Ex Parte 6703403 et al

Patent Trials and Appeals Board

Nov 26, 2014

95000569 - (D) (P.T.A.B. Nov. 26, 2014)

UNITED STATES PATENT AND TRADEMARKOFFICE
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.
95/000,569 09/30/2010 6703403 2563
7590 11/26/2014
DR. STEVEN R. CROWLEY
ABBOTT LABORATORIES
DEPT. 377 AP6D-2
100 ABBOTT PARK ROAD
ABBOTT PARK, IL 60064-6050
EXAMINER
CAMPELL, BRUCE R
ART UNIT PAPER NUMBER
3991
MAIL DATE DELIVERY MODE
11/26/2014 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 PATENT TRIAL AND APPEAL BOARD
____________

PUBPAT
Requester and Respondent

v.

ABBVIE INC.
Patent Owner and Appellant
____________

Appeal 2014-007786
Reexamination Control 95/000,569
Patent 6,703,403 B2
Technology Center 3900
____________

Before JAMES T. MOORE, LORA M. GREEN, and RICHARD M. LEBOVITZ,
Administrative Patent Judges.

LEBOVITZ, Administrative Patent Judge.

DECISION ON APPEAL
This is a decision on the appeal by the Patent Owner from the Patent
Examiner’s decision to reject claims 1-8, 12-26, 30-44, 48-53, 57-71, and 75-89 in
the above-identified inter partes reexamination of US 6,703,403 B2. This is also a
decision on the cross-appeal by the Third Party Requester appealing the
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Examiner’s decision to not adopt the proposed rejection of claims 9-11, 27-29, 45-
47, 54-56, 72-74, and 90-92 and confirming their patentability.
The Board’s jurisdiction for this appeal is under 35 U.S.C. §§ 6(b), 134, and
315. We affirm.
I. BACKGROUND
The patent in dispute in this appeal is US 6,703,403 B2 (“the ’403 patent”),
which issued Mar. 9, 2004. The patent is subject to a terminal disclaimer over US
6,037,157 (“the ’157 patent”). The terminal disclaimer is filed in Serial No.
09/957,171, the application upon which the ’403 patent is based. The real party in
interest and assignee is listed as AbbVie, Inc. (“Patent Owner”). Patent Owner
(“PO”) Appeal Br. 4 (dated April 12, 2013). Assignment 029756/0593 (recorded
Feb. 5, 2013).
A request for inter partes reexamination of the ’403 patent under 35 U.S.C.
§§ 311-318 and 37 C.F.R. §§ 1.902-1.997 was filed August 25, 2010 (“Request”)
by the Public Patent Foundation (“PUBPAT”).
According to Patent Owner, there are related pending litigations in district
court involving the ’403 patent and related patents, and reexaminations involving
related patents. PO Appeal Br. 5-6.
The claimed subject matter of the ’403 patent relates to methods for
improving the pharmacokinetics of drugs which are metabolized by cytochrome
P450 monooxygenase. Cytochrome P450 monooxygenase is an enzyme which
metabolizes certain drugs leading to unfavorable pharmacokinetics and the need
for higher doses and more frequent doses when such drugs are administered to
humans. ’403 patent, col. 1, ll. 52-57. The ’403 patent states that it has been
discovered that the HIV protease inhibitor ritonavir “is an inhibitor of the
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metabolic enzyme cytochrome P450 monooxygenase.” Id. at col. 1, ll. 52-53. The
’403 patent teaches that administration of ritonavir with drugs metabolized by
cytochrome P450 monooxygenase “will improve the pharmacokinetics (i.e.,
increase half-life, increase the time to peak plasma concentration, increase blood
levels) of the drug.” Id. at col. 1, ll. 59-63. The ’403 patent discloses a list of
drugs which are metabolized by cytochrome P450 monooxygenase, which include
HIV protease inhibitors. Id. at col. 2, ll. 21-35 and ll. 54-56.
The ’403 patent teaches that ritonavir is (2S,3S,5S)-5-(N-(N-((N-Methyl-N-
((2-isopropyl-4-thiazolyl)methyl)amino)carbonyl)-L-valinyl)amino)-2-(N-((5-
thiazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-hydroxyhexane,which was
known prior to the ’403 patent. ’403 patent, col. 2, ll. 57-67.
.
II. CLAIMS
Claims 9-11, 27-29, 45-47, 54-56, 72-74 and 90-92 have been confirmed.
Claims 1-8, 12-26, 30-44, 48-53, 57-71, and 75-89 stand rejected by the
Examiner under 35 U.S.C. § 102(e) as anticipated by Kempf (U.S. Patent No.
5,866,036; issued Mar. 23, 1999)(“the ’036 patent”).
There are three broad classes of rejected claims.
The first class of rejected claims includes independent claims 1 and 2, which
are drawn to methods of inhibiting cytochrome P450 monooxygenase. Claim 1
includes the disputed “human in need thereof” limitation, but claim 2 does not.
The second class of rejected claims includes independent claims 3, 21, and
39 which are drawn to methods “for improving the pharmacokinetics of a drug
which is metabolized by cytochrome P450 monooxygenase.” Claims 21 and 39
include the phrase “human in need of” limitation, but claim 3 does not.
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The third class of rejected claims includes independent claims 48, 66, and 84
which are drawn to methods “for increasing the blood level of a drug which is
metabolized by cytochrome P450 monooxygenase.” Claims 66 and 84 include the
phrase “human in need of” limitation, but claim 48 does not.
Claim 21 is representative and reads as follows:
21. A method for improving the pharmacokinetics of a drug
which is metabolized by cytochrome P450 monooxygenase
comprising administering to a human in need of such treatment an
amount effective to inhibit cytochrome P450 monooxygenase of
ritonavir or a pharmaceutically acceptable salt thereof.

III. CLAIM INTERPRETATION
We begin with claim interpretation because, before a claim can be compared
to the prior art, it must be properly interpreted. During reexamination of an
unexpired patent, claim terms are given their broadest reasonable interpretation
consistent with the patent specification as they would be understood by one of
ordinary skill in the art. In re Suitco Surface, Inc., 603 F.3d 1255, 1259 (Fed. Cir.
2010); In re Abbott Diabetes Care Inc., 696 F.3d 1142 (Fed. Cir. 2012).
Patent Owner contends claim 21, when properly interpreted, requires the
claimed method to be practiced with the intent to achieve the claimed objective of
“improving the pharmacokinetics of a drug which is metabolized by cytochrome
P450 monooxygenase” in “a human in need of such treatment.” PO Appeal Br. 24.
Patent Owner bases this argument on Jansen v. Rexall Sundown, Inc., 342 F.3d
1329 (Fed. Cir. 2003).

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Jansen
Jansen was a patent infringement suit involving claims which recited a
“method of treating or preventing macrocytic-megaloblastic anemia in humans.”
Jansen, 343 F.3d at 1330. The patented claims comprised a step of administering
vitamin B12 and folic acid “to a human in need thereof.”
The original claims did “not specify the type of anemia being treated and
says nothing about any need on the part of the human subject.” Jansen, 343 F.3d
at 1330. The claims were found to be obvious by the PTO. Id. at 1331. Jansen
attempted to get the claims allowed, filing a series of seven applications. “In the
prosecution of his seventh application, Jansen . . . submitted an article that asserted
that the medical community had come to realize the effectiveness of [the claimed]
folic acid-vitamin B12 combination therapy to treat pernicious anemia only after
Jansen’s invention date.” Id. The Examiner agreed, but found that the claims were
still “directed to unspecified anemia” and “were not commensurate in scope with
Jansen’s showing of unexpected results.” Id. In response, Jansen narrowed his
method claims by limiting them to macrocytic-megaloblastic anemia and by
adding the phrase “to a human in need thereof.” Id.
Rexall was selling a combination of folic and vitamin B12, the same
combination as claimed by Jansen. Jansen, 343 F.3d at 1331. Rexall’s product
was labeled and advertised to treat anemia, but not for prevention or treatment of
macrocytic-megaloblastic anemia as in the Jansen claims. Id. Jansen sued Rexall
for inducement of and contributory infringement of the Jansen patent. Id. The
district court “construed the phrase ‘treating or preventing macrocytic-
megaloblastic anemia’ to require that, in order to infringe the patent, the human
subject must take the compound with the intent of treating or preventing
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macrocytic-megaloblastic anemia.” Id. The court found no such intent on the part
of Rexall’s customers and granted summary judgment of non-infringement. Id.
On appeal to the Federal Circuit, Jansen complained that the district court
improperly construed the claim to require the intent to treat macrocytic-
megaloblastic anemia. Jansen, 343 F.3d at 1332. Jansen argued that “the phrase
‘a human in need thereof’ encompasses a person who does not know that his or her
serum levels of folic acid and vitamin B12 are adequate.” Id.
The Federal Circuit interpreted ‘‘‘treating or preventing’ macrocytic-
megaloblastic anemia” by administering folic acid and vitamin B12 “to a human in
need thereof” to mean that the method be practiced with the intent to achieve the
objective of the claim as set forth in the claim preamble. Jansen, 343 F.3d at 1333.
The court held that the “[claim] preamble is therefore not merely a statement of
effect that may or may not be desired or appreciated. Rather, it is a statement of
the intentional purpose for which the method must be performed.” Id. The Federal
Circuit held that its interpretation was “bolstered by an analysis of the prosecution
history” in which the disputed phrases were added to the claims to gain allowance
after repeated unsuccessful attempts. Id.
Jansen is not dispositive in this appeal because it is distinguishable from the
claims under reexamination in this appeal.
First, the reexamined claims in this appeal are interpreted under the
“broadest reasonable” standard (Suitco, 603 F.3d at 1259; Abbott Diabetes, 696
F.3d 1142) which differs from the standard applied in an infringement suit in a
district court.
Second, Jansen had narrowed the claims in order to get allowance of the
claimed subject matter. “In other words, administering the claimed vitamins in the
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claimed doses for some purpose other than treating or preventing macrocytic-
megaloblastic anemia is not practicing the claimed method, because Jansen limited
his claims to treatment or prevention of that particular condition in those who need
such treatment or prevention.” Jansen, 343 F.3d at 1334. Jansen specifically cited
Smith v. Magic City Kennel Club, Inc., 282 U.S. 784, 790 (1931) for this principle:
The applicant[,] having limited his claim by amendment and accepted
a patent, brings himself within the rules that if the claim to a
combination be restricted to specified elements, all must be regarded
as material, and that limitations imposed by the inventor, especially
such as were introduced into an application after it had been
persistently rejected, must be strictly construed against the inventor
and looked upon as disclaimers.
It has not been established by AbbVie that claim 21 was so limited by
amendment as the claims were in Jansen.
Third, the dispute in Jansen involved infringement, not a determination of
whether the claims are valid over prior art. Thus, a different issue was under
consideration in the Jansen case.
For these reasons, Jansen is not applicable to the claims under reexamination
in this appeal.
Rapoport v. Dement, 254 F.3d 1053 (Fed. Cir. 2001), is also mentioned in
AbbVie’s Brief. PO Appeal Br. 24, fn. 1. Rapoport involved claims to a method
of treatment of sleep apnea comprising administering an azapirone compound.
The court found that the cited prior art reference, which described administering an
azapirone compound to treat anxiety, did not anticipate the claims because the
reference did not inherently treat patients for sleep apnea and it had not been
shown that such administration that did occur in Rapoport would necessarily result
in treating sleep apnea. Rapoport, 254 F.3d at 1062-63. In other words, in
Rapoport the issue was whether the drug inherently accomplished the purpose
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recited in the claims. It is not disputed in this case that ritonavir necessarily
accomplishes the claimed improvement in pharmacokinetics. Thus, Rapoport does
not demand that the claims under reexamination in this appeal be read to require an
overt recognition of the need to improve the pharmacokinetics of the
co-administered drug.

“a human in need of treatment”
The claimed method is “for improving the pharmacokinetics of a drug which
is metabolized by cytochrome P450 monooxygenase.” Claims 3, 21, and 39.
There is one recited step in the claims which involves administering ritonavir to a
human. The claims recite in the body of the claim that the human must be “in need
of such treatment,” a phrase that Patent Owner argues requires recognition that the
pharmacokinetics of the co-administered drug will be improved by the ritonavir.
This phrase also appears in independent claims 1, 39, 66, and 84.
It is well-established by case precedent that merely recognizing something
that was not known before is insufficient to render an old process again patentable.
In re Cruciferous Sprout Litig., 301 F.3d 1343, 1351 (Fed. Cir. 2002); see also In
re Woodruff, 919 F.2d 1575 (Fed. Cir. 1990); In re Omeprazole Patent Litig., 483
F.3d 1364, 1373 (Fed. Cir. 2007).
In MEHL/Biophile Int’l Corp. v. Milgraum, 192 F.3d 1362, 1365 (Fed. Cir.
1999), the patentee claimed a “method of hair depilation” utilizing steps which had
been described in a prior art publication. The prior art method did not perform the
steps for the purpose of hair depilation, but it was determined that hair depilation
would have been a necessary, albeit unrecognized and inherent, consequence of
carrying out the method. MEHL, 192 F.3d at 1366. Although the claim preamble
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expressly required the method to be performed for the purpose of hair depilation,
the court did not find it necessary that the article’s authors “appreciate the results”
of their process to constitute an anticipation of the claimed process. Id.
Similarly, in Perricone v. Medicis Pharm. Corp., 432 F.3d 1368, 1378-79
(Fed. Cir. 2005), a method claim preamble which required “preventing sunburn
damage to exposed skin surfaces,” was found satisfied by a prior art skin
composition which had been applied to skin surfaces, but for a different purpose.
“[T]he new realization alone [that the old composition would prevent sunburn
damage] does not render the old invention patentable.” Perricone, 432 F.3d at
1377.
Claim 21 stands on the same footing. Had the claim preamble been the only
reference to the newly discovered mechanism, this case would readily have fit the
same facts of MEHL and Perricone. Patent Owner has at least superficially
distinguished claim 21 by reciting that the human is “in need of” pharmacokinetic
improvement. However, the recitation of a “human in need of such treatment”
does not distinguish the claim from what it really is: a known process being
performed for a different purpose. Patent Owner contends that this phrase
demands recognition that a human treated by the method of claim 21 needs to have
the pharmacokinetics of the drug improved. We see no such requirement in the
language of the claim. Rather, we interpret “a human in need of such treatment” to
indicate the class of patients to whom the ritonavir is administered: humans who
have also been administered a drug metabolized by cytochrome P450
monooxygenase.
Moreover, the contention that to anticipate the claim it must be appreciated
that the treated human needs to improve the pharmacokinetics of the
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co-administered drug is legally defective. The reason is that the requirement that a
human be in need of treatment does not change how the process is performed,1 but
rather requires appreciation or recognition that the method is carried out for that
purpose, a mental process which numerous Federal Circuit cases have found to be
insufficient to distinguish over prior art disclosing the same method steps.
MEHL/Biophile Int’l Corp., 192 F.3d at 1365 (Fed. Cir. 1999); In re Cruciferous
Sprout Litig., 301 F.3d at 1351; Perricone, 432 F.3d at 1377-79.

Lower doses
Patent Owner contends the amounts of HIV protease inhibitor administered
with ritonavir are less than the amounts that would be administered when given
alone. PO Appeal Br. 18. To support this position, a declaration by Dale. J.
Kempf, Ph.D., an employee of Abbott Laboratories (original assignee of the ’403
patent), was provided by Patent Owner. First Kempf Declaration, dated February
9, 2011 (“First Kempf Decl.”). Dr. Kempf has a Ph.D. and 26 years of experience
in the field of medicinal chemistry. First Kempf Dec. ¶ 1. Dr. Kempf is a co-
inventor of the ’403 patent and the ’036 patent.
Dr. Kempf testified that “lower effective amounts of companion HIV
protease inhibitor [are] required by the claims of the ’403 Patent.” First Kempf
Decl. ¶35 (emphasis added). However, Dr. Kempf did not identify language in the
claim that would have led to this narrow interpretation of the claim. Rather, it

1 In Bristol-Myers Squibb Co. v. Ben Venue Labs., Inc., 246 F.3d 1368, 1375-76
(Fed. Cir. 2001), the court treated a claim expression (“method for treating a
cancer patient to effect regression of a taxol-sensitive tumor, said method being
associated with reduced hematologic toxicity”) as non-limiting because “[t]he
expression does not result in a manipulative difference in the steps of the claim.”

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appears that Dr. Kempf is importing limitations into the claim which do not appear
in it. It may be true, as discussed by Dr. Kempf, that lower effective doses of a
HIV protease inhibitor are enabled by Patent Owner’s discovery that ritonavir
improves the pharmacokinetic activity of drugs metabolized by cytochrome P450
monooxygenase, but we have not been directed to any language in the claims that
require lower amounts. We find Dr. Kempf’s testimony with regard to the scope
of claim 21 to lack credibility because of the absence of factual underpinnings and
reasoning. Moreover, we note that this argument is not commensurate with the
scope of the claims. Claim 21, for instance, does not require co-administration of
an HIV protease inhibitor.

Summary
Under its broadest reasonable interpretation, claim 21 is construed to require
that ritonavir is administered in an amount which is “for improving the
pharmacokinetics of a drug which is metabolized by cytochrome P450
monooxygenase.” The claim does not require that it was appreciated that the
administered ritonavir improved the metabolized drug. The ritonavir is
administered to “a human in need of such treatment,” which is interpreted to
indicate the class of patients to whom the ritonavir is administered: humans who
have also been administered a drug metabolized by cytochrome P450
monooxygenase.
The ritonavir is administered in “an amount effective to inhibit cytochrome
P450 monooxygenase.” Claim 21. The claim does not limit the amount of
ritonavir administered, the amount of inhibition of the monooxygenase achieved,
or the consequent degree of improvement in pharmacokinetics of the metabolized
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drug. Consequently, the claim encompasses even minimal amounts of
improvement.

IV. REJECTION
Claim 21
Claim 21 is directed to a “method for improving the pharmacokinetics of a
drug which is metabolized by cytochrome P450 monooxygenase.” The claim
comprises a single recited step of “administering to a human in need of such
treatment an amount effective to inhibit cytochrome P450 monooxygenase of
ritonavir or a pharmaceutically acceptable salt thereof.”
The Examiner found that the claim is anticipated by the ‘036 Patent.

Finding of Facts
The following facts are pertinent to the Examiner’s determination.
FF1. The Examiner found that the ’036 patent discloses ritonavir (Example
1U). The Examiner specifically identified the disclosure of ritonavir (compound U
of Example 1 or Example 1U) at column 29, lines 60-65, of the ’036 patent. RAN
4:8.
FF2. The ’036 patent repeatedly refers to Example 1U in its manufacture of
other compounds. ’036 patent, col. 32, l. 54; col, 33, l. 29; col. 34, ll. 45, 59; col.
35, l. 42; col. 38, l. 25; etc.
FF3. The Examiner also cited the disclosure at column 105 of the ’036
patent disclosing that “the compounds of the invention can be administered . . . in
combination with one or more immunomodulators, antiviral agents, other
antiinfective agents or vaccines.” ’036 patent, col. 105, ll. 33-37.
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FF4. Ritonavir (“Example 1U”) is expressly disclosed in the paragraph
immediately preceding the paragraph describing combinations of the inventive
compounds with other agents:
The concentration of the product of Example 1U (mg/g of
granulation) in the granulation was determined by HPLC analysis.
Capsules (gelatin, No. 00, iron gray opaque) were filled with the
appropriate amount of the dried granulation to provide the desired
dose per capsule.
’036 patent, col. 105, ll. 29-32.
FF5. The Examiner found that the ’036 patent teaches the compounds, such
as ritonavir, “can be administered in combination with other drugs including FK-
506, clarithromycin, SC-52151, saquinavir (Ro 31-8959) and KNI-272, which are
named in the claims of the ’403 patent (col. 105-106).” RAN 4.
FF6. The Examiner also found that the “guidance regarding dosages in the
[’403 patent and ’036 patent] is virtually identical.” RAN 5.
FF7. The ’403 patent contains the following disclosure regarding dosage:
The total daily dose of ritonavir to be administered to a human
or other mammal host in single or divided doses may be in amounts,
for example, from 0.001 to 300 mg/kg body weight daily and more
usually 0.1 to 50 mg/kg and even more usually 0.1 to 25 mg/kg.
Dosage unit composition may contain such amounts of submultiples
thereof to make up the daily dose.
’403 patent, col. 9, ll. 50-56 (emphasis added).
FF8. The ’403 patent contains the following disclosure regarding dosage:
Total daily dose administered to a human or other mammal host
in single or divided doses may be in amounts, for example, from 0.001
to 300 mg/kg body weight daily and more usually 0.1 to 10 mg.
Dosage unit compositions may contain such amounts of submultiples
thereof to make up the daily dose.
’036 patent, col. 103, ll. 49-54 (emphasis added).
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FF9. Based on the finding that the co-administration of ritonavir is the same
in claim 21 and in the ’036 patent, and the identity of the doses (FF7 and FF8), the
Examiner found:
While the ’036 patent does not disclose inhibition of cytochrome P450
monooxygenase 3A4, or the resulting improvement in
pharmacokinetics and increase in blood level of drugs which are
metabolized by cytochrome P450 monooxygenase 3A4 when
co-administered with ritonavir, these results would inherently be
obtained by following the guidance of the ’036 patent.
RAN 4.

Patent Owner
Patent Owner challenges the Examiner’s findings that the ’036 patent
anticipates claim 21. Specifically, Patent Owner contends:
1. The ’036 patent drug combinations are based on virological activity, not
on the pharmacokinetic boosting activity of ritonavir as claimed. PO Appeal Br.
16.
2. The effective amounts required by the claims are different from those in
the ’036 patent. A full dose of antiviral agent as disclosed in the ’036 patent would
be toxic when administered with ritonavir. PO Appeal Br. 17-21.
3. Claim 21 requires that the patient be in need of pharmacokinetic
improvement which would not have been appreciated at the time of the ’036
patent. PO Appeal Br. 22-28.
4. The pharmacokinetic boosting activity of ritonavir is not necessarily
present in the ’036 patent. PO Appeal Br. 25.
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5. The same rejection (over a patent with the same specification as the ’036
patent) was overcome by Patent Owner in a related patent (the ’157 patent). PO
Appeal Br. 14.

Virological activity versus pharmacokinetic; effective amounts
Patent Owner argues that ’036 patent drug combinations are based on
virological activity, not on the pharmacokinetic boosting activity of ritonavir as
claimed. PO Appeal Br. 16. For this reason, Patent Owner contends that the
effective amounts required by the claims are different from those disclosed in the
’036 patent. Specifically, Patent Owner argues that a full dose of antiviral agent as
disclosed in the ’036 patent would be toxic when administered with ritonavir. PO
Appeal Br. 17-21.
Dr. Kempf testified in his first declaration that a “person having ordinary
skill in the art would understand from these portions of the specification of the
’403 patent (and its claims) that different dosages would be used for boosting than
the amounts which would have been administered per the teachings of the ’036
Patent.” First Kempf Decl. ¶ 37. The cited portions of the ’403 patent are as
follows:
It has also been discovered that ritonavir is an inhibitor of the
metabolic enzyme cytochrome P450 monooxygenase.
Some drugs and, in particular, some HIV protease inhibitors are
metabolized by cytochrome P450 monooxygenase, leading to
unfavorable pharmacokinetics and the need for more frequent and
higher doses than are most desirable. Administration of such drugs
with an agent that inhibits metabolism by cytochrome P450
monooxygenase will improve the pharmacokinetics (i.e., increase
half-life, increase the time to peak plasma concentration, increase
blood levels) of the drug.
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’403 patent, col. 1, ll. 53-63.
Clarithromycin (500 mg/BIAXIN® tablet every 12 hours) and a
combination of ritonavir (200 mg of liquid formulation every 8 hours)
and clarithromycin (500 mg every 12 hours) were administered to
groups of 4 healthy human volunteers. Blood samples were collected
on day four of dosing for HPLC determination of plasma
concentrations of clarithromycin.
’403 patent, col 8, ll. 43-45.
The total daily dose of the drug which is metabolized by
cytochrome P450 monooxygenase to be administered to a human or
other mammal is well known and can be readily determined by one of
ordinary skill in the art.
’403 patent, col. 9, ll. 57-60.
The ’403 patent teaches that co-administration of ritonavir with a drug
metabolized by cytochrome P450 monooxygenase improves the drug’s
pharmacokinetics and that without ritonavir, there is a “need for more frequent and
higher doses” of the drug. ’403 patent, col. 1, ll. 55-63 (reproduced above).
However, the claim only requires an improvement in the pharmacokinetics of the
metabolized drug but does not require any specific amount of improvement. See
“Claim interpretation” supra. Patent Owner did not provide sufficient evidence
that improvement in the metabolized drugs would not occur at the dosages ranges
described in the ’036 patent. To the contrary, the Examiner observed that the
dosages ranges are “virtually identical” in the two patents, giving the Examiner a
reasonable basis to believe2 that following the guidance in the ’036 patent to

2 When the limitations of a claim are not expressly described in the prior art, the
PTO must show “sound basis for believing” that despite the failure of the prior art
to describe them, the limitations are inherently there and “the products of the
applicant and the prior art are the same.” In re Spada, 911 F.2d 705, 708 (Fed. Cir.
1990).
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combine ritonavir with other antiviral agents would result in an improvement in the
pharmacokinetics of those drugs in the ’036 patent which are metabolized by
cytochrome P450 monooxygenase.
Patent Owner contends because the drugs in the ’036 patent are selected for
their virological activity they would not be used in the same amounts when
selected for an improvement in pharmacokinetic activity as described in the ’403
patent. However, Patent Owner has not provided sufficient evidence that the
dosages are necessarily different than those required by the claims.
Dr. Kempf attempts to rebut Examiner’s presumption by identifying drugs
which he states would have been inferior or problematic in the doses required to
treat HIV. Kempf Decl. ¶¶ 42, 44. However, claim 21 is not limited to these
drugs.
Dr. Kempf also mentions toxicity problems: the “boosting effect of ritonavir
has allowed several HIV drugs to become available for use in lower dosage forms
thereby avoiding potential toxicity and alleviating patient compliance issues that
were prevalent due to large dosage requirements and/or the frequency with which
the known HIV drugs needed to be administered.” Id. at ¶ 44. Claim 21 is not
limited to these mentioned drugs, as well. Simply put, Dr. Kempf’s arguments do
not address the full scope of the claim. Even if there are embodiments
encompassed by the claim in which the doses described in the ’036 patent would
be too high because of toxicity or other problems, Dr. Kempf has not established
that this would be the case for every co-administered drug metabolized by
cytochrome P450 monooxygenase which is described in the ’036 patent.
Furthermore, Examiner reasonably found that the ritonavir would have
increased the co-administered drug’s pharmacokinetics (i.e., increase half-life,
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increase the time to peak plasma concentration, increase blood levels) at the
dosages of ritonavir described in the ’036 patent because this property is a property
of the ritonavir. Dr. Kempf did not provide sufficient evidence to the contrary. Dr.
Kempf showed that the inhibitory activity of ritonavir is dosage dependent (Kempf
Decl. ¶¶ 23, 24) and testified that even small doses “significantly elevated plasma
saquinavir levels” (id. at ¶ 25). Based on Dr. Kempf’s testimony, it would have
been reasonably expected that any of the dosages described in the ’306 patent
would have been effective at “improving the pharmacokinetics of a drug which is
metabolized by cytochrome P450 monooxygenase” in “a human in need of such
treatment.” Claim 21. In fact, as indicated above, the dosage range is the same in
the two patents. FF7 and FF8.
Patent’s Owner argument that the skilled worker would have picked
different dosages of the co-administered metabolized drug when combining it with
ritonavir for its pharmacokinetic property, rather than when combining it with
another antiviral drug, is supported by testimony by Dr. Kempf for at least the
specific drugs described in his first declaration. PO Appeal Br. 18. However, this
argument fails to appreciate the scope of claim 21. Claim 21 merely requires
“improving the pharmacokinetics of a drug which is metabolized by cytochrome
P450 monooxygenase.”
As long as a metabolized drug is selected and co-administered with
ritonavir, it would have been reasonably expected that the drug’s pharmacokinetics
would be improved. Dr. Kempf’s testimony, as discussed above, fully supports
this expectation since ritonavir’s activity is dose-dependent and ritonavir is active
even at low doses. Patent Owner appears to be reading limitations into claim 21
that are not recited in it. For example, Patent Owner has not identified language in
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the claim that would require the amounts of the metabolized drug to be lower in
the presence of ritonavir than in its absence.
Dr. Kempf repeatedly emphasizes that “the ’403 Patent fundamentally
altered the treatment landscape for HIV and AIDS in a manner that a person
having ordinary skill in the art in June 1995 simply would not have understood
from the disclosure of the ’036 Patent.” Second Kempf Decl. ¶ 14 (dated May 31,
2012). Dr. Kempf’s opinion is based, in part, on the discovery that ritonavir
improved the efficacy of drugs without increasing their toxicity and at lower doses.
Id. at ¶¶ 17-18. However, neither Dr. Kempf nor Patent Owner have persuasively
distinguished the claimed method from the method practiced in the ’036 patent.
Discovery of a different mechanism of action does not necessarily impart
patentability to the claims.

Appreciation of pharmacokinetic boosting activity; boosting activity not
necessarily present
Patent Owner states that the ’036 patent “does not teach that the companion
drug needs pharmacokinetic improvement (or increased blood levels) or is
administered in an amount that would provide for its desired therapeutic effect
without pharmacokinetic improvement.” PO Appeal Br. 23. Patent Owner
contends “[w]hatever combinations are taught by the ’036 Patent, the companion
drug in those combinations would not have been appreciated in June 1995 as
needing pharmacokinetic improvement or improved blood levels to achieve its
intended effect.” Id.
This argument has already been addressed in the “Claim interpretation”
section. The claims do not require appreciation that ritonavir improves the
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pharmacokinetics of the metabolized drug. The issue is whether the ’036 patent
teaches the steps of the claimed method and whether following these steps would
necessarily result in improving the metabolized drug’s pharmacokinetics.
First, the Examiner found that the’036 patent disclosed ritonavir. FF1-FF2.
Consistent with the Examiner’s findings, ritonavir is repeatedly mentioned in the
patent and a formulation of it is described in the section immediately before the
discussion of combinations of drugs. FF4. The Examiner also found that
combinations of drugs are disclosed, including drugs which are metabolized by
cytochrome P450 monooxygenase.3 FF5. Even though there is “a long list of
compounds” disclosed in the ’036 patent which may be combined with ritonavir
(PO Appeal Br. 15), anticipation has been found where each of the specific
ingredients in the claimed formula was recited in a longer list of alternative agents.
WM. Wrigley Jr. Co. v. Cadbury Adams USA LLC, 683 F.3d 1356, 1361-62 (Fed.
Cir. 2012).
Patent Owner contends that Examiner has not given the claim preamble
patentable weight. PO Appeal Br. 25-27. We do not agree. The Examiner did not
ignore the requirement in the claim preamble that the method must improve the
drug’s pharmacokinetics. The Examiner simply rejected Patent Owner’s
interpretation that the claim requires appreciation of this improvement. Rather, the
Examiner found that following the disclosure of the ’036 patent, the improvement
would have inherently been achieved.
Patent Owner also contends that ritonavir’s “boosting effects are not
‘necessarily present’ in all the drug combinations suggested by the ’036 Patent, and

3 As pointed about by Requester in the Request, the ’036 patent even claims
ritonavir in combination with specification HIV protease inhibitors that are
metabolized by the claimed monooxygenase. Request 24-25.
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is thus not an inherent property of the drug combinations disclosed by the ’036
Patent.” PO Appeal Br. 25.
A “prior art reference may anticipate without disclosing a feature of the
claimed invention if that missing characteristic is necessarily present, or inherent,
in the single anticipating reference.” SmithKline Beecham Corp. v. Apotex Corp.,
403 F.3d 1331, 1343 (Fed. Cir. 2005) (citing Continental Can Co. v. Monsanto
Co., 948 F.2d 1264, 1268 (Fed.Cir.1991).
The Examiner found that the ’036 patent teaches a combination of ritonavir
and a drug which is metabolized by cytochrome P450 monooxygenase. Since
ritonavir improves the pharmacokinetics of this class of metabolizable drugs, it is
unclear why the boosting effect is not necessarily present when such combination
is administered.
Patent Owner contends the “RAN is also wrong that ‘all HIV patients are in
need of (i.e. would benefit from) treatment with ritonavir in combination with SC-
52151, saquinavir or KNI-272.’” PO Appeal Br. 25. Patent Owner argues patients
taking a full dose of saquinavir would not benefit from ritonavir because this
combination would lead to an overdose of the saquinavir. Id.
Even if this rationale for saquinavir is correct, there are other anticipatory
combinations described in the ’036 patent of ritonavir and a drug metabolized by
cytochrome P450 monooxygenase which Patent Owner did not establish would
lead to drug overdose. See RAN 4 (listing other drug combinations).
In sum, with the explicit disclosure of ritonavir in various places in the’036
patent and with drug combination expressly disclosed, the Examiner’s position that
claim 21 is anticipated by the ’036 patent to be supported by a preponderance of
the evidence.
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Rejection in the ’157 patent related to ’403 Patent
Patent Owner states that ’403 Patent is related to US 6,037,157 (“the ’157
Patent”). According to Patent Owner, the claims of the ’157 Patent and the claims
of the ’403 Patent are both directed to using ritonavir to boost bioavailability of
another HIV protease inhibitor, “and in fact the claims of the ’403 Patent were the
subject of an obviousness-type double patenting rejection based on claims of the
’157 Patent.” PO Appeal Br. 14. Patent Owner states the claims of the ’157 Patent
were rejected as obvious over US 5,674,882 (“the ’882 patent”), “which has the
same specification as (and is related to) the ’036 Patent cited in the present Office
Action) based on substantially the same rationale at issue in the present
reexamination.” Id. Patent Owner argues that this rejection was withdrawn and,
for this reason, the rejection should be withdrawn in this reexamination. Id.
We are not bound by the actions of an Examiner in separate proceeding
involving a different patent. Thus, we will not withdraw the rejection involving
the ’036 patent because of prosecution that took place in an allegedly related
application having a different set of claims.

Claims 1-3, 39, 48, 66, and 84
Claims 3 and 39 also are drawn to methods of improving pharmacokinetics.
Patent Owner did not argue these claims separately, and therefore, we affirm the
rejection of these claims for the same reasons as for claim 21.
Claims 1, 2, 48, 66, and 84 involve methods of inhibiting cytochrome P450
monooxygenase and increasing blood levels of a drug metabolized by the
monooxygenase comprising administering ritonavir. The Examiner found that
administering ritonavir as a combination in accordance with the ’036 patent would
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achieve the stated goals. RAN 4. Patent Owner did not argue these claims
separately. The Examiner’s position that inhibiting the enzyme and raising the
drug’s blood levels is reasonable because even small amounts of ritonavir were
found to inhibit the enzyme and, thus, would be reasonably expected to raise blood
levels of a drug metabolized by the enzyme. Thus, we affirm the anticipation
rejection of these claims for the same reason as for claim 21.
Dependent claims 3-8, 12-20, 22-26, 30-44, 49-53, 57-65, 67-71, 75-83, and
85-89 were not argued separately and fall with independent claims 1, 2, 21, 48, 66,
and 84 for the reasons given by the Examiner and as set forth in the Request.

V. CROSS-APPEAL
The Examiner did not adopt the rejection of claims 9-11, 27-29, 45-47, 54-
56, 72-74 under 35 U.S.C. § 102(e) as anticipated by Kempf. RAN 4. The
rejection was not adopted “because the genus disclosed within Kempf of an ‘agent
useful for the treatment of HIV/AIDS’ does not anticipate the specific drugs MK-
639, VX-478 and AG1343” recited in the claims. RAN 14.
Requester appeals the Examiner’s decision not to adopt the rejection.
Requester Appeal Br. 3. Requester argues that the recited drugs are “retroviral
protease inhibitors” as disclosed in the ’036 patent. Id. at 5. Requester contends
that this description constitutes anticipation because the genus is small and there is
only one variable, a drug used with ritonavir. Id.
To anticipate, one skilled in the art must be able to “at once envisage” the
claimed subject matter in the prior art disclosure. In re Petering, 301 F.2d 676,
681 (CCPA 1962). Requester did not provide evidence to support their contention
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that the genus of retroviral protease inhibitors is small, and one of ordinary skill in
the art would have immediately envisaged the specifically claimed drugs.

TIME PERIOD FOR RESPONSE
In accordance with 37 C.F.R. § 41.79(a)(1), the “[p]arties to the appeal may
file a request for rehearing of the decision within one month of the date of: . . .
[t]he original decision of the Board under § 41.77(a).” A request for rehearing
must be in compliance with 37 C.F.R. § 41.79(b). Comments in opposition to the
request and additional requests for rehearing must be in accordance with 37 C.F.R.
§ 41.79(c)-(d), respectively. Under 37 C.F.R. § 41.79(e), the times for requesting
rehearing under paragraph (a) of this section, for requesting further rehearing under
paragraph (d) of this section, and for submitting comments under paragraph (c) of
this section may not be extended.
An appeal to the United States Court of Appeals for the Federal Circuit
under 35 U.S.C. §§ 141-144 and 315 and 37 C.F.R. § 1.983 for an inter partes
reexamination proceeding “commenced” on or after November 2, 2002 may not be
taken “until all parties’ rights to request rehearing have been exhausted, at which
time the decision of the Board is final and appealable by any party to the appeal to
the Board.” 37 C.F.R. § 41.81. See also MPEP § 2682 (8th ed., Rev. 7, July 2008).
In the event neither party files a request for rehearing within the time
provided in 37 C.F.R. § 41.79, and this decision becomes final and appealable
under 37 C.F.R. § 41.81, a party seeking judicial review must timely serve notice
on the Director of the United States Patent and Trademark Office. See 37 C.F.R.
§§ 90.1 and 1.983.

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AFFIRMED

Patent Owner:

Dr. Steven R. Crowley
ABBOTT LABORATORIES
Dept. 377 AP6D-2
100 Abbott Park Road
Abbott Park, IL 60064-6050

Third Party Requester:

PUBLIC PATENT FOUNDATION
55 Fifth Avenue, Suite 928
New York, NY 10003