem when the drug was
taken without food. (Id. at 5-6.) The Walker disclosure, according to the
Examiner, suggested to one of ordinary skill in the art that patients should be
advised to take the drug with food. The Examiner noted that Walker

2 Ganesh Raghu et al., Treatment of Idiopathic Pulmonary Fibrosis with a
New Antifibrotic Agent, Pirfenidone, 159 AM. J. RESPIR. CRIT. CARE MED.
1061-1069 (1999).
3 Jonathan E Walker et al., Pirfenidone for chronic progressive multiple
sclerosis, 7 MULTIPLE SCLEROSIS 305-312 (2001).
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administered the pirfenidone to treat multiple sclerosis, rather than
pulmonary fibrosis, but found “the value of Walker et al. is that dosages of
2400mg were tolerated and the advantage of taking with food was known.”
(Id. at 6.) The Examiner found that the Cmax level of the drug is the result
of administering the drug, and giving “the same dosage of pirfenidone to the
same patient under the same conditions (with food) would have the same
results.” (Id. at 6.) The Examiner found that the results recited in claims 3
and 21 were the same results that follow from Raghu’s therapy. (Id. at 6-7.)
Appellants contend that a prima facie case of obviousness was not
established “because Raghu is not properly combined with Walker, and
because the combination of references still fail[s] to show all elements of
claims 1, 3 and 21 in the prior art.” (App. Br. 14.) Appellants further argue
that the Examiner (1) “ignored the advising steps in determining
patentability;” (2) “failed to consider Appellants’ rebuttal evidence that the
art teaches away from the claimed methods;” and (3) failed to consider
Appellants’ evidence of unexpected results.” (Id.)
The issues are:
if the combination of references failed to show all elements of the
claims were in the prior art, were the claims properly rejected;
did the Examiner ignore or fail to accord the advising steps due
consideration;
did the art teach away from the claimed methods; and
did the Examiner fail to consider or fail to accord evidence of
unexpected results due consideration?

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Findings of Fact
We adopt the Examiner’s findings of fact.
Principles of Law
A rejection for obviousness must include “articulated reasoning with
some rational underpinning to support the legal conclusion.” KSR Int’l Co.
v. Teleflex Inc., 550 U.S. 398, 418 (2007), quoting In re Kahn, 441 F.3d 977,
988 (Fed. Cir. 2006).
Inherent properties of the prior art need not be disclosed by the prior
art for a process to be held obvious. In re Woodruff, 919 F.2d 1575, 1577-78
(Fed. Cir. 1990) (obviousness rejection affirmed where using claimed
elements in the manner suggested by the prior art necessarily resulted in
claim-recited effect). “Newly discovered results of known processes
directed to the same purpose are not patentable because such results are
inherent.” Bristol-Myers Squibb Co. v. Ben Venue Labs., 246 F.3d 1368,
1376 (2001). See also, In re Wiseman, 596 F.2d 1019, 1023 (CCPA 1979)
(rejecting the argument “that a structure suggested by the prior art, and,
hence, potentially in the possession of the public, is patentable to
[Applicants] because it also possesses an inherent, but hitherto unknown,
function which they claim to have discovered. This is not the law. A patent
on such a structure would remove from the public that which is in the public
domain by virtue of its inclusion in, or obviousness from, the prior art.”
(original emphasis)).
Two criteria have evolved for determining whether prior art is
analogous: (1) whether the art is from the same field of endeavor, regardless
of the problem addressed, and (2) if the reference is not within the field of
the inventor’s endeavor, whether the reference still is reasonably pertinent to
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the particular problem with which the inventor is involved. In re Clay,
966 F.2d 656, 658-9 (Fed. Cir. 1992). A prior art reference is said to teach
away from an Applicant’s invention “when a person of ordinary skill, upon
reading the reference, would be discouraged from following the path set out
in the reference, or would be led in a direction divergent from the path that
was taken by the applicant.” In re Gurley, 27 F.3d 551, 553 (Fed. Cir.
1994). “The prior art’s mere disclosure of more than one alternative does
not constitute a teaching away from any of these alternatives because such
disclosure does not criticize, discredit, or otherwise discourage the solution
claimed.” In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004).
Analysis
Claim 1
We find that the evidence supports the Examiner’s fact finding, and
that the Examiner’s reasoning meets the criteria for establishing a case of
obviousness.
The Specification tells us the invention is based on the unexpected
finding that administering pirfenidone around the time food is consumed
decreases the adverse events associated with the oral drug (see Spec. at
2:[0009]). However, the Examiner’s evidence belies the idea that the result
was “unexpected.” The problem of adverse side effects of pirfenidone and
its solution, i.e., the food effect that alleviated pirfenidone side effects, were
known to ordinarily skilled artisans before Appellants filed their patent
application. Raghu and Walker each disclosed the food effect put to
effective use for patients receiving pirfenidone. We find Appellants’
arguments that (i) the result was unexpected and (ii) the food effect was
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unpredictable are both unpersuasive because the Raghu and Walker evidence
disproves both arguments. (App. Br. 24-25.)
Appellants also argue that the pharmacokinetic behavior that
Appellants discovered “was quite unexpected.” (App. Br. 27.) According to
Appellants, “Nagai taught that one would expect no correlation between
plasma concentration and adverse events for pirfenidone therapy. (Id.)
Nagai4 disclosed that “plasma pirfenidone concentrations did not seem to
relate to the appearance of adverse effects or differences in therapeutic
effects.” (Nagai, Abstract.) However, the two steps in the claimed method
were suggested by Raghu and Walker, whether the inherent
pharmacokinetics were unexpected or not. See, e.g., Bristol-Myers Squibb,
246 F.3d at 1376; see also MEHL/Biophile Int’l Corp. v. Milgraum,
192 F.3d 1362, 1365 (Fed. Cir. 1999) (“Inherency is not necessarily
coterminous with knowledge of those of ordinary skill in the art. Artisans of
ordinary skill may not recognize the inherent characteristics or functioning
of the prior art.”).
As to Appellants’ argument that Raghu and Walker are not
combinable because Raghu treated idiopathic pulmonary fibrosis patients
and Walker treated multiple sclerosis patients (App. Br. 17), we disagree.
Both addressed the same problem: adverse side effects associated with
pirfenidone administration. They are therefore pertinent to each other and
meet the test for combination. See Clay, 966 F.2d at 658-9. Contrary to
Appellants’ view, we think that a person of ordinary skill in the art who

4 Sonoko Nagai et al., Open-label Compassionate Use One Year-treatment
with Pirfenidone to Patients with Chronic Pulmonary Fibrosis, 41 INTERN.
MED. 1118-1123 (2002).
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planned to administer pirfenidone would have looked to these publications
disclosing pirfenidone side effect problems and would have found their
common solution, to take the drug at meal time, instructive.
The fact that Raghu and Walker treated different patient populations
with pirfenidone and advised both populations to take the drug with food is
not a teaching away from Appellants’ method. (App. Br. 26.) Neither
reference would have led a person of ordinary skill in a direction divergent
from the path that was taken by the other or by Appellants, see Gurley,
27 F.3d at 553, nor did either criticize, discredit, or otherwise discourage the
solution claimed by the other or by Appellants, see Fulton, 391 F.3d 1201.
We also agree that the evidence supports the Examiner’s finding that
the claim 1, 3 and 21 recitations concerning Cmax are results that naturally
flow from Raghu’s administration of pirfenidone to fed and fasted
pulmonary fibrosis patients. (Ans. 6-7.) We reject Appellants’ arguments
that the Examiner ignored those properties or results. (App. Br. 27.) We
find the Examiner’s reasoning on this point sufficient to have shifted the
burden to Appellants to show that the Examiner was mistaken.
The Examiner found that Raghu explicitly taught advising patients to
take pirfenidone at meal times (Ans. 5), and that Walker’s disclosure
suggested the same precaution (id. at 5-6). Thus, there is no factual basis for
us to agree with Appellants’ allegation that the Examiner “ignored” the
advising step. (App. Br. 21.) That the later Azuma5 paper “makes no
mention of food” (id. at 23) does not contradict the Raghu or Walker

5 Arata Azuma et al., Double-blind, Placebo-controlled Trial of Pirfenidone
in Patients with Idiopathic Pulmonary Fibrosis, 171 AM. J. RESPIR. CRIT.
CARE MED. 1040-1047 (2005).
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disclosure; nor does it persuade us that a person of skill in the art would have
discounted the Raghu or Walker instructions.
We agree with the Examiner that it would have been obvious to advise
patients that taking pirfenidone with food would reduce known potential side
effects. We agree with the Examiner’s reasoning that talking with patients
about the particular side effects recited in the claims, including headache or
dizziness, is not a patentable distinction over Raghu or Walker’s instructions
to patients regarding side effects. (Ans. 7 and 9-10.) Appellants cite Nagai6
for the disclosure that “plasma pirfenidone concentrations did not seem to
relate to the appearance of adverse effects or differences in therapeutic
effects.” We find Nagai’s observation irrelevant to Raghu or Walker’s
instructions to patients. To the extent Appellants rely on Nagai as evidence
that a person of ordinary skill would have discounted Raghu or Walker’s
instructions to patients, we do not agree that Nagai weighs against the
obviousness of applying Raghu or Walker’s instructions.
We also give little weight to Appellants’ argument that “the existence
of a food effect for pirfenidone is not only unpredictable, but also fails to
render obvious how the skilled artisan would advise a patient regarding
pirfenidone administration, e.g. take with food, take on an empty stomach,
or take without regard to meals.” (App. Br. 25.) The predictability
argument contradicts the evidence that Raghu and Walker disclosed the food
effect. The food effect may have been unpredictable before Raghu’s 1999
paper, but it was no longer unpredictable at the time Appellants filed their

6 Sonoko Nagai et al., Open-label Compassionate Use One Year-treatment
with Pirfenidone to Patients with Chronic Pulmonary Fibrosis, 41 INTERN.
MED. 1118-1123 (2002).
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Application. We cannot agree that the level of skill in this art is so low that
a person of ordinary skill, aware that Raghu reminded patients to take the
drug with food to avoid side effects, would have missed the point that
pirfenidone should be taken with food to reduce side effects.
We therefore affirm the Examiner’s rejection of claim 1. Dependent
claims 4, 5 and 7 have not been argued separately and stand or fall with
claim 1. 37 C.F.R. § 41.37(c)(1)(vii).
Claim 3
Claim 3 differs from claim 1 at the wherein clause by adding:
. . . and the area under the curve of the absorption curve of
pirfenidone when administered under fed conditions (AUCfed) is
at least about 80% of the area under the curve of the absorption
curve of pirfenidone when administered under fasted conditions
(AUCfasted).

(App. Br. 34.)
We again agree with the Examiner that the additional wherein clause
states results that were inherently present in Raghu’s administration of
pirfenidone to fed and fasted pulmonary fibrosis patients. There is no
evidence that stating the result of a Cmax analysis differentiates the claimed
method from Raghu’s method.
Claim 21 Claim 21 reads:
A method of providing pirfenidone therapy to a human patient
suffering from idiopathic pulmonary fibrosis comprising

(a) orally administering pirfenidone with food, at a total daily dose
that is not a reduced dose, wherein said total daily dose is 2400 mg or
2403 mg pirfenidone, to reduce the incidence of dizziness;

(b) advising the patient that administering pirfenidone under fed
conditions results in reduced mean maximum plasma concentration of
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pirfenidone (Cmax) compared to fasted conditions, wherein the ratio of
(Cmax) under fed conditions divided by (Cmax) under fasted conditions
is about 0.35 to about 0.7; and

(c) advising the patient that taking pirfenidone with food reduces the
incidence of dizziness.

The Examiner’s findings concerning dosages are supported by the
evidence. The Examiner reasonably explained how a total daily does of
2400 mg would have been obvious. To the extent Appellants argue that both
of the alternative dosages 2400 mg and 2403 mg must be accounted for, we
disagree. In any event, we think that Appellants have not established error
in the Examiner’s view that 3 mg does not make a patentable distinction
between 2400 mg and 2403 mg. As with claims 1 and 3, there is no
evidence that stating the result of a Cmax analysis differentiates the claimed
method from Raghu’s method.
Dependent claims 11-13 have not been argued separately and stand or
fall with claim 21. 37 C.F.R. § 41.37(c)(1)(vii).
CONCLUSIONS
The evidence in Raghu and Walker established that all the elements of
the claimed methods were explicitly or inherently in the prior art.
The Examiner did not ignore or fail to accord the advising steps due
consideration.
Raghu and Walker did not teach away from the claimed methods.
The Examiner did not fail to consider the evidence Appellants
describe as showing unexpected results or unpredictability; instead, the
Examiner gave it due consideration.
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SUMMARY
We affirm the rejection of claims 1, 3-5, 7, 11-13 and 21 under
35 U.S.C. § 103(a) as unpatentable over Raghu and Walker.

No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).

AFFIRMED

lp

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