ipr2015 01993 instituted
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[email protected] Paper 20
571-272-7822 Entered: 22 March 2016
UNITED STATES PATENT AND TRADEMARK OFFICE
__________
BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________
COALITION FOR AFFORDABLE DRUGS V LLC;
HAYMAN CREDES MASTER FUND, L.P.;
HAYMAN ORANGE FUND SPC – PORTFOLIO A;
HAYMAN CAPITAL MASTER FUND, L.P.;
HAYMAN CAPITAL MANAGEMENT, L.P.;HAYMAN OFFSHORE MANAGEMENT, INC.;
HAYMAN INVESTMENTS, LLC;
NXN PARTNERS, LLC;
IP NAVIGATION GROUP, LLC;
J KYLE BASS, and ERICH SPANGENBERG,
Petitioners,
v.
BIOGEN MA INC.,
Patent Owner.
__________
Case IPR2015-01993
Patent 8,399,514 B2
__________
Before FRED E. McKELVEY, SALLY GARDNER LANE, and
DEBORAH KATZ, Administrative Patent Judges.
McKELVEY, Administrative Patent Judge.
DECISION
Institution of Inter Partes Review
37 C.F.R. § 42.108
mailto:[email protected]:[email protected]:[email protected]
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I. Introduction
A. BackgroundA second petition seeking to institute an inter partes review in
connection with U.S. Patent No. 8,399,514 B2 (“ʼ514 patent”) is before the
Board. Paper 1.
A first petition seeking to institute an inter partes review was denied.
Coalition for Affordable Drugs V LLC v. Biogen MA Inc., IPR2015-01136,
2015 WL 5169256 (Paper 23) (PTAB Sept. 2, 2015), reh’g denied ,
IPR2015-01136 (Paper 29) (PTAB Oct. 23, 2015).
The ʼ514 patent is also involved in Biogen MA Inc. v. Forward
Pharma, Interference 106,023 (PTAB Declared Apr. 13, 2015).
Patent Owner timely filed a Preliminary Response. Paper 11.
Petitioner was invited to file a Reply. Paper 13.
Petitioner timely filed the Reply.1 Paper 17.
B. The Parties
Petitioner is:
(1) Coalition for Affordable Drugs V LLC,
(2) Hayman Credes Master Fund, L.P.,
1 The Reply is styled REPLY TO PATENT OWNER’S PRELIMINARY
RESPONSE IN SUPPORT OF PETITION FOR INTER PARTES REVIEW
OF U.S. PATENT 8,399,514 UNDER 35 U.S.C. §§ 311-319. In the future
the style of any paper filed in this IPR shall not exceed one line. A more
appropriate style would have been REPLY TO PRELIMINARY
RESPONSE. Use of a single line renders entry of papers into Board data
records much easier. Failure to adhere to the one-line rule established in this
IPR may result in a paper being expunged.
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(3) Hayman Orange Fund SPC – Portfolio A,
(4) Hayman Capital Master Fund, L.P.,(5) Hayman Capital Management, L.P.,
(6) Hayman Offshore Management, Inc.,
(7) Hayman Investment, LLC,
(8) NXN Partners, LLC,
(9) IP Navigation Group, LLC,
(10) J. Kyle Bass, and
(11) Erich Spangenberg.
Paper 1, pages 1 – 2.
Patent Owner is Biogen MA Inc. Paper 11, page 1.
C. Abbreviations
BG00012 or BG12 Dimethyl fumarate
DMF Dimethyl fumarate
ICH International Conference on Harmonisation
MMF Monomethyl fumarate
MRI Magnetic resonance imaging
RRMS Relapsing-remitting multiple sclerosis
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D. Evidence Relied Upon2
The following evidence is relied upon in support of the Petition:Name Exhibit
No.
Description Date
Kappos 2006 1003
Efficacy of a Novel Oral
Single-Agent Fumarate,
BG00012, in Patients with
Relapsing-Remitting Multiple
Sclerosis: Results of a Phase2 Study, J. NEUROL (2006)
253 (SUPPL 2); II/1 – II/170,
page II27
May 2006
Kappos 2006 is prior art under 35 U.S.C. § 102(b) based on the filing
date of Biogen’s PCT application (7 February 2008). If Biogen is entitled to
a benefit date of its Provisional Application (8 February 2007), Kappos 2006
is prior art under 35 U.S.C. § 102(a).
Further discussion of Kappos 2006 occurs later in this opinion.
Clinical Trials 1022
Double-Blind, Placebo-
Controlled, Dose-Ranging
Study to Determine the Effacacy and Safety of
BG00012 in Subjects with
Relapsing-Remitting Multiple
Sclerosis,
CLINICALTRIALS.GOV
ARCHIVE
14 Sept. 2005
Clinical Trials is prior art under 35 U.S.C. § 102(b).
2 Because the application maturing into the ʼ514 patent was filed before
the enactment of the Leahy-Smith America Invents Act (“AIA”), Pub. L.
No. 112-29, 125 Stat. 284 (2011), we apply the pre-AIA version of 35 U.S.C.
§§ 102, 103, 112, and 119.
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Name Exhibit
No.
Description Date
Joshi ʼ999 1030 U.S. Patent 7,320,999 B2
22 Jan. 2008
filed
17 July 2002
Joshi ʼ999 is prior art under 35 U.S.C. § 102(a) having issued prior to
Biogen’s PCT filing date (7 February 2008). If Biogen is entitled to a
benefit date of its Provisional Application (8 February 2007), then Joshi
ʼ999 is prior art under 35 U.S.C. § 102(e) based on its filing date (17 July
2002).
ICH Guideline 1004 ICH Harmonised TripartiteGuideline, DOSE-R ESPONSE
I NFORMATION TO SUPPORT
DRUG R EGISTRATION E4
10 Mar. 1994
Joshi ʼ992 1036 U.S. Patent 6,436,992 B1 20 Aug. 2002
Begleiter 1027
Dietary Induction of NQOI
Increases the Antitumour
Activity of Mitomycin C in
Human Colon Tumours in
vivo,
91 BRITISH J. CANCER 1624 –
1631
2004
ICH Guideline, Joshi ʼ992, and Begleiter are prior art under 35 U.S.C.
§ 102(b).
E. Grounds of Unpatentability
Claims 1 – 20 appear in the ʼ514 patent. Ex. 1001, col. 27:58 through
col. 30:27.The following grounds of unpatentability are urged in the Petition.
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Statutory
Basis
Prior Art
Relied On
Claims
Ground 1 § 103(a)
Kappos 2006
ClinicalTrials,
Joshi ʼ999, and
ICH Guideline
1 – 6, 8 – 16, and 20
Ground 2 § 103(a)
Kappos 2006,
ClinicalTrials,
Joshi ʼ999,
ICH Guideline, and
Joshi ʼ992
7
Ground 3 § 103(a)
Kappos 2006,
ClinicalTrials,
Joshi ʼ999,
ICH Guideline and
Begleiter
17 – 19
F. Kappos 2006
The application maturing into the ʼ514 patent was filed on
13 February 2012. Ex. 1001, page 1.
Biogen claims benefit of Provisional Application 60/888,921, filed
8 February 2007.
The Petition has not challenged Patent Owner’s 7 February 2008
claim to priority based on Patent Owner’s PCT application. Paper 1, page 4.
The Petition alleges that Patent Owner is not entitled to benefit of its
Provisional Application based on Patent Owner having not been accorded
benefit in Interference 106,023. Id .
Patent Owner was accorded benefit of its Provisional Application at
the time Interference 106,023 was declared. Interference 106,023, Paper 1,
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page 4. There came a time in Interference 106,023 when the Board
determined that Patent Owner was not entitled to claim benefit of itsProvisional Application filing date of 8 February 2007. Interference
106,023, Paper 171. Subsequent to the Board’s determination, Biogen was
authorized to file a motion to revive its abandoned application 12/526,296
for the purpose of entry of an amendment to make a specific reference to its
Provisional Application. Interference 106,023, Paper 197. The motion to
revive was timely filed. Interference 106,023, Paper 122. Upon
consideration of the motion to revive, the Board ordered that application
12/526,296 be revived and further ordered that an amendment making a
specific reference to Biogen’s Provisional Application be entered.
Interference 106,023, Paper 611. In ordering revival and entry of the
amendment, the Board did not determine on the merits whether Biogen is
entitled to the benefit of its Provisional Application 60/888,921 under
35 U.S.C. § 119(e)(1) — in other words, the Board did not determine in
Interference 106,023 whether the invention claimed in the ʼ514 patent is
disclosed in the Provisional Application in the manner required by the first
paragraph of 35 U.S.C. § 112.
The prior art date of Kappos 2006 is May of 2006. As noted earlier in
this opinion, Kappos 2006 is prior art under 35 U.S.C. § 102(b) if Biogen is
not entitled to benefit of the 7 February 2007 filing date of its ProvisionalApplication. Kappos 2006 is prior art under 35 U.S.C. § 102(a) if Biogen is
entitled to benefit of the 8 February 2007 filing date of its Provisional
Application — less than one year after May of 2006.
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In its Preliminary Response, Patent Owner does not assert that it is
entitled to benefit of its Provisional Application.At this stage, Kappos 2006 will be treated as prior art under 35 U.S.C.
§ 102(b), without prejudice to Patent Owner establishing its right to a benefit
date as of the filing date of its Provisional Application. The mere fact that
Petitioner has not challenged the sufficiency of the PCT application does not
establish that Patent Owner is entitled to benefit of its Provisional
Application. There was no need for Petitioner to challenge benefit of the
PCT because Kappos 2006 is prior art under 35 U.S.C. § 102(b) as to the
PCT application.
Should Patent Owner elect to seek benefit of its Provisional
Application, it is noted that the written description portion of the
Specification of the ʼ514 patent contains the following:
For example, an effective dose of DMF or MMR [sic —
MMF] to be administered to a subject orally can be fromabout 0.1 g to 1 g per pay, 200 mg to about 800 mg per
day (e.g., from about 240 mg to about 720 mg per day; or
from about 480 mg to about 720 mg per day; or about
720 mg per day). For example, the 720 mg per day may
be administered in separate administrations of 2, 3, 4, or
6 equal doses.
Ex. 1001, page 24, col. 18:58 – 64 (italics added).
Atofina v. Great Lakes Chemical Corp., 441 F.3d 991, 1000 (Fed. Cir.
2006), states that a disclosure of a range of 150 to 350 C does not constitute
a specific disclosure of the endpoints of that range, i.e., 150ºC and 350º C;
the disclosure is only that of a range, not a specific temperature in that range
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and the disclosure of a range is not a disclosure of end points of the range
any more than it is of each of the intermediate points.Since the description of 480 mg in the ʼ514 patent is an end point, in
the event Patent Owner elects to seek benefit of its Provisional Application,
it should address why benefit should be accorded in light of Atofina.
II. Analysis
A. Challenge — Claims 1, 11, 15, and 20
According to Petitioner, claims 1 – 6, 8 – 16, and 20 are unpatentable
under 35 U.S.C. § 103(a) over a combination of (1) Kappos 2006,
(2) ClinicalTrials, (3) Joshi ʼ999, and (4) ICH Guideline.
B. Claims 1, 11, 15, and 20
The invention can be readily understood by reference to independent
claims 1, 11, 15, and 20, all reproduced below (indentation added; principal
limitation in dispute italicized):
Claim 1
A method of treating a subject in need of treatment
for multiple sclerosis comprising
orally administering to the subject in need thereof
a pharmaceutical composition consisting essentially of
(a) a therapeutically effective amount of dimethyl
fumarate, monomethyl fumarate, or a combination
thereof, and
(b) one or more pharmaceutically acceptable
excipients,
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wherein the therapeutically effective amount of
dimethyl fumarate, monomethyl fumarate, or a
combination thereof is about 480 mg per day.
Ex. 1001, col. 27:59 – 67.
Claim 11
A method of treating a subject in need of treatment
for multiple sclerosis consisting essentially of
orally administering to the subject about 480 mg
per day of dimethyl fumarate, monomethyl fumarate, or acombination thereof.
Claim 15
A method of treating a subject in need of treatment
for multiple sclerosis comprising
orally administering to the subject [a] pharma-
ceutical composition consisting essentially of
(a) a therapeutically effective amount of dimethyl
fumarate and
(b) one or more pharmaceutically acceptable
excipients,
wherein the therapeutically effective amount of
dimethyl fumarate is about 480 mg per day.
Claim 20
A method of treating a subject in need of treatment
for multiple sclerosis comprising
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treating the subject in need thereof with a
therapeutically effective amount of dimethyl fumarate,
monomethyl fumarate, or a combination thereof,
wherein the therapeutically effective amount of
dimethyl fumarate, monomethyl fumarate, or a
combination thereof is about 480 mg per day.
C. Kappos 2006
Kappos 2006 is a 27 page document. Ex. 1003. The only relevant
parts of Kappos 2006 are (1) page 1 of 27 identifying the publication date of
Kappos 2006 and (2) article number O108 in column 2 of page 27 of 27.
The remaining parts of Kappos (1) have not been relied upon by
Petitioner, (2) sua sponte are excluded from evidence, (3) will not be
considered and (4) are not considered to be part of the record before the
Board.
Petitioner is directed to forthwith refile Exhibit 1003 as Exhibit
1003A containing only pages 1 and 27. Upon filing of Exhibit 1003A,
Exhibit 1003 will be expunged.
The relevant description in Kappos 2006 is generally self-explanatory
and reads as follows (some indentation added):
Objective: To determine the efficacy of three dose levels
of BG00012, a novel oral fumarate preparation, on brain
lesion activity as measured by magnetic resonance
imaging (MRI) in patients with relapsing-remittingmultiple sclerosis (RRMS).
Methods: This was a randomised, double-blind,
placebo-controlled clinical trial of BG00012 in patients
with RRMS. Men and women 18 to 55 years of age were
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eligible for the study if they had a diagnosis of RRMS
and an Expanded Disability Status Scale (EDSS) score
between 0.0 and 5.0. In addition, patients must have had
either ≥ 1 relapse within 12 months prior to
randomisation or gadolinium-enhancing (Gd+) lesions on
cranial MRI at screening. Patients were assigned to four
treatment groups and received BG00012 capsules 120 mg
by mouth (PO)
[1] once daily (120 mg/day),
[2] 120 mg three times daily (360 mg/day),
[3] 240 mg three times daily (720 mg/day), or[4] placebo for 24 weeks.
The treatment period was followed by a 24-week
dose-blinded safety-extension period during which all
patients received BG00012. The primary end point was
the total number of Gd+ lesions over four MRI scans at
weeks 12, 16, 20, and 24 (calculated as the sum of the
four scans). Secondary end points included the
cumulative number of new Gd+ lesions from week 4 to
week 24 and the number of new/enlarging
T2-hyperintense lesions at week 24. Additional end
points included the number of new T1-hypointense
lesions at week 24, relapse rate, and disability
progression as measured by EDSS.
Results: A total of 257 patients were enrolled in
the study; 64 patients each were randomly assigned to
receive one of the three BG00012 doses and 65 patients
to placebo. Approximately 90% of patients completedthe 24-week treatment period. BG00012 (720 mg/day)
significantly reduced the mean number of new Gd+
lesions (the primary end point) compared with placebo.
In addition, BG00012 reduced the cumulative number of
new Gd+ lesions, the number of new/enlarging
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T2-hyperintense lesions, and the number of new
T1-hypointense lesions compared with placebo.
Conclusion: BG00012 significantly reduces brain
lesion activity, in a dose-dependent manner, as measured
by MRI in patients with RRMS over 24 weeks of
treatment.
This study was sponsored by Biogen Idec and
Fumapharm AG.
Ex. 1003, page 27, col. 2.“BG00012” and “BG12” are designations for dimethyl
fumarate (also referred to the record as “DMF”). See Linberg
Testimony, Ex. 1005, ¶ 23, last three lines referring to Ex. 1002,
page 1 and Ex. 1022, page 1.
Kappos 2006 differs from the subject matter of claims 1, 11, 15,
and 20 of the ʼ514 patent in that Kappos 2006 does not explicitly
describe the use of a therapeutically effective amount of dimethyl
fumarate that is “about 480 mg per day.”
D. Joshi ʼ999
Joshi ʼ999 (Ex. 1030) relates to the use of dialkyl fumarates,
including dimethyl fumarate (col. 6:16 – 17 and 60; col. 8:19), for preparing
pharmaceutical preparations for use in transplantation medicine or the
therapy of autoimmune diseases, including multiple sclerosis (col. 1:29;
col. 4:45; and col. 8:15), and pharmaceutical preparations in the form of
micro-tablets or micro-pellets containing dialkyl fumarates.
Joshi ʼ999 claim 1 reads [indentation added]:
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A method of treating multiple sclerosis comprising
treating a patient in need of treatment for multiple
sclerosis
with an amount of a pharmaceutical preparation
effective for treating said multiple sclerosis,
wherein the only active ingredient for the
treatment of multiple sclerosis present in said
pharmaceutical preparation is dimethyl fumarate.
Ex. 1030, col. 8:14 – 19.Claim 2 reads:
The method of claim 1, wherein 10 to 300 mg of
dimethyl fumarate is present in said pharmaceutical
preparation.
Ex. 1030, col. 8:20 – 22.
Claim 9 reads:
The method of claim 1, wherein 120 mg of
dimethyl fumarate is present in said pharmaceutical
preparation.
Ex. 1030, col. 8:38 – 39.
Claim 18 reads:
The method of claim 1, wherein the
pharmaceutical preparation comprises one or more
excipients.
Ex. 1030, col. 8:62 – 63.
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According to Joshi ʼ999:
The dialkyl fumarates used according to theinvention may be used alone or as a mixture of several
compounds, optionally in combination with the
customary carriers and excipients. The amounts to be
used are selected in such a manner that the preparations
obtained contain the active ingredient in an amount
corresponding to 10 to 300 mg of fumaric acid.
Preferred preparations according to the invention
contain a total amount of 10 to 300 mg of dimethyl
fumarate and/or diethyl fumarate.
Ex. 1030, col. 4:39 – 48 (italics added).
Joshi ʼ999 differs from the subject matter of claims 1, 11, 15,
and 20 of the ʼ514 patent in that Joshi ʼ999 does not describe the use
of a therapeutically effective amount of dimethyl fumarate that is
“about 480 mg per day.”
E. ICH Guideline
ICH Guideline (Ex. 1004) describes guidelines for determining
appropriate dosages of pharmaceutical products.
ICH means “International Conference on Harmonisation.”
According to ICH:
Knowledge of the relationships among dose, drug-
concentration in blood, and clinical response
(effectiveness and undesirable effects) is important forthe safe and effective use of drugs in individual patients.
This information can help identify an appropriate starting
dose, the best way to adjust dosage to the needs of a
particular patient , and a dose beyond which increases
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would be unlikely to provide added benefit or would
produce unacceptable side effects. . . .
Historically, drugs have often been initially
marketed at what were later recognized as excessive
doses (i.e., doses well onto the plateau of the dose-
response curve for the desired effect), sometimes with
adverse consequences (e.g. hypokalemia and other
metabolic disturbances with thiazide-type diuretics in
hypertension). This situation has been improved by
attempts to find the smallest dose with a discernible
useful effect or a maximum dose beyond which no furtherbeneficial effects is seen, but practical study designs do
not exist to allow for precise determination of these doses.
Further, expanding knowledge indicates that the concepts
of minimum effective dose and maximum useful dose do
not adequately account for individual differences and do
not allow a comparison, at various doses, of both
beneficial and undesirable effects. Any given dose
provides a mixture of desirable and undesirable effects,
with no single dose necessarily optimal for all patients.
Ex. 1004, page 5 of 14 (italics added).
Further according to ICH:
In adjusting the dose in an individual patient after
observing the response to an initial dose, what would be
most helpful is knowledge of the shape of individual
dose-response curves, which is usually not the same as
the population (group) average dose-response curve.
Study designs that allow estimation of individual dose-response curves could therefore be useful in guiding
titration, although experience with such designs and their
analysis is very limited.
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In utilizing dose-response information, it is
important to identify, to the extent possible, factors that
lead to differences in pharmacokinetics of drugs amongindividuals, including demographic factors (e.g. age,
gender, race), other diseases (e.g. renal or hepatic
failure), diet , concurrent therapies, or individual
characteristics (e.g. weight , body habitus, other drugs,
metabolic differences).
Ex. 1004, page 6 of 14 (italics added).
“The choice of the size of an individual dose is often
intertwined with the frequency of dosing.” Ex. 1004, page 7 of 14.
ICH teaches that:
Assessment of dose-response should be an integral
component of drug development with studies designed to
assess dose-response an inherent part of establishing the
safety and effectiveness of the drug.
Ex. 1004, page 7 of 14; Ex. 1005, ¶ 32.
Following up on discussion on page 7 of 15, second paragraph, ICH
further teaches:
It is all too common to discover, at the end of a
parallel dose-response study, that all doses were too high
(on the plateau of the dose-response curve), or that doses
did not go high enough. A formally planned interim
analysis (or other multi-stage design) might detect such a
problem and allow study of the proper dose range.
Ex. 1004, page 10 of 27; Ex. 1005, ¶ 32.
Pages 13 of 14 and 14 of 14 describe guidance and advice for
determining dosages.
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F. ClinicalTrials
ClinicalTrials addresses a proposed study of a “Double-Blind,Placebo-Controlled, Dose-Range Study to Determine the Effacacy and
Safety of BG00012 in Subjects with Relapsing-Remitting Multiple
Sclerosis.” Ex. 1022, page 1 of 7.
As noted earlier, BG00012 is dimethyl fumarate. Ex. 1022, page 1
of 7; Ex. 1005, ¶ 28.
In Part 1 of the study, the described dose ranges to be tested are
essentially the same as the dosages described as having been tested by
Kappos 2006. Ex. 1022, page 2 of 7; Ex. 1003, page 27 of 27; Ex. 1005,
¶ 31.
In Part 2, ClinicalTrials notes that “[d]ose reduction will be allowed
for subjects who are unable to tolerate investigational drug.” Ex. 1022,
page 2 of 7; Ex. 1005, ¶ 31.
G. Dr. Steven E. Linberg
Petitioner relies on the direct Declaration testimony of Dr. Steven E.
Linberg. Ex. 1005.
With respect to differences between (1) the subject matter of claim 1
of the ʼ514 patent vis-à-vis (2) Joshi ʼ999 and Kappos 2006, Dr. Linberg
testifies:
In my opinion, the ICH Guideline E4 would haveinstructed a POSITA [“person of skill in the art”] as
follows: “Assessment of dose-response should be an
integral component of drug development with studies
designed to assess dose-response [being] an inherent part
of establishing the safety and effectiveness of the drug.
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If development of dose-response information is built into
the development process it can usually be accomplished
with no loss of time and minimal extra effort comparedto development plans that ignore dose-response.”
Ex. 1004, 7[ of 14]:27 – 32. ICH Guideline E4 also would
have instructed that: “It is all too common to discover, at
the end of a parallel dose-response study, that all doses
were too high (on the plateau of the dose-response curve),
or that doses did not go high enough.” Ex. 1004, 10[ of
14]:39 – 41. In my opinion, the ICH Guideline E4
instructed a POSITA to perform dosing studies as a
standard procedure in drug development in order to“allow study of the proper dose range” in phase III.
Kappos 2006 . . . [does] not disclose doses between 360
mg/day and 720 mg/day. However, in my opinion,
Kappos 2006 . . . disclose[s] that single dosage forms
were readily available in 120 mg units (“120 mg by
mouth once daily”), making dose ranges of 480 mg daily
and 600 mg daily readily apparent intervals for further
testing. Further, ClinicalTrials . . . indicates that side
effects such as gastrointestinal distress were known and
were enough of a concern, that dosing could be reduced“for subjects who are unable to tolerate investigational
drug” (Ex. 1022, page 2). Joshi also discloses unwanted
side effects from the administration of the drug (“By
administration of the dialkyl fumarates in the form of
micro-tablets, which is preferred, gastrointestinal
irritations and side effects, which are reduced already
when conventional tablets are administered but is still
observed, may be further reduced vis-a-vis fumaric acid
derivatives and salts.” Ex. 1030, col. 5:29 – 33.) Becauseside effects are always a concern in drug development, as
they were for DMF, and because doses in multiples of
120 mg were readily available, a POSITA, in my opinion,
would have been motivated to develop a method of
treating a subject in need of treatment for multiple
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sclerosis by administering dimethyl fumarate at about
480 mg per day (as well as 600 mg per day) in order to
identify an appropriate dose of DMF that minimized sideeffects. It would have been apparent to a POSITA that
the teaching of Kappos 2006 in view of at least
ClinicalTrials . . . , Joshi, and ICHGuideline E4 would
have enabled just such a development of a method such
as described at alternative dosing levels with a reasonable
expectation of success because the intervals were readily
available for a standard process of drug development.
Ex. 1005, ¶ 32.H. Discussion
1. Case for Likelihood of Obviousness
Consistent with applicable precedent, a claimed range within a range
described by the prior art is typically prima facie obvious. In re Boesch,
617 F.2d 272, 275 (CCPA 1980) (where ranges overlap, a prima facie case
of obviousness is made out). The Federal Circuit has consistently followed
Boesch. See, e.g., In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003) (a
prima facie case of obviousness typically exists when the ranges of a
claimed composition overlap the ranges disclosed in the prior art); In re
Harris, 409 F.3d 1339, 1341 (Fed. Cir. 2005) (a prima facie case of
obviousness arises when the ranges of a claimed composition are completely
encompassed by the prior art); In re Huang , 100 F.3d 135, 139 (Fed. Cir.
1996) (same).
In the case before us, Patent Owner’s range of “about 480 mg per
day” squarely falls within the combined ranges described by Kappos 2006
(720 mg/day on the high end) and Joshi ʼ999 (10 to 300 mg/day on the low
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end, it being noted that Joshi ʼ999 claim 1 calls for a broader “amount of a
pharmaceutical preparation effective for treating . . . multiplesclerosis . . . .”). The combined “effective” ranges described by Kappos
2006 and Joshi ʼ999 are consistent with Patent Owner’s statement in its
Specification that “an effective dose of DMF or MMR . . . can be from about
0.1 to 1 g [1000 mg] per [d]ay.” Ex. 1001, page 24, col. 18:59– 60.
The ICH Guideline provides convincing evidence of how a person of
ordinary skill in the art likely would go about determining an appropriate
dosage for a particular person having multiple sclerosis.
For example, if a dose is too high for a particular individual, one
skilled in the art likely would have tested lower dosages for that individual
in an attempt to find a most appropriate dose to achieve a result, all the while
minimizing side-effects.
Petitioner has made out a sufficient case to establish a reasonable
likelihood of success as to each of the independent claims.
2. Preliminary Response
The Preliminary Response asserts numerous reasons why an
inter partes review should not be instituted.
(a) Non-merits Arguments
In determining whether to institute an inter partes review, “the
Director may take into account whether, and reject the petition . . . because,the same or substantially the same prior art or arguments previously were
presented to the Office.” 35 U.S.C. § 325(d).
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According to Patent Owner, the prior art and arguments here are
the same as those made in IPR2015-01136 involving the same parties.Paper 11, pages 5 – 14. An inter partes review was not instituted in
IPR2015-01136. Coalition for Affordable Drugs V LLC v. Biogen MA Inc.,
IPR2015-01136, 2015 WL 5169256 (PTAB Sept. 2, 2015), reh’g denied ,
IPR2015-01136 (Paper 29) (PTAB Oct. 23, 2015).
In IPR2015-01136, Petitioner did not cite or rely on (1) the two Joshi
patents relied upon in this IPR or (2) Kappos 2006.
Kappos 2006 has a highly relevant and significant teaching not
present in Kappos 2005 (Ex. 1003A of IPR2015-01136). Compare the
(1) “Results” in Kappos 2006, which states that BG00012 at 720 mg/day
significantly reduced Gd+ lesions, with (2) the “Results” in Kappos 2005
detailing only what a paper based on tests might reveal.
We have taken into account the differences in prior art cited and relied
upon in IPR2015-01136 vis-à-vis the different prior art cited and relied upon
in this IPR. In view of those differences, and because we find the prior art
cited and relied upon in this IPR to be considerably more persuasive, we see
no reason for not instituting an inter partes review in this IPR.
In support of its position, Patent Owner cites numerous decisions in
other IPRs. Whether an inter partes review is instituted in a particular IPR
based on alleged obviousness manifestly depends on the precise facts.Cf. In re Jones, 958 F.2d 347, 350 (Fed. Cir. 1992). Accordingly, institution
or non-institution decisions in other IPRs based on different facts are of little
help in resolving whether to institute in the IPR before us.
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According to Patent Owner, “[t]he Board’s practice is to prevent
petitioners from using failed institution attempts as ‘how-to guide(s)’ in preparing later challenges.” Paper 11, page 15. We are unaware of any
established per se rule of this Board declining to institute based on so-called
“how-to guide(s).” While it may be true that some cases determined that it
was inappropriate to institute based on a second petition, § 325(d) gives the
Director discretion to consider the merits of a second petition, apart from
any refusal to institute on the basis of a first petition. As noted earlier,
because the prior art here is significantly different from that in IPR2015-
01136, we find that it is appropriate to institute an inter partes review in this
proceeding.
We have considered all the remaining non-merits arguments presented
by Patent Owner, but find them unpersuasive on the issue of whether an
inter parties review should be ordered in this IPR.
(b) Merits Arguments
According to Patent Owner, one skilled in the art would have had no
reason to select a dose of 480 mg/day. Paper 11, page 20.
Further according to Patent Owner, “the [P]etition presents no
evidence that one of ordinary skill based on the asserted prior art, would
have had a reasonable expectation that a dose of about 480 mg/day of DMF
would [have been] therapeutically effective or useful in treating MS asclaimed.” Id . See also Paper 11, page 25.
Still further according to Patent Owner, “one of ordinary skill would
not have been motivated to add a dose of about 480 mg/day to an already
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well-designed [Kappos 2006] Phase II study.” Paper 11, page 21, last
sentence.Patent Owner also maintains that gastrointestinal side-effects would
have provided no reason to select a dose of 480 mg/day. Paper 11, page 22.
KSR International Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007)
instructs:
Often, it will be necessary . . . to look to interrelated
teachings of multiple patents; the effects of demands
known to the design community or present in themarketplace; and the background knowledge possessed
by a person having ordinary skill in the art, all in order to
determine whether there was an apparent reason to
combine the known elements in the fashion claimed by
the patent at issue. To facilitate review, this analysis
should be made explicit. See In re Kahn, 441, F.3d 977,
988 (C.A.Fed.2006) (“[R]ejections on obviousness
grounds cannot be sustained by mere conclusory
statements; instead, there must be some articulated
reasoning with some rational underpinning to support thelegal conclusion of obviousness”). As . . . [Supreme
Court] precedents make clear, however, the analysis need
not seek out precise teachings directed to the specific
subject matter of the challenged claim, for a court can
take account of the inferences and creative steps that a
person of ordinary skill in the art would employ.
In re O’Farrell , 853 F.2d 894, 903 – 04 (Fed. Cir. 1988), further
instructs that o bviousness does not require absolute predictability of
success; all that is required is a reasonable expectation of success.
Patent Owner’s “selection” argument does not undermine a reasonable
likelihood of success on the part of Petitioner. Petitioner has not made any
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selection; rather, it is Patent Owner who selected 480 mg/day from broad
dosage ranges described in the prior art. Based on the public domain priorart before us, absent an unexpected result, a person having ordinary skill in
the art was free to use any dosage that would be effective in treating multiple
sclerosis. Further, based on ICH, we find that one skilled in the art would
have been capable of determining effective dosages vis-à-vis non-effective
dosages.
Joshi ʼ999 teaches that a dosage of range of 10 to 300 mg/day is
effective. See, e.g., claim 2 of the Joshi ʼ999 patent. Ex. 1030, page 7,
col. 8:20 – 22. Kappos 2006 teaches that a dosage of 720 mg/day is effective.
Not apparent is why dosages between 300 mg/day and 720 mg/day
reasonably would not also have been expected to be effective, a fact Patent
Owner is in somewhat of a poor position to challenge given its assertion in
the ʼ514 patent that dosages from 0.1 g/day to 1000 g/day constitute an
“effective dosage.” ClinicalTrials reveals that one skilled in the art would
have recognized that a “[d]ose reduction will be allowed for subjects who
are unable to tolerate [an] investigational drug.” Ex. 1022, page 2. Hence,
on this record there was ample reason for one skilled in the art to have
looked into dosages below 720 mg/day.
(c) Unexpected Results
Patent Owner argues that “Petitioner did not attempt to rebut theclaimed invention’s unexpected results established during prosecution.”
Paper 11, page 30. The unexpected results are said to have been established
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via ex parte Rule 132 Declarations of Dr. Katherine Dawson (Ex. 1 of
Ex. 1007) and Dr. Richard Rudick (Ex. 2011). Id. at 31.We disagree that Petitioner made no attempt to rebut the ex parte
evidence asserting unexpected results. Paper 1, pages 11 – 14.
Apart from the fact that there was a rebuttal in the Petition, there are
at least two additional reasons why Patent Owner’s “fail to rebut” argument
is not persuasive.
First , the unexpected results evidence was presented in an ex parte
examination. The results of that examination are not binding on Petitioner.
See Keystone Bridge Co. v. Phoenix Iron Co., 95 U.S. 274, 279 (1877)
(patents are procured ex parte; the public is not bound by decision of the
Patent Office to issue the patent); Sze v. Bloch, 458 F.2d 137, 140 (CCPA
1972) (decision during ex parte examination cannot be binding in
subsequent inter partes case involving same application in which decision
was made); Switzer v. Sockman, 333 F.2d 935, 767 – 8 (CCPA 1964) (same).
Second , Petitioner has not had a chance to cross-examine Dr. Dawson
or Dr. Rudick. Whether unexpected results have been established is a
question of fact. In re Harris, 409 F.3d 1339, 1341 (Fed. Cir. 2005)
(whether an invention produces an unexpected result is a question of fact);
In re Geisler , 116 F.3d 1465, 1469 (Fed. Cir. 1997) (same). At this stage of
the proceeding, resolution of whether the Dawson/Rudick showingestablishes unexpected results is a disputed question of fact, best resolved at
trial — which could include cross-examination if Patent Owner places the
Dawson/Rudick testimony in evidence as part of its opposition on the merits.
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Because the Petition establishes a prima facie case of obviousness, it
follows that Petitioner has made out a case “that there is a reasonablelikelihood that . . . [it] would prevail with respect to . . . claims [1, 11, 15,
and 20] challenged in the petition.” 35 U.S.C. § 314(a).
I. Remaining Claims and Challenges
Patent Owner does not separately address on the merits Grounds 2
and 3 or dependent claims involved in Ground 1.
We have considered the arguments made in, and evidence presented
with, the Petition and find, for the reasons given, that those arguments and
evidence support a finding that Petitioner has made out a case “that there is a
reasonable likelihood that . . . [it] would prevail with respect to . . . [the
remaining] claims [on Grounds 1, 2, and 3 as] challenged in the petition.”
35 U.S.C. § 314(a).
III. ORDER
Upon consideration of the Petition (Paper 1), the Preliminary
Response (Paper 11), and Reply to the Preliminary Response (Paper 17), and
for the reasons given, it is
ORDERED that pursuant to 35 U.S.C. § 314(a), an inter partes
review trial is hereby instituted on the following grounds.
Ground 1: claims 1 – 6, 8 – 16, and 20 of the ’514 patent as
unpatentable under § 103(a) over Kappos 2006, ClinicalTrials, Joshi ʼ999,and ICH Guideline.
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Ground 2: claim 7 of the ’514 patent as unpatentable under
§ 103(a) over Kappos 2006, ClinicalTrials, Joshi ʼ999, ICH Guideline, andJoshi ʼ992.
Ground 3: claims 17 – 19 of the ’514 patent as unpatentable
under § 103(a) over Kappos 2006, ClinicalTrials, Joshi ʼ999, ICH Guideline,
and Begleiter.
FURTHER ORDERED that inter partes review of the ʼ514
patent is hereby instituted commencing on the date of this DECISION.
35 U.S.C. § 314(a).
FURTHER ORDERED that notice is hereby given of the
institution of an inter partes review trial. 35 U.S.C. § 314(c); 37 C.F.R.
§ 42.4.
FURTHER ORDERED that the trial is limited to the grounds
and claims identified above.
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PETITIONER:
Robert W. HahlRobert Mihail
John K. Pike
NEIFELD IP LAW
James T. CarmichaelCarmichael IP, PLLC
PATENT OWNER:
Michael Flibbert
Maureen D. Queler
FINNEGAN, HENDERSON, FARABOW, GARRETT & DUNNER, LLP
mailto:[email protected]:[email protected]:[email protected]:[email protected]