-
For the Patent Owner Paper No. __ Backup counsel: Robert W.
Hahl, Reg. No. 33,893 Backup counsel: Robert Mihail, Reg. No.
66,021 Neifeld IP Law, PC
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
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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
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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
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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
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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
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v
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 Double-
Blind 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
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vi
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
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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
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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%
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3
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).
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Lead Counsel for Petitioner Backup 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: [email protected]
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: [email protected]
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: [email protected]; and
[email protected].
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)
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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:
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6
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
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7
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.
1 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.
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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, micro-
tablets, pellets or granulates, optionally in capsules or
sachets and tablets, micro-
tablets, 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
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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,
2 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.
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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
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11
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;
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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.
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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, micro-
pellets, 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, micro-
tablets, capsules (such as soft and hard gelatin capsules),
granulates and tablets
cited above, .Pharmaceutical preparations in the form of
micro-tablets or micro-
pellets 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
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14
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
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15
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 micro-
pellets 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
-
16
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 micro-
pellets 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, micro-
pellets, tablets and micro-tablets indicate that these are
interchangeable terms
that mean the same thing. Id.
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17
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
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18
(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 micro-
tablets. 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
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19
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
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20
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.
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21
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.
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22
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
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23
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
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24
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
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25
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.
The second element of claim 8 requires that the pharmaceutical
preparation
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, 2:35-
38. 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.
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26
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)).
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27
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
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28
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.
The second element of claim 1 requires that the pharmaceutical
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 small microtablets with a mean
diameter in the
range of 1-3 mm. Ex. 1003, 2:42-46. Kolter teaches that [t]he
microtablets
-
29
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
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30
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
through the gastrointestinal tract and, moreover, do not become
attached to the
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
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31
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
-
32
[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
-
33
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.
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34
[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.
Claim 4: The pharmaceutical preparation of claim 3, wherein the
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,
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35
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.
[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). 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.
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36
In sum, the Kolter microtablet size meets a pharmaceutical
preparation of
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
view of Kolter. Ex. 1004, 61.
Claim 5: The pharmaceutical preparation of claim 4, wherein the
preparation contains 10 mg to 300 mg of dimethyl fumarate. Claim 5
is dependent on claim 4 and incorporates all its limitations.
The
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.
In sum, claim 5 of the 393 patent would have been obvious over
Nieboer in
view of Kolter. Ex. 1004, 64.
Claim 6: The pharmaceutical preparation of claim 5, wherein the
preparation contains about 120 mg of dimethyl fumarate. Claim 6 is
dependent on claim 5 and incorporates all its limitations. The
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
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37
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.
In sum, claim 6 of the 393 patent would have been obvious over
Nieboer in
view of Kolter. Ex. 1004, 66.
Claim 7: The pharmaceutical preparation of claim 5, wherein the
microtablets are contained in one or more capsules. Claim 7 is
dependent on claim 5 and incorporates all its limitations. The
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
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38
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.
In sum, claim 7 of the 393 patent would have been obvious over
Nieboer in
view of Kolter. Ex. 1004, 68.
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. The first element of independent claim 8 requires [a]
pharmaceutical
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, 2:35-
38. 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
The second element of claim 8 requires that the pharmaceutical
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,
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39
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.
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, 71.
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, 72. 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, 72.1. 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.
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40
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, 72.2. . Kolter discloses that prior art
large diameter
tablets 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 the 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
through the gastrointestinal tract and, moreover, do not become
attached to the
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, 73 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
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41
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 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.
In sum, claim 8 of the 393 patent would have been obvious over
Nieboer in
view of Kolter. Ex. 1004, 75.
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
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42
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.
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, 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.
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43
[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). Kolter teaches
microtablets having a
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 a pharmaceutical
preparation of
claim 8, wherein the mean diameter of the microtablets is about
2,000m,
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
Claim 10: The pharmaceutical preparation of claim 9, wherein the
preparation contains 10 mg to 300mg of dimethyl fumarate. Claim 10
is dependent on claim 9 and incorporates all its limitations.
The
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.
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44
In sum, claim 10 of the 393 patent would have been obvious over
Nieboer
in view of Kolter. Ex. 1004, 80.
Claim 11: The pharmaceutical preparation of claim 10, wherein
the preparation contains about 120 mg of dimethyl fumarate. Claim
11 is dependent on claim 10 and incorporates all its limitations.
The
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.
In sum, claim 11 of the 393 patent would have been obvious over
Nieboer
in view of Kolter. Ex. 1004, 82.
Claim 12: The pharmaceutical preparation of claim 10, wherein
the microtablets are enteric coated and are contained in one or
more capsules. Claim 12 is dependent on claim 10 and incorporates
all its limitations. The
first element of claim 12 requires that the microtablets are
enteric coated.
Nieboer teaches enteric coating of the pharmaceutical
preparation. Ex. 1002, p603,
-
45
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 micro-
tablets. 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
-
46
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.
In sum, claim 12 of the 393 patent would have been obvious over
Nieboer
in view of Kolter. Ex. 1004, 86.
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. The first
element of independent claim 13 requires [a] pharmaceutical
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
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47
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.
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48
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.
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
-
49
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.
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, 92. 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, 92.1.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.
Ex. 1004, 92.1.
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, 92.2. Kolter discloses that prior art
large diameter tablets
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 the 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
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50
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
through the gastrointestinal tract and, moreover, do not become
attached to the
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, 93. 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
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
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51
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.
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, 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.
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52
[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). Kolter teaches
microtablets having a
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
claim 13, wherein the mean diameter of the microtablets is about
2,000m,
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/ Robert W. Hahl, Reg. No. 33,893 Lead Counsel
for the Petitioner Tel: 1-703-415-0012 Ext. 103 Email:
[email protected] Backup Counsel for Petitioner Robert Mihail, Reg.
No. 66,021 Tel: 1-703-415-0012 Ext. 107 Email: [email protected]
Fax for lead and backup counsel for the Petitioner: 1-703-415-0013
Postal address for lead and backup counsel:
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53
Neifeld IP Law, PC, 4813-B Eisenhower Avenue, Alexandria, VA
22304
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54
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 Number
Description
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