Amarin Corp Plc (AMRN)

[HDGabor]

The reality … and a possibility (in case of loss at CAFC)

The reality

When a generic drug is approved by FDA, it receives a therapeutic equivalence code that is entered in the Orange Book beside the drug name to indicate whether it is approved as therapeutically equivalent to the pioneer drug (an “A” code) or not therapeutically equivalent (a “B” code). FDA considers drugs to be therapeutic equivalents if they are pharmaceutical equivalents and if they can be expected to have the same clinical effect and safety profile when administered to patients under the conditions specified in the labeling. Significantly, FDA states that “products classified as therapeutically equivalent can be substituted with the full expectation that the substituted product will produce the same clinical effect and safety profile as the prescribed product.”. Thus, under the current system, “skinny labeled” generics are designated by FDA and listed in the Orange Book as being fully substitutable for pioneers irrespective of their labeled uses.

HIKMA PHARMACEUTICALS USA INC (ICOSAPENT ETHYL) has “AB” TE code.
(The coding system for therapeutic equivalence evaluations is designed to allow users to determine quickly whether the Agency has evaluated a particular approved product (e.g., a particular strength of an approved drug) as therapeutically equivalent to other pharmaceutically equivalent products (first letter) and to provide additional information on the basis of FDA's evaluations (second letter).

A Drug products that FDA considers to be therapeutically equivalent to other pharmaceutically equivalent products, i.e., drug products for which: … (2) actual or potential bioequivalence problems have been resolved with adequate in vivo and/or in vitro evidence supporting bioequivalence. These are designated AB.)

In almost all cases, neither the prescribing physician, nor the pharmacist or the insurance carrier, has any idea what uses are approved on an A-rated generic label, because there is no compendium that tracks such information. Doctors typically write prescriptions for brandname drugs without reference to the indication or condition being treated, so there is no practical way for a pharmacist to determine (short of calling the doctor) what the drug is to be used for when the substitution decision is made.
In 14 states, pharmacists are required by law to substitute “equivalent” generic drugs for pioneer prescriptions unless the doctor specifies “brand only.” In 36 other states, pharmacists have the discretion to substitute equivalent generics unless the prescription is designated “brand only.” Forty-seven states allow generic drug substitution if requested by the patient, which, as a practical matter, means the decision to substitute is in the hands of the patient’s health insurance carrier, which charges much lower co-payment fees for generic equivalent drugs. As for how pharmacists determine whether a generic is equivalent to (and substitutable for) a brand-name drug, 30 states (including the District of Columbia) require use of the Orange Book, with several other states accepting the Orange Book rating system as an option. Three states publish their own formularies, and 18 others define “generic equivalence” essentially to include any generic that is A-rated by FDA. In other words, a generic drug that is A-rated by FDA will be substituted by pharmacies throughout the country and used by consumers regardless of the approved uses on the generic label.

HIKMA PHARMACEUTICALS USA INC (ICOSAPENT ETHYL) (and any gV in the future) is (will be) A-rated …

A possibility (???)

Using a patent-protected generic drug for a carved-out indication directly infringes the patent. Prescribing or dispensing the drug for such use indirectly infringes the patent. The problem, of course, is that no sensible pioneer drug company will pursue doctors, pharmacies or patients for patent infringement. Generic manufacturers, on the other hand, would make an ideal target, but historically they have managed to avoid litigation by making certain they do not actively promote their “skinny labeled” drugs for any patent-protected uses. Nevertheless, these drugs are placed on the market every day by generic manufacturers knowing they will inevitably be used by some consumers in an infringing manner. However, knowledge is not conduct, and without some manner of conduct, it has been difficult to charge generic drug manufacturers with the specific intent required to induce infringement. (The Federal Circuit’s holding in Warner-Lambert Co. v. Apotex Corp. that “where a product has substantial noninfringing uses intent to induce infringement cannot be inferred even when the [alleged inducer] has actual knowledge that some users of its product may be infringing the patent.”.)

There can be no disputing that direct infringement occurs whenever a generic drug is taken by or administered to consumers for a condition of use that is protected by patent. It does not matter what the prescribing physician intended, what the pharmacist is required to do or what the Orange Book therapeutic equivalence rating dictates. What matters is that “skinny labeled” drugs are being marketed by generic manufacturers with the knowledge that they will be used by some consumers in an infringing manner. The only question has been whether such infringement is being induced by the generic manufacturer’s conduct.

Astra Zeneca LP v. Apotex Inc. (Nos. 2009-1381, 1424 (Fed. Cir. Nov. 1, 2010) suggests that it may well be …

The Federal Circuit makes clear in AstraZeneca that liability for inducing infringement may be found where the evidence goes beyond a product’s characteristics, or the knowledge that it may be put to infringing uses, and shows “actions directed to promoting infringement.” It is sufficient, the court said, for a patent holder to show evidence of a manufacturer’s intent to induce infringement along with plans to market the drug knowing that such infringement will occur. In the case of a “skinny labeled” drug, the generic manufacturer appears to be in this same boat.

In AstraZeneca, the Federal Circuit equated labeling with conduct and rejected the defense that nonspecific label recommendations could not demonstrate specific intent. The court said it did not matter if the labeling contains only general recommendation – what matters is whether the labeling language would inevitably lead some users to practice the claimed method. This same reasoning would appear to hold true for “skinny labeled” generics, only here it is not the physical label that inevitably leads to infringement, but rather, the A-rating bestowed by FDA, published in the Orange Book and promoted by the generic manufacturers. In the end, the result is the same. The generic manufacturer effectively relies on an “extrinsic label” for its drug that will inevitably lead some users to practice the pioneer’s patent. It is this overall conduct that AstraZeneca seems to say is sufficient to show specific intent to induce infringement.

Best,
G

sources:
- Skinny Labeling and the Inducement of Patent Infringement
- Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations
- Orange Book Preface