The Name Game The USPTO and FDA Approval Process Selection and Protection of New Drug Names

1. The Name GameThe USPTO and FDA Approval Process Selection and Protection of New Drug Names Lisa M. Tittemore, Esq.

2. Presentation Overview • U.S. Patent & Trademark Office (USPTO) procedures and issues relevant to prosecution of drug name trademarks • U.S. Food & Drug Administration’s drug name review process and criteria, and FDA’s pilot project • Strategies for trademark prosecution as a part of drug name selection and approval process

3. Trademarks • What is a trademark? • Word(s) • Symbol • Device (design) • Sound • Any combination thereof • An identifier of source

4. Likelihood of Confusion • U.S. Courts and USPTO apply likelihood of confusion analysis • Similarity of sight, sound and meaning of marks, goods, channels of trade, sophistication of purchasers, etc. • USPTO doesn’t investigate actual use in the marketplace • USPTO analysis is conducted by attorneys based on the likelihood of confusion factors • Consideration of heightened review for pharmaceutical trademarks • Doctrine of “Greater Care” applies to pharmaceutical trademarks

5. Examination and Opposition • USPTO examination • Applications filed based on use or “intent to use” • Descriptiveness, genericness, and other grounds for rejection, likelihood of confusion • Allowed marks published in Official Gazette • Must prove use before registration will issue • Opposition proceedings • Interested third parties can oppose based on registered or common-law trademarks • Oppositions conducted before the Trademark Trial and Appeal Board, with a right of appeal to the Federal Courts

6. Common Trademark Issues for Drug Names Paradox of the pharmaceutical industry • Glut of “strong” fanciful marks contributes to confusion Bona fide intent in the drug name context • ITU applications require a bona fide intent to use the mark • Contingent intent to use; common practice of filing for multiple marks for a single product Limited shelf life of ITU applications • Generally must commence use in approximately 4 years from application date • Must consider uncertainties involved in the drug development time frame

7. USPTO Review practices designed for trademarks across all industries Focuses on likelihood of confusion Priority based on first to file or use (regardless of registration date) Review conducted by attorneys who only review registered trademarks and pending applications FDA Review procedures built with pharmaceutical industry in mind Focuses on health and safety Priority based on first allowed (regardless of filing date) Review conducted by medical specialists, who gather empirical evidence about the marketplace USPTO v. FDA: Differing Approaches

8. FDA and USPTO • Success with USPTO does not guarantee success with the FDA • Likelihood of confusion v. health and safety • FDA considers names in the order presented to them; trademark priority dates not considered by FDA • FDA approval may influence USPTO • But USPTO likelihood of confusion may consider marks and factors not considered by FDA • Courts may have their own view • FDA approved ALTOCOR (prescription cholesterol reducing drug) and 3d Cir. found confusion with ADVICOR

9. FDA Proprietary Name Review • 2007 PDUFA IV Act broadened FDA drug safety program • FDA committed to goal of minimizing medication errors which are “any preventable event that may cause or lead to inappropriate medication use or patient harm . . .” • In 2004, FDA reviewed 338 applications, rejecting 36% • Sharing Information with Industry • September 2008: PDUFA Pilot Project for Proprietary Name Review (voluntary) • February 2010: Guidance for Industry: Contents of a Complete Submission for the Evaluation of a Proprietary Name

10. Office of Drug Safety: Name Approval Players • CDER and CBER • Center for Drug Evaluation and Research and Center for Biological Evaluation • OSE • Office of Surveillance and Epidemiology (formerly Office of Drug Safety) • OPDP • Office of Prescription Drug Promotion (formerly DDMAC); performs first-line consultation on potential names • DMEPA • Division of Medication Error Prevention and Analysis, part of OSE; reviews medication error reports and prospectively reviews proprietary names, labeling, packaging and product design prior to drug approval

11. Overview of FDA Approval Process • Company may seek “initial evaluation” of proposed name while product under IND, but FDA will not evaluate until product completes phase 2 trials • 180-day timeline for review for names submitted during IND phase • May submit up to two names at a time • Preliminary name approval evaluated when is filed (90 day timeline), and re-evaluated 90 days before product approval • Need back up alternatives right up to time of final approval

12. OPDP Review • OSE has lead responsibility within CDER for communications to industry re new drug names • OPDP reviews for false or misleading promotional claims • Names that overstate efficacy, minimize risk, broaden indication, claim unsubstantiated superiority, or overly “fanciful” by misleadingly implying unique effectiveness or composition, etc. (e.g., SUPERCORTIZONE) • OPDP consults with DMEPA • OPDP performs first-line consultation; if no issues, followed by review by DMEPA for safety and prevention of medication errors • If rejection letter received from OSE, opportunity for sponsor to reply to rejection

13. DMEPA’s Process • Step 1: Screening for common causes of medical errors and USAN Stem Names • Includeslabeling and packaging analysis (if submitted with application) • Step 2: Generation of list of potentially similar names • Database searching • POCA Computer algorithm • Active ingredient medication errors • Step 3: Assessment of Risk • Failure Mode and Effects Analysis (FMEA) • Expert panel analysis • Handwriting and verbal confusion experimentation

14. Common causes of medication errors • Words or phrases used in the name • Dosing interval terminology (e.g., MARKBID) • Dosage form and routes of administration (e.g., MARKCAPS, MARKORAL) • Common medical and product name abbreviations • Names that suggest fewer than all active ingredients, or suggests ingredient not included • Use of United States Adopted Names (USAN) and International Nonproprietary Name (INN) stems (stems are for generic names, not proprietary names) • Labeling/packaging based issues

15. Developing list of similar drug names • Database searching • Review numerous pharmaceutical, medical, and trademark data bases for similar names • Computer Analysis • FDA developed tool to identify look-alike, sound-alike names • Phonetic Orthographic Computer Analysis (POCA) • Released to public February 2009 • Active ingredient medication error data • If any active ingredients are marketed, DMEP reviews incidents and causes of reported medication errors

16. Assessment of risk • Handwriting and verbal analysis • Prescription analysis studies • Simulate prescription ordering process • Conducted within FDA to determine degree of confusion in visual appearance or pronunciation between proposed name and existing names • Nurses, pharmacists and physicians interpret written prescriptions and verbal orders

17. Assessment of risk, cont. • Internal expert panel analysis • Physicians, nurses, and pharmacists • Use expertise to evaluate and expand list of problematic names • Failure mode and effects analysis • Analyzing how errors may occur and likely effects • Considers findings of review steps, and additional factors, including storage, dosage, indications etc. • More rigorous than prior “all things considered” analysis

18. Assessment of risk, cont. • Factors to weigh in determining risk: • Similarity with established (generic) names • Strength of the dose • Recommended dose and unit of measure • Similar storage conditions • Similar patient populations • Similar prescriber populations

19. Sample Problem Names • Amaryl (Reminyl) • Amaryl (diabetes) • Reminyl (Alzheimer’s); name changed to Razadyne • Avandia (Coumadin) • Avandia (oral diabetes) • Coumadin (anticoagulant)

20. Avandia or Coumadin? The results of FDA’s handwriting analysis are often hard to predict

21. What To Do if Proposed Name is Rejected • FDA rejection rate continues upward • ~ 42% new drug names refused in 2011 • Seek reconsideration • Work with the FDA to identify and alleviate concerns • May be able to use regulatory screening investigation results to support reconsideration • Submit two new names • Need back up alternatives right up to time of final approval

22. FDA PDUFA Proprietary Name Review Pilot Project • PDUFA Initiative, Sept. 2008-2011 • Procedure inspired by NDA/BLA procedure • Company conducts name review under FDA guidelines and best practices; FDA reviews results and methodology • Insufficient Data; Guidance Coming? • FDA hoped to have 20-25 participants, only 3 registered and FDA received only one complete submission, which was not sufficient to assess feasibility of industry conducting reviews of proposed proprietary names • FDA announced public meeting would not be held due to insufficient data; unclear whether FDA will publish draft guidance describing best test methods for proprietary name evaluation in future

23. Foreign Drug Approval Process • Each jurisdiction has its own rules and procedures • European Medicines Agency (EMA) • Reviewed drug names since 1995 (formerly European Agency for the Evaluation of Medicinal Products or EMEA) • Published guidelines • Guideline on the Acceptability of Names for Human Medicinal Products Processed Through the Centralized Procedure • Does not consider third party trademark rights In 2011, “(Invented) Name Review Group” (NRG) ~48% rejection rate

24. Putting It All Together . . .Overview of the Drug Name Selection Process • Ultimate goal is to have a name that: • Satisfies branding and marketing goals • Minimizes the risk of medication errors • Is approved by the USPTO and foreign trademark offices • Is acceptable to the FDA, EMA, and other regulatory bodies • Timing is important • Need to have a name ready and approved on launch day

25. Step 1: Initial List of Candidates • Start with a list of about 10-12 marks • Too few, and risk of none being acceptable to USPTO and FDA • Too many, prohibitive costs and potential issues with trademark filings • Selection considerations • Brand identity, consumer reaction • Domain name availability • Connotations in foreign markets (remember NOVA) • FDA and trademark prescreening • Secrecy important at this stage • No rights in name candidates until applications are filed

26. Step 2: Research Trademark Availability • Trademark search (U.S. and International) • Advisable at earliest stage of process • Indispensable step in selection process • Identify pre-existing use by others and evaluate chances of successful registration with the USPTO • Limits of trademark prescreening • Helpful to generate potentially similar names to do risk analysis on as part of the Safety Investigation

27. Step 3: Apply with USPTO • U.S. Patent and Trademark Office • File early, but remember application starts clock ticking • Must commence use in approximately 4 years from application date • Describe goods broadly, but accurately • “Pharmaceutical preparations” – Class 5 only? • Usually required to narrow during examination process • Cannot expand description once on file (file separate application) • Domain name registrations • timing important –domain name registration can reveal intentions)!

28. Step 4: Safety Investigation • Some companies opt to simulate look-alike, sound-alike investigations conducted by the FDA • Not required under the current FDA rules • Helpful to evaluate chances of FDA name approval • Can serve as ammunition for an appeal of rejection • Timing • Best to conduct the Safety Investigation early in the process to eliminate problem marks • But, may be desirable to wait until trademark applications are on file before the costs associated with such an investigation are incurred

29. Step 5: Foreign Trademark Filing • Trademark rights are territorial • Each jurisdiction has its own rules and procedures • Paris Convention filing deadline – 6 months from U.S. application date • U.S. priority date becomes foreign priority date • If possible, trim list of candidates to reduce cost prior to filing

30. Step 6: Apply with the FDA • The earlier the better • FDA recommends applying as early as the end of Phase II, beginning of Phase III • May submit up to 2 marks at once to expedite process • Approval is only preliminary until 90 days before NDA approval

31. Summary of the Name Selection Process • Step 1: Initial List of Candidates • Step 2: Research Availability • Step 3: Apply with USPTO • Step 4: Safety Investigation • Step 5: Foreign Trademark Filing • Step 6: Apply with the FDA

32. Closing Thoughts • Drug name selection process must be started early, well before (sometimes years) target launch date • Trademark counsel plays important role in establishing and protecting rights in name • Communication between trademark counsel and those involved in the FDA regulatory process is critical

33. Useful Web Sites • USPTO • www.uspto.gov • European Trademark Authority • oami.europa.eu • FDA Pilot Program to Evaluate Proposed Name • http://www.gpo.gov/fdsys/pkg/FR-2009-10-01/html/E9-23620.htm • European Agency for the Evaluation of Medicinal Products • www.ema.europa.eu

34. Thank You • Lisa M. Tittemore, Esq. • (617) 443-9292 x. 274 • ltittemore@sunsteinlaw.com