Amarin Corp Plc (AMRN)

[HDGabor]

A layman summary of the patent case (Part 2; see Part 1 here)
[Mod - who sticked Part 1 - please replace with this]

Plaintiff: Amarin
Defendant: Generics (Hikma & Dr. Reddy)

The litigation is about the MARINE
(i) Patents (obviousness)
(ii) Indication / label (infringement)

REDUCE-IT indication (label); usage (treatment; off-label), study (other than support non-obviousness) and patents are not relevant. (E.g. Existence of direct infringement by physicians – treating patients for CVE is not enough without inducement … and MARINE label (package insert) does not encourage treatment for CVE).
Nothing – other than the MARINE label – is relevant regarding infringement. Hikma JPM presentation (which is not a forecast or Hikma’s expected revenue; see more details about it here or Generics "real aim", (unspecific) intent or knowledge of off-label usage does not matter. (See more below at; “Inducement”)

The topic of the litigation is obviousness and infringement. I will focus on infringement, since I see obviousness as the easier (easy) part, as Generics bear the burden of proving patents are obvious. They refer to small studies, small pieces (as prior art) that are - maximum - good to raise questions, to establish theories but these are not (are far away from) a “clear-and-convincing-evidence(s)”, does not prove anything. Furthermore, many secondary considerations support non-obviousness.

Secondary considerations are a reality check on the determination reached through three factual inquiries [(1) Determining the scope and content of the prior art.; (2) Ascertaining the differences between the claimed invention and the prior art.; (3) Resolving the level of ordinary skill in the pertinent art].
The invention may appear on paper to be obvious, but if reality does not match theory then the invention can be established as being non-obvious.

[“Secondary considerations” often come later (or secondary) in time but it does not mean that it is secondary in importance,” may often be the most probative and cogent evidence in the record”. Stratoflex, Inc. v. Aeroquip Corp., 713 F.2d 1530, 1538 (Fed Cir. 1983).

Courts consider the following secondary considerations in determining obviousness:
(1) The invention’s commercial success,
(2) Long felt but unresolved needs,
(3) The failure of others,
(4) Skepticism by experts,
(5) Praise by others,
(6) Teaching away by others,
(7) Recognition of a problem,
(8) Copying of the invention by competitors, and
(9) Other relevant factors.]

Infringement

The issue is “around” the 12-weeks (but not as most of the people think … see more at contributory and induced infringement below).

Meanwhile the patent contains the explicit definition about treatment duration, admittedly present in all asserted claims (“requires administering icosapent [another name for EPA] to a patient with severe hypertriglyceridemia (TG ≥500 mg/dL) for at least 12 weeks.”) the label does not.

The infringement could be (in this case … other types – e.g.: the Willful Infringement, Literal Infringement – are not a topic):
1. Direct
2. Indirect
2.1. Contributory
2.2. Induced (Inducement)

The Federal Circuit determined that while both physicians and patients could be the direct infringers the ANDA filer could not be but the ANDA filer could be liable for indirect infringement. Eli Lilly & Co. v. Teva Parenteral Medicines, Inc., 845 F.3d 1357 (Fed. Cir. 2017). It is the case here also: “Defendants cannot directly infringe them—as method claims, they can only be infringed if a doctor were to treat a patient using one of Defendants’ ANDA drugs.”. Amarin Pharma Inc. et al v. Hikma Pharmaceuticals USA Inc. et al; D278.

Amarin claimed (i) contributory and (ii) induced infringement (both are indirect). “Plaintiffs allege that Defendants either induce infringement of, or contributorily infringe.” Amarin Pharma Inc. et al v. Hikma Pharmaceuticals USA Inc. et al; D278.

Amarin bear the burden of proving patent infringement.

This is true whether the patent owner initiated the lawsuit by suing for infringement or the accused infringer initiated the suit by seeking a declaratory judgment that it does not infringe the patent or that the patent is invalid or both. Medtronic, Inc. v. Mirowski Family Ventures, LLC, (U.S. Supreme Court, 2013).

(i) Contributory

Generics contributorily infringes a method patent when the Generic: (1) knows its product is “made or especially adapted for use in an infringement of” that method patent; and (2) the product is “not a staple article or commodity of commerce suitable for substantial non infringing use.”
There is no real dispute that Vascepa [V] — and therefore Generics’ ANDA drugs [GV] — are, and can be for legitimate reasons, prescribed for fewer than 12 weeks. That means that reducing triglycerides in less than 12 weeks using Generics’ ANDA drugs is a substantial non-infringing use of those drugs. The existence of this substantial non-infringing use for Generics’ ANDA drugs therefore defeats Plaintiffs’ contributory infringement claim. Because there is no genuine dispute of material fact on this issue, the Court granted Generics summary judgment that, they do not contributorily infringe Plaintiffs’ Asserted Claims. Amarin Pharma Inc. et al v. Hikma Pharmaceuticals USA Inc. et al; D278.

The less than / more than 12 weeks were relevant for this only. Based on experts’ testimony less than 12 weeks treatment exist, it is substantial and the patents do not cover it.

(ii) Inducement

To determine induced infringement the prerequisites are the existence of
(1) Direct infringement (by physician or other health care provider of the patient) AND
(2) Specific intent, encouragement (by Generics) for direct infringement. "inducement requires evidence of culpable conduct, directed to encouraging another's infringement, not merely that the inducer had knowledge of the direct infringer's activities." DSU Med. Corp. v. JMS Co., 471 F.3d 1293, 1306 (Fed.Cir.2006). The culpable conduct is the wording of a drug label (see below).

"In order to prevail on an inducement claim, the patentee must establish first that there has been direct infringement, and second that the alleged infringer knowingly induced infringement and possessed specific intent to encourage another's infringement." ACCO Brands, Inc. v. ABA Locks Mfrs. Co., 501 F.3d 1307, 1312 (Fed.Cir.2007)

Inducement is not about how prescribing doctors use V, how long is the treatment. It is beyond dispute that the majority (>95%) of the physicians prescribe V (and / or will prescribe GV) longer than 12 weeks (Generics have “knowledge of the direct infringer's activities”). but is about why they prescribe it for longer than 12 weeks?

In this type of Hatch-Waxman Act patent litigation, where Generics have filed ANDAs, the question of whether Generics may be held liable for inducing infringement turns on whether Generics “have the specific intent, based on the contents of their proposed labels, to encourage physicians to use their proposed ANDA products” Grunenthal GMBH v. Alkem Labs. Ltd., 919 F.3d 1333, 1339 (Fed. Cir. 2019). in a way that (the physician) infringes the asserted claims. In other words, the Court must ask whether the label encourages, recommends, or promotes infringement. In addition, because the asserted claims are method claims, the “pertinent question is whether the proposed label instructs users to perform the patented method.” AstraZeneca LP v. Apotex, Inc., 633 F.3d 1042, 1060 (Fed.Cir.2010).

The question comes down to whether or not the label is the cause (for longer than 12 weeks treatment) or not, since that is the way how the Generics could commit inducement, the one and only way how Generics could encourage, recommend, or promote infringement (by physicians).

The label does not have to encourage all physicians it is sufficient that Generics' labels will encourage some physicians to prescribe GV to patients for longer than 12 weeks and will thus inevitably lead to infringing uses. "Even if [Defendant] were correct that the [language in the label] may be applied to other dosing regimens, the language ... would inevitably lead some consumers to practice the claimed method." AstraZeneca LP v. Apotex, Inc., 633 F.3d 1042, 1060 (Fed.Cir.2010).

Argument (regarding inducement)

Generics argue they will not induce infringement of the asserted claims because their proposed labelling, which mirrors Amarin’s (MARINE label), does not encourage doctors to prescribe the drug for at least 12 weeks.

(i) Chronic condition

Generics argue, “the most common causes of severe hypertriglyceridemia are not chronic or immutable factors. Rather, the causes can be acute and short-term”. Both parties’ experts agree that this indication is not limited to treating chronic forms of severe hypertriglyceridemia. Doctors can (and do) prescribe Vascepa for non-chronic forms of severe hypertriglyceridemia.

Generic did not disprove – more precisely admitted – that severe hypertriglyceridemia could be chronic. (E.g., genetics could be the cause … what else is chronic if genetic is not …)

Generics argue, that “regardless of whether the condition is chronic, it often does not require drug treatment for at least 12 weeks.”

“often does not require” means it requires in other cases (see below: (ii)

Regarding the treatment of chronic condition, “The Court finds this argument intuitively persuasive—chronic conditions require indefinite treatment

(ii) When taken in conjunction with a lipid-lowering diet, as required by the label, Vascepa® reduces triglyceride levels below 500 mg/dL in only four weeks. Some patients may be able to follow the indication for Vascepa® and Defendants’ ANDA products and lower their triglyceride levels below 500 mg/dL with a short course of the drug in conjunction with diet and exercise, and then maintain such levels through diet and exercise alone.

Amarin’s MARINE study showed that about 21% of patients in the placebo arm were able to achieve and maintain levels below 500 mg/dL with diet and exercise alone. These 21% will not get V but the remaining 79% will.
Meanwhile some patients may be able to lower their triglyceride levels below 500 mg/dL with a short course of the drug in conjunction with diet and exercise, and then maintain such levels through diet and exercise alone … (i) not all of them and (ii) not all of them able to lower their triglyceride levels below 500 mg/dL within 12 weeks.
These should be treated with V for longer than 12 weeks to maintain (or lower) their triglyceride levels below 500 mg/dL in conjunction with diet and exercise.

In this case the label contains “reduce triglyceride (TG) levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia” (aka below TG 500) meanwhile the patent contains “requires administering icosapent [another name for EPA] to a patient with severe hypertriglyceridemia (TG ≥500 mg/dL) for at least 12 weeks.”.

Inducement need not be premised on explicit instructions to perform the infringing method, where the proposed label "would inevitably lead some consumers to practice the claimed invention." In case of “Pulmicort respules”® the label contains “titrate down” meanwhile the patent contains “once daily.” administration. The court concluded that, for patients the downward-titration language would necessarily lead patients to use the drug once daily. AstraZeneca LP v. Apotex, Inc., 633 F.3d 1042 (Fed.Cir.2010)

For patients who could not lower their triglyceride levels below 500 mg/dL within 12 weeks or could not maintain such levels despite “an appropriate lipid-lowering diet and exercise regimen” the treatment will be longer than 12 weeks. … the “lack of result” (triglyceride levels stay above 500 mg/dL at 12 weeks) would necessarily lead patients to use the drug for more than 12 weeks.

(iii) “Indications and Usage” & “Dosage and Administration” section [Sections] vs. full label (package insert)

Generics argue that “[t]he “Indications and Usage” section of Defendants’ labels is silent as to the duration of icosapent drug treatment.”.

The District of Delaware found induced infringement based on a clinical trial described in the label. (Note [Generics noted also]: In that case the “Indications and Usage” section contains an explicit reference: “see Clinical Studies (14)”.) Sanofi v. Glenmark Pharm. Inc., USA, 204 F. Supp. 3d 665 (D. Del.2016). The prescribing physician would read the (full) label before prescribing it to patients … explicit reference to the “Clinical Studies” section is not necessary. Theory of inducement does not require a prescribing physician to look outside the label or go on the type of "scholarly scavenger hunt", all that inducement essentially requires is that a prescribing physician actually read the label.

The “14. Clinical Studies” section is the “ section must discuss those clinical studies that facilitate an understanding of how to use the drug safely and effectively.” Based on MARINE study the prescribing physician will understand that the adequate treatment duration is (at least) 12 weeks.

The label (14. Clinical Studies) encourages, recommends and promotes 12 weeks treatment.
(Note: The label does not contain any data about less than 12 weeks treatment, does not encourages, , recommends or promotes less than 12 weeks treatment.)

(iv) (Primarily) Rely on Takeda Pharm. U.S.A., Inc. v. W.-Ward Pharm. Corp.,785 F.3d 625, 632 (Fed. Cir. 2015) … the proposed labelling lacks specific statements that encourage or will inevitably lead to infringement

The Court is not persuaded. The expert testimony in Takeda (and in Defendants’ supplemental authority (ECF No. 273-1), HZNP Medicines LLC v. Actavis Laboratories UT, Inc., — F.3d. —, 2019 WL 5076226, *15-18 (Fed. Cir. Oct. 10, 2019)), provided an implausible interpretation of the labelling in an attempt to show induced infringement of the asserted patent claims, whereas here, Amarin’s expert testimony offers a plausible interpretation of the labelling that suggests the Court could find induced infringement.

(v) Generics further argued that because of the likelihood of a substantial number of non-infringing uses of GV, inducement cannot be implied or inferred. Warner-Lambert Co. v. Apotex Corp., 316 F.3d 1348, 1365 (Fed. Cir. 2003)

Generics are wrong as:
a.) While it is true that in Warner-Lambert there was evidence of significant non-infringing use (as high as 89% of the total) and the Federal Circuit had found that there was no infringement under 35 U.S.C. § 271(b), the case was very different. Importantly the alleged infringing act was not promoted by the label. (Apotex was seeking FDA approval for an equivalent of Warner-Lambert’s Neurontin® (active ingredient gabapentin) to treat partial seizures, but only after the patent protecting Neurontin® for the same use had expired.)
b.) The statute addressing inducement of infringement does not contain a “substantial non-infringing use” restriction.
c.) The Supreme Court of the United States has held the opposite, finding that a person can be liable for inducing an infringing use of a product even if the product has substantial non-infringing use. MGM Studios, Inc. v. Grokster, Ltd., 545 U.S. 913 (2005).


Defendants had been failed two times already.

(i) Summary Judgement was denied as “Plaintiffs’ proffered expert testimony creates a genuine issue of material fact inappropriate for resolution at summary judgment as to “whether the label encourages, recommends, or promotes infringement.”” and ““The purpose of summary judgment is to avoid unnecessary trials when there is no dispute as to the facts before the court.” … The Court finds it more appropriate to consider expert testimony from both sides as to whether induced infringement may be inferred from the labelling at the upcoming bench trial, and resolve the meaning of the labelling at trial.”
(Note: the “burden of proof” to deny Summary Judgement is lower than at trial … Amarin did not have to prove inducement … existing dispute was enough to discuss the inducement at trial.)

(ii) Generics' Motion to dismiss immediately the induced infringement claim (Trial, 01/14) was denied as "the plaintiff has met the initial burden of proof."

- - - - - - - - -
I do not have first have info about the trial (other than Jefferies Daily Coverage – which was silent about how Jonathan Scheinberg (Generics’s expert regarding inducement) examination went on Day 2/3, TheWyseKid’s post on ST and relocatedmetsfan post about Day 2)

but:
- They are ahead of schedule
- The topic was / will be the obviousness (Generics’ experts) on Friday and (at least) on Monday
- The examination of Amarin obviousness experts will come next (?) by late Monday and /or during week Jan 27.
- Looks like Carl Peck, M.D. (Amarin) and Peter R. Mathers (Generics) will not testify (“the Court will let Dr. Peck testify in rebuttal to Dr. Sheinberg if Dr. Sheinberg opines about "the scope of FDA approval reflected in the Vascepa label[.]"”

Maybe the (basic / core) discussion about inducement is over …

- - - - - - - - -

Based on these

I think Amarin’s chance is good; probability of the win is high … however, it is not a sure thing

But my opinion is irrelevant … At the end of the day the only person that opinion matters is the judge.

(Note: I tried to be as clear as I could … if you disagree with something: please check / read my basis, references first.)

Best,
G

ps.: If you are not persuaded by me than read a “respected” Research who concluded

Our takeaway on these points is that Judge Du will find Defendants’ ANDA labels as inducing infringement regarding the “for at least 12-weeks” mention in the Vascepa patent claims.

?