Trials@uspto.gov Paper 18 571.272.7822 Entered: October 27, 2015

UNITED STATES PATENT AND TRADEMARK OFFICE ____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD

____________

COALITION FOR AFFORDABLE DRUGS V LLC, Petitioner,

v.

BIOGEN INTERNATIONAL GmbH, Patent Owner. ____________

Case IPR2015-01086 Patent 8,759,393 B2

____________

Before LORA M. GREEN, JACQUELINE WRIGHT BONILLA, and TINA E. HULSE, Administrative Patent Judges.

HULSE, Administrative Patent Judge.

DECISION Denying Institution of Inter Partes Review; Dismissing Motion for Additional Discovery

37 C.F.R. § 42.108

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INTRODUCTION I.

Coalition for Affordable Drugs V LLC (“Petitioner”) filed a Petition

requesting an inter partes review of claims 1–13 of U.S. Patent No.

8,759,393 B2 (Ex. 1001, “the ’393 patent”). Paper 1 (“Pet.”). Biogen

International GmbH (“Patent Owner”) filed a Preliminary Response to the

Petition. Paper 14 (“Prelim. Resp.”).

We have jurisdiction under 35 U.S.C. § 314, which provides that an

inter partes review may not be instituted “unless . . . there is a reasonable

likelihood that the petitioner would prevail with respect to at least 1 of the

claims challenged in the petition.” 35 U.S.C. § 314(a). Upon considering

the Petition and Preliminary Response, we determine that Petitioner has not

established a reasonable likelihood that it would prevail in showing the

unpatentability of claims 1–13. Accordingly, we decline to institute an inter

partes review of those claims.

A. Related Proceedings

Petitioner states that, to the best of its knowledge, there are no related

matters to this proceeding. Pet. 3.

B. The ’393 Patent

Dialkyl fumarates are used for treating, reducing, or suppressing

rejection reactions of a tissue or organ transplant by a recipient or vice versa.

Ex. 1001, 1:20–25. Dialkyl fumarates can also be used to treat autoimmune

diseases such as polyarthritis, multiple sclerosis, and juvenile onset diabetes.

Id. at 1:25–31. The ’393 patent relates to pharmaceutical preparations for

certain dialkyl fumarates in the form of microtablets or micropellets. Id. at

1:15–19. According to the Specification, dialkyl fumarates according to the

invention “are prepared by processes known in the art.” Id. at 4:21–23.

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“Preferably, the active ingredients are used for preparing oral preparations in

the form of tablets, micro-tablets, pellets or granulates, optionally in

capsules or sachets.” Id. at 4:24–26. The oral preparations may also be

provided with an enteric coating. Id. at 4:29–30.

C. Illustrative Claim

Petitioner challenges claims 1–13 of the ’393 patent. Claim 1 is

illustrative and is reproduced below:

1. A pharmaceutical preparation, comprising dimethyl fumarate, wherein the pharmaceutical preparation is in the form of microtablets.

D. The Asserted Grounds of Unpatentability

Petitioner challenges the patentability of claims 1–13 of the

’393 patent on the following grounds:

Reference(s) Basis Claims challenged

Nieboer1 § 102 1, 2, and 8

Nieboer and Kolter2 § 103 1–13

ANALYSIS II.

A. Claim Construction

In an inter partes review, the Board interprets claim terms in an

unexpired patent according to the broadest reasonable construction in light

of the specification of the patent in which they appear. See In re Cuozzo

1 Nieboer et al., Systemic Therapy with Fumaric Acid Derivates: New Possibilities in the Treatment of Psoriasis, 20 J. AMER. ACAD. DERM. 601–08 (Apr. 1989) (Ex. 1005).

2 Kolter et al., US 5,681,588, issued Oct. 28, 1997 (Ex. 1003).

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Speed Techs., LLC, 793 F.3d 1268, 1278–79 (Fed. Cir. 2015); 37 C.F.R.

§ 42.100(b). Under that standard, and absent any special definitions, we

give claim terms their ordinary and customary meaning, as would be

understood by one of ordinary skill in the art at the time of the invention.

See In re Translogic Tech., Inc., 504 F.3d 1249, 1257 (Fed. Cir. 2007). Any

special definitions for claim terms must be set forth with reasonable clarity,

deliberateness, and precision. See In re Paulsen, 30 F.3d 1475, 1480

(Fed. Cir. 1994).

1. “microtablets”

The term “microtablets” appears in each claim of the ’393 patent.

Petitioner asserts that the broadest reasonable interpretation of the term

“microtablets” is “any oral solid pharmaceutical preparation forms small

enough to be filled into capsules.” Pet. 12. Citing the testimony of its

declarant, Dr. James E. Polli, for support, Petitioner argues that the

Specification does not define “microtablets,” and the term does not have a

special meaning in the pharmaceutical arts. Id. (citing Ex. 1004 ¶ 25).

Petitioner further argues that the Specification uses the term interchangeably

with the other dosage forms identified in the Specification, such as

“granulates,” “pellets,” “micro-pellets,” and “tablets.” Id. at 15–16.

Petitioner also argues that the Specification does not teach that the

microtablets are made in any particular way. Id. at 17.

Patent Owner disagrees, contending that Petitioner’s construction is

too broad. Petitioner proposes the narrower construction of “small tablets

made by compression or molding methods.” PO Resp. 11. Petitioner argues

this construction is supported by the claim language, the Specification, the

prosecution history, and the extrinsic evidence. Id. at 4–11.

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As an initial matter, we note that the main issue in dispute for

purposes of this Decision is whether the term “microtablets” encompasses

granulates. After considering the arguments and evidence, we determine

that it does not.

As Patent Owner notes, the Specification identifies different forms of

pharmaceutical preparations: tablets, microtablets, pellets, micropellets, and

granulates. Ex. 1001, 4:24–26. The Specification then states that

“[p]reparations in the form of micro-tablets or pellets, optionally filled in

capsules or sachets are preferred.” Id. at 4:26–28. Thus, contrary to

Petitioner’s assertion, the Specification does not equate microtablets and

granulates. Rather, the Specification distinguishes microtablets from

granulates by stating they are “preferred.”

The Specification also distinguishes microtablets from granulates in

Example 1. Example 1 describes the preparation of enteric-coated

microtablets. Id. at 6:6–47. According to Example 1, the active ingredient

is mixed to obtain a “binder granulate,” which is then “compressed in the

usual manner to obtain convex tablets.” Id. at 6:18–26. Thus, the

Specification identifies the binder granulate as a precursor to a microtablet,

not as the same pharmaceutical form, as Petitioner asserts.

We further agree with Patent Owner that the extrinsic evidence is

consistent with this construction. Prelim. Resp. 8–11. For example, the

Interpharm International Dictionary of Biotechnology and Pharmaceutical

Manufacturing—which both parties rely on—defines “granulation” as a step

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in the preparation of tablets. Ex. 2011, 100.3 Similarly, Kolter states that

microtablets are produced “in conventional pharmaceutical equipment by the

following steps: granulation, drying, mixing, tableting.” Ex. 1003, 3:49–51.

Patent Owner also cites several treatises that describe the preparation of

tablets via the formation of granulates that are compressed into tablets.

Prelim. Resp. 10 (citing Ex. 2012, 1623–26; Ex. 2013, 195).

Accordingly, on this record, we determine that the broadest

reasonable interpretation of the term “microtablets” does not encompass

granulates. Because this issue is determinative, we need not consider

whether the construction of “microtablets” further requires a particular

method of preparation. See Wellman, Inc. v. Eastman Chem. Co., 642 F.3d

1355, 1361 (Fed. Cir. 2011) (“[C]laim terms need only be construed ‘to the

extent necessary to resolve the controversy.’”) (quoting Vivid Techs., Inc. v.

Am. Sci. & Eng’g, Inc., 200 F.3d 795, 803 (Fed. Cir. 1999)).

B. Anticipation by Nieboer

Petitioner asserts that claims 1, 2, and 8 are anticipated by Nieboer.

Pet. 23–26. Petitioner relies on the testimony of its declarant, Dr. Polli (Ex.

1004). Patent Owner opposes Petitioner’s assertion. Prelim. Resp. 11–13.

Based on the current record, we determine that Petitioner has not established

a reasonable likelihood that it would prevail in showing the claims are

anticipated by Nieboer.

1. Nieboer (Ex. 1002)

Nieboer describes a study investigating fumaric acid therapy to treat

psoriasis. Ex. 1002, Abstract. Nieboer reports the results of several studies

3 THE INTERPHARM INTERNATIONAL DICTIONARY OF BIOTECHNOLOGY AND

PHARMACEUTICAL MANUFACTURING (Dean E. Snyder ed. 1992) (Exs. 1009, 2011).

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using different forms of fumaric acid therapy, including two different studies

using dimethyl fumaric ester (“DMFAE”). Id. at 603. The studies using

DMFAE administered “capsules filled with 60 mg enteric-coated granulate

of DMFAE.” Id. at 603–04. Although Nieboer observed improvement in

the DMFAE-treated group versus the placebo group, Nieboer also reports

several patients who had to stop therapy because of “serious gastrointestinal

complaints.” Id. Nieboer states a “possible explanation of the adverse

reactions to enteric-coated DMFAE granules is the comparatively rapid

release in the stomach.” Id. at 607.

2. Analysis

Petitioner argues that Nieboer anticipates claims 1, 2, and 8. Claims

1, 2, and 8 each recite a pharmaceutical preparation in the form of

“microtablets.” Nieboer, however, discloses the use of “enteric-coated

granulate.” Ex. 1002, 603. As explained above, the broadest reasonable

interpretation of the term “microtablets” does not encompass granulates.

Accordingly, we conclude that Petitioner has failed to establish a reasonable

likelihood that it would prevail in showing that Nieboer anticipates claims 1,

2, and 8 of the ’393 patent.

C. Obviousness over Nieboer and Kolter

Petitioner argues that claims 1–13 are unpatentable as obvious over

Nieboer and Kolter. Pet. 26–52. Patent Owner opposes. Prelim. Resp. 13–

30. Based on the current record, we determine that Petitioner has not

established a reasonable likelihood that it would prevail in showing claims

1–13 are unpatentable over the cited references.

1. Kolter (Ex. 1003)

Kolter relates to delayed release microtablets of β-

phenylpropiophenone derivates. Ex. 1003, Abstract. Kolter describes the

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drug release from the microtablets as being independent of the force used to

compress tablets. Id. at 2:47–50. Kolter also states that the delayed-release

microtablets have no release-delaying ancillary substances. Id. at 2:17–21.

According to Kolter, the microtablets 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.” Id. at 3:25–30. Kolter

further explains that “[s]ticking or adhesion properties of this type are

displayed, for example, by small articles with hydrophilic release-delaying

polymers.” Id. at 3:30–33.

Kolter also discloses that another element in the control of drug

release “is the addition of wetting agents which increase the rate of

dissolution.” Id. at 4:26–28. Kolter explains that “[i]n this case the rate of

release increases in parallel with the rise in the wetting agent concentration.”

Id. at 4:36–37.

2. Analysis

Petitioner asserts that claims 1–13 are unpatentable as obvious over

Nieboer and Kolter. Independent claims 1, 8, and 13 each require a

pharmaceutical preparation comprising dimethyl fumarate in the form of

microtablets. Petitioner asserts that Nieboer discloses a pharmaceutical

preparation comprising DMFAE, which is another term for dimethyl

fumarate. Pet. 28 (citing Ex. 1004 ¶ 47). Petitioner further asserts that

Kolter teaches delayed-release microtablets. Id. (citing Ex. 1003, 2:42–46).

We are persuaded that Petitioner has shown sufficiently that

pharmaceutical preparations of dimethyl fumarate, as well as pharmaceutical

preparations in the form of microtablets, were known independently in the

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prior art. To establish the claims are obvious, however, Petitioner must also

identify a reason that would have led a person of ordinary skill in the art to

combine the elements of Nieboer and Kolter in the manner specified by the

claims. See KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007) (“[I]t

can be important to identify a reason that would have prompted a person of

ordinary skill in the relevant field to combine elements in the way the

claimed new invention does.”); see also id. (“[A] patent composed of several

elements is not proved obvious merely by demonstrating that each of its

elements was, independently, known in the prior art.”).

To establish a reason to combine, Petitioner argues that Nieboer

recognizes that the gastrointestinal complaints are caused by the rapid

release of the DMFAE. Pet. 29 (citing Ex. 1002, 607); Ex. 1004 ¶ 49.

Petitioner’s declarant, Dr. Polli, testifies that Kolter solves Nieboer’s

gastrointestinal 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 to alleviate unwanted

gastrointestinal symptoms using microtablets. Ex. 1004 ¶ 50. Dr. Polli

concludes that it would have been obvious to a person of ordinary skill in the

art to use the teachings of Kolter’s microtablets to modify the Nieboer

pharmaceutical preparation to alleviate the gastrointestinal irritation by

controlling the release rate of DMFAE and by ensuring the drug is

distributed throughout the digestive tract. Pet. 30; Ex. 1004 ¶ 51.

In its Preliminary Response, Patent Owner argues that Petitioner has

not established that a person of ordinary skill in the art would have had a

reason to combine the references with a reasonable expectation of success.

First, Patent Owner argues that Petitioner fails to address a reasonable

expectation of success at all in its Petition. Prelim. Resp. 14–16. That

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alone, Patent Owner argues, is grounds for denying the Petition. Id.

Second, Patent Owner argues a person of ordinary skill in the art would have

had no reasonable expectation of success in combining Nieboer and Kolter.

Id. at 16–26.

After considering the evidence and arguments, we are not persuaded

that Petitioner has shown sufficiently that a person of ordinary skill in the art

would have had a reason to combine Nieboer and Kolter with a reasonable

expectation of success of controlling the release rate of DMFAE and

ensuring the drug is distributed throughout the digestive tract. In particular,

we find that Petitioner has not explained sufficiently why a person of

ordinary skill in the art would have modified Nieboer’s pharmaceutical

preparation with Kolter’s microtablets to solve the gastrointestinal problems

observed in Nieboer.

As explained above, Dr. Polli testifies that Kolter solves Nieboer’s

gastrointestinal 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 to alleviate unwanted

gastrointestinal symptoms using microtablets. Pet. 29; Ex. 1004 ¶¶ 49–50.

Regarding the first way Kolter solves the problem, Dr. Polli states only that

Kolter “controls the rate of release of the active ingredient by adding a

controlled amount of a wetting agent to the granules.” Pet. 29; Ex. 1004

¶ 50.1. Kolter explains that the addition of wetting agents “increase[s] the

rate of dissolution.” Ex. 1004 ¶ 50.1 (quoting Ex. 1003, 4:26–37).

Dr. Polli, however, does not explain adequately why a person of

ordinary skill in the art would have expected the addition of wetting agents,

and the resulting increase in the rate of dissolution, to control the rate of

release of the DMFAE of Nieboer as it did for the β-phenylpropiophenone

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derivates of Kolter. As Patent Owner notes, dimethyl fumarate is highly

soluble in water, whereas propafenone HCl is only slightly soluble in water.

Prelim. Resp. 21–22; Ex. 1008, 8; Ex. 2014, 12. Rather than acknowledge

and address the different properties of the different active ingredients

disclosed in Nieboer and Kolter, Dr. Polli offers a conclusory opinion that

adding the wetting agent of Kolter to Nieboer will control the rate of release

of DMFAE and solve the gastrointestinal problems observed in Nieboer.

We do not find Dr. Polli’s testimony persuasive, as we give such

unsupported expert testimony little to no weight. See 37 C.F.R. § 42.65(a)

(stating opinion testimony that does not disclose underlying facts or data “is

entitled to little or no weight”); Ashland Oil, Inc. v. Delta Resins &

Refractories, Inc., 776 F.2d 281, 294 (Fed. Cir. 1985) (finding a lack of

objective support for expert opinion “may render the testimony of little

probative value in a validity determination”).

Dr. Polli also opines that Kolter’s microtablets solve the

gastrointestinal problems of Nieboer by ensuring that the dosage amount of

active ingredient is distributed throughout the digestive tract. Ex. 1004

¶ 50.2. According to Dr. Polli, Kolter achieves this in two ways. First,

Dr. Polli asserts that Kolter achieves this distribution “by making small size

microtablets.” Id. Dr. Polli also notes that Kolter addresses the

disadvantages of large diameter tablets in the prior art by using small sized

microtablets. Id.

Nieboer, however, does not teach the use of large diameter tablets.

Rather, Nieboer teaches the use of granulates that are small enough to be

filled into capsules. Ex. 1002, 603 (“The medication consisted of capsules

filled with 60 mg enteric-coated granulate of DMFAE . . . .”). Neither

Petitioner nor Dr. Polli has explained sufficiently how Nieboer or Kolter

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suggest that the use of small granulates, as compared to microtablets,

contributed to gastrointestinal irritation as seen with large diameter tablets.

Thus, Dr. Polli does not explain persuasively why a person of ordinary skill

in the art would have modified the small granulates of Nieboer to form

microtablets as taught in Kolter with a reasonable expectation that the

dosage amount of the DMFAE would be distributed throughout the digestive

tract, thereby causing fewer gastrointestinal symptoms.

Dr. Polli also asserts that the microtablets of Kolter “show no

tendency to stick or adhere[, which] 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 goes on to explain that “[s]ticking or adhesion

properties of this type are displayed, for example, by small articles with

hydrophilic release-delaying polymers.” Id. at 3:31–33. Dr. Polli, however,

does not address whether the drug formulation of Nieboer exhibited sticking

and adhesion properties of the type that would have benefited from the

formation of microtablets according to Kolter, thereby alleviating the

gastrointestinal irritation. Once again, Dr. Polli does not explain sufficiently

why a person of ordinary skill in the art would have modified the granulates

of Nieboer to form the microtablets of Kolter.

Accordingly, without adequate evidence to suggest that the

microtablets of Kolter would have solved the gastrointestinal problems of

Nieboer’s granulate DMFAE, we are not persuaded that Petitioner has

shown sufficiently that a person of ordinary skill in the art would have

looked to the teachings of Kolter to modify the drug formulation of Nieboer

with a reasonable expectation of success.

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Thus, based on the current record, we determine that Petitioner has

not established a reasonable likelihood that it would prevail in its assertion

that claims 1–13 are unpatentable as obvious over Nieboer and Kolter.

D. Pending Motion for Additional Discovery

Patent Owner filed a motion for additional discovery, seeking

documents related to its claim of abuse of process and improper use of the

proceeding. Paper 9.

In light of the foregoing determination that Petitioner has failed to

establish a reasonable likelihood that it would prevail in challenging the

asserted claims, Patent Owner’s motion is dismissed as moot.

CONCLUSION III.

We conclude that Petitioner has not established a reasonable

likelihood of prevailing on its assertions that claims 1–13 of the ’393 patent

are unpatentable as obvious.

ORDER IV.

In consideration of the foregoing, it is hereby ordered that the Petition

is denied.

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PETITIONER: Robert W. Hahl, rhahl@neifeld.com Robert Mihail rmihail@neifeld.com John K. Pike jkpike@neifeld.com PATENT OWNER: Michael Flibbert michael.flibbert@finnegan.com Maureen Queler maureen.queler@finnegan.com