Pharma Licensing

1
Pharma Licensing Case Studies Pointers
Dr. Richie Paul Director, Intellectual
Property Elan Drug Technologies

• IP Summit Ireland 2008, February 2008

2
Major Products are Losing Patent Protection with
Reformulation Opportunities for Both Innovator
and Specialty Pharma
Estimated Annual Sales of Major Brands Losing
Patent Protection 1.
96B worth of pharmaceutical products will go
off patent from 2007-2012 and by 2016 it will be
140B in sales.2

• Sources
• Merrill Lynch Industry Report, Jan 06.
• Datamonitor Report, 2007.

3
It is Becoming Increasingly Difficult and
Expensive to Develop New Drugs Reformulations
are Cost Effective
US NDA Drug Approvals (2003-2006)3.
New ester, salt or non-covalent derivative,
new formulation, OTC switch and/or new
combination. Over two-thirds of FDA product
approvals are for reformulations (note generics
not included in count)

• Sources
• 1. TUFTS Centre for Study of Drug Development
  website
• 2. Defending brand revenue - Pharmaceutical
  Lifecycle management planning, June 2005 -
  Cutting Edge Information Report
• 3. FDA website

4
Technology Providers can a Play Role in Both
Enabling NCE-based Products and Lifecycle
Management

• Key issue developing a flexible sustainable
  licensing approach that allows you to
  simultaneously
• Account for the needs of different clients
• Make a profit from enabling (other peoples)
  products
• Technology must provide an advantage over the
  competition
• Different revenue streams
• Continue to develop your technology base
• RD efforts
• Control development rights
• Fend off imitators
• Enforcement of IPR
• Limit the prospects of licensees becoming
  competitors

5
Case Studies Based on Different Technologies
Developed at Elan

• ProStepTM / Nicotine patch Launched in 1992,
  marketed in US by Wyeth
• Pioneering product in nicotine replacement
  therapy
• Industry / university collaboration

• Avinza / Once-a-day CR morphine Launched by
  Ligand in 2002
• Controlled release form matches pain coverage of
  twice-a-day products
• Fast onset minimizes fluctuation in blood levels

• Emend (aprepitant NCD) NCE launched by Merck
  in 2003
• Elimination of food requirement for drug (drug
  would otherwise have been abandoned) with 600
  improvement in bioavailability

• Megace ES (megestrol acetate NCD) LCM launched
  by Par in 2005
• Equivalent efficacy achieved with dramatically
  lower dosage strength
• Easier administration

6
Case Study 1. ProStepTM - nicotine transdermal
patch

• An early example of successful industry /
  university collaboration in Ireland
• Patch RD and clinical development carried out in
  conjunction with Chemistry Department and School
  of Pharmacy at Trinity College
• Marketing rights out-licensed
• Acknowledging each partys strengths and
  priorities, and having appropriate procedures in
  place
• US 4,946853 Elan Transdermal Ltd Method for
  the treatment of withdrawal symptoms associated
  with smoking cessation and preparation for use in
  said method
• Transdermal delivery of nicotine in normal human
  volunteers a single dose and multiple dose
  study Y. B. Bannon et al Eur J Clin Pharmacol
  (1989) 37 285-290
• Managing the relationship(s) - importance of
  having good communication with inventors you
  might need them!
• Roles responsibilities in litigation

7
Case Study 2. Avinza - once-a-day morphine

• Morphine, while a well-known and trusted
  analgesic
• has a short half-life
• break-though pain is a significant problem
• no product offered true once-daily dosing
• fed fasted variability
• not suitable for monotherapy - did not have a
  fast onset of action coupled with full day
  relief      

• Using its proprietary SODAS technology Elan
  developed a controlled release (CR) once-a-day
  morphine formulation differentiated by
• true once daily CR achieved, with therapeutic
  plasma levels maintained for 24 hours
• immediate release component enables fast onset of
  action, eliminating need for co-administration of
  fast acting product

Avinza is a registered trade mark of King
Pharmaceuticals Research Development,
Inc SODAS is a registered trade mark of Elan
Pharma International Limtied
8
Case Study 2. Avinza - once-a-day
morphineBenefits to patients
9
Case Study 2. Avinza - once-a-day morphine
Benefits to Commercial Partner

• The once daily morphine product was launched by
  Ligand in 2002 now marketed by King
  Pharmaceuticals
• Patented formulation with clear marketable
  advantages over other oral products

Avinza US Sales1. (USMM)
1. Source IMS US audited ex-factory sales
10
Case Study 2. Avinza - once-a-day morphine

• Even with patent protection, dont dismiss the
  value of know-how other competitive advantages
  (e.g. ability to work with controlled substances)
• Licence should anticipate issues arising
  throughout the complete lifetime of the product
  (e.g. patent enforcement rights and
  responsibilities, assignment / transfer
  provisions, lifecycle management)

11
Case Study 3. Emend (aprepitant) - NCE

• Aprepitant poorly water soluble NCE discovered
  by Merck for treating nausea induced by
  chemotherapy or surgery
• NanoCrytsal technology used to overcome
  formulation challenges (which were such that
  product would have otherwise been shelved)

Emend is a registered trade mark of Merck Co,
Inc NanoCrystal is a registered trade mark of
Elan Pharma International Limited
12
Case Study 3. Emend (aprepitant) - NCE

• An example of enabling technology
• Be clear on who is responsible for what!
• Regulatory / IP overlap
• Reporting obligations
• Separate, but complementary patent strategies
• Rights obligations in patent prosecution,
  maintenance and enforcement
• Step-in rights

Emend is a registered trade mark of Merck Co,
Inc NanoCrystal is a registered trade mark of
Elan Pharma International Limited
13
Case Study 4. Megace - Lifecycle Management

• Megestrol - compound for treatment of anorexia
  and significant weight loss in patients with AIDS
  marketed by Par Pharmaceuticals however this
  compound used to stimulate appetite was
• a thick viscous liquid that was difficult to
  swallow
• 20ml a day had to be taken daily
• had to be taken with food
• Re-formulation with Elans NanoCrystal
  solubility enhancing technology, led to
• a superior, more palatable product with a
  significantly lower dose than the original
  product
• viscosity reduced 16 fold
• volume swallowed reduced by 75
• taken with or without food - a significant
  benefit for those with poor/no appetite

Megace is a registered trade mark of
Bristol-Myers Squibb Company licensed to Par
Pharmaceuticals, Inc
14
Improving quality of Life Through NanoCrystal
Technology Megace ES Case Study
15
Improving quality of Life Through NanoCrystal
Technology Megace ES Case Study

• Pars first branded medication, marking
  strategic shift for the company
• Par has hired own sales force to market Megace
  ES in US
• Annual sales expected to reach 100M

16
Case Study 4 Megace - Lifecycle Management

• Using lifecycle management to benefit patients
  and create new proprietary products
• Clinical / Regulatory / IP overlap
• different agreements for different stages of
  product development
• who pays for what?
• who owns what?
• consequences of termination
• Future LCM plays whos entitled to do what?

17
NanoCrystal Technology Platform

• Proven innovation for poorly water-soluble
  compounds
• Over US1.3bn annual in-market sales 1.
• Large patent portfolio2.
• Improvement in bioavailability of up to 6003.
• 4 time reduction in dosage volume 4.
• 10 fold maximum tolerated dose achieved in cancer
  drug 5.
• Can reduce or eliminates fed-fasting effect 6.
• Fast, elegant, simple solution for poorly water
  soluble compounds 7.
• Applicable to any dosage form
• underpinning extensive patenting licensing
  programmes

• Sources
• 1. 2005 sales of technology based marketed
  products in US
• 2. 490 Issued patents in US, EU and Japan
• 3. Emend bioavailability was improved by 600
  
• 4. Megace ES dose reduced from 20ml to 5ml

5. Animal studies conducted by Elan in-house on
leading anti-cancer product 6. Eliminated/reduced
fed/fasted effect in TriCor and Emend ( a
registered trade mark of Fournier Industrie et
Sante SA) 7. TriCor reformulated and approved
within 36 months
18
Elans NanoCrystal Pipeline
19
(No Transcript)