Author: Hermann A.M. Mucke, Ph.D.

Executive Summary

Chapter 1
INTRODUCTION: A SECOND LIFE FOR DRUGS AND DRUG CANDIDATES
1.1. Targets and Agents: Approaching the Limits
1.2. Human Physiology as a Network of Interdependencies
1.3. Leveraging Drug Repurposing To Turn the Tables on Pipeline Erosion
1.4. Finding Another Disease To Treat: On-Target and Off-Target

Chapter 2
DRUG REPOSITIONING AND INTELLECTUAL PROPERTY
2.1. Considerations Regarding the Patentability Criteria
2.2. Searching Prior Art to Assess Repurposing Opportunities
2.3. Searching For Intellectual Property Gaps
2.4. Data Support: An Indispensable Requirement for Second Use Patenting
2.5. Case Study: Developer Actelion Claims Bosentan for Ovarian Cancer

Chapter 3
THE STRATEGIC CONCEPT, THE SCIENCE, AND THE TOOLS OF THE THERAPEUTIC SWITCH
3.1. What Strategic Considerations Make a Compound a Repositioning Candidate?
3.2. Identification of Repurposing Opportunities
Know the Science
Know the Resources
Hypothesis-Driven Approaches
3.3. Targeted High-Throughput Screening and Inverse High-Content Screening
Phenotypic Screening: Parameter-Free High-Content Screening
Multiplexing Animal Tests
3.4. Putting Informatics to Work
Case Study for Gene Expression: VVP808
Case Study for Virtual Screening and In Silico Docking: SOSA and Entacapone
Case Study for Systems Biology: Optimata
Data Mining and Ligand-Similarity Approaches
New Opportunities Through Grid Computing?
3.5. Repurposing Aided By Drug Reformulation and New Forms of Delivery
3.6. Repurposing for Biodefense: A Strategy Outside of the Mainstream

Chapter 4
REPOSITIONED DRUGS AND REGULATORY AUTHORITIES
4.1. The FDA’s 505(b)(2) New Drug Application
4.2. The EMEA “Hybrid Application”

Chapter 5
EXAMPLES OF DRUG REPURPOSING
5.1. Successfully Repositioned Compounds That Were Never Marketed For Their Original Development Targets or Were Withdrawn From the Market
Pfizer’s Sildenafil: From Failed Antihypertensive, to Lifestyle Drug, to Orphan Disease
Thalidomide: A Colossal Tragedy and a New Beginning
Azidothymidine: A Cancer Drug Candidate Repurposed as an HIV Therapeutic and Vice Versa
5.2. Drugs That Were Moderately Successful and Were (Or Are Being) Repurposed
Galantamine: Transformed Into an Alzheimer’s Drug, With More Perspectives
Cicletanine: An Antihypertensive for Pulmonary Hypertension…And Diabetes?
Ropinirole and Pramipexole: Parkinson’s Drugs for Restless Leg Syndrome
Benzbromarone: A Potentially Problematic Gout Drug Applied To MRSA Infections
Clioquinol: An Old Antiprotozoal As a Lead Compound for Neuroprotection
Astemizole: A Problematic Antihistamine with Significant Alternative Perspectives
5.3. Successful Primary-Use Drugs in Repurposing Scenarios
Milnacipran and Duloxetine: Two Antidepressants Now Approved for Fibromyalgia
Finasteride: From Prostate to Hair Loss
Imatinib for Diabetes and Rheumatoid Arthritis
5.4. Failed, and Failed Again…Perhaps For the Wrong Reasons
MCI-225: From Psychiatry Drug Candidate, to Gastrointestinal and Urinary Tract Agent

Chapter 6
COMPANIES IN THE DRUG REPURPOSING BUSINESS
6.1. Business Models Centered On Drug Repurposing: Different From Those for Discovery?
6.2. The Small, Drug-Repurposing Specialists
Sosei Group Corp.
CombinatoRx, Inc.
Ore Pharmaceutical Holdings, Inc.
Biovista, Inc.
Melior Discovery, Inc.
Numedicus Ltd.
Vifor Pharma/Galenica Group
Aureus Pharma
Horizon Discovery Ltd.
Tangent Reprofiling Ltd.
Anaxomics Biotech SL
SOM Biotech SL
SWITCHBIOTECH LLC
Celentyx Ltd.
Almac Group Ltd.
6.3. “Big Pharma” And Drug Repositioning
Pfizer
Novartis
Eli Lilly
6.4. Public Efforts to Facilitate Drug Repurposing

Chapter 7
THE ECONOMIC POTENTIAL OF DRUG REPURPOSING
7.1. Cost Savings of Repurposing In Discovery and Development
7.2. Acceleration of Drug Development: Time Equals Sales
7.3. The Benefits of De-Risking
7.4. The Repurposing Service Provider’s Perspective
7.5. Summary and Outlook

References

Company Index with Web Addresses