Professional Documents
Culture Documents
gov
571-272-7822
Paper 20
Entered: 22 March 2016
IPR2015-01993
Patent 8,399,514 B2
I. Introduction
A. Background
A second petition seeking to institute an inter partes review in
connection with U.S. Patent No. 8,399,514 B2 (514 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), rehg denied,
IPR2015-01136 (Paper 29) (PTAB Oct. 23, 2015).
The 514 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.,
IPR2015-01993
Patent 8,399,514 B2
(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 12.
Patent Owner is Biogen MA Inc. Paper 11, page 1.
C. Abbreviations
BG00012 or BG12
Dimethyl fumarate
DMF
Dimethyl fumarate
ICH
MMF
Monomethyl fumarate
MRI
RRMS
IPR2015-01993
Patent 8,399,514 B2
D. Evidence Relied Upon2
The following evidence is relied upon in support of the Petition:
Name
Exhibit
No.
Description
Date
Because the application maturing into the 514 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.
2
IPR2015-01993
Patent 8,399,514 B2
Name
Exhibit
No.
Description
Date
22 Jan. 2008
Joshi 999
1030
U.S. Patent 7,320,999 B2
filed
17 July 2002
Joshi 999 is prior art under 35 U.S.C. 102(a) having issued prior to
Biogens PCT filing date (7 February 2008). If Biogen is entitled to a
benefit date of its Provisional Application (8 February 2007), then Joshi
999 is prior art under 35 U.S.C. 102(e) based on its filing date (17 July
2002).
ICH Harmonised Tripartite
ICH Guideline
1004
Guideline, DOSE-RESPONSE
10 Mar. 1994
INFORMATION TO SUPPORT
DRUG REGISTRATION E4
Joshi 992
1036
U.S. Patent 6,436,992 B1
20 Aug. 2002
Dietary Induction of NQOI
Increases the Antitumour
Begleiter
1027
2004
Activity of Mitomycin C in
Human Colon Tumours in
vivo,
91 BRITISH J. CANCER 1624
1631
ICH Guideline, Joshi 992, and Begleiter are prior art under 35 U.S.C.
102(b).
E. Grounds of Unpatentability
Claims 120 appear in the 514 patent. Ex. 1001, col. 27:58 through
col. 30:27.
The following grounds of unpatentability are urged in the Petition.
IPR2015-01993
Patent 8,399,514 B2
Statutory
Basis
Ground 1
103(a)
Ground 2
103(a)
Ground 3
103(a)
Prior Art
Relied On
Kappos 2006
ClinicalTrials,
Joshi 999, and
ICH Guideline
Kappos 2006,
ClinicalTrials,
Joshi 999,
ICH Guideline, and
Joshi 992
Kappos 2006,
ClinicalTrials,
Joshi 999,
ICH Guideline and
Begleiter
Claims
1719
F. Kappos 2006
The application maturing into the 514 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 Owners 7 February 2008
claim to priority based on Patent Owners 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,
IPR2015-01993
Patent 8,399,514 B2
IPR2015-01993
Patent 8,399,514 B2
IPR2015-01993
Patent 8,399,514 B2
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 514 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. ChallengeClaims 1, 11, 15, and 20
According to Petitioner, claims 16, 816, and 20 are unpatentable
under 35 U.S.C. 103(a) over a combination of (1) Kappos 2006,
(2) ClinicalTrials, (3) Joshi 999, 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,
IPR2015-01993
Patent 8,399,514 B2
10
IPR2015-01993
Patent 8,399,514 B2
IPR2015-01993
Patent 8,399,514 B2
IPR2015-01993
Patent 8,399,514 B2
IPR2015-01993
Patent 8,399,514 B2
14
IPR2015-01993
Patent 8,399,514 B2
According to Joshi 999:
The dialkyl fumarates used according to the
invention 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. 4:3948 (italics added).
Joshi 999 differs from the subject matter of claims 1, 11, 15,
and 20 of the 514 patent in that Joshi 999 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, drugconcentration in blood, and clinical response
(effectiveness and undesirable effects) is important for
the 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
15
IPR2015-01993
Patent 8,399,514 B2
16
IPR2015-01993
Patent 8,399,514 B2
17
IPR2015-01993
Patent 8,399,514 B2
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 514 patent vis--vis (2) Joshi 999 and Kappos 2006, Dr. Linberg
testifies:
In my opinion, the ICH Guideline E4 would have
instructed 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.
18
IPR2015-01993
Patent 8,399,514 B2
IPR2015-01993
Patent 8,399,514 B2
IPR2015-01993
Patent 8,399,514 B2
end, it being noted that Joshi 999 claim 1 calls for a broader amount of a
pharmaceutical preparation effective for treating . . . multiple
sclerosis . . . .). The combined effective ranges described by Kappos
2006 and Joshi 999 are consistent with Patent Owners 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. 18:5960.
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).
21
IPR2015-01993
Patent 8,399,514 B2
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 514. 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), rehg 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--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.
22
IPR2015-01993
Patent 8,399,514 B2
According to Patent Owner, [t]he Boards 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 IPR201501136, 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 as
claimed. 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
23
IPR2015-01993
Patent 8,399,514 B2
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 the
marketplace; 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 the
legal 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 OFarrell, 853 F.2d 894, 90304 (Fed. Cir. 1988), further
instructs that obviousness does not require absolute predictability of
success; all that is required is a reasonable expectation of success.
Patent Owners selection argument does not undermine a reasonable
likelihood of success on the part of Petitioner. Petitioner has not made any
24
IPR2015-01993
Patent 8,399,514 B2
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 prior
art 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--vis non-effective
dosages.
Joshi 999 teaches that a dosage of range of 10 to 300 mg/day is
effective. See, e.g., claim 2 of the Joshi 999 patent. Ex. 1030, page 7,
col. 8:2022. 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 514 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 the
claimed inventions unexpected results established during prosecution.
Paper 11, page 30. The unexpected results are said to have been established
25
IPR2015-01993
Patent 8,399,514 B2
26
IPR2015-01993
Patent 8,399,514 B2
27
IPR2015-01993
Patent 8,399,514 B2
Ground 2: claim 7 of the 514 patent as unpatentable under
103(a) over Kappos 2006, ClinicalTrials, Joshi 999, ICH Guideline, and
Joshi 992.
Ground 3: claims 1719 of the 514 patent as unpatentable
under 103(a) over Kappos 2006, ClinicalTrials, Joshi 999, ICH Guideline,
and Begleiter.
FURTHER ORDERED that inter partes review of the 514
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.
28
IPR2015-01993
Patent 8,399,514 B2
PETITIONER:
Robert W. Hahl
Robert Mihail
John K. Pike
NEIFELD IP LAW
rhahl@neifeld.com
rmihail@neifeld.com
jkpike@neifeld.com
general@neifeld.com
James T. Carmichael
Carmichael IP, PLLC
jim@carmichaelip.com
PATENT OWNER:
Michael Flibbert
Maureen D. Queler
FINNEGAN, HENDERSON, FARABOW, GARRETT & DUNNER, LLP
michael.flibbert@finnegan.com
maureen.queler@finnegan.com
29