FDA, PATENT TERM EXTENSIONS AND THE HATCH WAXMAN ACT. Dr.Sumesh Reddy- Dr. Reddys Lab Hyderabad-

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1 FDA, PATENT TERM EXTENSIONS AND THE HATCH WAXMAN ACT Dr.Sumesh Reddy- Dr. Reddys Lab Hyderabad-

2 FDA Regulatory approval-time and cost Focus of FDA approval process-safety and efficacy Difference between the conditions for patentability and approval Only one out of every 2,500 patents make it to the market

3 Market exclusivity New chemical entities (NCE) 505(b)(1) or New Drug Applications Contains full reports of investigations of safety and effectiveness Five year exclusivity 505(b)(2) Application At least some of the information required for approval comes from studies not conducted by or for the applicant

4 Exlusivity Examples: different salt, isomers Entering the market on a 505(b)(2) application to establish non-infringement Three year exclusivity Orphan drug exclusivity- seven years Pediatric exclusivity- six months 505(j) or ANDAs or Generic Drug Application Requirement to show bio-availability

5 The Hatch-Waxman Act Full name- Drug Price Competition and Patent Term Restoration Act Enacted in 1984 Purpose of the act-dual balancing act Effect on the pharmaceutical industry

6 Salient features of the Act Patent challenges and generic exclusivity Patent term extension Exemption to infringement

7 Patent challenges and generic exclusivity Overview of the legal process ANDA Requirements: i. Information to show that that the listed drug is approved; ii.that the listed drug has the same active ingredient as the new drug; iii.that the route of administration, the dosage forms, the strength of new drug etc are the same as the listed drug; Iv.That the new drug is bio-equivalent to the listed drug.

8 Certifications Section 505(j)(2)(A)(vii) (1) That such patent information has not been filed; (2) That such patent has expired; (3) That the proposed drug will not be marketed until expiration of the patent. (4) That either the proposed generic drug does not infringe the patent or the patent is invalid. This is known as Paragraph IV certification.

9 Para I to IV If the applicant makes a certification under paragraphs I or II, the statute provides that the FDA may approve the ANDA effective immediately If the applicant makes a certification under paragraph III, the FDA may approve the ANDA effective on the date that the applicant certifies that the patent will expire

10 When an applicant makes a certification under paragraph IV the statute begins by providing a fortyfive-day window during which the patent-holder may bring suit against the applicant If the patent-holder brings suit during that forty-fiveday period, the statute says that the FDA's approval of the ANDA must be delayed for thirty months

11 Provision that is intended to allow the patentholder time to vindicate its patent in court If the court finds that the patent is invalid or is not infringed, the FDA's approval becomes effective as of the date of that ruling

12 Bases for Non-infringement All Elements Rule Pennwalts case Unmistakable surrender (by amendment or argument) Estoppel Festo Corp. v. Shoketsu Kinzoku Kogyo Kabushiki Co., Ltd., 234 F.3d 558, 56 U.S.P.Q.2d 1865 (Fed. Cir. 2000) -Designing around a valid US patent-professor Keyton s approach.

13 Basis for invalidity Anticipation Obviousness Prior art date to be kept in mind Combining two references-motivation to combine When a reference cannot be used as prior art against the challenged patent Species and genus situations Obviousness type double patenting

14 Para IV Certification & Patent Litigation (summary) Notice to the patent holder Legal and factual basis Non-infringement or invalidity 45 day period to bring suit Stay of approval 30 month period Judgment of the court

15 180 days Market Exclusivity Section 505(j)(5)(B)(IV) First to file When does it start Judgment trigger Commercial marketing trigger

16 Mova v Shalala & the successful defense requirement FDA approved an application by a drug manufacturer, Mylan Pharmaceuticals, Inc. to market a generic version of micronized glyburide, a drug used to treat diabetes Mova Pharmaceutical Corp.had filed an earlier application to market a generic version of the same drug

17 Mova's application had not yet been approved, because of a patent infringement suit brought by Pharmacia & Upjohn Company Upjohn claimed that Mova's product infringed Upjohn claimed that Mova's product infringed a patent belonging to Upjohn

18 When Mova learned that the FDA had approved Mylan's application, it brought suit relying on 21 U.S.C. 355(j)(5)(B)(iv) (1994), to compel the FDA to delay the effective date of this approval until 180 days after the earlier of the dates that Mova won its suit or began to market its product

19 Mova argued that it was entitled to 180-day market exclusivity period running from the date Mova won its suit or began marketing its product, and the FDA was barred from approving Mylan's similar application until after the end of that 180-day period In response, the FDA cited a regulation- The successful defense requirement

20 355(j)(5)(B)(iv) seems to grant exclusivity to the first to file irrespective of whether he has been successful in the infringement suit or not FDA argues that a literal reading would produce absurd consequences FDA s interpretation was that the first Paragraph IV applicant was required to have successfully defended against a suit for patent infringement before the applicant is eligible for the 180-day marketing exclusivity period

21 Where the applicant is never sued (1) cases in which the first applicant is never sued, and (2) cases in which the first applicant loses its suit If the first applicant is never sued, the FDA claims, then the court-decision trigger will never be satisfied Later ANDA applicants will be unable to market their products until the first applicant decides to put its product on the market

22 The first applicant could in theory wait indefinitely to begin selling its product, and thereby block all sales by later applicants If the first applicant colludes with the pioneer drug If the first applicant colludes with the pioneer drug company to eliminate generic competition, or if the first applicant is simply unable to obtain FDA approval of its production facilities and so cannot put its product on the market

23 First applicant loses its suit If the first applicant loses its infringement suit, the first applicant would then be able to satisfy neither the court-decision trigger nor the commercial-marketing trigger Thus, the FDA claims, no generic drugs could enter the market until after the pioneer company's patent expired

24 The successful-defense requirement, according to the FDA, is calculated to eliminate both occurrences. An applicant that is never sued or that loses its suit will not have "successfully defended against a suit for patent infringement

25 Arguments against the requirement The Practical effect of the FDA s regulation is to write the commercial-marketing trigger out of the statute It serves the public interest to permit a It serves the public interest to permit a prudent ANDA holder in that situation to stay off the market until the litigation is resolved, thereby minimizing potential damages

26 Congress may have intended to reward the first ANDA applicant for his enterprise whether or not he is later sued The statutory scheme only runs into problems if the The statutory scheme only runs into problems if the first applicant never starts selling his product. An alternative might be to prescribe a period within which a first applicant who has not been sued must bring his product to market in order to benefit from the exclusivity period

27 First applicants who lose their suit FDA's current regulations suggests a possible way of addressing this problem That regulation provides that, if an ANDA applicant who makes a certification under paragraph IV later loses its patentinfringement suit, it must amend its ANDA to make a new certification under paragraph III

28 First applicants who enter into an agreement with the NDA holder First ANDA applicant to file a patent challenge may never trigger the start of the 180-day period, thereby blocking the FDA from granting approval to any generic product. First generic challenger will enter into a lucrative cash settlement with the patent owner that results in a judgment in favor of the patent Ex: Hoechst-Roussel v Andrx

29 Literal reading of the section sought to be avoided by the FDA But that would prevent a person who has done a good job in designing around and thus avoided suit from entering the market- Purepac v. Friedman

30 Court decision trigger satisfied by a subsequent applicant The 180-day exclusivity period never starts. No subsequently filed ANDA can be approved unless a final judgment adverse to the patent is obtained by one of the subsequent applicants. Even if the patent is subsequently challenged and declared invalid, the benefit will go to the first to file

31 Decision of a court Interpretation of "court decision" FDA s interpretation: Court Decision is the final decision of a court The Tor Pharm and Mylan case Any decision of the court satisfies the trigger

32 Improper listing of patents The orange book Holders of NDAs to identify all patents claiming an approved drug product or a method of using such a product As to which a claim of patent infringement might reasonably be asserted Must update list within 30 days of receiving relevant patent.

33 Provided no guidance whatsoever as to what patents should or should not be listed and no mechanism for determining if a patent was properly or improperly listed Court has held that FDA performs purely ministerial function in listing patents There is no cause of action to de-list a patent alleged to be improperly listed

34 Abuse of listing provision Listing irrelevant patents The '84 Act does not prevent an NDA holder from listing a newly acquired patent This further delays generic competition Only one thirty month stay proposed Shared Exclusivity

35 Patent term extensions 35 U.S.C. 156 To make up for the time lost in approval To make up for time lost in prosecution FDA decides regulatory delay and PTO decides term extension. Patent Term Restoration- maximum five years Total extension (Patent term remaining upon approval + restoration =14 years or less.

36 Drug product Under 35 U.S.C. 156 must claim a product, or a method of manufacturing or using a product A drug product means the active ingredient found in the final dosage form prior to administration of the product to the patient

37 Case A patent that claimed a metabolite of an approved drug was held not to claim the approved drug, even though the court recognized that use or sale of the metabolite would have infringed the patent claiming the approved drug product- Hoechst-Roussel Pharmaceuticals Inc. v. Lehman, 109 F.3d 756, 759 (Fed. Cir. 1997)

38 Other conditions A patent is only eligible for one term extension, so term extension is effectively available for only one product per patent The product must have been subject to The product must have been subject to regulatory review before its commercial marketing or use, and the resulting permission for commercial marketing or use must be the first granted

39 Summary A patent can be extended only once Patent must claim the active ingredient of the approved product One extension per regulatory review period Extension only applicable to the approved product, not all the claims of the patent

40 Infringement (the Bolar exception) Roche Products V. Bolar Pharmaceutical Co. (Fed. Cir. 1984) Roche was the assignee of the rights in U.S. Patent No. 3,299,053 (the '053 patent), which expired on January 17, 1984 Novel 1 and/or 4-substituted alkyl 5-aromatic-3H- 1,4-benzodiazepines and benzodiazepine-2-ones The active ingredient in Roche's successful brand name prescription sleeping pill "Dalmane."

41 In early 1983, Bolar became interested in marketing, after the '053 patent expired, a generic drug equivalent to Dalmane Because a generic drug's commercial success is related to how quickly it is brought on the market after a patent expires, and because approval for an equivalent of an established drug can take more than 2 years, Bolar, not waiting for the '053 patent to expire, immediately began its effort to obtain federal approval to market its generic version of Dalmane

42 In mid-1983, Bolar obtained from a foreign manufacturer 5 kilograms of flurazepam hcl to form into "dosage form capsules, to obtain stability data, dissolution rates, bioequivalency studies, and blood serum studies" necessary for a New Drug Application to the FDA

43 Roche filed a complaint in the District Court against Bolar Issue: Does the limited use of a patented drug for testing and investigation strictly related to FDA drug approval requirements during the last 6 months of the term of the patent constitute infringement?

44 271(a) : Whoever without authority makes, uses or sells any patented invention, within the United States during the term of the patent therefore, infringes the patent The patentee does not need to have any evidence of damage or lost sales to bring an infringement action

45 The experimental use defense It could never have been the intention of the legislature to punish a man who constructed such a machine merely for philosophical experiments Thus where it is made or used as an experiment, whether for the gratification of scientific tastes, or for curiosity, or for amusement it is not infringement

46 The Court held that.. Tests, demonstrations, and experiments which are in keeping with the legitimate business of the alleged infringer are infringements for which experimental use is not a defense Bolar's intended "experimental" use is solely for business reasons and not for amusement, to satisfy idle curiosity, or for strictly philosophical inquiry

47 Policy arguments Helps make up time lost in approval De-facto monopoly, allowing patentee to extend his monopoly indefinitely This court is not the place to debate these questions Bolar infringes Roche s Patent