University of Ottawa - Faculty of Law CML 3396 / DCL 7315 PHARMACEUTICAL LAW Patrick Smith February 27, 2008

RECENT PHARMACEUTICAL LITIGATION Presentation Topics DATA PROTECTION PM(NOC) REGULATIONS RECENT PHARMACEUTICAL LITIGATION

Government Jurisdiction: Pharmaceuticals Federal Drug Approvals Federal Formulary List of drugs approved for reimbursement under federal drug benefit plans (Approximately 1 million Canadians eligible for federal drug benefits) Price Control (PMPRB) PM(NOC Regulations) Provincial Interchangeability Provincial Formulary List of drugs approved for reimbursement under provincial drug benefit plans (Over 9 million Canadians eligible for provincial drug benefits)

Court Jurisdiction: Patents and Pharmaceuticals Federal Patent Infringement (jointly with provincial courts) Patent Validity Judicial Review: PMPRB Section 55.2 proceedings under PM(NOC) Regulations Drug approvals Provincial Patent Infringement (jointly with federal courts) Provincial Formulary Issues

Data Protection Regulations – Part I History of Data Protection Article 1711 of NAFTA / Article 39 TRIPS Section C.08.004.1 of the Food and Drug Act Regulations – 1995 Bayer Inc. v. Canada (Attorney General ) - 1999

Data Protection Regulations Food and Drug (Data Protection) Regulations Provides effective data protection for drug submissions that receive a NOC after June 17, 2006 Amendments registered October 5, 2006

Data Protection Regulations Protection provided to “Innovative Drugs”: includes: drugs that contain medicinal ingredients not previously approved does not include: variation of a previously approved medicinal ingredient, eg. salt, ester, enantiomer, solvate, or polymorph ‘arguably’ includes: metabolites No further protection for NOC’s for new uses or combinations of previously approved medicinal ingredients

Data Protection Regulations Eight Year Term of Data Protection 6 year “no filing” period for generic submissions Exceptions: Where consent of manufacturer is given Where manufacturer files application for authorization to export to third world country (Jean Chretien Pledge to Africa Act – JCPA Act). However, no NOC will issue until expiry of data protection term. 2 year no marketing period during which the Minister will not grant a NOC to a generic

Data Protection Regulations Pediatric Extension There is a 6-month “pediatric extension” in addition to the the 8-year period Pediatric clinical studies must be submitted with innovator’s NDS or contained in a supplement within 5 years of issuance of NOC Minister must determine that clinical trials were conducted to increase knowledge of the use of the innovative drug and this knowledge provides a health benefit to pediatric populations

Data Protection Regulations Loss of Protection Data Protection is lost if the drug is “not being marketed in Canada” Applies to the 6, 8 or 8 ½-year term It is questionable whether protection can be restored if the product is reintroduced onto the market

Data Protection Regulations Register of Innovative Drugs Includes: the name of the drug the medicinal ingredient expiry date of data protection

Data Protection Regulations Challenges to New Data Protection Regulations In November 2006, separate judicial review applications were launched by the CGPA and Apotex in the Federal Court Both are seeking a declaration that the Data Protection Regulations are ultra vires and of no force or effect

Data Protection Regulations Generic Attacks Data Protection Regulations are unnecessary Data Protection Regulations are not connected with the grant of the authority of section 30(3) of the Food and Drugs Act Data Protection Regulations are beyond the jurisdiction of the Federal Government as they are a matter of property and civil rights exclusively within the jurisdiction of the provinces

PM(NOC) Regulations – Part II A patent enforcement scheme which works in conjunction with, not in lieu of, the standard patent enforcement scheme under the Patent Act Purpose: Balances the effective enforcement of patents against the timely market entry of generic medicines Designed to balance out the effect of the “early-working exception” in the Patent Act

Patented Medicines (Notice of Compliance) Regulations Process Under the Regulations A second person (i.e. generic) wishing to bring a drug to market must file a submission for a notice of compliance (NOC) (ANDS, similar to an ANDA in the U.S.) When a submission makes reference to or compares a drug with another drug for which an NOC is already issued to a first person (i.e. innovator) and a patent list has been submitted, the second person has 2 choices: Accept that the NOC will not issue until the patent expires; or Allege that the patent has expired, the patent is invalid, or the drug will not infringe the patent A detailed statement of the legal and factual basis for the above allegations must be served on the Minister of Health and the first person

Patented Medicines (Notice of Compliance) Regulations Process Under the Regulations (continued) Within 45 days, the first person may apply for an order preventing the Minister from issuing an NOC to the second person First person obtains a 24 month stay preventing the second person from entering the market until the litigation is resolved If the first person’s application is dismissed, withdrawn, or overturned on appeal, the first person is liable to second person for any loss suffered from the date the NOC would have been issued (section 8) First person maintains the right to sue for patent infringement under the Patent Act despite the outcome of any NOC proceedings Recent case found patent valid and infringed despite having dismissed prohibition proceeding under the Regulations

Patented Medicines (Notice of Compliance) Regulations Process Under the Regulations (continued) If first person is successful, the second person can send another NOA as long as it does not constitute an abuse of process If first person is not successful, the NOC will likely issue to the second person Appeal is moot

Patented Medicines (Notice of Compliance) Regulations Eligibility for Protection under the Old Regulations Timing: the Canadian filing date of the patent must precede the date of the drug submission (priority filing does not count) The patent must contain a claim for the medicine itself or its use, or a formulation in which the medicine is the active medicinal ingredient Patents without direct therapeutic application such as processes, intermediates or vectors do not come within the protection of the Regulations Relevance: the patent sought to be listed must be relevant to the dosage form, strength, and route of administration of the drug in respect to which the NOC was filed

Amendments to the PM(NOC) Regulations Amendments to the PM(NOC) Regulations came into force on October 5, 2006

Amendments to the PM(NOC) Regulations A patent on a patent list in relation to a NDS is eligible to be added to the Register if the patent contains: A claim for the medicinal ingredient and the medicinal ingredient has been approved through the issuance of a NOC in respect of the submission; A claim for the formulation that contains the medicinal ingredient and the formulation has been approved through the issuance of a NOC in respect of the NDS; A claim for the dosage form and the dosage form has been approved through the issuance of a NOC in respect of the NDS; or

Amendments to the PM(NOC) Regulations A patent on a patent list in relation to a NDS is eligible to be added to the Register if the patent contains (CONT’D): A claim for the use of the medicinal ingredient, and the use has been approved through the issuance of a NOC in respect of the NDS There is no opportunity to list patents with an NDS based solely on the change of name of the manufacturer

Amendments to the PM(NOC) Regulations With respect to an SNDS, a patent is eligible to be listed if the supplement is for a change in formulation, a change in dosage form or a change in use of the medicinal ingredient and the patent contains a claim for the new formulation, a claim for the new dosage form or a new use of the medicinal ingredient that has been approved through the issuance of a NOC

Amendments to the PM(NOC) Regulations Transitional Rules The prior rules on listing will apply to patents submitted prior to June 17, 2006 The current rules on listing, including those on relevance, apply to patents submitted after June 17, 2006 Patents submitted after this date but before October 5, 2006, which do not comply with the new rules, will be audited on a complaints-driven basis

Amendments to the PM(NOC) Regulations Cancellation of DIN – Section 3(3) Manufacturers are required to notify the Minister if a product is not being sold, and its DIN will be cancelled The Minister is now required to delist patents associated with a product when the DIN is cancelled because the product is not being sold Innovator has 90-day grace period before Minister will de-list Does not apply where DIN is cancelled due to change in manufacturer

Amendments to the PM(NOC) Regulations Innovator can add the patents to the Patent Register if the product is sold again  But a generic could file its ANDS while the product is not on the market and would not have to address patents added afterwards

Amendments to the PM(NOC) Regulations SECTION 5 – when notice is required NOA is required if a second person files a submission for a NOC that directly or indirectly compares the drug with, or makes reference to, another drug marketed in Canada under a NOC issued to a first person and in respect of which a patent list has been submitted

Amendments to the PM(NOC) Regulations SECTION 5 – when notice is not required A second person is not required to send a NOA in respect of a patent added to the Register in respect of the innovator’s drug on or after the date of filing of the second person’s submission [similar timing as a result of the AstraZeneca Supreme Court decision for existing proceedings] The deemed date of filing of the second person’s submission or supplement is 6 years after the date of issuance of the first NOC in respect of the innovative drug (i.e. data package rules) If the brand name product is not currently being marketed

Amendments to the PM(NOC) Regulations SECTION 5 – when to retract the notice A second person who has served a NOA shall retract the NOA and serve a notice of the retraction on the first person within 90 days after either of the following dates: The date on which the Minister notifies the second person of their non-compliance with the requirements of the Food and Drug Regulations; or The date of the cancellation by the second person of the submission or supplement to which the allegation relates

Amendments to the PM(NOC) Regulations SECTION 5 – when to retract the notice If the NOA is retracted by the second person, the first person who has commenced a prohibition proceeding shall apply without delay for discontinuance of the proceedings

Amendments to the PM(NOC) Regulations SECTION 5 – transitional provisions Subsection 5(1) of the NOC Regulations applies to a second person who has filed a submission prior to the coming into force of these Regulations and the date of filing of the submission is deemed to be the date of the coming into force of these Regulations, namely October 5, 2006 The same applies with respect to subsection 5(2)

Amendments to the PM(NOC) Regulations Allegation re: Use Patents – Section 6(5) Under the new Regulations, an allegation of non-infringement is to be determined only with respect to whether the generic’s “making, constructing, using or selling” would infringe a patent So infringement by others – eg. patients via formulary substitution policies and practices – is not an issue for determination in NOC proceedings This revision is an attempt to clarify case law on this issue

Amendments to the PM(NOC) Regulations Partial Summary Judgment – Section 6(5) The amended Section 6(5) allows the court, on the motion of a generic, to summarily dismiss a proceeding brought by an innovator “in whole or in part” in respect of those patents that were not eligible for inclusion on the register Case law had held that the previous provision only applied where the proceeding could be dismissed against all patents

Amendments to the PM(NOC) Regulations Damages - Section 8 Under the new amendments, the court may make “any order for relief by way of damages” in respect of any loss incurred by a generic due to delayed market entry The Minister is not liable for damages under this section The previous section referred to “damages or profits” -- the word “profits” does not appear in the amended section, so innovators’ profits should not be reachable under the section Only applicable to Section 8 damages cases brought after October 5, 2006

Recent Pharmaceutical Patent Decisions Merck & Co. v. Apotex Inc.– Prinivil/Zestril (lisinopril) Patent infringement action Patent found valid and infringed Upheld on appeal Janssen Ortho Inc. v. Novopharm Ltd. – Levaquin (levofloxacin) After prohibition proceeding dismissed, patentee brought action for infringement Patent found valid and infringed in infringement action Sanofi v. Apotex Inc. – Plavix (clopidogrel bisulfate) Prohibtion order granted