Case 2:15-cv-01202-WCB Document 396 Filed 08/25/17 Page 1 of 79 PageID #: 24524
`
`ERFINDERGEMEINSCHAFT UROPEP
`GbR,
`
`
`Plaintiff,
`
`
`
`
`ELI LILLY AND COMPANY,
`
`
`v.
`
`Defendant.
`
`IN THE UNITED STATES DISTRICT COURT
`FOR THE EASTERN DISTRICT OF TEXAS
`MARSHALL DIVISION
`
`
`§
`§
`§
`§
`§
`§
`§
`§
`§
`§
`
`
`MEMORANDUM OPINION AND ORDER
`
`
`
`Case No. 2:15-CV-1202-WCB
`
`
`
`In this patent infringement case, the plaintiff Erfindergemeinschaft UroPep GbR
`
`(“UroPep”), a German association of urology researchers and physicians, sued the defendant Eli
`
`Lilly and Company (“Lilly”) for infringement of U.S. Patent No. 8,791,124 (“the ’124 patent”).
`
`Claim 1 of the ’124 patent is to a method of administering an effective amount of a compound
`
`known as an inhibitor of the enzyme phosphodiesterase (“PDE”) V, in order to treat the
`
`condition of benign prostatic hyperplasia (“BPH”). UroPep alleged that Lilly induced
`
`infringement of claim 1 by marketing and selling the drug Cialis for the treatment of BPH. Lilly
`
`denied infringement and asserted various invalidity defenses. After a trial, a jury found the ’124
`
`patent infringed and not invalid. The jury awarded damages in the amount of $20 million.
`
`Pursuant to Rules 50(b) and 59, Fed. R. Civ. P., Lilly now moves for judgment as a
`
`matter of law or, in the alternative, a new trial. Dkt. No. 375. The motion is denied.
`
`
`
`1
`
`

`

`Case 2:15-cv-01202-WCB Document 396 Filed 08/25/17 Page 2 of 79 PageID #: 24525
`
`BACKGROUND
`
`I. The Invention of ’124 Patent
`
`UroPep owns the ’124 patent, entitled “Use of Phosphordiesterase [sic] Inhibitors in the
`
`Treatment of Prostatic Diseases.” The disclosure was originally filed as part of a PCT
`
`application on July 9, 1997—the undisputed priority date of the ’124 patent. The application
`
`under 35 U.S.C. § 371 (“the 371 application”) was filed in April 2000 and later abandoned. The
`
`371 application, in turn, gave rise to a continuation application that issued as U.S. Patent No.
`
`8,106,061 (“the ’061 patent) in January 2012. The ’124 patent is a continuation of the patent
`
`application that matured into the ’061 patent. ’124 patent, col. 1, ll. 5-8.
`
`The original specification filed in July 1997 begins by describing BPH, a condition in
`
`which the benign growth of the prostate gland in older males causes constriction of the
`
`neighboring urethra and results in lower urinary tract symptoms, including difficulties in
`
`urinating. See id., col. 1, ll. 9-24. One prior art treatment method for BPH was surgery to reduce
`
`the size of the prostate. Id., col. 1, ll. 14-15. Another prior art method was the administration of
`
`drugs, such as alpha-receptor blockers or drugs that interfere with hormonal regulation of the
`
`prostate, to induce relaxation of human prostatic muscle. Id., col. 1, ll. 20-28. Those drugs,
`
`however, were not particularly effective and had significant side effects. Id., col. 1, ll. 24-31; id.,
`
`col. 1, line 67 through col. 2, line 2.
`
`
`
`The inventors of the ’124 patent identified a new drug target: phosphodiesterase (“PDE”)
`
`enzymes. ’124 patent, col. 1, ll. 32-35. At that time, it was known that smooth muscle cells
`
`contain molecules called cyclic adenosine monophosphate (“cAMP”) and cyclic guanosine
`
`monophosphate (“cGMP”), which promote the relaxation of smooth muscle. Id., col. 1, ll. 39-
`
`42. It was also known that PDE enzymes break down cAMP and cGMP. Id., col. 1, ll. 43-44.
`
`
`
`2
`
`

`

`Case 2:15-cv-01202-WCB Document 396 Filed 08/25/17 Page 3 of 79 PageID #: 24526
`
`Finally, it was known that inhibitors of PDEs prevent the breakdown of cAMP and cGMP, which
`
`promotes smooth muscle relaxation. Id., col. 1, ll. 44-52.
`
`Those skilled in the art had studied PDEs and knew that PDEs come in different types
`
`(subesterases), including PDE1 through PDE5.1 ’124 patent, col. 1, ll. 53-60. Publications
`
`reported that those PDE types are distributed differently throughout the body’s organs and organ
`
`systems, and that the activity of those PDE types varies depending on where they are located.
`
`Id., col. 1, ll. 60-65; see also, e.g., Dkt. No. 342, Trial Tr. at 307-08 (a particular PDE type may
`
`not be present in a particular tissue; or, even if the PDE type is present in that tissue, the PDE
`
`type may not be functionally relevant in that tissue because other conditions in the tissue render
`
`the activity of the PDE meaningless).
`
`The prior art also identified compounds that selectively inhibit specific PDE types, i.e.,
`
`compounds that suppress the activity of a specific PDE type. ’124 patent, col. 1, ll. 44-52; see
`
`also id., col. 1, ll. 66-67; id., col. 7, ll. 35-40, 43-45. In particular, hundreds of selective
`
`inhibitors of PDE5 were known at that time, including the selective PDE5 inhibitor tadalafil,
`
`which is the active ingredient in Lilly’s product Cialis. Dkt. No. 344, Trial Tr. at 1254
`
`(UroPep’s expert describes the advanced state of the art regarding selective PDE5 inhibitors);
`
`Dkt. No. 343, Trial Tr. at 791-93 (Lilly’s expert acknowledges that tadalafil, as well as 118 other
`
`compounds disclosed in a document published in 1995, were known PDE5 inhibitors before the
`
`priority date of the ’124 patent).
`
`The inventors of the ’124 patent performed several experiments. See Dkt. No. 342, Trial
`
`Tr. at 316-17 (referencing experiments described in patent disclosure). The first set of
`
`
`1 The PDE subesterases were initially identified by Roman numerals, the convention
`followed in the ’124 patent (e.g., PDE V). It is now more common to use Arabic numerals (e.g.,
`PDE5). For consistency, except where quoting record materials, the modern convention will be
`used throughout.
`
`
`
`3
`
`

`

`Case 2:15-cv-01202-WCB Document 396 Filed 08/25/17 Page 4 of 79 PageID #: 24527
`
`experiments revealed that PDE1, PDE4, and PDE5 were present and had significant activity in
`
`human prostatic tissue. ’124 patent, col. 2, ll. 6-11. The second set of experiments showed that
`
`compounds that selectively inhibit PDE1, PDE4, and PDE5 caused the relaxation of strips of
`
`human prostatic tissue. Id., col. 7, ll. 11-34. Based on those results, the inventors determined
`
`that compounds that selectively inhibit those three PDEs would treat BPH. See id., col. 7, ll. 35-
`
`37; id., col. 8, ll. 5-16. The disclosure identifies a number of “preferred selective inhibitors of
`
`PDE I, IV, and V,” including 10 discrete chemical compounds and two classes of chemical
`
`compounds. Id., col. 2, line 28 through col. 4, line 46.2 For convenience, those “preferred
`
`selective inhibitors of PDE I, IV, and V” will be referred to as “the identified preferred selective
`
`inhibitors.” Tadalafil is not among those identified preferred selective inhibitors.
`
`The disclosure also describes and incorporates “known methods” to determine whether
`
`any particular compound is a “selective inhibitor” of a specific PDE type. ’124 patent, col. 7,
`
`line 35 through col. 8, line 16. If a compound is a selective inhibitor of one of the identified
`
`PDE types (PDE1, PDE4, or PDE5), then that compound is “suitable for the purpose according
`
`to the invention,” id., col. 7, ll. 35-37—namely, for the prophylaxis and treatment of BPH and
`
`other prostatic diseases, id., col. 2, ll. 17-27.
`
`
`
`In the original Patent Cooperation Treaty (“PCT”) application, the patentees claimed the
`
`“[u]se of [any of the identified preferred selective inhibitors] in the prophylaxis and treatment of
`
`prostatic diseases, in particular benign prostatic hyperplasia” and others. PCT Application, at 4
`
`(claim 1); see also id. at 5 (claim 2 covers “medicaments for” the prophylaxis and treatment of
`
`BPH and other prostatic diseases using any of the identified preferred selective inhibitors); id. at
`
`
`2 The disclosure also identifies, as “preferred selective inhibitors of PDE I, IV, and V,”
`the “pharmacologically compatible salts” of those 10 compounds and two classes of compounds.
`’124 patent, col. 4, line 47.
`
`
`
`4
`
`

`

`Case 2:15-cv-01202-WCB Document 396 Filed 08/25/17 Page 5 of 79 PageID #: 24528
`
`6 (claim 3 covers the use of the identified preferred selective inhibitors “in the preparation of
`
`medicaments for the prophylaxis and treatment of” BPH and other prostatic diseases). The ’061
`
`patent, filed in May 2003, claims “[a] method of treating” BPH or prostatism by “administering a
`
`selective inhibitor of [PDE] IV and/or [PDE] V,” selected from a group of six of the identified
`
`preferred selective inhibitors. ’061 patent, col. 8, ll. 4-26 (independent claim 1); see also id., col.
`
`8, ll. 29-53 (independent claim 3 is to a method of “relaxing prostatic muscles” by administering,
`
`to someone with BPH or prostatism, a selective inhibitor of PDE4 and/or PDE5 selected from a
`
`group of nine of the identified preferred selective inhibitors).
`
`
`
`In the 1980s and 1990s, some drug companies were investigating PDE5 inhibitors for the
`
`treatment of other conditions, such as erectile dysfunction. See, e.g., Dkt. No. 342, Trial Tr. at
`
`314-16 (Pfizer was investigating the PDE5 inhibitor sildenafil (Viagra) in the 1980s and 1990s).
`
`Lilly was one of them: Lilly developed Cialis (with tadalafil as the active ingredient) as a drug
`
`for erectile dysfunction, and Lilly sought approval of Cialis in the United States and Europe for
`
`that indication in mid-2001. See Dkt. No. 343, Trial Tr. at 955. Then, in December 2001, Lilly
`
`began discussing other possible indications for Cialis, including whether to develop Cialis as a
`
`treatment for BPH. See id., Trial Tr. at 958, 996. Lilly decided to engage in that development
`
`and obtained FDA approval for the BPH indication in 2011. Id., Trial Tr. at 1003. Lilly then
`
`began marketing and selling Cialis for the treatment of BPH.
`
`
`
`The ’061 patent was in effect at that time. The claims of the ’061 patent, however, do not
`
`cover Cialis, because tadalafil is not one of the identified preferred selective inhibitors required
`
`by the claims of the ’061 patent.
`
`In December 2011, the patentees filed a continuation application that later issued as the
`
`’124 patent. During prosecution, the examiner rejected the claims on the basis of nonstatutory
`
`
`
`5
`
`

`

`Case 2:15-cv-01202-WCB Document 396 Filed 08/25/17 Page 6 of 79 PageID #: 24529
`
`double-patenting over the ’061 patent. See Dkt. No. 106-8, at 63-64. The patentees then
`
`amended claim 1 to exclude many of the identified preferred compounds required in the claims
`
`of the ’061 patent. See Dkt. No. 106-8, at 115.3 Claim 1 of the issued ’124 patent recites:
`
`A method for prophylaxis or treatment of benign prostatic hyperplasia comprising
`administering to a person in need thereof an effective amount of an inhibitor of
`phosphodiesterase (PDE) V excluding a compound selected from the group
`consisting of
`
`
`dipyridamole,
`2-(N-(4-carboxypiperidine)-6-chloro-4(3,4-
`(methylendioxy)benzyl)amino)quinazoline,
`2,3-dihydro-8-hydroxy-7-nitro-1,4-benzodioxine-2-methanol,
`alpha-nitrate.
`4((3,4-(methylendioxy)benzyl)amino)-6,7,8-trimethoxy-
`quinazoline,
`1-methyl-3-propyl-6-(5-(N-(4-methylmorpholino)sulfonyl)-2-
`ethoxyphenyl)pyrazole[4,5]pyrimidin-4(5H)one,
`2-n-butyl-5-chloro-1-(2-chlorobenzyl)-4-methylacetate-imidazole,
`1-cyclopentyl-3-methyl-6-(4-pyridinyl)pyrazolo(3,4-d)pyrimidin-
`4(5H)-one,
`7-(3-(4-acetyl-3-hydroxy-2-propyl-phenoxy)-2-hydroxy-propoxy)-
`2-carboxy-2,3-didehydro-chronan-4-one,
`and pharmacologically compatible salts thereof.
`’124 patent, col. 8, ll. 18-41 (duplicate compound removed).4 Those eight compounds excluded
`
`from claim 1 are all among the identified preferred selective inhibitors. Thus, claim 1 of the
`
`’124 patent on its face includes selective PDE5 inhibitors such as tadalafil, which is not among
`
`the identified preferred selective inhibitors.
`
`
`3 After that amendment, the examiner rejected the claims as anticipated by the claims of
`the ’061 patent. The patentees entered a terminal disclaimer with respect to the ’061 patent, and
`the examiner then allowed the claims of the ’124 patent. See Dkt. No. 106-8, at 121-28.
`4 Claim 1, as set forth in the ’124 patent, contains a duplicate listing of 1-methyl-3-
`propyl-6-(5-(N-(4-methylmorpholino)sulfonyl)-2-ethoxyphenyl)pyrazole[4,5]pyrimidin-
`4(5H)one.
`
`
`
`6
`
`

`

`Case 2:15-cv-01202-WCB Document 396 Filed 08/25/17 Page 7 of 79 PageID #: 24530
`
`
`
`The ’124 patent issued in July 2014. In October 2014, UroPep notified Lilly by letter of
`
`potential infringement of the ’124 patent. Lilly received the letter but did not respond. In July
`
`2015, UroPep filed this action for infringement.
`
`II. The Trial
`
`
`
`At trial, the parties introduced evidence from several sets of competing experts, including
`
`physicians skilled in urology, medicinal chemists skilled in drug development, and economists.
`
`In addition, UroPep called one of the named inventors of the ’124 patent, Dr. Stefan Ückert, to
`
`testify about the invention. Lilly called employees Dr. Lars Viktrup and Janelle Sabo to speak
`
`about Lilly’s development of Cialis for the BPH indication.
`
`
`
`In its Rule 50 and Rule 59 motions, Lilly has not challenged the sufficiency of the
`
`evidence of infringement. UroPep introduced ample evidence that the administration of Cialis
`
`for BPH infringed claim 1 of the ’124 patent. The Court construed claim 1 of the ’124 patent to
`
`require that an effective amount of a “selective PDE5 inhibitor”—i.e., a compound that is at least
`
`20 times more selective for PDE5 than for PDE1 through PDE4—be administered to treat an
`
`individual suffering from BPH. See Dkt. No. 149, at 27; Dkt. No. 234, at 16. At trial, UroPep
`
`introduced the Cialis drug label approved by the U.S. Food & Drug Administration (“FDA”).
`
`That drug label expressly identifies tadalafil, the active ingredient in Cialis, as an inhibitor more
`
`than 20 times more selective for PDE5 than for PDE1, PDE2, PDE3, and PDE4. The label also
`
`states that five milligrams of Cialis is an effective amount to treat BPH, and the label directs
`
`physicians to prescribe Cialis as a treatment for individuals suffering from BPH. Dkt. No. 341,
`
`Trial Tr. at 216, 218. UroPep’s expert urologist, Dr. Anthony Sliwinski, went through the Cialis
`
`label and explained how it met each of the limitations of claim 1. Id., Trial Tr. at 222-23; see
`
`also Dkt. No. 342, Trial Tr. at 323-24, 327 (UroPep’s expert medicinal chemist, Dr. Andrew
`
`
`
`7
`
`

`

`Case 2:15-cv-01202-WCB Document 396 Filed 08/25/17 Page 8 of 79 PageID #: 24531
`
`Bell, did the same). Dr. Sliwinski also testified about his medical practice, in which he
`
`diagnoses patients with BPH and prescribes Cialis for the treatment of that condition. Dkt. No.
`
`341, Trial Tr. at 216-18.5
`
`
`
`Second, UroPep provided evidence that Lilly had induced infringement by marketing
`
`Cialis for the treatment of BPH. For example, the Cialis label, which is addressed to physicians
`
`and patients, counsels the administration of Cialis for the treatment of BPH. See Dkt. No. 341,
`
`Trial Tr. at 216-19. UroPep also introduced numerous advertisements, brochures, coupons, and
`
`other marketing materials that Lilly has distributed to physicians and consumers regarding the
`
`use of Cialis as a treatment for BPH. See Dkt. No. 341, Trial Tr. at 223-27; see also Dkt. No.
`
`342, Trial Tr. at 394-95 (evidence that Lilly spent over $100 million to run one television
`
`advertisement regarding the use of Cialis for BPH and erectile dysfunction); id., Trial Tr. at 396-
`
`97 (same message regarding the administration of Cialis for BPH and erectile dysfunction on
`
`Lilly’s websites). In addition, Dr. Sliwinski testified about his receipt of such materials, Cialis
`
`drug samples, and visits from Lilly pharmaceutical representatives, all of which caused him and
`
`the partners in his practice to prescribe Cialis for BPH. See Dkt. No. 341, Trial Tr. at 206-07,
`
`220, 223-27.
`
`
`
`Lilly presented four primary invalidity defenses: lack of written description under 35
`
`U.S.C. § 112, ¶ 1; lack of enablement under that same provision; anticipation under 35 U.S.C.
`
`
`5 Lilly’s only challenge to the evidence of infringement was the suggestion that doctors
`may prescribe Cialis to treat BPH without correctly diagnosing the patients’ condition as BPH,
`i.e., lower urinary tract symptoms resulting from an enlarged prostate. See Dkt. No. 346, Trial
`Tr. at 1482 (Lilly’s closing argument on noninfringement: “Did they prove an enlarged prostate?
`I’ll leave that to you.”). Dr. Sliwinski, however, explained how he appropriately diagnoses BPH
`before prescribing Cialis. See, e.g., Dkt. No. 341, Trial Tr. at 218-19 (explaining that, before
`prescribing Cialis for BPH, he rules out all other possible causes of the patient’s symptoms to
`conclude that the patient in fact suffers from BPH). In the absence of contrary evidence, the jury
`could reasonably infer that his experience was representative.
`8
`
`
`
`

`

`Case 2:15-cv-01202-WCB Document 396 Filed 08/25/17 Page 9 of 79 PageID #: 24532
`
`§ 102; and obviousness under 35 U.S.C. § 103. Although the jury rejected each defense, Lilly
`
`argues that each is a ground for judgment as a matter of law or, in the alternative, a new trial.
`
`Lilly also contends that the Court improperly rejected Lilly’s argument that claim 1 of the ’124
`
`patent is indefinite and that the Court’s claim constructions are erroneous, requiring judgment as
`
`a matter of law or a new trial. Finally, according to Lilly, the Court gave several erroneous jury
`
`instructions and made several erroneous evidentiary rulings, each of which requires a new trial.
`
`DISCUSSION
`
`Lilly asserts that the Court should enter judgment in Lilly’s favor pursuant to Rule 50(b)
`
`based on (1) any one of Lilly’s invalidity defenses asserted at trial, (2) indefiniteness of the claim
`
`term “inhibitor of phosphodiesterase (PDE) V,” and (3) any of the rejected claim constructions.
`
`Lilly also argues that it is entitled to a new trial pursuant to Rule 59 on any of those grounds, or
`
`based on (4) the Court’s jury instruction on enablement, (5) the Court’s failure to give an
`
`instruction based on 35 U.S.C. § 101, (6) the exclusion of certain evidence based on untimely
`
`disclosures, or (7) the assertedly improper impeachment of one of Lilly’s experts.
`
`I. Legal Standard
`
`
`
`Fifth Circuit law determines what legal standards apply to a motion for judgment as a
`
`matter of law under Rule 50(b) and a motion for a new trial under Rule 59. Wi-Lan, Inc. v.
`
`Apple, Inc., 811 F.3d 455, 461 (Fed. Cir. 2016). A motion for judgment as a matter of law “is a
`
`challenge to the legal sufficiency of the evidence supporting the jury’s verdict.” Dresser-Rand
`
`Co. v. Virtual Automation Inc., 361 F.3d 831, 838 (5th Cir. 2004); see also Vadie v. Miss. State
`
`Univ., 218 F.3d 365, 372 (5th Cir. 2000) (“A jury verdict must be upheld unless ‘there is no
`
`legally sufficient evidentiary basis for a reasonable jury to find’ as it did.”) (quoting Fed. R. Civ.
`
`P. 50). The court must “draw[] all reasonable inferences and resolv[e] all credibility
`
`
`
`9
`
`

`

`Case 2:15-cv-01202-WCB Document 396 Filed 08/25/17 Page 10 of 79 PageID #: 24533
`
`determinations in the light most favorable to the non-moving party.” Dresser-Rand, 361 F.3d at
`
`838. The court “grants great deference to a jury’s verdict and will reverse only if, when viewing
`
`the evidence in the light most favorable to the verdict, the evidence points so strongly and
`
`overwhelmingly in favor of one party that the court believes that reasonable jurors could not
`
`arrive at any contrary conclusion.” Id.; accord Wi-Lan, 811 F.3d at 461 (applying Fifth Circuit
`
`law).
`
`As for the alternative motion for a new trial, Lilly must show that “it is reasonably clear
`
`that prejudicial error has crept into the record or that substantial justice has not been done.”
`
`Laxton v. Gap Inc., 333 F.3d 572, 586 (5th Cir. 2008) (internal quotation marks omitted). In
`
`making that determination, the “court weighs all of the evidence,” but the court “need not view
`
`[the evidence] in the light most favorable to the nonmoving party.” Id. The court, however, may
`
`not grant a new trial “unless the verdict is against the great weight of the evidence.” Dresser-
`
`Rand, 361 F.3d at 838; accord Wi-Lan, 811 F.3d at 461 (applying Fifth Circuit law); see also
`
`Laxton, 333 F.3d at 586 (“A new trial is warranted if the evidence is against the great, and not
`
`merely the greater, weight of the evidence.”).
`
`II. Written Description
`
`
`
`The written description requirement of 35 U.S.C. § 112, ¶ 1 provides, in pertinent part:
`
`The specification shall contain a written description of the invention, and of the
`manner and process of making and using it, in such full, clear, concise, and exact
`terms as to enable any person skilled in the art to which it pertains, or with which
`it is most nearly connected, to make and use the same . . . .
`
`35 U.S.C. § 112 ¶ 1 (2006). For purposes of written description, that clause has been interpreted
`
`to require that the specification “describe the invention sufficiently to convey to a person of skill
`
`in the art that the patentee had possession of the claimed invention at the time of the application,
`
`
`
`10
`
`

`

`Case 2:15-cv-01202-WCB Document 396 Filed 08/25/17 Page 11 of 79 PageID #: 24534
`
`i.e., that the patentee invented what is claimed.” Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d
`
`1336, 1345 (Fed. Cir. 2010) (en banc).
`
`
`
`Both parties offered expert testimony and numerous exhibits addressed to the written
`
`description issue. The primary point of contention was whether the disclosure supports the claim
`
`term “an inhibitor of phosphodiesterase (PDE) V,” construed as “a selective inhibitor of PDE5,
`
`which is at least 20 times more effective in inhibiting PDE5 as compared to PDE1 through
`
`PDE4.” See Dkt. No. 346, Trial Tr. at 1412-13. Lilly’s theory at trial was that the disclosure is
`
`inadequate to describe the genus encompassed by that claim term as construed. In response,
`
`UroPep presented evidence that the disclosure described both a sufficient number of
`
`representative species within the scope of that genus and structural features common to the
`
`members of the genus. See Ariad, 598 F.3d at 1351.
`
`
`
`Over UroPep’s objection, the Court adopted Lilly’s proposed instruction regarding the
`
`written description requirement. Compare Dkt. No. 344, Trial Tr. at 1357 (Lilly “suggest[s] ‘a
`
`sufficient number of representative compounds’”) with Dkt. No. 346, Trial Tr. at 1427 (Court
`
`instructs jury that written description must include “a sufficient number of representative
`
`compounds or a common structural feature so that a person of ordinary skill in the art would
`
`understand, from reading the patent, that the inventor invented the full scope of the claimed
`
`method.”); see also Dkt. No. 346, Trial Tr. at 1397-98 (Court rejects UroPep’s proposed
`
`reference to “one or more representative compounds”). Under Lilly’s proposed instruction, the
`
`jury found that Lilly had failed to prove invalidity by clear and convincing evidence.
`
`
`
`11
`
`

`

`Case 2:15-cv-01202-WCB Document 396 Filed 08/25/17 Page 12 of 79 PageID #: 24535
`
`A. Written Description Support for the Claim Limitation of a Selective Inhibitor of
`PDE5
`
`In its post-trial motion, Lilly argues that the evidence introduced at trial shows that Lilly
`
`
`
`is entitled to a judgment of invalidity for lack of an adequate written description of a selective
`
`inhibitor of PDE5, or a new trial. The Court disagrees.
`
`According to Lilly, the claim term describes a genus using functional language—that is,
`
`“a selective inhibitor of PDE5” is defined by its function as a compound that selectively inhibits
`
`PDE5. Lilly contends that no reasonable jury could find that the disclosures contained within the
`
`“four corners” of the specification describe a sufficient number of representative species within
`
`the scope of the genus, or structural features common to the members of the genus. See Dkt. No.
`
`375, at 15 (quoting Ariad, 598 F.3d at 1351); see also Dkt. No. 393, at 6-7 (Lilly argues that
`
`UroPep is restricted to the “four corners” of the patent and cannot rely upon “that which is
`
`undescribed but allegedly obvious from the art.”).
`
`Lilly proceeds from the wrong premise. As the Federal Circuit explained in Ariad, the
`
`possession inquiry is not limited to what is expressly described within the “four corners” of the
`
`specification. Instead, the possession inquiry is an objective one that is viewed from the
`
`perspective of a person of ordinary skill in the art:
`
`The term “possession” . . . has never been very enlightening. It implies that as
`long as one can produce records documenting a written description of a claimed
`invention, one can show possession. But the hallmark of written description is
`disclosure. Thus, “possession as shown in the disclosure” is a more complete
`formulation. Yet whatever the specific articulation, the test requires an objective
`inquiry into the four corners of the specification from the perspective of a person
`of ordinary skill in the art. Based on that inquiry, the specification must describe
`an invention understandable to that skilled artisan and show that the inventor
`actually invented the invention claimed.
`
`
`598 F.3d at 1351.
`
`
`
`12
`
`

`

`Case 2:15-cv-01202-WCB Document 396 Filed 08/25/17 Page 13 of 79 PageID #: 24536
`
`Because “the patent specification is written for a person of skill in the art, and such a
`
`person comes to the patent with the knowledge of what has come before . . . it is unnecessary to
`
`spell out every detail of the invention in the specification; only enough must be included to
`
`convince a person of skill in the art that the inventor possessed the invention . . . .” LizardTech,
`
`Inc. v. Earth Res. Mapping, Inc., 424 F.3d 1336, 1345 (Fed. Cir. 2005). The level of detail
`
`required to satisfy the written description requirement therefore “varies depending on the nature
`
`and scope of the claims and on the complexity and predictability of the relevant technology.”
`
`Ariad, 598 F.3d at 1351; see also Capon v. Eshhar, 418 F.3d 1349, 1357 (Fed. Cir. 2005) (what
`
`is required “varies with the nature and scope of the invention at issue, and with the scientific and
`
`technologic knowledge already in existence”).
`
`
`
`Under the proper legal standard, Lilly cannot establish that it is entitled to the requested
`
`relief. As the Federal Circuit has emphasized, in written description cases, “[t]he primary
`
`consideration is factual and depends on the nature of the invention and the amount of knowledge
`
`imparted to those skilled in the art by the disclosure.” Union Oil Co. of Cal. v. Atl. Richfield
`
`Co., 208 F.3d 989, 996 (Fed. Cir. 2000); see also ScriptPro, LLC v. Innovation Assocs., Inc., 762
`
`F.3d 1355, 1359 (Fed. Cir. 2014) (sufficiency of the written description is a question of fact).
`
`There was sufficient evidence for the jury to find that Lilly did not prove by clear and convincing
`
`evidence that the ’124 patent failed to disclose “either a representative number of species falling
`
`within the scope of the genus or structural features common to members of the genus so that one
`
`of skill in the art [could] ‘visualize or recognize’ the members of the genus.” Ariad, 598 F.3d at
`
`1350.
`
`
`
`13
`
`

`

`Case 2:15-cv-01202-WCB Document 396 Filed 08/25/17 Page 14 of 79 PageID #: 24537
`
`1. Representative Number of Selective PDE5 Inhibitors
`
`
`
`A reasonable jury could have found that Lilly failed to show that the disclosure lacked a
`
`sufficient number of representative compounds falling within the scope of the genus of selective
`
`PDE5 inhibitors. The specification describes a number of “preferred selective inhibitors of PDE
`
`I, IV, and V.” ’124 patent, col. 2, line 28. Those “preferred selective inhibitors” include 10
`
`discrete compounds (a) through (j), and two classes of compounds (k) and (l). Id., col. 2, line 29
`
`through col. 4, line 47. The patent identifies those compounds and classes of compounds by
`
`chemical name and, in most cases, structural drawings. Id.
`
`The evidence at trial showed that many of the compounds identified in the ’124 patent as
`
`“preferred selective inhibitors of PDE I, IV, and V” were known to be selective PDE5 inhibitors
`
`in July 1997. Based on his expert knowledge and pointing to printed publications, UroPep’s
`
`expert Dr. Andrew Bell testified that the compounds identified as (a), (c), (d), and (g) in the ’124
`
`patent were publicly known as selective PDE5 inhibitors before July 1997. See Dkt. No. 342,
`
`Trial Tr. at 314-15 (sildenafil, MY5445, and zaprinast—compounds (a), (c), and (g) in the
`
`specification—were known selective PDE5 inhibitors); Dkt. No. 344, Trial Tr. at 1260-61, 1265-
`
`66 (compound E4021—compound (d) in the specification—was a known selective PDE5
`
`inhibitor). Experts called by Lilly also testified as to the known PDE5 activity of those
`
`compounds in July 1997. Dr. Nicholas Terrett noted that the scientific literature showed that a
`
`number of quinazoline compounds—within the class of compounds (k) in the specification—
`
`were known to inhibit PDE5. Dkt. No. 343, Trial Tr. at 710-11. Lilly’s expert Dr. David Rotella
`
`explained that sildenafil (compound (g)) is a pyrazolopyrimidone and within the class of
`
`compounds (l) in the specification. Id., Trial Tr. at 740; see also id., Trial Tr. at 723 (Dr. Rotella
`
`admits sildenafil was a known selective PDE5 inhibitor in July 1997).
`
`
`
`14
`
`

`

`Case 2:15-cv-01202-WCB Document 396 Filed 08/25/17 Page 15 of 79 PageID #: 24538
`
`In addition to the compounds expressly disclosed in the ’124 patent, the jury heard
`
`undisputed evidence that hundreds of PDE5 inhibitors were known by July 1997. Dr. Bell
`
`testified about the advanced state of the art regarding selective PDE5 inhibitors in July 1997:
`
`“There were hundreds of known inhibitors, selective inhibitors of PDE5 known at that time.
`
`This was a pretty mature area.” Dkt. No. 342, Trial Tr. at 318; see also Dkt. No. 344, Trial Tr. at
`
`1254 (explaining that hundreds of selective PDE5 inhibitors were known by July 1997); id., Trial
`
`Tr. at 1267-68 (explaining that skilled artisans were aware of hundreds of other selective PDE5
`
`inhibitors beyond those expressly named in a 1995 review article). Lilly’s expert Dr. Rotella
`
`admitted that tadalafil, as well as 118 other compounds in one sample paper published in 1995,
`
`were known PDE5 inhibitors before July 1997. Dkt. No. 343, Trial Tr. at 792-93. There was
`
`also evidence that at least two selective PDE5 inhibitors—in particular, sildenafil and
`
`zaprinast—had been subjected to human clinical testing long before July 1997, albeit for
`
`conditions other than BPH. Dkt. No. 344, Trial Tr. at 1293-94; see also Dkt. No. 342, Trial Tr.
`
`at 315-18 (Dr. Bell describes Viagra clinical trials in 1980s and 1990s).
`
`Given the evidence of the knowledge of a person of skill in July 1997 regarding PDE5
`
`inhibitors, including tadalafil, a reasonable jury could have found that the specification disclosed
`
`a sufficient number of representative species of selective PDE5 inhibitors. Written description is
`
`a question of fact, and “[f]or generic claims, [there are] a number of factors for evaluating the
`
`adequacy of the disclosure, including ‘the existing knowledge in the particular field, the extent
`
`and content of the prior art, the maturity of the science or technology, [and] the predictability of
`
`the aspect at issue.’” Ariad, 598 F.3d at 1351 (quoting Capon v. Eshhar, 418 F.3d at 1359).
`
`UroPep presented evidence as to all of those factors, much of which Lilly failed to rebut. The
`
`jury was entitled to credit UroPep’s evidence and find that Lilly failed to meet its burden.
`
`
`
`15
`
`

`

`Case 2:15-cv-01202-WCB Document 396 Filed 08/25/17 Page 16 of 79 PageID #: 24539
`
`Lilly nevertheless contends that the disclosure of several species of selective PDE5
`
`inhibitors in the ’124 patent is insufficient, because Lilly’s evidence showed that the genus of
`
`selective PDE5 inhibitors is large. For example, one witness put on by Lilly testi