Patents in the pharmaceutical industry Lars Sparre Conrad Senior Patent Counsel Corporate Patents and Trademarks Version 1 - Juli 2004

The patent department Chemical engineer, DTU (chemistry), 1990 PhD, DTU (bio-inorganic chemistry), 1992 European Patent Attorney, 2005 Research chemist, Novo Nordisk, enzyme business, 1992-2000 Patent departments 2000-2003 Leo Pharma 2003-2005 Novo Nordisk 2005- H Lundbeck

The Patent Department Lundbeck 11 patent counsels 5 Chemical engineers 2 Human biolog 2 Cand Pharm 1 Chemists 1 Lawyer 5 Counsels in the US

Role of the Patent Department Target Assay Compound Indication Salts Polymorphs Formulation Process Device More indications Biomarkers Life Cycle Management Prosecution Drug Discovery Drug Development On the Market Freedom-To-Operate

Examples from real life Duloxetine (SNRI) from Lilly approved 2004 in the US and 2005 in EP First compound application 1986 In the period 1986-2003 (at least) 2 compound applications 11 indication applications 13 combo application 2 formulation applications 1 process application Janssen lists 16 patents for Risperidone in Orange Book

Why Patents Value of company not associated with tangible assets Value associated with an “idea” and exclusive execution of the “idea” IPR is they way to protect ideas Protection of investments The average cost of developing a prescription drug is about 800 mill $

Patent Department involvement Extreme cost and duration of pharmaceutical development => Focus on exclusivity “The right to prevent others form doing something” => Focus on Freedom-to-Operate “The right to do what you plan to do”

Why

The number of application is ever increasing Why The number of application is ever increasing

Version 1 - Juli 2004 Roles for patents Defensive Protection against copying Freedom-of-operation Prior art effect Cross-licensing Bargaining power Offensive Sale/outlicensing/enforce-ment Attract partners or investments Access to technology Barrier of entry (competitive blocking) Customer/supplier control Version 1 - Juli 2004

Børsen, 30 Juli 2003

What is a patent A patent is an exclusive right which is granted in return for the technical contribution to the society

Limitations of Rights Time – 20 years Geography – Country by country Scope – The claims

What rights Gives the right to stop others from making offering putting on the market or using the product or process using/importing a product obtained by a process which is patented

What rights A patent does not give you the right to: Exercise your own invention Somebody may have a dominating patent Freedom-to-operate Circumvent legislation in particular fields (pharmaceuticals, agrochemicals, chemicals in general, biotechnology, weapons, broadcasting etc.)

What can not be patented Discoveries, scientific theories and mathematical methods Artistic creations Plans, rules or methods for intellectual activity, for games or for business activity or computer programs (outside US) Presentation of information

What can not be patented Methods for surgery / therapy / diagnosis (Patentable in the US!!!!!) Cloning human beings Germ line modification Uses of human embryos Modifying the genetic identity of humans Metoder, der erstatter læger er ikke patenterbare. Methoder, der kan udføres af teknikere er patenterbare Metoder til aflivning af dyr er patenterbare. Apparater anvendt til diagnostic /operation er patenterbare Cloning af mennesker og anvendelse af fostre er specifikt undtaget, som et specialtilfælde af at moralsk og etisk stødende patenter ikke udstedes. Modification af dyrene – ikke tilladt hvis det påfører dem lidelse. Dog – hvis det giver en tilstrækkeligt stort bidrag til menneskeheden, så er det alligevel patenterbart. Generelt er plante-sorter og dyre-arter ikke patenterbare. Dog er ikke-stabile ændringer patenterbare. Version 1 - Juli 2004

Claims in the Pharma Industry Compounds Salts Enantiomers Polymorphs Use of compound in therapy Known compound; first use in therapy Pharmaceutical composition comprising compound E.g. in combination with specific excipients

Claims in the Pharma Industry US Only A method of treating X by the administration of compound Compound for use in the treatment of X Use of compound in the manufacture of a medicament for the treatment of X Process of manufacture Dosing regimes Combination treatments

Claims in the Pharma Industry Biomarkers/patient selection/personalized medicine Assays Devices

Claims in the Pharma Industry Method of treatment claims Allowed in the US Not allowed in EP Not considered industrially applicable – pre-2007 Not considered patentable for moral reasons – post-2007 Second medical use claims the equivalent outside US

Requirements for patentability Three separate criteria: Novelty Inventive step Industrial applicability - seldom a problem The criteria are examined individually and all must be fulfilled!

Novelty Absolute novelty approach Everything which is made public available prior to the filing date belongs to prior art Photographic identity Written, orally or in any other way Not a question of whether somebody has actually read the document but whether it was available to anyone who wanted to see it

Novelty

Novelty

Inventive step The invention must not be obvious to the skilled person in view of the state of art A leap in cognition Known to use alkali metal salts  Probably obvious to use the sodium salt Allowed to combine documents or information when evaluating inventive step

Inventive step Insulin solution characterised in that it comprises Zn2+ ions in an amount of above 4 Zn2+ per hexamer insulin but below the limit for precipitation of zinc-insulin complexes Prior art disclosed insulin solutions with 4 Zn2+ per hexamer insulin

Inventive step Inventive step Stability factor Zn++ / insulin hexamer

Novelty Inventive step Not novel Invention Invention Prior art Prior art Inventive?

PAUSE!!!!

From cradle to grave 18 months 30 months 2-7 years 7-10 years Grant PCT filing Priority filing Publication Opposition Enforcement National/regional filings

How to obtain a patent File application, pay fees and prosecute Priority application (T=0) One application in one country Filing date determines what is prior art Provides 12 months period to evaluate the invention PCT – Patent Corporation Treaty (T=12 months) One application for “the whole world” Does not issue patents Issues a preliminary opinion on patentability Delays need for expensive translations

How to obtain a patent National/regional filings (T=30 months) EPO – European Patent Office One application for ~35 European countries Issues patents – bundle of national patents

Stakeholders Innovative Pharma Generic Industry Society/Payers Long exclusivity for ensure revenue on investments Generic Industry Short exclusivity for early Market entry Society/Payers Stimulate innovation - Make innovation worthwhile - No resting on the laurels Affordable medicine

Patent peculiarities in Pharma 1st medical use claim Patent term extension Limitation of exclusivity Rewards for challenging pharma patents in courts (Hatch-Waxman act)

Supplementary Protection Certificate Counsel regulation 1768/92 Pharmaceutical research plays a decisive role in public health Pharmaceutical research long and costly Effective exclusivity period ineffective to cover investment Extension of the patent term

SPC – conditions for grant Product must be protected by the patent in force MA has been issued An SPC has not already been issued for the active compound The MA is the first MA in EU

SPC - Term A balance of interests (Market authorisation – Patent Filing)-5 years Max 5 years extension Max 15 years market exclusivity Market entry 20 +5 A balance of interests

SPC – Scope of protection Only the product covered by the patent within the limits of the patent The patent as such is not extended Esters and salts covered – ECJ392/97

Patent Term Extension Investigational New Drug New Drug Application IND NDA MA Investigational New Drug New Drug Application Marketing Authorisation PTE= Maximum 5 years extension Maximum 14 years market exclusivity

Limitation of scope Bolar Provision 2004/27/EC Conducting the necessary studies and trials with a view to the application of paragraphs 1, 2, 3 and 4 and the consequential practical requirements shall not be regarded as contrary to patent rights or to supplementary protection certificates for medicinal products 35 U.S.C §271(e)(1) It shall not be an act of infringement to make, use, offer to sell, or sell within the United States or import into the United States a patented invention (..)solely for uses reasonably related to the development and submission of information under a Federal law which regulates the manufacture, use, or sale of drugs or veterinary biological products.

Generic Avenue Patents Data Exclusivity Tech. Reg. Difficulties Environ ment Data Exclusivity Patents

Data Exclusivity EU Counsel regulation 2001/83 and 2004/27 A generic may refer to the originators registration data 8 years after originators MA A generic drug cannot be marketed before 10 years after originators MA Global Marketing Authorisation

Data Exclusivity EU Data exclusivity extended to 11 years if originator obtains MA for new indication Within 8 years Requiring clinical trials Superior to existing treatment

Data Exclusivity EU Generic drug Same active substance Salt, ester, ether, derivative etc unless they differ significantly Same pharmaceutical form All oral IR formulation are ”same” Bio-equivalence

Orphan drug EU EU regulation 141/2000 Life-threatening or debilitating disease affecting less than 5 out of 10000, or Where the development of drug is unlikely to generate sufficient return, and With no existing treatment 10 years exclusivity for similar drug and same indication

Orphan drug EU Exclusivity period reduced or annuled if There is a profitable return A superior product is brought to the market

Paediatric exclisivity EU 1901/2006 Paediatric Investigation Plan (PIP) after Phase I Deferral Waiver Data must be included in MA application and leaflet Incentives 6 months extension of SPC Paediatric Use Marketing Authorisation (PUMA) 10 years data exclusivity Orphan drug period extended to 12 years

Questions

Data exclusivity US NDA – New Drug Application ANDA – Abbreviated New Drug Application 505(b)(2) FDA cannot accept an ANDA for same active moiety before 5 years after originators MA 4 years if §IV certification Certification No patent Patent expired Patent will expire before marketing Patent not infringed or invalid

Data Exclusivity US Orange Book List all patents allegedly covering a product If patent owner challenges ANDA => 30 months stay at FDA §IV certification is patent infringement in and of itself 180 days exclusivity for first §IV applicant

Data Exclusivity US 3 additional years New indication for already marketed drug Requiring clinical investigations Exclusivity only for same drug and new indication

Generic Drug Same active ingredient Same strength, dosage form and route of administration Bio-equivalent