Bass Biogen

For the Patent Owner
Backup counsel: Robert W. Hahl, Reg. No. 33,893

Backup counsel: Robert Mihail, Reg. No. 66,021
Neifeld IP Law, PC
Paper No. __
UNITED STATES PATENT AND TRADEMARK OFFICE

____________
BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________
Coalition For Affordable Drugs V LLC
Petitioner
v.
Biogen IDEC International GmbH
Patent Owner
____________
Case IPR Unassigned
Patent 8,759,393
Title: UTILIZATION OF DIALKYLFUMARATES
____________
PETITION FOR INTER PARTES REVIEW OF

U.S. PATENT NO. 8,759,393
UNDER 35 U.S.C. 312 AND 37 C.F.R. 42.104
Mail Stop PATENT BOARD

U.S. Patent Trial & Trademark Office
P.O. Box 1450
Alexandria, VA 22313-14
TABLE OF CONTENTS
I. INTRODUCTION .............................................................................................1
II.
MANDATORY NOTICES ............................................................................2
A.
Real Party-In-Interest 37 C.F.R. 42.8(b)(1) ...............................................2
B.
Related Matters 37 C.F.R. 42.8(b)(2).........................................................3
C.
Designation of Lead and Backup Counsel 37 C.F.R. 42.8(b)(3) ...............3
D.
Notice of Service Information (37 C.F.R. 42.8(b)(4)) ...............................4
III. FEES 37 C.F.R. 42.15(a) .............................................................................4

IV. REQUIREMENTS UNDER 37 C.F.R. 42.104..........................................4
A.
Grounds for Standing 37 C.F.R. 42.104(a) ................................................4
B.
Identification of Challenge and Precise Relief Requested 37 C.F.R.
42.104(b) .................................................................................................................4
2. Specific Statutory Grounds for Challenge 42.104(b)(2) ..................................5
V.
UNPATENTABILITY OF THE 393 PATENT .........................................6
A.
Brief History of dimethyl fumarate therapy ..................................................6
B.
Prosecution History of the 393 Patent .........................................................8
C.
Person of Ordinary Skill in the Art .............................................................10

i
D.
Claim Construction......................................................................................11
VI. DETAILED EXPLANATION OF THE CHALLENGES........................22

A.
Ground 1: Claims 1, 2, and 8 are anticipated by Nieboer ...........................22
B.
Ground 2: Claims 1-13 are obvious over Nieboer in view of Kolter..........26
VII.
CONCLUSION ..........................................................................................52
ii
TABLE OF AUTHORITIES
Cases
In re Cuozzo Speed Technologies, LLC, 2014-1301 (Fed. Cir. 2015) .....................18
KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007) ........................... 31, 32
Titaniium Metals Corp. v. Banner, 778 F.2d 775 (Fed. Cir. 1985) ...... 38, 40, 48, 57
Verdegaal Bros. v. Union Oil Co. of California, 814 F.2d 628 (Fed. Cir. 1987)....21
Statutes
35 U.S.C. 102 ............................................................................................... 5, 6, 23
35 U.S.C. 103 ................................................................................................... 6, 26
Rules
37 C.F.R. 42.82, 3, 8
37 C.F.R. 42.15..4
37 C.F.R. 42.22..6
37 C.F.R. 42.100..11
37 C.F.R. 42.104....4, 5
iii
LIST OF EXHIBITS
Exhibit 1001
U.S.
Patent
No.
8,759,393,
titled
Utilization
of
Dialkylfumarates to Joshi et al. (393 patent)

Exhibit 1002
C. Nieboer, et al., Systemic therapy with fumaric acid

derivatives: New possibilities in the treatment of psoriasis,
Journal of the American Academy of Dermatology, April 1989
Vol. 20, Number 4, pg. 601-608 (Nieboer)
Exhibit 1003
U.S. Patent No. 5,681,588, titled Delayed Release Microtablet

of -Phenylpropiophenone Derivatives to Kolter et al. (Kolter)
Exhibit 1004
Declaration of Dr. James E. Polli
Exhibit 1005
Prosecution history of the 393 patent as contained in the Image

File Wrapper on PAIR
Exhibit 1006
Assignment record of the 393 patent as contained in USPTOs

Assignments on The Web at
http://assignment.uspto.gov/#/search?adv=patNum%3A875939
3&q=&sort=patAssignorEarliestExDate%20desc%2C%20id%2
0desc&synonyms=false
Exhibit 1007
Julian H. Fincher, Dictionary of Pharmacy, University of South

Carolina Press, 1986
iv
Exhibit 1008
PubChem entry for Dimethyl Fumarate, U.S. National Library

of Medicine, National Center for Biotechnology Information,
the National Institute of Health at
https://pubchem.ncbi.nlm.nih.gov/compound/637568
Exhibit 1009
Dean E. Snyder, The Interpharm International Dictionary of

Biotechnology and Pharmaceutical Manufacturing, Interpharm
Press, Inc., 1992
Exhibit 1010
Friedrick Moll et al., Biodegradable Microtablets Made of Low

Molecular Weight Polyglycolic Acid, 1991
Exhibit 1011
Unassigned
Exhibit 1012
Curriculum Vitae of Dr. James E. Polli
Exhibit 1013
Nieboer et al., Fumaric Acid Therapy in Psoriasis: A DoubleBlind Comparison between Fumaric Acid Compound Therapy
and
Monotherapy
with
Dimethylfumaric
Acid
Ester
Dermatologica 1990; 181:33- 37

Exhibit 1014
Kokelj et al., Fumaric Acid and Its Derivatives in the Treatment

of Psoriasis Vulgaris: Our Experience in Forty-One Patients,
Acta Dermatovenerol Croat, 2009; 17(3):170-175
Exhibit 1015
FDA News Release, FDA approves new multiple sclerosis

treatment: Tecfidera, available at
v
http://www.fda.gov/NewsEvents/Newsroom/PressAnnounceme
nts/ucm345528.htm
Exhibit 1016
Follonier et al., Various ways of modulating the release of

diltiazem hydrochloride from hot-melt extruded sustained
release pellets prepared using polymeric materials., Journal of
Controlled Release 36 (1995) 243-250
Exhibit 1017
Conine et al., Special Tablets, Pharmaceutical Dosage Forms,

Marcel Dekker, Inc., 1989, 329-366
vi
I.
INTRODUCTION
The 393 patent, entitled Utilization of Dialkylfumarates and filed on
March 4, 2011 is a continuation of application no. 12/405,665 (now US 7,915,310)

filed on March 17, 2009, which is a continuation of application no. 11/765,578
(now US 7,619,001) filed on June 20, 2007, which is a continuation of application
no. 10/197,077 (now US 7,320,999) filed on July 17, 2002 which is a division of
application no. 09/831,620 (now US 6,509,376) filed on May 10, 2001 which is the
National Stage Entry of PCT/EP99/08215 filed on October 29, 1999 and published
in German on June 2, 2000, which claims priority to German application no.
19853487 filed on November 19, 1998. (Ex. 1005). The 393 patent was originally
assigned to Fumapharm AG. Fumapharm AG was acquired by Biogen IDEC
International AG in 2006 and the 393 patent was assigned to Biogen IDEC
International AG on May 15, 2007. (Ex. 1006). Biogen IDEC International AG
changed its name to Biogen IDEC International GMBH on May 15, 2007. (Ex.
1006).
In accordance with 35 U.S.C. 311-319 and 37 C.F.R. 42.1-.80 &
42.100-123, inter partes review is respectfully requested for claims 1-13 of U.S.
Patent No. 8,759,393 to Joshi et al., titled Utilization of Dialkylfumarates (393
patent) (Ex. 1001). This petition demonstrates that there is a reasonable likelihood
that the petitioner will prevail on at least one of the claims challenged in the
1
petition based on one or more prior art references. For the reasons provided herein,
claims 1-13 of the 393 patent should be canceled as unpatentable.
II. MANDATORY NOTICES
A.
Real Party-In-Interest 37 C.F.R. 42.8(b)(1)
Pursuant to 37 C.F.R. 42.8(b)(1), Petitioner certifies that Coalition For

Affordable Drugs V LLC (CFAD), Hayman Credes Master Fund, L.P.
(Credes), Hayman Orange Fund SPC Portfolio A (HOF), Hayman Capital
Master Fund, L.P. (HCMF), Hayman Capital Management, L.P. (HCM),
Hayman Offshore Management, Inc. (HOM), Hayman Investments, L.L.C.
(HI), nXn Partners, LLC (nXnP), IP Navigation Group, LLC (IPNav), J
Kyle Bass, and Erich Spangenberg are the real parties in interest (collectively,
RPI). The RPI hereby certify the following information: CFAD is a wholly
owned subsidiary of Credes. Credes is a limited partnership. HOF is a segregated
portfolio company. HCMF is a limited partnership. HCM is the general partner
and investment manager of Credes and HCMF. HCM is the investment manager of
HOF. HOM is the administrative general partner of Credes and HCMF. HI is the
general partner of HCM. J Kyle Bass is the sole member of HI and sole
shareholder of HOM. CFAD, Credes, HOF and HCMF act, directly or indirectly,
through HCM as the general partner and/or investment manager of Credes, HOF
and HCMF. nXnP is a paid consultant to HCM. Erich Spangenberg is 98.5%
2
member of nXnP. IPNav is a paid consultant to nXnP. Erich Spangenberg is the

98.5% member of IPNav. Other than HCM and J Kyle Bass in his capacity as the
Chief Investment Officer of HCM and nXnP and Erich Spangenberg in his
capacity as the Manager/CEO of nXnP, no other person (including any investor,
limited partner, or member or any other person in any of CFAD, Credes, HOF,
HCMF, HCM, HOM, HI, nXnP or IPNav) has authority to direct or control (i) the
timing of, filing of, content of, or any decisions or other activities relating to this
Petition or (ii) any timing, future filings, content of, or any decisions or other
activities relating to the future proceedings related to this Petition. All of the costs
associated with this Petition will be borne by HCM, CFAD, Credes, HOF and/or
HCMF.
B.
Related Matters 37 C.F.R. 42.8(b)(2)
To the best of Petitioners knowledge, there are no pending litigations or

other related matters related to the 393 patent that would affect, or be affected by,
a decision in this proceeding.
C.
Designation of Lead and Backup Counsel 37 C.F.R. 42.8(b)(3)
Pursuant to 37 C.F.R. 42.8(b)(3) and 42.10(a), Petitioner hereby

identifies its lead and backup counsel as shown below. A Power of Attorney is
being filed concurrently herewith in accordance with 37 C.F.R. 42.10(b).
Lead Counsel for Petitioner

Robert W. Hahl, Reg. No. 33,893
Neifeld IP Law, PC, 4813-B
Eisenhower Avenue, Alexandria, VA
22304
Tel: 1-703-415-0012 Ext. 103
Fax: 1-703-415-0013
Email: rhahl@neifeld.com
Backup Counsel for Petitioner

Robert Mihail, Reg. No. 66,021
Neifeld IP Law, PC, 4813-B
Eisenhower Avenue, Alexandria, VA
22304
Tel: 1-703-415-0012 Ext. 107
Fax: 1-703-415-0013
Email: rmihail@neifeld.com
D.
Notice of Service Information (37 C.F.R. 42.8(b)(4))
Please direct all correspondence to counsel at the above address. Petitioner

consents to email service at: rhahl@neifeld.com; and rmihail@neifeld.com.
III. FEES 37 C.F.R. 42.15(a)
Petitioner authorizes the Director to charge the fee specified by 37 C.F.R.
42.15(a) and any additional fees associated with this Petition to Deposit Account
No. 50-2106.
IV. REQUIREMENTS UNDER 37 C.F.R. 42.104
A.
Grounds for Standing 37 C.F.R. 42.104(a)
In accordance with 37 C.F.R. 42.104(a), Petitioner certifies that the

393 patent is available for inter partes review. Petitioner further certifies that
Petitioner is not barred or estopped from requesting an inter partes review
challenging the 393 patent on the grounds identified in this Petition.
B.
Identification of Challenge and Precise Relief Requested 37 C.F.R.
42.104(b)
4
1.
Patents and Printed Publications 37 C.F.R. 42.104(b)(2)
Petitioner relies on the following patents and printed publications to support

its grounds of challenge to claims 1-13 of the 393 patent in this Petition:
1. Nieboer, D. de Hoop, A.C. van Loenen, P.N.J. Langendijk, and E. van Dijk,
Systemic therapy with fumaric acid derivatives: New possibilities in the
treatment of psoriasis, Journal of the American Academy of Dermatology,
April 1989 (Nieboer). Ex. 1002. Nieboer is a printed publication at least under
35 U.S.C. 102(b) (pre-AIA) because it was published, catalogued, and
shelved at least as early as April 3, 1989, as can be seen on the University of
Wisconsin library intake stamp, more than one year prior to November 19,
1998, the earliest effective filing date for the claims of the 393 patent.
2. U.S. Patent No. 5,681,588, titled Delayed Release Microtablet of Phenylpropiophenone Derivatives to Kolter et al. (Kolter). Ex. 1003. Kolter is
a patent at least under 35 U.S.C. 102(b) (pre-AIA) because it was published
more than one year prior to November 19, 1998, the earliest effective filing date
for the claims of the 393 patent.
2.
Specific Statutory Grounds for Challenge 42.104(b)(2)
Petitioner challenges claims 1-13 (the challenged claims) of the 393 patent
on the following grounds:
Ground 1: Claims 1, 2, and 8 are unpatentable under 35 U.S.C. 102(b) as

anticipated by Nieboer.
Ground 2: Claims 1-13 are unpatentable under 35 U.S.C. 103 as obvious
over Nieboer in view of Kolter.
None of these grounds is redundant. Challenged claims 1, 2, and 8 are
challenged in Ground 1 by a single reference and in Ground 2 by a combination of
references.
This Petition, supported by the Declaration of Dr. James Polli (Ex 1004)
filed with this Petition, demonstrates that there is a reasonable likelihood that
Petitioner will prevail with respect to at least one of the challenged claims and that
each of the challenged claims is unpatentable for the reasons cited in this Petition.
See 35 U.S.C. 314(a).
In accordance with 37 C.F.R. 42.22, Petitioner respectfully requests
cancellation of claims 1-13 of the 393 patent.
V. UNPATENTABILITY OF THE 393 PATENT
A.
Brief History of dimethyl fumarate therapy
Since at least 1969, fumaric acid was reported to have been a popular
treatment for psoriasis. Ex. 1002, Abstract. In 1966, Schweckendiek, a biochemist
who himself had psoriasis, introduced fumaric acid esters such as
monoethylfumaric ester (MEFAE) and dimethylfumaric ester (DMFAE) as a
6
treatment because fumaric acid was poorly absorbed by the gastrointestinal tract.
Ex. 1002, p601, 2:2-7. Fumaderm, a closely related product to the claimed
invention, comprises a combination of dimethyl fumarate1 with other fumaric acid
esters and was approved in Germany in 1994 for the treatment of psoriasis. See
Ex. 1014, Summary and p173, 2:12-16. However, several years prior to the
approval of Fumaderm, dimethyl fumarate monotherapies were being conducted.
Nieboer et al. found dimethyl fumarate given as enteric coated (EC) tablets given
orally were effective for treating psoriasis (Ex. 1013, Abstract and p34, 1:1-9,
narrative following Table I), concluding that [i]n summary one could state that the
treatment of psoriasis with FAC-EC (fumaric acid combination enteric coated)
does not result in a better therapeutic result compared to DMFAE-EC
(dimethylyfumaric acid ester enteric coated) monotherapy. Ex. 1013, p37, 1:1-3.
In March of 2013, the FDA approved the use of dimethyl fumarate monotherapy
for the treatment of multiple sclerosis in the United States. Ex. 1015, p1.
As Dr. Polli attests and as supported by Ex. 1008, dimethyl fumarate may be
referred to by any of several common, interchangeable names including dimethyl

fumaric acid; DMF; fumaric acid dimethyl ester; dimethylfumaric acid ester;
DMFAE; as well as the IUPAC designation of dimethyl (E)-but-2-enedioate. Ex.
1004, 20.
7
B.
Prosecution History of the 393 Patent
The 393 patent was filed on March 4, 2011 and claims priority to German
application no. 19853487 filed on November 19, 1998. The prosecution history
shows that applicant used the terms tablets, micro-tablets, pellets, and
granulates without patentable distinction. Initially submitted claims 6 and 16
refer to the active ingredient being formulated in the form of tablets, microtablets, pellets or granulates, optionally in capsules or sachets and tablets, microtablets, pellets in capsules or sachets, respectively. Ex. 1005, p 585-86. On July
22, 2011, Applicant submitted a preliminary amendment cancelling all the claims
and submitting 13 new claims. Ex. 1005, pp542-43. The new claims recite only
the term micro-tablets.
On November 26, 2012, an Office Action was issued rejecting the newly
added claims on four separate grounds of nonstatutory obviousness-type double
patenting over certain claims of U.S. Patent No. 6,277,882 (microtablets
comprising one alkyl hydrogen fumarate and optionally in admixture with dialkyl
fumarate) to Joshi et al. and assigned to Fumapharm AG; U.S. Patent No.
6,335,676 [sic] (microtablets comprising one alkyl hydrogen fumarate and
optionally in admixture with dialkyl fumarate)2, U.S. Patent No. 6,509,376

(microtablets comprising one alkyl hydrogen fumarate and optionally in admixture
with dialkyl fumarate) to Joshi et al. and assigned to Fumapharm AG; and U.S.
Patent No. 7,915,310 (microtablets with dimethyl fumarate as the active ingredient
in dosage ranges from 10mg to 300mg) to Joshi et al. and assigned to Biogen Idec
International GmbH. Ex. 1005, p124-33.
In response to the Office Action of November 26, 2012, Applicant agreed to
submit terminal disclaimers over the 376 and the 310 patents and requested
reconsideration of the grounds for rejection over the 882 and 676 patents. Ex.
1005, p103-10. In the Office Action of April 26, 2013 the rejections over the 376
and the 310 patents were maintained by the USPTO while the rejections over the
882 and the 676 patents were withdrawn in view of the of Applicants previous
response. Ex. 1005, p94-100. On October 16, 2013 terminal disclaimers were
filed over the 376 and the 310 patents. Ex. 1005, p85-86. On February 14, 2014,
The patent number is in error because U.S. Patent No. 6,335,676 is entitled
Radio selective call receiver. The correct patent number should be U.S. Patent
No. 6,355,676 as evidenced in Footnote 1 of Applicants Remarks filed on
February 26, 2013 in response to the Office Action issued on November 26, 2012.
Ex. 1005, p106.
9
a notice of allowance was issued and the 393 patent was granted on June 24, 2014.
Ex. 1005, p15-17. The Examiner never entered a substantive rejection against any
of the pending claims nor was any prior art cited against the claims by the
Examiner during prosecution of the 393 patent in any Office Action. Ex. 1005.
The Examiner issued 393 patent claims 1-13 that only claim a
pharmaceutical preparation in the form of microtablets containing the active
pharmaceutical ingredient, dimethyl fumarate. Ex. 1001, 8:21-57. The 393 patent
claims do not claim a method of making the active pharmaceutical ingredient, but
instead only claim the pharmaceutical preparation. The 393 patent claims do not
claim a method of use of the active pharmaceutical. More importantly, the 393
patent claims do not claim to a method of making the preparation, generally, nor to
a method of making microtablets specifically.
C.
Person of Ordinary Skill in the Art
The level of skill in the art at the time of the alleged invention may be
derived from a review of the relevant prior art. Petitioner submits an expert
declaration from Dr. Polli, Professor of Pharmaceutical Sciences and Ralph F.
Shangraw/Noxell Endowed Chair in Industrial Pharmacy and Pharmaceutics at the
University Of Maryland School Of Pharmacy. (Ex. 1004) Dr. Polli attests that a
person of ordinary skill in the art (POSITA) at the time of the alleged invention of
the 393 patent would have held a Ph.D. in industrial pharmacy, pharmaceutics or
10
pharmaceutical sciences or a related discipline, or a Pharm D degree; additionally

he or she would have had at least 3 years of experience with pharmaceutical
preparation and formulation of orally administered medicines. Ex. 1004, 11.
D.
Claim Construction
The claims in an inter partes review should be accorded the broadest

reasonable construction, as commonly understood by those of ordinary skill in the
art in light of the specification of the patent in which it appears. See 37 C.F.R.
42.100(b). The Federal Circuit has recently affirmed the broadest reasonable
interpretation standard. See In re Cuozzo Speed Technologies, LLC 2014-1301, 16
(Fed. Cir. 2015) (stating We conclude that Congress implicitly adopted the
broadest reasonable interpretation standard in enacting the AIA.). Petitioner
contends that all of the terms in the challenged claims should be given their plain
and ordinary meaning.
Microtablets
The term microtablets or micro-tablets is used throughout the 393
patent, including in:
the abstract of the 393 patent, [t]he present invention relates to the use of
certain dialkyl fumarates for the preparation of pharmaceutical preparationsin
the micro-tablets;
11
certain dialkyl fumarates for preparing pharmaceutical preparationsin the

form of micro-tablets and micro-pellets containing these dialkyl fumarates. Ex.
1001, 3:1-6.
Preparations in the form of micro-tablets or pellets, optionally filled in
capsules or sachets are preferred Ex. 1001, 4:26-28;
According to a preferred embodiment, the size or the mean diameter,
respectively, of the pellets or micro-tablets is in the range from 300 to 2,000 m
Ex. 1001, 4:41-43;
In addition to the preparations for peroral administration in the form of
micro-pellets, micro-tablets, capsules Ex. 1001, 4:54-55;
This means that enteric-coated micro-tablets in the same dosage are
distributed already in the stomach and passed to the intestine in portions Ex. 1001,
5:41-42; and other locations in the 393 patent.
Dr. Polli explains that the claimed term, microtablets, is not defined in the
393 patent. Ex. 1004, 25. Moreover, a POSITA would have understood that the
term, microtablets, does not carry a special meaning in the pharmaceutical arts.
Id. Rather, the broadest reasonable interpretation of the term, microtablets, in
light of the 393 patent specification, is simply any oral solid pharmaceutical
preparation forms small enough to be filled into capsules. Id.
12
Dr. Polli attests that the 393 patent not only does not provide a definition
for the term microtablets, but in fact uses the terms granulates, pellets,
micro-pellets, tablets, and micro-tablets interchangeably and without any
distinction. Ex. 1004, 26. First, the 393 patent does not disclose that the
function of granulates, pellets, micro-pellets, tablets and micro-tablets
differs in any way. The 393 patent discloses that granulates, pellets, micropellets, tablets and micro-tablets are suitable pharmaceutical preparations for
the invention citing Ex. 1001, 4:54-59. Id. The 393 patent states that the object of
the invention is to use certain dialkyl fumarates for preparing pharmaceutical
preparationsin the form of micro-tablets and micro-pellets containing these
dialkyl fumarates. citing Ex. 1001, 3:1-6. Id. The 393 patent also states:
Preferably, the active ingredients are used for preparing oral preparations in the
form of tablets, micro-tablets, pellets or granulates, optionally filled in capsules or
sachets. citing Ex. 1001, 4:25-26. Id. Also, the 393 patent states: In addition
to the preparations for peroral administration in the form of micro-pellets, microtablets, capsules (such as soft and hard gelatin capsules), granulates and tablets
cited above, .Pharmaceutical preparations in the form of micro-tablets or micropellets are preferred for the therapy of all autoimmune diseases mentioned above
citing Ex. 1001, 4:54-65. Id. In sum, Dr. Polli attests that the 393 patent discloses
that granulates, pellets, micro-pellets, tablets and micro-tablets do not
13
differ in function because they are all suitable pharmaceutical preparations for the
invention. Id.
Second, Dr. Polli attests that the 393 patent does not define that
granulates, pellets, micro-pellets, tablets and micro-tablets have any
difference in size. Ex. 1004, 27. The only mention of size in the description
section of the 393 patent is in column 4:41-44. Id. Dr. Polli points out that 393
patent states in column 4:41-44: According to a preferred embodiment, the size or
mean diameter, respectively, of the pellets or micro-tablets is in the range from 300
to 2,000 m . Id. This would have indicated to a POSITA that the pellets
and micro-tablets can have the same size, since they may take any size within the
range of 300 to 2,000m. Id. In Examples 1-4, the 393 patent does not disclose
that granulates, pellets, micro-pellets, tablets and micro-tablets have
any distinction in size. Id. Example 1 is titled, Preparation of Enteric-Coated
Micro-Tablets in Capsules, but refers to the preparation as containing
granulates, tablets and micro-tablets that are enteric coated that are filled
into capsules citing Ex. 1001, 6:3-47. Id. Example 1 of the 393 patent does not
disclose that that there is a difference in size between granulates, micro-tablets, or
tablets. Id. Example 2 is titled, Preparation of Enteric-Coated Micro-Tablets in
Capsules, but refers to the preparation as containing tablets or micro-tablets that
are enteric coated then filled into capsules citing Ex. 1001, 6:48-7:7. Id. Example
14
2 of the 393 patent discloses that the tablets and the enteric coated micro-tablets
that are filled into capsules are 2 mm in diameter, and thereby teaches that the size
of the tablets and micro-tablets are the same citing Ex. 1001, 6:64-7:7. Id.
Example 3 is titled, Preparation of Micro-Pellets in Capsules, but refers to the
preparation as being pellets or micro-pellets that are coated with Kollidon K-30 are
that filled into capsules citing Ex. 1001, 7:8-25. Id. Example 3 of the 393 patent
does not disclose that there is a difference in size between the pellets and micropellets citing Ex. 1001, 6:64-7:7. Id. Example 4 describes granulates filled into
enteric coated capsules citing Ex. 1001, 7:26-53. Id. In Dr. Pollis opinion, a
POSITA would find that Examples 1-4 in the 393 patent show that granulates,
pellets, micro-pellets, tablets and micro-tablets do not differ in size. Id.
Third, Dr. Polli attests that the 393 patent specification uses the terms
granulates, pellets, micro-pellets, tablet and micro-tablet
interchangeably. Ex. 1004, 28. Dr. Polli points out that the 393 patent states:
The present invention relates to the use of dialkyl fumarates for preparing
pharmaceutical preparations for use in transplantation medicine or the therapy of
autoimmune diseases and pharmaceutical preparations in the form of micro-tablets
or micro-pellets containing dialkyl fumarates citing Ex. 1001, 1:15-19. Id. By
this statement, the 393 patent acknowledges that micro-tablets and micro-pellets
are interchangeable terms having the same meaning. Id. The 393 patent
15
Examples 1-4 use the terms granulates, pellets, micro-pellets, tablets and
micro-tablets interchangeably. Id. Example 1 uses the terms micro-tablet and
tablet interchangeably. Id. The title of Example 1 refers to Preparation of
Enteric-Coated Micro-Tablets in Capsules, while the protocol itself uses
granulates, tablets, and micro-tablets interchangeably citing Ex. 1001, 6:3-47. Id.
Example 2 uses the terms tablet and micro-tablet interchangeably. Id. The
title of Example 2 refers to Preparation of Enteric-Coated Micro-Tablets in
Capsules while the protocol itself describes making enteric coated tablets
citing Ex. 1001, 6:48-7:7. Id. Example 3 uses the terms pellets and micropellets interchangeably. Id. The title of Example 3 refers to Preparation of
Micro-Pellets in Capsules..., while the protocol itself uses the word pellets four
times, ending with: After that, the pellets are filled into hard gelatine capsules
(126.5 mg pellets/capsule) citing Ex. 1001, 7:8-25. Id. Example 4 uses the term
granulates filled into a capsule. Id. Example 4 describes making a powder
mixture that is processed into a granulate in the customary manner and filled
into suitable capsules and may also be filled into suitable enteric-coated
capsules citing Ex. 1001, 7:26-53. Id. In Dr. Pollis opinion, a POSITA would
find that the 393 patents usage of the terms granulates, pellets, micropellets, tablets and micro-tablets indicate that these are interchangeable terms
that mean the same thing. Id.
16
Fourth Dr. Polli attests that the 393 patent does not disclose that
granulates, pellets, micro-pellets and micro-tablets have any distinction as
to how they are made. Ex. 1004, 29. Moreover, Dr. Polli attests that the 393
patent does not teach that the micro-tablet has to be made in any particular way.
Id. The 393 patent discloses that the tablets or micro-pellet is made in classical
tableting processes citing Ex. 1001, 5:60-61. Id. Also, Dr. Polli points out that the
393 patents discloses [i]nstead of such classical tableting processes, other
methods for the preparation of tablets may be used, such as direct tableting and
processes for preparing solid dispersions in according with the melt method and
the spray drying method citing Ex. 1001, 5:61-65. Id. Dr. Polli attests that in
Examples 1 and 2, the 393 patent discloses that the tablets are made via
compression citing Ex. 1001, 6:25-64. Id. Dr. Polli attests that in Example 3, the
393 patent discloses that the Micro-Pellets are made via spraying onto
nonpareilles pellets citing Ex. 1001, 7:10-18. Id. Dr. Polli attests that in
Example 4, the 393 patent discloses that granulates are made via wet granulation
citing Ex. 1001, 7:42. Id. Dr. Polli attests that, moreover, a POSITA would have
known that classical tableting making processes for the 393 patent granulates,
pellets, micro-pellets and micro-tablets would not only include compression
and spraying but, also for example, hot-melt extrusion (see Ex 1016), and tablet
molding methods where a wet mortar mix is molded into tablets and then dried
17
(see Ex. 1017, p336-339). Id. In sum, the 393 patent claim term, micro-tablets
does not require a particular tablet making process. Id.
Dr. Polli attests that the 393 patents method of making microtablets is
consistent with prior art tablet making processes. Ex. 1004, 30. For example,
microtablets are well known to be made via wet granulation (such as in 393
patents Example 4) or dry granulation. Id. Spray drying (such as 393 patents
example 3) is a classic method to make microtablets. Id. Microtablets can be
made via compression (such as 393 patents Examples 1 and 2) or via a melt, as
performed by Moll. Ex. 1010, p940. Id. A POSITA would have known that
microtablets can also be manufactured via molding (i.e. to make molded tablets),
as described by Conine et al. (see Ex. 1017, p336-339) or can also be manufactured
via hot-melt extrusion, as performed by Follonier. Ex. 1016. Id.
Fifth, Dr. Polli attests that the 393 patent claims do not recite a distinction
between the terms, granulate, pellets, micro-pellets, tablets and microtablets. Ex. 1004, 31. The 393 patent claims 1-13 only use the term
microtablets. Id.
Independent claims 1 and 8 do not limit the size of the claimed microtablets.
Claim 3, depending on claim 1, recites a mean diameter size in the range of 300
m to 2,000 m exclusive of any coating on the microtablets. Claim 4, ultimately
depending on claim 1, recites the mean diameter of the microtablets is about 2,000
18
m, exclusive of any coating on the microtablets. Claim 9, depending on

independent claim 8, recites microtablets having a core size of mean diameter
about 2,000 m, exclusive of any coating on the microtablets. Thus, based on the
doctrine of claim differentiation, the size of microtablets as recited in claims 1 and
8 is not limited. Because the size of microtablets as recited in claims 1 and 8 is
not limited, Dr. Polli attests that the claim term microtablets encompasses
granulates, pellets, micro-pellets, tablets and micro-tablets even if
arguably there could be a size difference. Id.
Claim 13 likewise recites a mean diameter of the microtablets is about
2,000 m, exclusive of any coating on the microtablets. In Dr. Pollis opinion the
term microtablets does not require any particular size, therefore microtablets in
claim 13 encompasses granulates, pellets, micro-pellets, tablets and
micro-tablets even if arguably there could be a size difference between these
forms. Ex. 1004, 31.1
Independent claims 1 and 8 do not limit the amount of the dimethyl fumarate
in the preparation. Claim 5, ultimately depending on claim 1, recites that the
preparation contains 10 mg to 300 mg of dimethyl fumarate. Claim 10, ultimately
depending on claim 8, recites that the preparation contains 10 mg to 300 mg of
dimethyl fumarate. The amount of dimethyl fumarate as recited in claim 1 and 8
therefore covers any amounts of dimethyl fumarate. Based upon claim
19
differentiation, the term microtablets as recited in claims 1 and 8 does not

require any specific amount of dimethyl fumarate. Dr. Polli attests that the term
microtablets encompasses granulates, pellets, micro-pellets, tablets and
micro-tablets even if arguably there could be a dosing difference between these
forms. Ex. 1004, 31.2.
Claim 13 likewise recites that the preparation contains 10 mg to 300 mg of
dimethyl fumarate. Because claim 13 limits the dosage amount with this additional
limitation, the term microtablets alone in claim 13 does not require any specific
amount of dimethyl fumarate. Dr. Polli attests that because the term
microtablets does not alone limit the claim to any specific amount of dimethyl
fumarate, microtablets encompasses granulates, pellets, micro-pellets,
tablets and micro-tablets even if arguably there could be a dosing difference
between these forms. Ex. 1004, 31.3.
In sum, the 393 patent claim term microtablets, under the broadest
reasonable interpretation in light of the 393 specification, is any oral
pharmaceutical preparation form small enough to be filled into capsules. Dr. Polli
attests that the 393 patent claim term microtablets, under the broadest
reasonable interpretation in light of the 393 specification, is any oral
pharmaceutical preparation form small enough to be filled into capsules. Ex. 1004,
32.
20
Carriers
The term carriers is used throughout the 393 patent, including in:
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. Ex. 1001, 4:32-35; and
13. A pharmaceutical preparation consisting essentially of an active
ingredient and one or more carriers and excipients, Ex. 1001, 8:50-51.
Dr. Polli explains in his declaration that the term carriers is not
specifically defined in the 393 patent. Ex. 1004, 33. However, a POSITA would
have looked at extrinsic evidence such as the Dictionary of Pharmacy for a
definition. Id. The term carriers is defined as [a] vehicle used to transport a
drug to its site of absorption or use. citing Ex. 1007, p4. Id.
Dr. Polli explains that examples of carriers as vehicles for the active
ingredient include capsules and enteric coatings. Ex. 1004, 34. The only mention
of the term carrier apart from Claim 13 appears as [t]he 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
citing Ex. 1001,4:32-35. Id.
In sum, the term carriers, under the broadest reasonable interpretation, are
vehicles used to transport a drug to its site of absorption or use. Ex. 1004, 35.
21
Excipients
The term excipients or excipient is used throughout the 393 patent,
including in:
Then an excipient mixture with the following composition is prepared: Ex.
1001, 6:14-15;
Then an excipient mixture composed as follows is prepared: Ex. 1001,
6:57-58; and
13. A pharmaceutical preparation consisting essentially of an active
ingredient and one or more carriers and excipients, Ex. 1001, 8:50-51.
Dr. Polli explains in his declaration that the term excipients is not
specifically defined in the 393 patent. Ex. 1004, 36. However, a POSITA would
have looked at extrinsic evidence such as the Dictionary of Pharmaceutical and
Pharmaceutical Manufacturing for a definition. The term excipients is defined as
nondrug component of a pharmaceutical formulation; excipients include diluents,
binders and adhesives, fillers, disintegrants, lubricants, glidants and flow
promoters, colors, flavors and sweeteners citing Ex 1009, p4.
In sum, the term excipients, under the broadest reasonable interpretation,
are any nondrug component of a pharmaceutical formulation. Ex. 1004, 37.
VI. DETAILED EXPLANATION OF THE CHALLENGES
A.
Ground 1: Claims 1, 2, and 8 are anticipated by Nieboer

22
A patent claim is anticipated under 35 U.S.C. 102 if "each limitation of a

claim is found in a single reference, either expressly or inherently." Verdegaal
Bros. v. Union Oil Co. of California, 814 F.2d 628, 631 (Fed. Cir. 1987).
Nieboer teaches every element of claims 1, 2, and 8. Together these claims
generally recite four elements: 1) a pharmaceutical preparation comprising
dimethyl fumarate; 2) dimethyl fumarate as an active ingredient; 3) a
pharmaceutical preparation in the form of microtablets; and 4) enteric coated
microtablets. Each of those elements is plainly taught by Nieboer.
Claim 1: A pharmaceutical preparation, comprising dimethyl
fumarate wherein the pharmaceutical preparation is in the form
of microtablets.
The first element of claim 1 requires a pharmaceutical preparation
comprising dimethyl fumarate. Nieboer teaches a pharmaceutical preparation
comprising dimethyl fumarate. Nieboer discloses that [t]he medication consisted
of capsules filled with 60 mg enteric-coated granulate of DMFAE (dimethyl
fumaric acid ester) or with placebo granulate to a maximum dosage of up to four
capsules a day. Ex. 1002, p603, 2:35-38. Dr. Polli explains that DMFAE (or
dimethylfumaric acid ester) is simply another term for dimethyl fumarate. Ex.
1004, 20 and 38. See also Ex. 1008, p1.
The second element of claim 1 requires that the pharmaceutical preparation
is in the form of microtablets. As shown above in Section V. D., the broadest
23
reasonable interpretation of microtablets in light of the specification is any oral

pharmaceutical preparation form that can be filled into a capsule. Nieboers
teaching of granulates that can be filled into capsules reads on microtablets as
recited in claim 1 of the 393 patent. Nieboer teaches capsules filled with 60 mg
enteric-coated granulate of DMFAE. Ex. 1002, p604, 1:2-4, narrative following
Table I. The granulates of Nieboer are therefore within the scope of the 393
patent claim limitation microtablets. Ex. 1004, 39.
In sum, Nieboer teaches a pharmaceutical preparation comprising dimethyl
fumarate, wherein the pharmaceutical preparation is in the form of microtablets.
Thus, Nieboer anticipates claim 1 of the 393 patent. Ex. 1004, 40.
Claim 2: The pharmaceutical preparation of claim 1, wherein
the microtablets are enteric coated
Claim 2 is dependent on claim 1 and therefore incorporates all its
limitations. Claim 2 further requires that the microtablets are enteric coated.
Nieboer further discloses that [t]he medication consisted of capsules filled with 60
mg enteric-coated granulate of DMFAE Ex. 1002, p603, 2:35-38, emphasis
added. In sum, Nieboer teaches the microtablets are enteric coated microtablets.
Thus, Nieboer anticipates claim 2 of the 393 patent. Ex. 1004, 41.
Claim 8: A pharmaceutical preparation, comprising an active
ingredient, wherein the pharmaceutical preparation is in the form
of microtablets and the active ingredient consists of dimethyl
fumarate
24
The first element of independent claim 8 requires [a] pharmaceutical

preparation, comprising an active ingredient. Nieboer teaches a pharmaceutical
preparation comprising an active ingredient. Ex. 1004, 42. Nieboer discloses that
[t]he medication consisted of capsules filled with 60 mg enteric-coated granulate
of DMFAE. Ex. 1002, p603, 2:35-38. Dr. Pollis explains that Nieboer teaches
pharmaceutical preparations that contain an active ingredient. Id.
is in the form of microtablets. As argued above in Section VI.A., the granulates
of Nieboer meets the 393 patent claim limitation of microtablets. Ex. 1004,
43.
The third element of claim 8 requires that the active ingredient consists of
dimethyl fumarate. Nieboer discloses that [t]he medication consisted of capsules
filled with 60 mg enteric-coated granulate of DMFAE. Ex. 1002, p603, 2:3538. Dr. Polli explains that dimethylfumaric acid ester or DMFAE are simply other
terms for the active ingredient dimethyl fumarate. Ex. 1004, 44. See also Ex.
1008, p1.
In sum, Nieboer teaches a pharmaceutical preparation comprising an active
ingredient, wherein the preparation form is microtablets and the active ingredient
consists of dimethyl fumarate. Thus, Nieboer anticipates claim 8 of the 393
patent. Ex. 1004, 45.
25
B.
Ground 2: Claims 1-13 are obvious over Nieboer in view of Kolter
A claim is unpatentable for obviousness when "the differences between the

subject matter sought to be patented and the prior art are such that the subject
matter as a whole would have been obvious at the time the invention was made to a
person having ordinary skill in the art to which said subject matter pertains." 35
U.S.C. 103.
The factual inquiries enunciated by the Supreme Court for an obviousness
analysis require: (1) the scope and content of the prior art; (2) the differences
between the claims and the prior art; (3) the level of ordinary skill in the pertinent
art; and (4) objective indicia of non-obviousness. KSR International Co. v. Teleflex
Inc., 550 U.S. 398, 406 (2007) (citing Graham v. John Deere Co. of Kan. City, 383
U.S. 1, 17-18 (1966). The rationale to support a conclusion that a claim would
have been obvious is that all claimed elements were known in the prior art and one
skilled in the art could have combined the elements as claimed by known methods
with no change in their respective function, and the combination yielded no more
than predictable results to one of ordinary skill in the art. KSR International Co. v.
Teleflex Inc., 550 U.S. 398, 416 (2007) (citing United States v. Adams, 383 U.S.
39, 40 (1966); Anderson's-Black Rock, Inc. v. Pavement Salvage Co., 396 U.S. 57
(1969); and Sakraida v. AG Pro, Inc., 425 U.S. 273 (1976)).
26
As shown in Ground 1 above, Nieboer teaches the use of enteric-coated

granulates of dimethyl fumarate filled into capsules. Dr. Polli attests that Kolter
teaches microtablets produced by means of conventional pharmaceutical
equipment following well known and standard procedures such as granulation,
drying, mixing and tableting citing Ex 1003, 3:49-51. Ex. 1004, 46. Kolter also
teaches delayed-release microtablets that minimize gastrointestinal irritation. Id.
Kolter states that [t]he microtablets according to the invention furthermore have
the advantage that when introduced into gastric or intestinal fluid they show no
tendency to stick or adhere. This ensures that they pass as individual articles
through the gastrointestinal tract and, moreover, do not become attached to the
wall of the stomach or intestine and induce irritation. Ex. 1003, 3:25-30. Kolter
further discloses microtablets having a diameter of 1-3 mm and preferably 2mm.
Id. The microtablets of the examples always had a diameter and height each of 2
mm. Ex 1003, 4:65-66. See also A cylindrical delayed release microtabletthe
height and diameter are, independently of one another, 1-3mm. Ex 1003, 8:18-31.
Kolter states that the particle size of the active ingredient is, within the
conventional pharmaceutical range, of only minor or no importance in the
production of the microtablets according the invention. Ex 1003, 3:52-55.
Nieboer in view of Kolter teaches every element of claims 1-13. These
claims generally recite the following elements: 1) dimethyl fumarate as an
27
ingredient of a pharmaceutical preparation; 2) dimethyl fumarate as the active

ingredient of a pharmaceutical preparation; 3) microtablets; 4) enteric coated
microtablets; 5) microtablets with a mean diameter ranging from 300 m to 2,000
m (0.3 to 2 mm) exclusive of any coating; 6) microtablets with a mean diameter
of about 2,000m (2 mm) exclusive of any coating; 7) microtablets that contain
between 100 mg to 300 mg of dimethyl fumarate; 8) microtablets that contain
about 120 mg of dimethyl fumarate; 9) capsules containing microtablets; and 10)
carriers and excipients.
Claim 1: A pharmaceutical preparation, comprising dimethyl
fumarate wherein the pharmaceutical preparation is in the form
of microtablets.
The first element of claim 1 requires a pharmaceutical preparation
comprising dimethyl fumarate. Nieboer discloses that [t]he medication consisted
of capsules filled with 60 mg enteric-coated granulate of DMFAE. Ex. 1002,
p603, 2:35-38. Dr. Polli explains that dimethylfumaric acid ester or DMFAE are
simply other terms for dimethyl fumarate. Ex. 1004, 47. See also Ex. 1008, p1.
is in the form of microtablets. Nieboer discloses that [t]he medication consisted
p603, 2:35-38. Kolter teaches small microtablets with a mean diameter in the
range of 1-3 mm. Ex. 1003, 2:42-46. Kolter teaches that [t]he microtablets
28
according to the invention are produced in conventional pharmaceutical equipment

by the following steps: granulation, drying, mixing, tableting. Ex. 1004, 48.
Nieboer recognizes that the cause of gastrointestinal complaints in the study
was due to the rapid release of the active ingredient DMFAE. Dr. Polli attests that
Nieboer discloses that the gastrointestinal symptoms were caused because more
than 80% DMFAE of the enteric-coated granulated capsules were released within
30 minutes in acid medium which is a rapid release in the stomach citing Ex.
1002, p607, 1:17-28. Ex. 1004, 49.
Dr. Polli attests that Kolter solves this problem in two ways: 1) by
controlling the rate of release of the active ingredient and 2) by ensuring that the
dosage amount of active ingredient is distributed throughout the digestive tract in
order to alleviate unwanted gastrointestinal symptoms using microtablets. Ex.
1004, 50. Dr. Polli attests that Kolter controls the rate of release of the active
ingredient by adding a controlled amount of a wetting agent to the granules. Ex.
1004, 50.1. Dr. Polli explains that Kolter teaches that the rate of release increases
in parallel with the rise in the wetting agent concentration citing Ex. 1003, 4:26-37.
Id.
Dr. Polli attests that Kolter ensures that the dosage amount of active
ingredient is distributed throughout the digestive tract by making small size
microtablets. Ex. 1004, 50.2. Kolter discloses that prior art large diameter tablets
29
can result in release and absorption of their total content of active ingredient
concentrated at one site in the gastrointestinal tract citing Ex. 1003, 1:37-49. Id.
Kolter discloses that it is an object of Kolters invention to overcome the
disadvantages of the prior art by using small sized microtablets citing Ex. 1003,
1:37-49. Id. Kolter discloses [t]he microtablets of the examples always had a
diameter and height each of 2mm. Ex. 1003, 4:65-66. Dr. Polli attests that Kolter
discloses that the Kolter microtablets have the advantage that they show no
tendency to stick or adhere and this ensures that they pass as individual articles
wall of the stomach or intestine and induce irritation citing Ex. 1003, 3:25-30. Id.
Dr. Polli attests that a POSITA would have looked to the teachings of Kolter
to improve the Nieboer pharmaceutical preparation in order to solve the Nieboer
recognized problem of the rapid release of the active ingredient in the stomach
resulting in gastrointestinal complaints. Ex. 1004, 51. Dr. Polli attests that it
would have been obvious to a POSITA to use the teachings of Kolters
microtablets to modify the Nieboer pharmaceutical preparation in order to alleviate
unwanted gastrointestinal symptoms by controlling the rate of release of the active
ingredient and by ensuring that the dosage amount of active ingredient is
distributed throughout the digestive tract. Id. Dr. Polli explains that a POSITA
would have a reason to combine the teachings of Kolter with Nieboer to modify
30
the Nieboer pharmaceutical preparation in order to reduce the rate of release of the
active ingredient in the stomach and ensure distributive absorption throughout the
digestive tract of the dosage of the active ingredient in order to avoid unwanted
gastrointestinal distress caused by the pharmaceutical preparation as described by
Nieboer. Id.
In sum, claim 1 of the 393 patent would have been obvious in over Nieboer
in view of Kolter. Ex. 1004, 52.
Claim 2: The pharmaceutical preparation of claim 1, wherein the
microtablets are enteric coated.
Claim 2 is dependent on claim 1 and incorporates all its limitations. The
element of claim 2 requires that the microtablets are enteric coated.
Nieboer teaches enteric coating of the pharmaceutical preparation. Ex.
1002, p603, 2:35-38. See also Ex. 1002, p604, 1:2-4, narrative following Table I,
All patients were treated with capsules filled with 60 mg enteric-coated granulate
of DMFAE. Dr. Polli attests that Nieboer teaches enteric coating of the
pharmaceutical preparation. Ex. 1004, 54. As argued above, it would have been
obvious to a POSITA to use the teachings of Kolters small microtablets to modify
the Nieboer pharmaceutical preparation.
Kolter does not teach away from using the Nieboer enteric coating. Ex.
1004, 54.1. Kolter states that [a]s a rule, the microtablets can be packed into
gelatin capsules directly using conventional filling machines. Kolter teaches that
31
[i]t may occasionally be advantageous for the microtablets, before the packing
[using these filling machines], to be provided with a readily soluble film coating
which does not influence the release. Ex. 1003, 4:49-53. Dr. Polli attests that this
Kolter passage does not teach away from using enteric coatings on micro-tablets.
Ex. 1004, 54.1. Dr. Polli explains that this is because Kolter is solving a
packaging problem by adding a packaging coating and does not want the
packaging coating to affect the designed release rate of the micro-tablet. In Dr.
Pollis opinion, Kolter does not suggest that enteric coatings should not be used on
microtablets. Ex. 1004, 54.1
In sum, claim 2 of the 393 patent would have been obvious over Nieboer in
view of Kolter. Ex. 1004, 55.
Claim 3: The pharmaceutical preparation of claim 2, wherein the mean
diameter of the microtablets ranges from 300m to 2,000m, exclusive of any
coating on the microtablets.
Claim 3 is dependent on claim 2 and incorporates all its limitations, i.e., an
enteric coating. Claim 3 requires the mean diameter of the microtablets ranges
from 300m to 2,000m, exclusive of any coating on the microtablets. Claim 3
only limits the size of the uncoated microtablet and does not limit the size of the
microtablet after it has been enteric coated.
Kolter teaches pharmaceutical preparation wherein the mean diameter of
the microtablets ranges from 300m to 2,000m, exclusive of any coating on the
32
microtablets. Ex. 1004, 58. First, Kolter teaches microtablets that are cylindrical
with a diameter and height which are preferably equal and, independently of
another, from 1 to 3, preferably 1.5 to 2.5mm, citing Ex. 1003, 2:42-46. Ex.
1004, 57.1. Second, Kolter teaches that the microtablets are made with a tableting
machine equipped with multiple microtablet punches resulting in a cylindrical
shape where the height and diameter can be varied independently of one another,
citing Ex. 1003, 4:18-22. Id.
Third, Kolter teaches that the microtablets dimensions are exclusive of any
coating on the microtablets. Ex. 1004, 57.2. Kolters examples 1-8 do not
include a coating on the microtablets citing Ex. 1003, 5:1-7:64. Id. Moreover
Kolter teaches that microtablets, as a rule, are packaged without a coating citing
Ex. 1003, 4:48-49. Id. Dr. Polli attests that Kolter teaches a range of sizes of the
microtablets where the mean diameter of the microtablets are within the ranges
from 300m to 2,000m, exclusive of any coating on the microtablets citing Ex.
1004, 57.2. Id. Dr. Polli attests that Kolter taught microtablets having a
cylindrical shape where the height and diameter each are approximately equal to
1.5mm, citing Ex. 1003, 2:42-46. Dr. Polli attests that the 1.5 mm diameter Kolter
microtablet exhibits one of the values in the claimed range of 0.3mm to 2mm
diameter, exclusive of any coating on the microtablets. Id.
33
[W]hen, as by a recitation of ranges or otherwise, a claim covers several

compositions, the claim is anticipated if one of them is in the prior art.
Titaniium Metals Corp. v. Banner, 778 F.2d 775, 782 (Fed. Cir. 1985) (citing In re
Petering, 301 F.2d 676, 682 (CCPA 1962).
In sum, the Kolter microtablet size meets a pharmaceutical preparation of
claim 3, wherein the mean diameter of the microtablets ranges from 300m to
2,000m, exclusive of any coating on the microtablets and therefore, claim 3 of
the 393 patent would have been obvious over Nieboer in view of Kolter. Ex.
1004, 58.
mean diameter of the microtablets is about 2,000m, exclusive of any coating
on the microtablets.
Claim 4 is dependent on claim 3 and incorporates all its limitations. Claim 4
requires the mean diameter of the microtablets is about 2,000m, exclusive of any
coating on the microtablets. Claim 4 only limits the size of the uncoated
microtablet and does not limit the size of the microtablet after it has been enteric
coated.
Kolter teaches pharmaceutical preparation having a mean diameter of the
microtablets of about 2,000m, exclusive of any coating on the microtablets. Ex.
1004, 60. First, Kolter teaches examples of uncoated microtablets having a
diameter of 2mm, which equals 2,000m citing Ex. 1003, 4:65-66. Ex. 1004,
34
59.1. Second, Kolters examples 1-8 do not include a coating on the microtablets
citing Ex. 1003, 5:1-7:64. Id. Moreover Kolter teaches that microtablets, as a rule,
are packaged without a coating citing Ex. 1003, 4:48-49. Id. Dr. Polli attests that
Kolter teaches that the size of the microtablets in examples 1-8 have a diameter of
2,000m, exclusive of any coating. Id.
Kolter teaches that the microtablets of the examples 1-8 always had a
diameter and height each of 2 mm, citing Ex. 1003, 4:65-66. Ex. 1004, 59.2.
Dr. Polli attests that the mean value of the diameter of the Kolter microtablets
having a height and diameter of 2mm is one of the values in the claimed range of
about 2,000m, exclusive of any coating on the microtablets. Id. Dr. Polli attests
that Kolter microtablets having a diameter and a height each of 2,000m meets the
claim requirement of microtablets having a mean diameter of about 2,000m,
exclusive of any coating. Ex. 1004, 59.2.
Petering, 301 F.2d 676, 682 (CCPA 1962). Kolter teaches microtablets having a
mean diameter of 2mm which is one of the values in the claim range of about 2
mm diameter and thereby reads on the claimed range.
35

claim 3, wherein the mean diameter of the microtablets is about 2,000m,
exclusive of any coating on the microtablets. Ex. 1004, 60. Therefore, Dr. Polli
attests that claim 4 of the 393 patent would have been obvious over Nieboer in
preparation contains 10 mg to 300 mg of dimethyl fumarate.
element of claim 5 requires that the preparation contains 10 mg to 300 mg of
dimethyl fumarate. Nieboer teaches that [a]ll patients were treated with capsules
filled with 60 mg enteric-coated granulate of DMFAE. Ex. 1002, p604, 1:2-4,
narrative following Table I. Dr. Polli explains that Nieboer teaches preparations
having dimethyl fumarate content within the range of 10 mg to 300 mg of dimethyl
fumarate. Ex. 1004, 63.
preparation contains about 120 mg of dimethyl fumarate.
element of claim 6 requires that the preparation contains about 120 mg of
dimethyl fumarate. Claim 6 does not limit the preparation to a single capsule, but
36
instead the claim scope covers more than one capsule. Nieboer also teaches that
the [t]he medication consisted of capsules filled with 60 mg enteric-coated
granulate of DMFAE a maximum dosage of up to four capsules a day. Ex
1002, p603, 2:35-38. Further all patients were treated with capsules filled with 60
mg enteric-coated granulate of DMFAE. Dosages ranged from 60 to 240 mg a
day. Ex 1002, p604, 1:2-4. Because 120 mg dosage is within the Nieboer dosage
range, the dosage taught by Nieboer includes a pharmaceutical preparation of 120
mg of dimethyl fumarate as required by the claim. Ex. 1004, 65. Dr. Polli attests
that Nieboer teaches a preparation that contains about 120 mg of dimethyl
fumarate. Id.
microtablets are contained in one or more capsules.
element of claim 7 requires that the microtablets are contained in one or more
capsules. Dr. Polli attests that Nieboer teaches that each capsule is filled with 60
mg enteric-coated granulate of dimethyl fumarate and that dosages of up to 240 mg
dimethyl fumarate were given to patients by increments of up to four capsules,
each capsule filled with 60 mg enteric-coated granulate of dimethyl fumarate,
citing Ex. 1002, p604, 1:2-4, narrative following Table I. Ex. 1004, 67. Kolter
37
also teaches that microtablets can be packed into gelatin capsules using
conventional filling machines. Ex. 1003, 4:49-50. Dr. Polli attests that both
Nieboer and Kolter teach the microtablets are contained in one or more capsules.
Id.
Claim 8: A pharmaceutical preparation, comprising an active ingredient,
wherein the pharmaceutical preparation is in the form of microtablets and the
active ingredient consists of dimethyl fumarate.
preparation, comprising an active ingredient. Nieboer discloses that [t]he
medication consisted of capsules filled with 60 mg enteric-coated granulate of
DMFAE a maximum dosage of up to four capsules a day. Ex. 1002, p603, 2:3538. In Dr. Pollis opinion, Nieboers study concerns a systemic therapy involving
pharmaceutical preparations comprising an active ingredient wherein that active
ingredient consists of dimethyl fumarate. Ex. 1004, 69. Kolter teaches a
pharmaceutical preparation comprising an active ingredient. Ex. 1003, 2:11-16. Ex.
1004, 69
is in the form of microtablets. Nieboer discloses that [t]he medication consisted
38
p603, 2:35-38. Kolter teaches small microtablets in the range of 1-3 mm. Ex.
1003, 2:42-46. Kolter teaches that [t]he microtablets according to the invention
are produced in conventional pharmaceutical equipment by the following steps:
granulation, drying, mixing, tableting. Ex 1003, 3:49-51. Ex. 1004, 70.
30 minutes in acid medium which is a rapid release in the stomach citing Ex. 1002,
p607, 1:17-28. Ex. 1004, 71.
1004, 72.1. Dr. Polli explains that Kolter teaches that the rate of release increases
Id.
39
microtablets. Ex. 1004, 72.2. . Kolter discloses that prior art large diameter
tablets can result in release and absorption of their total content of active ingredient
disadvantages of the prior art by using the small sized microtablets citing Ex. 1003,
resulting in gastrointestinal complaints. Ex. 1004, 73
Dr. Polli attests that it

40

would have had a reason to combine the teachings of Kolter with Nieboer to
modify the Nieboer pharmaceutical preparation in order to reduce the rate of
release of the active ingredient in the stomach in order to avoid unwanted
gastrointestinal distress caused by the pharmaceutical preparation as described by
Nieboer. Id.
The third element of claim 8 requires active ingredient consists of dimethyl
fumarate. Nieboer discloses that [t]he medication consisted of capsules filled
with 60 mg enteric-coated granulate of DMFAE. Ex. 1002, p603, 2-35-38. Dr.
Polli explains that dimethylfumaric acid ester or DMFAE are simply other terms
for dimethyl fumarate. Ex. 1004, 74. See also Ex. 1008, p1.
Claim 9: The pharmaceutical preparation of claim 8, wherein the mean
diameter of the microtablets is about 2,000 m, exclusive of any coating on the
microtablets
Claim 9 is dependent on claim 8 and incorporates all its limitations. Claim 9
requires that the mean diameter of the microtablets is about 2,000m, exclusive of
any coating on the microtablets. Claim 9 only limits the size of the uncoated
41
microtablet and does not limit the size of the microtablet after it has been enteric
coated.
Kolter teaches pharmaceutical preparations having a mean diameter of the
microtablets that about 2,000m, exclusive of any coating on the microtablets. Ex.
1004, 77 First, Kolter teaches examples of uncoated microtablets having a
diameter of 2mm, which equals 2,000m citing Ex. 1003, 4:65-66. Id. Second,
Kolters examples 1-8 do not include a coating on the microtablets citing Ex. 1003,
5:1-7:64. Id. Moreover Kolter teaches that microtablets as a rule are packaged
without a coating citing Ex. 1003, 4:48-49. Id. Dr. Polli attests that Kolter teaches
that the microtablets in examples 1-8 have a diameter of 2,000m, exclusive of any
coating. Id.
diameter and height each of 2 mm, citing Ex. 1003, 4:65-66. Ex. 1004, 78. Dr.
Polli attests that the mean value of the diameter of the Kolter microtablets having a
height and diameter of 2mm is one of the values in the claimed range of about
2,000m, exclusive of any coating on the microtablets.
Id. Dr. Polli attests that
the Kolter microtablets having a diameter and a height of 2,000m meet the claim
requirement of microtablets having a mean diameter of about 2,000m, exclusive
of any coating. Id.
42

mean diameter of 2mm which is one of the values in the claim range of about 2mm
diameter and thereby reads on the claimed range.
exclusive of any coating on the microtablets. Therefore, Dr. Polli attests that
claim 9 of the 393 patent would have been obvious over Nieboer in view of
Kolter. Ex. 1004, 78.1
preparation contains 10 mg to 300mg of dimethyl fumarate.
element of claim 10 requires that the preparation contains 10 mg to 300 mg of
dimethyl fumarate. Nieboer teaches that [a]ll patients were treated with capsules
filled with 60 mg enteric-coated granulate of DMFAE. Ex 1002,p 604, 1:2-4,
narrative following Table I. Dr. Polli explains that Nieboer teaches preparations
having dimethyl fumarate content within the range of 10 mg to 300 mg of dimethyl
fumarate. Ex. 1004, 79.
43
In sum, claim 10 of the 393 patent would have been obvious over Nieboer
preparation contains about 120 mg of dimethyl fumarate.
element of claim 11 requires that the preparation contains about 120 mg of
dimethyl fumarate. Nieboer also teaches that the [t]he medication consisted of
capsules filled with 60 mg enteric-coated granulate of DMFAE a maximum
dosage of up to four capsules a day. Ex 1002, p603, 2:35-38. Further all patients
were treated with capsules filled with 60 mg enteric-coated granulate of DMFAE.
Dosages ranged from 60 to 240 mg a day. Ex 1002, p604, 1:2-4. Because 120 mg
dosage is in the Nieboer dosage range, Nieboer teaches a dosage of 120 mg of
dimethyl fumarate. Ex. 1004, 81. Dr. Polli attests that Nieboer teaches a
preparation that contains about 120 mg of dimethyl fumarate as claimed. Id.
microtablets are enteric coated and are contained in one or more capsules.
first element of claim 12 requires that the microtablets are enteric coated.
Nieboer teaches enteric coating of the pharmaceutical preparation. Ex. 1002, p603,
44
2:35-38. See also Ex. 1002, p604, 1:2-4, narrative following Table I. (All patients
were treated with capsules filled with 60 mg enteric-coated granulate of
DMFAE.) Dr. Polli attests that Nieboer teaches enteric coating of the
pharmaceutical preparation. Ex. 1004, 84.
Kolter does not teach away from using the Nieboer enteric coating. Ex.
1004, 84.1. Kolter states that [a]s a rule, the microtablets can be packed into
gelatin capsules directly using conventional filling machines. Ex. 1003, 4:48-49.
Kolter teaches it may occasionally be advantageous for the microtablets, before the
packing using these filling machines, to be provided with a readily soluble film
coating which does not influence the release. Ex. 1003, 4:49-53. Dr. Polli attests
that this Kolter passage does not teach away from using enteric coatings on microtablets. Id. Dr. Polli explains that this is because Kolter is solving a packaging
problem by adding a packaging coating and does not want the packaging coating to
affect the designed release rate of the microtablet. In Dr. Pollis opinion, Kolter
does not suggest that enteric coatings should not be used on microtablets. Id.
The second element of claim 12 requires that the microtablets are contained
in one or more capsules. Dr. Polli attests that Nieboer teaches that each capsule is
filled with 60 mg enteric-coated granulate of dimethyl fumarate and that dosages
of up to 240 mg dimethyl fumarate were given to patients by increments of up to
four capsules, each capsule filled with 60 mg enteric-coated granulate of dimethyl
45
fumarate, citing Ex. 1002, p604, 1:2-4, narrative following Table I. Ex. 1004, 85.
Kolter also teaches that microtablets can be packed into gelatin capsules using
conventional filling machines. Ex. 1003, 4:49-50. Dr. Polli attests that both
Nieboer and Kolter teach the microtablets are contained in one or more capsules.
Id.
Claim 13: A pharmaceutical preparation consisting essentially of an active
ingredient and one or more carriers and excipients wherein the active
ingredient is dimethyl fumarate and the preparation contains 10 mg to 300 mg
of dimethyl fumarate and wherein the pharmaceutical preparation is in the
form of microtablets and the mean diameter of the microtablets is about 2,000
m, exclusive of any coating on the microtablets.
preparation consisting essentially of an active ingredient. Nieboer discloses that
[t]he medication consisted of capsules filled with 60 mg enteric-coated granulate
of DMFAE a maximum dosage of up to four capsules a day. Ex. 1002, p603,
2:35-38. In Dr. Pollis opinion, Nieboers study concerns a systemic therapy
involving a pharmaceutical preparations consisting of an active ingredient wherein
that active ingredient is dimethyl fumarate. Ex. 1004, 87. Kolter teaches a
pharmaceutical preparation consisting essentially of an active ingredient. Ex. 1003,
2:11-16. Ex. 1004, 87
46
The second element of independent claim 13 requires one or more carriers

and excipients. Nieboer teaches using dimethyl fumarate as an active ingredient
of a pharmaceutical preparation in the form of enteric coated granulates that are
contained in one or more capsules. Ex 1002, p604, 1:2-4, narrative following Table
I. As attested by Dr. Polli, the term carriers, under the broadest reasonable
interpretation, are vehicles used to transport a drug to its site of absorption or use.
Ex. 1004, 88. Nieboer teaches carriers because the Nieboer pharmaceutical
preparation has both enteric coatings and capsules. Ex. 1004, 88. Dr. Polli
explains that examples of carriers as vehicles for the active ingredient include
capsules and enteric coatings. Ex. 1004, 88. As attested by Dr. Polli, the term
excipients, under the broadest reasonable interpretation, means any nondrug
component of a pharmaceutical formulation. Ex. 1004, 88.1. Dr. Polli further
explains that excipients include wetting agents. Ex. 1004, 88.1. Kolter teaches the
use of wetting agent such as polyethylene glycol. Ex. 1003, 4:33-34. Therefore,
the combination of Nieboer and Kolter teach one or more carriers and excipients.
as recited in claim 13. Ex. 1004, 88.1.
The third element of independent claim 13 requires the active ingredient is
dimethyl fumarate. Dr. Polli attests that Nieboer teaches the active ingredient is
dimethyl fumarate. Ex. 1004, 89. Nieboer discloses that [t]he medication
consisted of capsules filled with 60 mg enteric-coated granulate of DMFAE Ex.
47
1002, p603, 2-35-38. Dr. Polli explains that DMFAE or dimethylfumaric acid
ester are simply other terms for dimethyl fumarate. Ex. 1004, 89. See also Ex.
1008, p1.
The fourth element of claim 13 requires that and the preparation contains
10mg to 300mg of dimethyl fumarate. Nieboer teaches that [a]ll patients were
treated with capsules filled with 60 mg enteric-coated granulate of DMFAE. Ex.
1002, p604, 1:2-4, narrative following Table I. Because 60 mg is within 10 to 300
mg, in my opinion, Nieboer teaches preparations having dimethyl fumarate content
within the range of 10 mg to 300 mg of dimethyl fumarate. Ex. 1004, 89.1.
The fifth element of independent claim 13 requires that the preparation is in
the form of microtablets. Nieboer discloses that [t]he medication consisted of
capsules filled with 60 mg enteric-coated granulate of DMFAE. Ex. 1002,
p603, 2:35-38. Kolter teaches that [t]he microtablets according to the invention
are produced in conventional pharmaceutical equipment by the following steps:
granulation, drying, mixing, tabletting. Ex 1003, 3:49-51. Ex. 1004, 90.
48
30 minutes in acid medium which is a rapid release in the stomach. citing Ex.
1002, Ex. 1002, p607, 1:17-28. Ex 1004, 91.
1004, 92.1.Dr. Polli explains that Kolter teaches that the rate of release increases
Ex. 1004, 92.1.
microtablets. Ex. 1004, 92.2. Kolter discloses that prior art large diameter tablets
can result in release and absorption of their total content of active ingredient
disadvantages of the prior art by using the small sized microtablets citing Ex. 1003,
49
resulting in gastrointestinal complaints. Ex. 1004, 93. Dr. Polli attests that it
would have a reason to combine the teachings of Kolter with Nieboer to modify
the Nieboer pharmaceutical preparation in order to reduce the rate of release of the
active ingredient in the stomach in order to avoid unwanted gastrointestinal distress
caused by the pharmaceutical preparation as described by Nieboer. Id.
The sixth element of independent claim 13 requires that the mean diameter
of the microtablets is about 2,000 m, exclusive of any coating on the
microtablets. The fifth element of claim 13 only limits the size of the uncoated
50
microtablets and does not limit the size of the microtablets after they have been
enteric coated.
Kolter teaches pharmaceutical preparation having a mean diameter of the
microtablets of about 2,000m, exclusive of any coating on the microtablets. Ex.
1004, 94.1. First, Kolter teaches examples of uncoated microtablets having a
diameter of 2mm, which equals 2,000m citing Ex. 1003, 4:65-66. Id. Second,
Kolters examples 1-8 do not include a coating on the microtablets citing Ex. 1003,
5:1-7:64. Id. Moreover Kolter teaches that microtablets, as a rule, are packaged
without a coating citing Ex. 1003, 4:48-49. Id. Dr. Polli attests that Kolter teaches
that the size of the microtablets in examples 1-8 have a diameter of 2,000m,
exclusive of any coating. Id.
diameter and height each of 2 mm, citing Ex. 1003, 4:65-66. Ex. 1004, 94.2.
Dr. Polli attests that the mean value of the diameter of the Kolter microtablets
having a height and diameter of 2mm is one of the values in the claimed range of
about 2,000m, exclusive of any coating on the microtablets. Id. Dr. Polli attests
that Kolter microtablets having a diameter and a height of 2,000m meet the claim
requirement of microtablets having a mean diameter of about 2,000m, exclusive
of any coating. Id.
51

mean diameter of 2mm which is one of the values in the claim range of about 2mm
diameter and thereby reads on the claimed range.
In sum, the Kolter microtablet size meets the pharmaceutical preparation of
exclusive of any coating on the microtablets. Ex. 1004, 95.
Therefore, claim 13 of the 393 patent would have been obvious over
Nieboer in view of Kolter. Ex. 1004, 96.
VII. CONCLUSION
For the foregoing reasons, the petitioner respectfully requests that trial be instituted
and that claims 1-13 of the 393 patent be canceled.
/RobertHahl#33,893/
Lead Counsel for the Petitioner
Tel: 1-703-415-0012 Ext. 103
Backup Counsel for Petitioner
Robert Mihail, Reg. No. 66,021
Tel: 1-703-415-0012 Ext. 107
Email: rmihail@neifeld.com
Fax for lead and backup counsel for the Petitioner: 1-703-415-0013
Postal address for lead and backup counsel:
52
Neifeld IP Law, PC, 4813-B Eisenhower Avenue, Alexandria, VA 22304
53
42.6(e) CERTIFICATE OF SERVICE

I certify that this document was served or simultaneously is being served on
each opposing party with the filing of this document. I certify that the following
exhibits being filed along with this document, if any, have been or simultaneously
are being served on each opposing party:
Exhibit Description
Number
1001
U.S. Patent No. 8,759,393, titled Utilization of Dialkylfumarates to
Joshi et al. (393 patent)
1002
C. Nieboer, et al., Systemic therapy with fumaric acid derivatives:
New possibilities in the treatment of psoriasis, Journal of the
American Academy of Dermatology, April 1989 Vol. 20, Number 4,
pg. 601-608 (Nieboer)
1003
U.S. Patent No. 5,681,588, titled Delayed Release Microtablet of Phenylpropiophenone Derivatives to Kolter et al. (Kolter)
1004
Declaration of Dr. James E. Polli
1005
Prosecution history of the 393 patent as contained in the Image File
Wrapper on PAIR
1006
Assignment record of the 393 patent as contained in USPTOs
Assignments on The Web at
http://assignment.uspto.gov/#/search?adv=patNum%3A8759393&q=
&sort=patAssignorEarliestExDate%20desc%2C%20id%20desc&syno
nyms=false
1007
Julian H. Fincher, Dictionary of Pharmacy, University of South
Carolina Press, 1986
1008
PubChem entry for Dimethyl Fumarate, U.S. National Library of
Medicine, National Center for Biotechnology Information, the
National Institute of Health at
https://pubchem.ncbi.nlm.nih.gov/compound/637568
1009
Dean E. Snyder, The Interpharm International Dictionary of
Biotechnology and Pharmaceutical Manufacturing, Interpharm Press,
Inc., 1992
1010
Friedrick Moll et al., Biodegradable Microtablets Made of Low
Molecular Weight Polyglycolic Acid, 1991
1011
Unassigned
54
1012
1013
1014
1015
1016
1017
Curriculum Vitae of Dr. James E. Polli

Nieboer et al., Fumaric Acid Therapy in Psoriasis: A Double-Blind
Comparison between Fumaric Acid Compound Therapy and
Monotherapy with Dimethylfumaric Acid Ester Dermatologica 1990;
181:33- 37
Kokelj et al., Fumaric Acid and Its Derivatives in the Treatment of
Psoriasis Vulgaris: Our Experience in Forty-One Patients, Acta
Dermatovenerol Croat, 2009; 17(3):170-175
FDA News Release, FDA approves new multiple sclerosis treatment:
Tecfidera, available at
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/uc
m345528.htm
Follonier et al., Various ways of modulating the release of diltiazem
hydrochloride from hot-melt extruded sustained release pellets
prepared using polymeric materials., Journal of Controlled Release
36 (1995) 243-250
Conine et al., Special Tablets, Pharmaceutical Dosage Forms,
Marcel Dekker, Inc., 1989, 329-366
42.6(e)(4) (iii)(A) The date and manner of service:

Manner of service: Priority Mail Express and email to the following firm of record
as listed on PAIR:
Jones Day
222 East 41st St.
New York, NY 10017
Date of Service: 4/22/2015
/RobertHahl#33,893/
Lead Counsel for the Petitioner
Neifeld IP Law, PC
4813-B Eisenhower Avenue
Alexandria, VA 22304
Tel: 1-703-415-0012 Ext. 103
Fax: 1-703-415-0013
55

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For the Patent Owner

Backup counsel: Robert W. Hahl, Reg. No. 33,893

UNITED STATES PATENT AND TRADEMARK OFFICE

PETITION FOR INTER PARTES REVIEW OF

Mail Stop PATENT BOARD

MANDATORY NOTICES ............................................................................2

Real Party-In-Interest 37 C.F.R. 42.8(b)(1) ...............................................2

Related Matters 37 C.F.R. 42.8(b)(2).........................................................3

Designation of Lead and Backup Counsel 37 C.F.R. 42.8(b)(3) ...............3

Notice of Service Information (37 C.F.R. 42.8(b)(4)) ...............................4

III. FEES 37 C.F.R. 42.15(a) .............................................................................4

Grounds for Standing 37 C.F.R. 42.104(a) ................................................4

Identification of Challenge and Precise Relief Requested 37 C.F.R.

UNPATENTABILITY OF THE 393 PATENT .........................................6

Brief History of dimethyl fumarate therapy ..................................................6

Prosecution History of the 393 Patent .........................................................8

Person of Ordinary Skill in the Art .............................................................10

VI. DETAILED EXPLANATION OF THE CHALLENGES........................22

Ground 1: Claims 1, 2, and 8 are anticipated by Nieboer ...........................22

Ground 2: Claims 1-13 are obvious over Nieboer in view of Kolter..........26

Dialkylfumarates to Joshi et al. (393 patent)

C. Nieboer, et al., Systemic therapy with fumaric acid

U.S. Patent No. 5,681,588, titled Delayed Release Microtablet

Declaration of Dr. James E. Polli

Prosecution history of the 393 patent as contained in the Image

Assignment record of the 393 patent as contained in USPTOs

Julian H. Fincher, Dictionary of Pharmacy, University of South

PubChem entry for Dimethyl Fumarate, U.S. National Library

Dean E. Snyder, The Interpharm International Dictionary of

Friedrick Moll et al., Biodegradable Microtablets Made of Low

Curriculum Vitae of Dr. James E. Polli

Dermatologica 1990; 181:33- 37

Kokelj et al., Fumaric Acid and Its Derivatives in the Treatment

FDA News Release, FDA approves new multiple sclerosis

Follonier et al., Various ways of modulating the release of

Conine et al., Special Tablets, Pharmaceutical Dosage Forms,

March 4, 2011 is a continuation of application no. 12/405,665 (now US 7,915,310)

Real Party-In-Interest 37 C.F.R. 42.8(b)(1)

Pursuant to 37 C.F.R. 42.8(b)(1), Petitioner certifies that Coalition For

member of nXnP. IPNav is a paid consultant to nXnP. Erich Spangenberg is the

Related Matters 37 C.F.R. 42.8(b)(2)

To the best of Petitioners knowledge, there are no pending litigations or

Designation of Lead and Backup Counsel 37 C.F.R. 42.8(b)(3)

Pursuant to 37 C.F.R. 42.8(b)(3) and 42.10(a), Petitioner hereby

Lead Counsel for Petitioner

Backup Counsel for Petitioner

Notice of Service Information (37 C.F.R. 42.8(b)(4))

Please direct all correspondence to counsel at the above address. Petitioner

Grounds for Standing 37 C.F.R. 42.104(a)

In accordance with 37 C.F.R. 42.104(a), Petitioner certifies that the

Identification of Challenge and Precise Relief Requested 37 C.F.R.

Patents and Printed Publications 37 C.F.R. 42.104(b)(2)

Petitioner relies on the following patents and printed publications to support

Specific Statutory Grounds for Challenge 42.104(b)(2)

Ground 1: Claims 1, 2, and 8 are unpatentable under 35 U.S.C. 102(b) as

Brief History of dimethyl fumarate therapy

referred to by any of several common, interchangeable names including dimethyl

Prosecution History of the 393 Patent

optionally in admixture with dialkyl fumarate)2, U.S. Patent No. 6,509,376

Person of Ordinary Skill in the Art

pharmaceutical sciences or a related discipline, or a Pharm D degree; additionally

The claims in an inter partes review should be accorded the broadest

certain dialkyl fumarates for preparing pharmaceutical preparationsin the

m, exclusive of any coating on the microtablets. Claim 9, depending on