Nucleic Acid Aptamers for Diagnostics and Therapeutics: Global Markets

• Publication date: October 2012
• Report size: 138 pages

REPORT HIGHLIGHTS This report provides: • An overview of the specific applications for nucleic acid aptamers for therapeutic and diagnostic purposes, with a focus on applications judged to be commercially viable rather than enabling of basic research • Analyses of global market trends, with data from 2011, estimates for 2012, and projections of compound annual growth rates (CAGRs) through 2017 • Identif...

REPORT HIGHLIGHTS

This report provides:

• An overview of the specific applications for nucleic acid aptamers for therapeutic and diagnostic purposes, with a focus on applications judged to be commercially viable rather than enabling of basic research
• Analyses of global market trends, with data from 2011, estimates for 2012, and projections of compound annual growth rates (CAGRs) through 2017
• Identification of emerging technology growth opportunities in aptamer use as adjuvants for siRNA delivery, vaccines, and antisense technologies
• Examination of high growth and market potential segments of the industry, and new and established companies in the arena
• Comprehensive company profiles of major players in the industry.

REPORT SCOPE

INTRODUCTION

STUDY GOALS AND OBJECTIVES

The goal of this study is to determine and describe the specific applications and global market demand for nucleic acid aptamers for therapeutic and diagnostic purposes. The report covers a 10-year period from 2008 to 2017. The original version of this report (BIO071A) was released in March 2010. Thus, while some of the data tables still include historical information, the focus of the most table updates is on the years 2011 with market predictions from 2012 to 2017. The years covered in the table are given in small increments due to the early nature of the market and a need to estimate as closely as possible small fluctuations, such as some recent and upcoming patent expirations that may have a disproportionate effect on this market, compared with any larger more mature markets. In addition to a breakdown by therapeutic or diagnostic application, markets are further divided by major disease type addressed, or diagnostic application (i.e., clinical, environmental, biodefense, etc.).

We also identify emerging technology growth opportunities in aptamer use as adjuvants for siRNA delivery, vaccines, and antisense technologies.

Although this report focuses on the 2008 to 2017 time frame, significant recent investments in aptamer technology indicates that the therapeutic modality may remain important for some time to come. Thus, while the aptamer field is yet an emerging niche of biotechnology, we highlight high growth and market potential segments of the industry and new as well as established companies in the arena.

In addition to a quantitative market analysis, this report includes a significant summary of the intellectual property landscape and thus will be particularly useful to companies deciding whether or not to enter the aptamer space. Finally, the study will be useful for the ever-increasing number of diagnostic and biosensor development start-ups interested in the unique aspects of aptamers as inexpensive, synthetic ligands for molecular recognition.


REASONS FOR DOING THE STUDY

Although aptamers and their directed selection in the laboratory were described in 1990, their widespread acceptance in therapeutics and diagnostics is still being realized. Aptamers have a number of advantages over their antibody counterparts, which are discussed in detail within the report. Perhaps most important in the therapeutic context, as nucleic acids, aptamers are readily chemically synthesized and therefore are comparably easy to characterize over antibodies produced by recombinant means. For similar reasons, aptamers are readily developed and used by boutique developers of novel diagnostics and biosensors, and larger firms are beginning to take notice. Finally, several of the initial patents in the aptamer field have recently expired, or are set to soon expire, which will make for a change in the intellectual property landscape. This report is therefore timely in that regard as well.


SCOPE OF REPORT

The scope of this report covers all major known applications of aptamers in the biotechnology arena. Nevertheless, the study focuses on applications judged to be commercially viable rather than enabling of basic research.


INTENDED AUDIENCE

This report should be of benefit to all executives and scientific personnel in the biotechnology industry. Those familiar with the concepts involved in therapeutic antibodies should be well prepared to receive the report. Similarly, those familiar with the role of antibodies in diagnostics (i.e., immunoassays of any type) will also find the report useful because it will explain the extended capability of aptamers in similar contexts.


INFORMATION SOURCES

BCC researchers surveyed biotechnology, pharmaceutical, and diagnostics companies to obtain data for this study. Included were life-science research tools, drug, biotechnology, and DNA synthesis firms, as well as leading life-science research institutions. We also spoke with industry thought leaders and academics in the field. In addition, we compiled data from secondary sources, including industry, trade, and government. Finally, active intellectual property professionals in the area were consulted.


ANALYST CREDENTIALS

Dr. George William (“Bill”) Jackson, Ph.D., serves as a Senior Scientist at BioTex, Inc. in Houston, Texas. Additionally, Dr. Jackson is founder and chief scientist of Base Pair Biotechnologies, Inc., a company specializing in aptamer discovery services. He is an active researcher in the molecular biology and diagnostics field with numerous federal grants in the area. Particularly, he has served as principal investigator (PI) on several projects utilizing aptamers for both sensing and bioremediation. Most recently, he serves as PI on a research grant from the National Institutes of Health to select “an aptamer to everything,” which was formally titled, “Platform for Massively Parallel Selection of Aptamer Ligands.” He has served on peer review panels at the National Institutes of Health and the Environmental Protection Agency on topics ranging from biodefense and medical diagnostics to water quality. Dr. Jackson has authored more than 30 peer-reviewed publications or conference proceedings and is the inventor on four issued and 13 pending patents.

Co-author, Dr. Ulrich Strych, Ph.D., is a Research Assistant Professor at the University of Houston. Dr. Strych is an experienced molecular biologist who has collaborated with Dr. Jackson for more than five years on various aptamer-related research projects. Dr. Strych has extensive modern molecular biology experience, methods development know-how in surface plasmon resonance (SPR) and other bioanalytical approaches, and hands-on experience with other methods of high-throughput combinatorial screening, such as phage display.

Global Diagnostics Industry

TABLE OF CONTENTS

CHAPTER 1 INTRODUCTION 1
STUDY GOALS AND OBJECTIVES 1
REASONS FOR DOING THE STUDY 1
SCOPE OF REPORT 1
INTENDED AUDIENCE 2
INFORMATION SOURCES 2
ANALYST CREDENTIALS 2
RELATED BCC REPORTS 2
BCC ONLINE SERVICES 3
DISCLAIMER 3
CHAPTER 2 SUMMARY 5
SUMMARY TABLE A GLOBAL MARKETS FOR APTAMERS, THROUGH 2017 ($ MILLIONS)* 5
SUMMARY FIGURE GLOBAL MARKETS FOR APTAMERS, 2011–2017 ($ MILLIONS)* 5
SUMMARY TABLE B POTENTIAL MARKETS FOR APTAMER THERAPEUTICS, THROUGH 2017
($ MILLIONS) 6
SUMMARY TABLE C HISTORICAL U.S. SALES FOR MACUGEN, THE FIRST FDA-APPROVED
APTAMER DRUG, 2005-2011 ($ MILLIONS) 7
SUMMARY TABLE D POTENTIAL MARKETS FOR APTAMER-BASED IN-VITRO DIAGNOSTICS,
THROUGH 2017 ($ MILLIONS) 8
CHAPTER 3 OVERVIEW 10
INTRODUCTION: APTAMERS AS AFFINITY REAGENTS 10
FIGURE 1 SIMPLIFIED SCHEMATIC OF SELEX PROCESS FOR IN-VITRO SELECTION OF (DNA)
APTAMERS 10
APTAMERS AS AFFINITY REAGENTS 11
TABLE 1 APTAMERS AND ANTIBODIES: KEY DIFFERENCES 12
INDUSTRY DEFINITION AND HISTORICAL DEVELOPMENT 12
ECONOMIC IMPORTANCE 13
PRODUCT LIFE CYCLE 13
INTELLECTUAL PROPERTY AND REGULATORY ISSUES 13
POTENTIAL FUTURE DEVELOPMENTS 14
CHAPTER 4 MARKETS BY TECHNOLOGY TYPE 16
INTRODUCTION 16
ENABLING TECHNOLOGY 16
OLIGONUCLEOTIDE SYNTHESIS 16
MODIFIED OLIGONUCLEOTIDES 17
Aptamer Modifications for Diagnostic Purposes 18
Nuclease Stability of Aptamers in the Body and ADME Properties 19
TABLE 2 MODIFICATIONS EMPLOYED TO ENHANCE APTAMERS 20
NANOPARTICLES AND QUANTUM DOT LABELS 20
NEXT-GENERATION SEQUENCING 20
TABLE 3 CURRENT PRICE PER MEGABASE FOR 'NEXT GENERATION' DNA SEQUENCING
($/MEGAPHASE) 21
SURFACE PLASMON RESONANCE AND BIOLAYER INTERFEROMETRY 21
BIOINFORMATICS 22
TRENDS IN ENABLING TECHNOLOGIES 23
APTAMERS AS DIAGNOSTIC SENSORS 23
SELF-REPORTING SENSORS 23
SENSOR PLATFORM TECHNOLOGIES 25
Homogeneous Solution Assays in Microplate Readers 25
Quartz Crystal Microbalance 25
Nano- and Microcantilever Sensors Using Aptamers 26
Surface Plasmon Resonance (SPR) and SPR Arrays 27
Biolayer Interferometry (BLI) 28
TRENDS IN APTAMERS AS DIAGNOSTICS 28
APTAMERS AS THERAPEUTICS 28
APTAMERS AS TARGETING AGENTS 30
APTAMERS AND INFECTIOUS DISEASE 30
APTAMER MODIFICATIONS 30
APTAMERS AS IMAGING LABELS 31
APPLICATION OF APTAMERS AS MODIFIERS OF SURGICAL IMPLANTS 31
WHOLE CELL SELEX 31
'CAPTAMERS' 32
VEGF APTAMERS 32
TABLE 4 MEDICALLY RELEVANT APTAMER TARGETS 33
MACUGEN'S PATH TO FDA APPROVAL 33
CLINICAL TRIALS INVOLVING APTAMERS 34
PRE-CLINICAL TRIAL STAGE 34
PHASE I TRIALS 35
PHASE II TRIALS 36
TABLE 5 APTAMER CLINICAL TRIALS (C: COMPLETED, R: RECRUITING, A: ACTIVE, NOT
RECRUITING, T: TERMINATED, W: WITHDRAWN, P: PENDING) 37
APTAMER DELIVERY 43
APTAMERS AND AGE-RELATED MACULAR DEGENERATION (AMD) 43
Valeant Pharmaceuticals International, Inc. (Valeant) 43
Ophthotech 44
APTAMERS IN CANCER 45
Antisoma/Archemix 45
Aptamers to Biomarkers-Tenascin-C 45
Enzon Pharmaceuticals, Inc. 46
Archemix/Merck KGaA 46
Aptamer-Drug Conjugates 46
Aptagen 47
APTAMERS AS ANTICOAGULANTS 47
APTAMERS IN OTHER INDICATIONS 48
TRENDS IN APTAMERS AS THERAPEUTICS 48
TABLE 6 EMERGING APPLICATIONS FOR APTAMERS IN THERAPEUTICS 49
APTAMERS IN BIOSEPARATION 49
APTAMERS AS RESEARCH TOOLS 50
TABLE 7 NUMBER OF NIH FUNDED GRANTS EMPLOYING APTAMERS, 2005–2011 51
TABLE 8 NIH FUNDING FOR DISEASES CONSIDERED AS POSSIBLE APPLICATIONS FOR
APTAMERS, 2008–2013 ($ MILLIONS) 51
TABLE 9 NIH FUNDING FOR TECHNOLOGIES CONSIDERED AS POSSIBLE APPLICATIONS
FOR APTAMERS, 2008–2013 ($ MILLIONS) 51
TABLE 10 TOTAL NIH FUNDING, 2005-2011 ($ MILLIONS) 52
TABLE 11 NUMBER OF PUBLICATIONS IN ISI WEB OF KNOWLEDGE UNDER THE TOPIC
“APTAMER,” 2005-2012 52
MARKET LEADERS (U.S.) 52
ARCHEMIX 52
Collaborations 53
OSI PHARMACEUTICALS 54
REGADO 54
OPHTHOTECH 55
MARKET LEADERS (INTERNATIONAL) 56
NOXXON 56
CHAPTER 5 MARKETS BY APPLICATIONS 60
INTRODUCTION 60
APPLICATION OF APTAMERS AS DIAGNOSTICS 60
APPLICATION OF APTAMERS IN HUMAN CLINICAL DIAGNOSTIC ASSAYS 60
Somalogic Somascan 61
APPLICATION OF APTAMERS IN ENVIRONMENTAL MONITORING AND FOOD AND
WATER SAFETY 62
Application Example #1-Veterinary Residue Testing 62
TABLE 12 EXAMPLE OF VETERINARY RESIDUE TESTS (ELISAS) OFFERED BY A LEADING U.S.
VENDOR (ABRAXIS KITS, LLC) 63
TABLE 13 OTHER ENVIRONMENTAL ELISAS OFFERED BY ABRAXIS KITS, LLC1 65
Application Example #2-Algal Toxin Sensing 66
APPLICATION OF APTAMERS IN VETERINARY DIAGNOSTICS 66
TABLE 14 NUMBERS OF RESEARCH GRANTS FROM THE USDA ON ZOONOTIC DISEASES 67
TABLE 15 USDA-SPONSORED RESEARCH GRANTS ON “APTAMERS” 68
Application Example #3-Foot and Mouth Disease (FMD) Virus 69
Application Example #4-Leptospira Detection 71
OVERALL MARKET POTENTIAL OF APTAMERS IN DIAGNOSTICS AND
ENVIRONMENTAL TESTING 71
TABLE 16 U.S. DIAGNOSTICS AND TESTING MARKETS IN WHICH APTAMERS COULD PLAY A
SIGNIFICANT ROLE, THROUGH 2017 ($ MILLIONS) 72
APPLICATION OF APTAMERS AS THERAPEUTICS 73
APTAMER DRUGS CURRENTLY ON THE MARKET 73
Pegaptanib 73
TABLE 17 MARKET COMPARISON (MACUGEN, LUCENTIS, AND AVASTIN), 2004-2011 73
PROJECTED TO REACH THE MARKET WITHIN FIVE YEARS 73
E10030 73
Nox-A-12 74
Nox-E-36 74
NU-172 74
REG1 74
CONDITIONS TARGETED BY APTAMERS 75
Stem Cell Technology 75
Acute Coronary Syndrome 75
AMD 75
APPLICATION OF APTAMERS AS DRUG DELIVERY VEHICLES IN CANCER 76
TABLE 18 GLOBAL THERAPEUTICS MARKETS ADDRESSABLE IN NEAR TERM BY APTAMERS,
THROUGH 2017 ($ MILLIONS) 77
TABLE 19 CANCER THERAPEUTICS MARKETS IN THE U.S. BY SUBINDICATION, THROUGH
2017 ($ BILLIONS) 78
APPLICATION OF APTAMERS AS MODIFIERS OF SURGICAL IMPLANTS 78
APPLICATION OF APTAMERS IN BIOSEPARATION PROCESSES 78
CHAPTER 6 INTELLECTUAL PROPERTY ANALYSIS 81
BRIEF HISTORY 81
APTAMERS AND SELEX AS PATENTABLE SUBJECT MATTER 81
ORIGINAL APTAMER AND SELEX PATENTS 83
VALIDITY, LEGAL ACTION, AND INFRINGEMENT 84
TABLE 20 MAJOR HOLDERS OF APTAMER/SELEX IP 85
TABLE 21 STRATEGIC (KNOWN OR PUBLISHED) TECHNOLOGY AND R&D ALLIANCES 86
TABLE 22 SELECTED APTAMER PATENTS 87
TABLE 23 SELECTED U.S. PATENT APPLICATIONS FOR THERAPEUTIC APTAMERS 96
CHAPTER 7 INDUSTRY STRUCTURE AND COMPETITIVE ANALYSIS 98
APTAMER TECHNOLOGY IN THE BIOSCIENCE INDUSTRY 98
FIGURE 2 COMPARISON OF TRADITIONAL SMALL MOLECULE, PROTEIN, AND
APTAMER-BASED MODALITIES 98
THE EVOLVING APTAMER IP LANDSCAPE 99
APTAMERS AND THE BIOTECHNOLOGY ECOSYSTEM 100
THERAPEUTICS 100
DIAGNOSTICS 101
OTHER APPLICATIONS 101
SIGNIFICANT OBSTACLES TO THE APTAMER INDUSTRY 101
CURRENT APTAMER MARKET LEADERS 102
FIGURE 3 APTAMER INDUSTRY STRUCTURE 102
PORTER MODEL ANALYSIS OF THE APTAMER INDUSTRY 105
THREAT OF SUBSTITUTE PRODUCTS IS HIGH 105
THREAT OF NEW ENTRANTS IS LOW (BUT LIKELY TO INCREASE) 105
BARGAINING POWER OF SUPPLIERS IS LOW 105
BARGAINING POWER OF CUSTOMERS IS HIGH 105
INTRA-INDUSTRY COMPETITION IS LOW 105
FIGURE 4 PORTER ANALYSIS OF THE APTAMER INDUSTRY 105
CHAPTER 8 COMPANY PROFILES 108
ABRAXIS KITS, LLC 108
ALIMERA SCIENCES 108
ALNYLAM PHARMACEUTICALS 109
AM BIOTECHNOLOGIES, LLC 109
ANGIOGENIX 110
APTAGEN, LLC 110
APTAMER SCIENCES INC. 111
APTASOL (APTAMER SOLUTIONS) LTD 112
ARCHEMIX CORP. 112
COLLABORATIONS 113
ANESIVA, INC. 113
BASE PAIR BIOTECHNOLOGIES, INC. 114
CYNVENIO BIOSYSTEMS, INC. 114
CYTOGENIX, INC. 115
ENVIROLOGIX, INC. 115
ENZON PHARMACEUTICALS INC. 115
EYETECH 116
ISIS PHARMACEUTICALS 116
MITSUI & CO. (U.S.A.), INC. 116
NEOVENTURES 116
NOXXON 117
OPHTHOTECH CORPORATION 119
OSI PHARMACEUTICALS, INC. 119
REGADO BIOSCIENCES 120
RINA GMBH 120
QUEST DIAGNOSTICS 121
SAW INSTRUMENTS GMBH 122
SOMALOGIC, INC. 122
SUMITOMO BAKELITE-NORTH AMERICA, INC. 123
CHAPTER 9 REFERENCES 125
REFERENCES 125


LIST OF TABLES


TABLE HEADING PAGE NO.
SUMMARY TABLE A GLOBAL MARKETS FOR APTAMERS, THROUGH 2017 ($ MILLIONS)* 5
SUMMARY TABLE B POTENTIAL MARKETS FOR APTAMER THERAPEUTICS, THROUGH 2017 ($
MILLIONS) 6
SUMMARY TABLE C HISTORICAL U.S. SALES FOR MACUGEN, THE FIRST FDA-APPROVED
APTAMER DRUG, 2005-2011 ($ MILLIONS) 7
SUMMARY TABLE D POTENTIAL MARKETS FOR APTAMER-BASED IN-VITRO DIAGNOSTICS,
THROUGH 2017 ($ MILLIONS) 8
TABLE 1 APTAMERS AND ANTIBODIES: KEY DIFFERENCES 12
TABLE 2 MODIFICATIONS EMPLOYED TO ENHANCE APTAMERS 20
TABLE 3 CURRENT PRICE PER MEGABASE FOR 'NEXT GENERATION' DNA SEQUENCING
($/MEGAPHASE) 21
TABLE 4 MEDICALLY RELEVANT APTAMER TARGETS 33
TABLE 5 APTAMER CLINICAL TRIALS (C: COMPLETED, R: RECRUITING, A: ACTIVE, NOT
RECRUITING, T: TERMINATED, W: WITHDRAWN, P: PENDING) 37
TABLE 6 EMERGING APPLICATIONS FOR APTAMERS IN THERAPEUTICS 49
TABLE 7 NUMBER OF NIH FUNDED GRANTS EMPLOYING APTAMERS, 2005–2011 51
TABLE 8 NIH FUNDING FOR DISEASES CONSIDERED AS POSSIBLE APPLICATIONS FOR
APTAMERS, 2008–2013 ($ MILLIONS) 51
TABLE 9 NIH FUNDING FOR TECHNOLOGIES CONSIDERED AS POSSIBLE APPLICATIONS FOR
APTAMERS, 2008–2013 ($ MILLIONS) 51
TABLE 10 TOTAL NIH FUNDING, 2005-2011 ($ MILLIONS) 52
TABLE 11 NUMBER OF PUBLICATIONS IN ISI WEB OF KNOWLEDGE UNDER THE TOPIC
“APTAMER,” 2005-2012 52
TABLE 12 EXAMPLE OF VETERINARY RESIDUE TESTS (ELISAS) OFFERED BY A LEADING U.S.
VENDOR (ABRAXIS KITS, LLC) 63
TABLE 13 OTHER ENVIRONMENTAL ELISAS OFFERED BY ABRAXIS KITS, LLC1 65
TABLE 14 NUMBERS OF RESEARCH GRANTS FROM THE USDA ON ZOONOTIC DISEASES 67
TABLE 15 USDA-SPONSORED RESEARCH GRANTS ON “APTAMERS” 68
TABLE 16 U.S. DIAGNOSTICS AND TESTING MARKETS IN WHICH APTAMERS COULD PLAY A
SIGNIFICANT ROLE, THROUGH 2017 ($ MILLIONS) 72
TABLE 17 MARKET COMPARISON (MACUGEN, LUCENTIS, AND AVASTIN), 2004-2011 73
TABLE 18 GLOBAL THERAPEUTICS MARKETS ADDRESSABLE IN NEAR TERM BY APTAMERS,
THROUGH 2017 ($ MILLIONS) 77
TABLE 19 CANCER THERAPEUTICS MARKETS IN THE U.S. BY SUBINDICATION, THROUGH
2017 ($ BILLIONS) 78
TABLE 20 MAJOR HOLDERS OF APTAMER/SELEX IP 85
TABLE 21 STRATEGIC (KNOWN OR PUBLISHED) TECHNOLOGY AND R&D ALLIANCES 86
TABLE 22 SELECTED APTAMER PATENTS 87
TABLE 23 SELECTED U.S. PATENT APPLICATIONS FOR THERAPEUTIC APTAMERS 96


LIST OF FIGURES


FIGURE TITLE PAGE NO.
SUMMARY FIGURE GLOBAL MARKETS FOR APTAMERS, 2011–2017 ($ MILLIONS)* 5
FIGURE 1 SIMPLIFIED SCHEMATIC OF SELEX PROCESS FOR IN-VITRO SELECTION OF (DNA)
APTAMERS 10
FIGURE 2 COMPARISON OF TRADITIONAL SMALL MOLECULE, PROTEIN, AND
APTAMER-BASED MODALITIES 98
FIGURE 3 APTAMER INDUSTRY STRUCTURE 102
FIGURE 4 PORTER ANALYSIS OF THE APTAMER INDUSTRY 105