Case 1:13—cv—O2046—GMS Document 360 Filed 06/03/15 Page 1 of 6 Page|D #: 4705
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`IN THE UNITED STATES DISTRICT COURT
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`FOR THE DISTRICT OF DELAWARE
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`IN RE BENDAMUSTINE CONSOLIDATED
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`CASES
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`OH
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`Civil Action No. 13-2046-GMS
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`CONSOLIDATED
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` __4
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`ORDER CONSTRUING THE TERMS OF U.S. PATENT NOS.
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`8,436,190; 8,609,863; 8,791,270; 8,445,524; 8,669,279; 8,883,836
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`The court having considered the submissions of the parties and having heard oral
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`argument on the matter—IT IS HEREBY ORDERED, ADJUDGED, and DECREED that, as
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`used in the asserted claims of U.S. Patent Nos. 8,436,190 (“the ’190 Patent”); 8,609,863 (“the
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`’863 Paten ”); 8,791,270 (“the ’270 Patent”); 8,445,524 (“the ’524 Patent”); 8,669,279 (“the ’279
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`Paten ”); and 8,883,836 (“the ’836 Patent”):
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`The ’524 Patent
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`1. The term “solid form of bendamustine hydrochloride, designated as bendamustine
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`hydrochloride Form 1”
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`is
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`construed to mean “anhydrous ’crystal
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`form of
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`bendamustine hydrochloride that can be distinguished from other forms by its X-ray
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`powder diffraction pattern?”
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`2. The terms:
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`’ Drawing on statements in the prosecution history, the defendants would construe the term to require a
`limitation that Form 1 compounds do not contain any water. See Biogen Idec, Inc. v. GlaxoSmithKline LLC, 713
`F.3d 1090, 1095 (Fed. Cir. 2013). The court, however, agrees with the plaintiff that the prosecution history
`statements explaining that Form 1 does not “contain” or “include” water refer to the crystal structure of Form 1—
`i.e., Form 1 is not a hydrate.
`(See e.g., D.I. 153 at JA002585, 1] 7 (“[B]endamustine hydrochloride Form 1 crystal
`structure does not include any water molecules, that is, Form 1 is not a hydrate.”).) The court is wary of including a
`limitation that could be read broader than what was originally disclaimed during prosecution. Thus, the court
`construes the term to include a limitation that is “consistent with the scope of the claimed surrender”: Form 1 is
`“anhydrous.” See Biogen, 713 F.3d at 1095. Such a limitation is undisputed by both parties and is in line with the
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`teachings of the specification.
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`FRESENIUS KABI 1016-OOO1
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`Case 1:13—cv—O2046—GMS Document 360 Filed 06/03/15 Page 2 of 6 Page|D #: 4706
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`0
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`0
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`0
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`“an X-ray powder diffraction pattern comprising the following reflections:
`8.3, 16.8, and 18.5i0.2 degrees 26”;
`“an X-ray powder diffraction pattern further comprising the following
`reflections: 14.0, 22.0, 22.9, 25.1, and 28.3i0.2 degrees 26”; and
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`“an X-ray powder diffraction pattern additionally including, but not limited to,
`a reflection at 14.0:t0.2 degrees 26”
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`are construed to mean:
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`0
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`0
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`0
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`“an X-ray powder diffraction pattern including, but not limited to, reflections
`at 8.3, 16.8 and 18.5 $0.2 degrees 26”;
`“X-ray powder diffraction pattern additionally including, but not limited to,
`the following reflections: 14.0, 22.0, 22.89, 25.1 and 28.3 :t0.2 degrees 26”;
`and
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`“X-ray powder diffraction pattern additionally including, but not limited to, a
`reflection at 14.0:t0.2 degrees 26,”
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`respectively?
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`The’190 Patent
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`3. The term “tertiary-butyl alcohol” is construed to have its plain and ordinary
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`meaning.3
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`2 The court declines to import additional limitations into these grouped terms and gives “comprising” its
`traditional meaning in the art.
`See Genentech,
`Inc.
`v.’ Chiron Corp, 112 F.3d 495, 501 (Fed. Cir. 1997)
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`(“‘Comprising’ is a term of art used in claim language which means that the named elements are essential, but other
`elements may be added and still form a construct within the scope of the claim”); MPEP § 2111.03 (“The
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`transitional
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`term ‘comprising,” which is synonymous with ‘including,’
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`‘containing,’ or ‘characterized by,’
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`is
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`inclusive or open-ended and does not exclude additional, unrecited elements or method steps.”). The defendants’
`proposal would require that the identified reflection “peaks” be freestanding and not overlapping with peaks of other
`forms. This limitation, however, conflicts with data in the specification, which shows that individual peaks of one
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`form may also be present in other forms. See ’524 Patent, col. 5 l. 51—col. 9 l. 34. It is the entire set of reflections—
`the signature pattern—that is unique to each form.
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`The defendants point to a statement in the prosecution history discussing previous versions of the claim
`language in question: “[The claims] provide a listing of XRPD peaks that are particularly characteristic of Form 1.
`These claims include peaks that are freestanding and do not overlap with any of the other disclosed forms of
`bendamustine” (D.I. 153 at JA002580.) But this statement does not require that each of the individual peaks be
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`unique; rather, the entire reflection profile must “include peaks that are freestanding and do not overlap.” (Id.
`(emphasis added).) Thus, this statement confirms that the overall pattern is the focus, and not any single reflection
`angle.
`It certainly is not unambiguous evidence of disclaimer. See Omega Eng’g, Inc, v. Raytek Corp, 334 F.3d
`1314, 1325-26 (Fed. Cir. 2003) (“[F]or prosecution disclaimer to attach, our precedent requires that the alleged
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`disavowing actions or statements made during prosecution be both clear and unmistakable”).
`3 “As a general proposition, a limitation that does not exist in a claim should not be read into that claim.”
`Biovail Corp. Int’I v. Andrx Pharm., Inc., 239 F.3d 1297, 1301 (Fed. Cir. 2001). Defendant Innopharma, Inc.
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`2
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`FRESENIUS KABI 1016-OOO2
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`Case 1:13—cv—O2046—GMS Document 360 Filed 06/03/15 Page 3 of 6 Page|D #: 4707
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`4. The term “pharmaceutical composition” is construed to mean “a composition that is
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`made under conditions such that it is suitable for administration to humans.”4
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`5. As used in the phrase “containing not more than about 0.5% bendamustine ethyl
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`ester,” the term “0.5%” is construed to mean “0.5 area percent relative to the amount
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`of bendamustine as determined by, e.g., HPLC.”5
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`(“Innopharma”) seeks to import a host of limitations into this straightforward claim term. The intrinsic record does
`not support doing so.
`Each of the proposed limitations, Innopharma argues, captures the inventive “magic” of having tertiary-
`butyl alcohol (“TBA”) in the claimed invention.
`(D.I. 327 at 60.) But as the plaintiff correctly points out, goals of
`the invention are not to be imported as claims, absent further evidence of disclaimer. See Intel Corp. v. ITC, 946
`F.2d 821, 836 (Fed. Cir. 1991). First, Innopharma would require a process limitation that TBA is “separately
`added,” to rule out the possibility that TBA is present as residue from an upstream process. The court disagrees that
`the specification and prosecution history statements “clearly and unmistakably” evidence that such a process
`limitation is required. See Sanofi-Aventis US. LLC v. Sandoz, Inc., 345 F. App’x 594, 597 (Fed. Cir. 2009).
`Second, Innopharma would require an amount or concentration limitation. The court once again sees inadequate
`language of disclaimer, and notes also that reading in an amount limitation would result in a claim differentiation
`problem in the dependent.claims, which recite explicit concentration limitations. See ’190 Patent, claims 2, 3, 5 & 6.
`Claims terms should be construed so as not to create redundancies. See Phillips v. AWH Corp, 415 F.3d 1303,
`1324-25 (Fed. Cir. 2005). The patent drafters and the examiner knew how to include amount limitations, had that
`been a condition of patentability.
`Finally, Innopharma would require a limitation that TBA “materially alters the solubility of bendamustine
`in water.” As already stated, a stated goal of the invention or its elements need not be limiting. Moreover, such a
`limitation has no definite or ascertainable met1ics—indeed the proposed phrase is never used in the intrinsic record.
`Unsurprisingly, the court disfavors a construction that injects considerable ambiguity into a term that has a readily
`understandable meaning.
`4 “Although words in a claim are generally given their ordinary and customary meaning, a patentee may
`choose to be his own lexicographer and use terms in a manner other than their ordinary meaning, as long as the
`special defmition of the term is clearly stated in the patent specification or file history.” Vitronics Corp. v.
`Conceptronic, Inc., 90 F.3d 1576, 1582 (Fed. Cir. 1996). The drafters clearly defined “pharmaceutical composition”
`in the specification, and therefore their lexicography guides the court’s construction.
`’190 Patent, col. 10 11. 53-55.
`The plaintiff’ s proposal includes an additional clause identifying a non-exhaustive list of embodiments meeting this
`definition. While this clause is also taken from the specification, the court is not persuaded that naming particular
`embodiments-even acknowledging that they are non-exhaustive—adds anything to the construction. Defendant
`Accord Healthcare Inc. (“Accord”) proposes a construction that ignores the explicit definition in the specification.
`The court sees no justification for straying from this well-accepted canon of construction.
`5 The parties agree that
`the meaning of “area percent of bendamustine” is defined in the patent
`specification: “the amount of a specified degradant, e.g., HP1, relative to the amount of bendamustine as
`determined, e.g., by HPLC.”
`’190 Patent, col. 11 11. 57-60. The parties disagree, however, as to whether the
`percentage figire in the claim term refers to area percent of bendamustine. The court finds that it does.
`The defmition of “area percent of bendamustine” confirms that it is used to measure degradants. Although
`only HP1 is specifically identified in the definition, bendamustine ethylester is also a degradant. The court sees no
`reason to measure only HP1 in terms of area percent of bendamustine, while using a different methodology for
`bendamustine ethylester. Indeed, the specification supports measuring bendamustine ethylester as an area percent of
`bendamustine: “the amount of bendamustine ethylester produced during lyophilization from about 0 to 24 hours
`does not exceed about 0.5% (area percent bendamustine).” ’ 190 Patent, col. 6 11. 11-13 (emphasis added).
`The court is not persuaded by the defendants’ contention that they advocate for the plain meaning. A
`percentage is a ratio of two quantities that must be defined—it has no standalone meaning. The defendants are
`unable to cite anything in the intrinsic record in support of their view.
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`3
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`FRESENIUS KABI 1016-OOO3
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`Case 1:13—cv—O2046—GMS Document 360 Filed 06/03/15 Page 4 of 6 Page|D #: 4708
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`The ’863 Patent
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`6. The term “trace amount of tertiary-butyl alcohol” is construed to mean a “non-zero
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`amount tertiary-butyl alcohol
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`that is equal
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`to or below recommended levels for
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`pharmaceutical products.”6
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`7. The term “stable lyophilized preparation” is construed to mean “solid material
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`obtained by freezedrying having sufficient stability to have utility as a pharmaceutical
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`product.”7
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`The ’270 Patent
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`8. The court declines to construe “amount of HP1 measured at
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`time zero after
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`reconstitution” at this time.8
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`4“
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`trace amount of an organic solvent’ means an amount of solvent that is equal to
`6 The specification states:
`or below recommended levels for pharmaceutical products .
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`. .” ’863 Patent, col. 11 11. 61-63. As explained above,
`“the inventor’s lexicography governs.” Phillips v. AWH Corp., 415 F.3d 1303, 1316 (Fed. Cir. 2005). The
`defendants seek to include an additional limitation—taken from the following sentence in the specification—that a
`trace amount must be “detectable.” ’863 Patent, col. 11 11. 66-67 (“The lower limit is the lowest amount that can be
`detected.”).
`While the court is sensitive to the defendants’ position, the proposed limitation injects ambiguity and
`uncertainty into the construction. Detectability is a variable parameter, changing over time and under different
`conditions. The specification makes no further mention of detection. The court’s inclusion of “non-zero” clarifies
`that an amount is a physical quantity.
`In the court’s view, this addresses the defendants’ concern without adding
`urmecessary vagueness.
`(See D.I. 125 at 24 (“Undetectable is not an amount; it is a phantom or an inference. Yet
`this is inconsistent with the fact that there must be an ‘amount’ of TBA, as required by the claim language”).
`Ultimately, the court does not necessarily read the disputed follow-on sentence as a limitation, as the
`defendants contend. Rather, it appears to emphasize the broad scope of “trace amount.” The court is reluctant to
`shoehorn an amorphous limitation into the construction, when it is not apparent that the language was indeed
`intended to be limiting.
`the commonly understood meaning of lyophilization—i.e.,
`7 The court’s construction combines
`freezedrying—with the explicit definition found in the specification. Defendant Innopharma seeks to include
`additional
`limitations concerning an amount of TBA.
`In other words, Innopharma seeks to overcome the
`presumptions both that “the inventor’s lexicography governs” and that limitations from the specification should not
`be imported into the claims. See Phillips, 415 F.3d at 1316, 1323. The intrinsic evidence does not support a
`departure from these presumptions.
`8 “A determination that a claim term ‘needs no construction’ or has the ‘plain and ordinary meaning’ may
`be inadequate when a term has more than one ‘ordinary’ meaning or when reliance on a terrn’s ‘ordinary’ meaning
`does not resolve the parties’ dispute.” 02 Micro Int’l Ltd. v. Beyond Innovation Tech. Co., 521 F.3d 1351, 1361
`(Fed. Cir. 2008). As explained during the hearing, the court is convinced that extrinsic evidence is necessary to
`determine how one skilled in the art would understand “at time zero.” (D.I. 110-11.) The court will hear testimony
`on this issue at trial.
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`FRESENIUS KABI 1016-OOO4
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`Case 1:13—cv—O2046—GMS Document 360 Filed 06/03/15 Page 5 of 6 Page|D #: 4709
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`9. The term “bendamustine degradants” is construed to mean “chemical compounds
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`resulting from a change in chemical structure of bendamustine.”9
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`10. The term “containing less than or equal to 4.0% (area percent of bendamustine) of
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`bendamustine degradants” is construed to mean “containing less than or equal to
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`4.0% of total chemical compounds resulting from a change in chemical structure of
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`bendamustine, relative to the amount of bendamustine as determined, e.g., by
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`HPLC.”‘°
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`11. The term “pharmaceutical composition” is construed to mean “a composition that is
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`made under conditions such that it is suitable for administration to humans.”“
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`12. The terms “lyophilized preparation” and “lyophilized composition” are construed to
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`mean “freezedried preparation” and “freezedried composition,” respectively.”
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`The ’279 & ’836 Patents
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`13. The term “an X-ray powder diffraction pattern comprising the following reflections:
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`7.9, 15.5, and 26.1i0.2 degrees 26” is construed to mean “an X-ray powder
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`9 The court’s construction comes from the explicit definition of “degrades,” found in the specification: “By
`‘degraded’ is meant that the active has undergone a change in chemical structure.” ’270 Patent, col 9 11. 56-57. As
`emphasized repeatedly, the court will adopt “special definition[s]” that are “clearly stated in the patent specification
`or file history.” See Vitronics, 90 F.3d at 1582. The defendants seek to limit the ambit of possible degradants to
`four specific compounds: monohydroxy bendamustine (i.e., HP1), bendamustine dimer, bendamustine ethylester,
`and BMIDCE (Formula V). Although the four named degradants figure prominently in the specification, the court
`does not see adequate disclaiming language to limit the claim term in such a fashion. Moreover, several claims
`reference HP1 in particular. Thus, the drafters knew how to specify individual degradants, had that been the intent.
`Without more, the court will not infer a disclaimer of claim scope.
`1° The court agrees with the plaintiff that the proper construction of this tenn is simply the combination of
`the agreed-upon construction of “area percent of bendamustine,” (D.I. 317), and the construction of “bendamustine
`degradants,” outlined above.
`Innopharma is the only defendant seeking an alternative construction. The intrinsic
`record does not support the importation of Innopharma’s additional limitations. Flo Healthcare Solutions, LLC v.
`Kappos, 697 F.3d 1367, 1375 (Fed. Cir. 2012) (“[I]t is not proper to import from the patent’s written description
`limitations that are not found in the claims themselves.”).
`” The court’s construction of this term is the same as outlined in the context of the ’190 Patent. See supra
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`note 4.
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`‘Z The court’s construction of these terms simply imports the plain meaning of lyophilization—i.e,
`freezedrying. Only Irmopharma seeks an additional limitation requiring an added alcohol that “materially alters the
`solubility of bendamustine.” Innopharma does not seek further construction of these terms (rather, their analogs) in
`the context of the ’524, ’279, and ’836 Patents.
`(D.I. 349.) The court does not see sufficient evidence of disclaimer
`to warrant a different construction for the ’270 Patent.
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`FRESENIUS KABI 1016-OOO5
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`Case 1:13—cv—O2046—GMS Document 360 Filed 06/03/15 Page 6 of 6 Page|D #: 4710
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`diffraction pattern including, but not limited to, reflections at 7.9, 15.5, and 26.li0.2
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`degrees 20””
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`Dated: June 3 , 2015
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`13 The court’s construction is consistent with those of similar terms in the ’524 Patent. See supra note 2.
`The court agrees with the plaintiff that defendants’ proposed construction——which requires that the reflection peaks
`be produced from Form 3—is redundant. The claims already explain that the reflection peak profile is produced by
`Form 3 bendamustine hydrochloride. Repetition of this requirement only serves to confuse.
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`6
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`FRESENIUS KABI 1016-0006