Antisense Products: Technology, Markets

REASONS FOR THE STUDY
OBJECTIVES OF THE STUDY
AUDIENCE FOR THE STUDY
SCOPE AND CONTENT OF THE STUDY
METHODOLOGY USED IN STUDY
ANALYST CREDENTIALS
RELATED BCC REPORTS
MONTHLY NEWSLETTERS
BCC ON-LINE SERVICES

Summary Table:
POTENTIAL MARKET FOR ANTISENSE THERAPEUTICS, 2007 ($ BILLIONS)

Summary Figure:
DISTRIBUTION ANTISENSE THERAPEUTICS MARKET VALUE BY APPLICATION, 2007 ($ MILLIONS)

GENE EXPRESSION
THE PROCESS OF GENE EXPRESSION
Step One: Signaling
Figure 1. SIGNALING TO BEGIN EXPRESSION OF A GENE
Step Two: Unwinding of DNA
Figure 2. UNWINDING AND SEPARATION OF DNA STRANDS
Step Three: Transcription
Figure 3. RNA TRANSCRIPTION
Step Four: RNA Processing
Figure 4. RNA SPLICING
Step Five: Translation
Figure 5. TRANSLATION OF A PROTEIN
HOW ANTISENSE CONTROLS GENE EXPRESSION
Figure 6. HYBRIDIZATION OF ANTISENSE OLIGO TO MRNA
BLOCKING OF MRNA SPLICING
Figure 7. HYBRIDIZED OLIGO INTERFERES WITH SPLICING
BLOCKING RIBOSOMES
Figure 8. ANTISENSE OLIGO INHIBITION OF RIBOSOMES
RNASE H CLEAVAGE OF MRNA
Figure 9. RNASE H DIGESTION OF RNA-DNA DUPLEX
CHEMISTRY OF ANTISENSE COMPOUNDS
THE ORIGINAL ANTISENSE COMPOUNDS
Figure 10. STRUCTURE OF DNA AND RNA
FIRST GENERATION ANTISENSE COMPOUNDS
Figure 11. FIRST GENERATION OF ANTISENSE MOLECULES
SECOND GENERATION ANTISENSE COMPOUNDS
Figure 12. SECOND GENERATION ANTISENSE MODIFICATIONS
2'-Ribose Modifications
N 3' to P 5' Modifications
Phosphorodiamidate Morpholino Modifications
Peptide Nucleic Acids (PNAs)
RIBOZYMES
Figure 13. RIBOZYMES
HAMMERHEAD RIBOZYMES
HAIRPIN RIBOZYMES
HISTORY OF ANTISENSE TECHNOLOGY
Figure 14. NUMBER OF ANTISENSE SCIENTIFIC PUBLICATIONS, 1973-2002

CANCER
BRAIN CANCER
BREAST CANCER
COLORECTAL CANCER
KIDNEY CANCER
LEUKEMIA
LUNG CANCER
LYMPHOMA
SKIN CANCER
MULTIPLE MYELOMA
OVARIAN CANCER
PANCREATIC CANCER
PROSTATE CANCER
OVERVIEW OF CURRENT CANCER TREATMENT STRATEGIES
ANTISENSE CANCER TREATMENT STRATEGIES
Table 1. ANTISENSE PRODUCTS FOR TREATMENT OF CANCER
CORONARY HEART DISEASE
RESTENOSIS
OVERVIEW OF CURRENT TREATMENTS
ANTISENSE TREATMENTS FOR RESTENOSIS
Table 2. ANTISENSE PRODUCTS FOR TREATMENT OF RESTENOSIS
DIABETES
TYPE 2 DIABETES
CURRENT TREATMENTS FOR TYPE 2 DIABETES
ANTISENSE TREATMENT FOR TYPE 2 DIABETES
Table 3. ANTISENSE PRODUCTS FOR TREATMENT OF TYPE 2 DIABETES
IMMUNOLOGICAL DISORDERS
ASTHMA
CROHN'S DISEASE AND ULCERATIVE COLITIS
MULTIPLE SCLEROSIS
PSORIASIS
RHEUMATOID ARTHRITIS
CURRENT TREATMENT FOR IMMUNOLOGICAL DISORDERS
ANTISENSE TREATMENTS FOR IMMUNOLOGICAL DISORDERS
Table 4. ANTISENSE PRODUCTS FOR TREATMENT OF IMMUNOLOGICAL DISORDERS
INFECTIOUS DISEASES
CYTOMEGALOVIRUS/RETINITIS
HEPATITIS B
HEPATITIS C
HUMAN IMMUNODEFICIENCY VIRUS
HUMAN PAPILLOMAVIRUS
CURRENT TREATMENT OF INFECTIOUS DISEASES
ANTISENSE TREATMENT FOR INFECTIOUS DISEASES
Table 5. ANTISENSE PRODUCTS FOR TREATMENT OF INFECTIOUS DISEASES
POLYCYSTIC KIDNEY DISEASE
POLYCYSTIC KIDNEY DISEASE
CURRENT TREATMENTS FOR POLYCYSTIC KIDNEY DISEASE
ANTISENSE TREATMENT FOR POLYCYSTIC KIDNEY DISEASE
RETINAL DISORDERS
AGE-RELATED MACULAR DEGENERATION
DIABETIC RETINOPATHY
PROLIFERATIVE VITREORETINOPATHY
CURRENT TREATMENTS FOR RETINA DISORDERS
ANTISENSE TREATMENT FOR RETINAL DISORDERS
Table 6. ANTISENSE PRODUCTS FOR TREATMENT OF RETINAL DISORDERS

AEGERA THERAPEUTICS INC.
ANTISENSE XIAP (X-LINKED INHIBITOR OF APOPTOSIS)
Type of Antisense Technology
Stage of Development
ANGIOGENE INC.
OLIGLOW™
Type of Antisense Technology
Stage of Development
ANTISENSE PHARMA GMBH
AP 12009
Type of Antisense Technology
Stage of Development
ANTISENSE THERAPEUTICS LTD.
ATL 1101
Type of Antisense Technology
Stage of Development
ATL 1102
Type of Antisense Technology
Stage of Development
AVI BIOPHARMA
AVI 4014
Type of Antisense Technology
Stage of Development
AVI 4126
Type of Antisense Technology
Stage of Development
AVI 4557
Type of Antisense Technology
Stage of Development
ONCOMYC-NG
Type of Antisense Technology
Stage of Development
Table 7. CLINICAL TRIAL STATUS OF ANTISENSE THERAPEUTIC ONCOMYC
RESTINE-NG
Type of Antisense Technology
Stage of Development
ENZO THERAPEUTICS
HGTV-43
Type of Antisense Technology
Stage of Development
EPIGENESIS PHARMACEUTICALS, INC.
DURASON™ (EPI-2010)
Type of Antisense Technology
Stage of Development
GENTA
GENASENSE™
Type of Antisense Technology
Stage of Development
Table 8. CLINICAL TRIAL STATUS OF ANTISENSE THERAPEUTIC GENASENSE™
HYBRIDON, INC.
ANTISENSE EPIDERMAL GROWTH FACTOR RECEPTOR
Type of Antisense Technology
Stage of Development
ANTISENSE NUCLEOTIDE EXCISION REPAIR PROTEIN XPA
Type of Antisense Technology
Stage of Development
ANTISENSE SURVIVIN
Type of Antisense Technology
Stage of Development
GEM®92
Type of Antisense Technology
Stage of Development
GEM®220
Type of Antisense Technology
Stage of Development
GEM®231
Type of Antisense Technology
Stage of Development
Table 9. CLINICAL TRIAL STATUS OF ANTISENSE THERAPEUTIC GEM®231
GEM®240
Type of Antisense Technology
Stage of Development
IMMUSOL INC.
PROLIFERASE™
Type of Antisense Technology
Stage of Development
RESTENASE™
Type of Antisense Technology
Stage of Development
VITRENASE™
Type of Antisense Technology
Stage of Development
ISIS PHARMACEUTICALS
AFFINITAC™ (ISIS 3521)
Type of Antisense Technology
Stage of Development
Table 10. CLINICAL TRIAL STATUS OF ANTISENSE THERAPEUTIC AFFINITAC™
ALICAFORSEN (ISIS 2302)
Type of Antisense Technology
Stage of Development
Table 11. CLINICAL TRIAL STATUS OF ANTISENSE THERAPEUTIC ALICAFORSEN
ISIS 2503
Type of Antisense Technology
Stage of Development
Table 12. CLINICAL TRIAL STATUS OF ANTISENSE THERAPEUTIC ISIS 2503
ISIS 13650
Type of Antisense Technology
Stage of Development
ISIS 14803
Type of Antisense Technology
Stage of Development
ISIS 104838
Type of Antisense Technology
Stage of Development
Table 13. CLINICAL TRIAL STATUS OF ANTISENSE THERAPEUTIC ISIS 104828
ISIS 113715
Type of Antisense Technology
Stage of Development
VITRAVENE™ (FOMIVIRSEN)
Type of Antisense Technology
Stage of Development
LORUS THERAPEUTICS
GTI 2040
Type of Antisense Technology
Stage of Development
Table 14. CLINICAL TRIAL STATUS OF ANTISENSE THERAPEUTIC GTI 2040
GTI 2501
Type of Antisense Technology
Stage of Development
METHYLGENE
MG 98
Type of Antisense Technology
Stage of Development
NEOPHARM
LERAF-AON
Type of Antisense Technology
Stage of Development
ONCOGENEX THERAPEUTICS
OGX-011
Type of Antisense Technology
Stage of Development
Table 15. CLINICAL TRIAL STATUS OF ANTISENSE THERAPEUTIC OGX-011
ORIGENIX TECHNOLOGIES
ORI-1001
Type of Antisense Technology
Stage of Development
PANACEA PHARMACEUTICALS
PAN 346
Type of Antisense Technology
Stage of Development
RIBOZYME PHARMACEUTICALS
ANGIOZYME®
Type of Antisense Technology
Stage of Development
Table 16. CLINICAL TRIAL STATUS OF ANTISENSE THERAPEUTIC ANGIOZYME®
HEPBZYME™
Type of Antisense Technology
Stage of Development
HEPTAZYME™
Type of Antisense Technology
Stage of Development
HERZYME™
Type of Antisense Technology
Stage of Development

CANCER THERAPEUTICS
Table 17. INCIDENCE OF CANCER IN THE U.S., THROUGH 2007 (NUMBER OF CASES)

Figure 15. INCIDENCE OF TYPES OF CANCERS, 2002, 2002 AND 2007 (NUMBER OF CASES)

Table 18. MARKET FOR CANCER THERAPEUTICS IN THE U.S., THROUGH 2007 ($ BILLIONS)

Table 19. COST OF CANCER THERAPEUTICS IN THE U.S., THROUGH 2007 ($/PATIENT/YEAR)

RESTENOSIS THERAPEUTICS
Table 20. STENTS USED IN ANGIOPLASTY PROCEDURES, THROUGH 2007 (MILLIONS OF UNITS)

Table 21. COST OF STENTS IN THE U.S., THROUGH 2007 ($/STENT)

Table 22. MARKET FOR STENTS IN THE U.S., THROUGH 2007 ($ BILLIONS)

TYPE 2 DIABETES THERAPEUTICS
Table 23. PREVALENCE OF TYPE 2 DIABETES, THROUGH 2007 (THOUSANDS OF CASES)

Table 24. COST OF TYPE 2 DIABETES THERAPEUTICS IN THE U.S., THROUGH 2007 ($/PATIENT/YEAR)

Table 25. MARKET FOR TYPE 2 DIABETES THERAPEUTICS IN THE U.S., THROUGH 2007 ($ BILLIONS)

IMMUNOLOGICAL DISORDER THERAPEUTICS
Table 26. PREVALENCE OF IMMUNOLOGICAL DISORDERS POTENTIAL TREATED WITH ANTISENSE THERAPEUTICS, THROUGH 2007 (THOUSAND CASES)

Figure 16. PREVALENCE OF IMMUNOLOGICAL DISORDERS, 2002, 2002 AND 2007 (THOUSAND CASES)

Table 27. MARKET FOR THERAPEUTICS FOR IMMUNOLOGICAL DISORDERS, THROUGH 2007 ($ BILLIONS)

ASTHMA
Table 28. COST OF ASTHMA THERAPEUTICS IN THE U.S., THROUGH 2007 ($/PATIENT/YEAR)

Table 29. MARKET FOR ASTHMA THERAPEUTICS IN THE U.S., THROUGH 2007 ($ BILLIONS)

CROHN'S DISEASE AND ULCERATIVE COLITIS
Table 30. COST OF CROHN'S DISEASE AND ULCERATIVE COLITIS THERAPEUTICS IN THE U.S., THROUGH 2007 ($/PATIENT/YEAR)

Table 31. MARKET FOR CROHN'S DISEASE AND ULCERATIVE COLITIS THERAPEUTICS IN THE U.S., THROUGH 2007 ($ BILLIONS)

MULTIPLE SCLEROSIS
Table 32. COST OF MULTIPLE SCLEROSIS THERAPEUTICS IN THE U.S., THROUGH 2007 ($/PATIENT/YEAR)

Table 33. MARKET FOR MULTIPLE SCLEROSIS THERAPEUTICS IN THE U.S., THROUGH 2007 ($ BILLIONS)

PSORIASIS
Table 34. COST OF PSORIASIS THERAPEUTICS IN THE U.S., THROUGH 2007 ($/PATIENT/YEAR)

Table 35. MARKET FOR PSORIASIS THERAPEUTICS IN THE U.S., THROUGH 2007 ($ BILLIONS)

RHEUMATOID ARTHRITIS
Table 36. COST OF RHEUMATOID ARTHRITIS THERAPEUTICS IN THE U.S., THROUGH 2007 ($/PATIENT/YEAR)

Table 37. MARKET FOR RHEUMATOID ARTHRITIS THERAPEUTICS IN THE U.S., THROUGH 2007 ($ BILLIONS)

INFECTIOUS DISEASE THERAPEUTICS
Table 38. PREVALENCE OF VIRAL DISEASES POTENTIALLY TREATED WITH ANTISENSE THERAPEUTICS, THROUGH 2007 (THOUSAND CASES)

Figure 17. PREVALENCE OF VIRAL DISEASE, 2000, 2002 AND 2007 (THOUSAND CASES)

Table 39 MARKET FOR INFECTIOUS DISEASE THERAPEUTICS, THROUGH 2007 ($ BILLIONS)

CYTOMEGALOVIRUS (CMV) RETINITIS
Table 40. COST OF CMV RETINITIS THERAPEUTICS IN THE U.S., THROUGH 2007 ($/PATIENT/YEAR)

Table 41. MARKET FOR CMV RETINITIS THERAPEUTICS IN THE U.S., THROUGH 2007 ($ MILLIONS)

HEPATITIS B VIRUS (HBV)
Table 42. COST OF HBV INFECTIONS AND CHRONIC DISEASE THERAPEUTICS IN THE U.S., THROUGH 2007 ($/PATIENT/YEAR)

Table 43. MARKET FOR HBV INFECTIONS AND CHRONIC DISEASE THERAPEUTICS IN THE U.S., THROUGH 2007 ($ BILLIONS)

HEPATITIS C VIRUS (HCV)
Table 44. COST OF HCV INFECTIONS AND CHRONIC DISEASE THERAPEUTICS IN THE U.S., THROUGH 2007 ($/PATIENT/YEAR)

Table 45. MARKET FOR HCV INFECTIONS AND CHRONIC DISEASE THERAPEUTICS IN THE U.S., THROUGH 2007 ($ BILLIONS)

HUMAN IMMUNODEFICIENCY VIRUS (HIV)
Table 46. COST OF HIV INFECTIONS THERAPEUTICS IN THE U.S., THROUGH 2007 ($/PATIENT/YEAR)

Table 47. MARKET FOR HIV INFECTIONS THERAPEUTICS IN THE U.S., THROUGH 2007 ($ BILLIONS)

HUMAN PAPILLOMAVIRUS (HPV)
Table 48. COST OF HPV INFECTIONS THERAPEUTICS IN THE U.S., THROUGH 2007 ($/PATIENT/YEAR)

Table 49. MARKET FOR HPV INFECTIONS THERAPEUTICS IN THE U.S., THROUGH 2007 ($ BILLIONS)

POLYCYSTIC KIDNEY THERAPEUTICS
Table 50. PREVALENCE OF POLYCYSTIC KIDNEY DISEASE, THROUGH 2007 (NUMBER OF CASES)

Table 51. COST OF POLYCYSTIC KIDNEY DISEASE THERAPEUTICS IN THE U.S., THROUGH 2007 ($/PATIENT/YEAR)

Table 52. MARKET FOR POLYCYSTIC KIDNEY DISEASE THERAPEUTICS IN THE U.S., THROUGH 2007 ($ BILLIONS)

RETINA DISORDERS THERAPEUTICS
Table 53. PREVALENCE OF RETINAL DISORDERS, THROUGH 2007 (THOUSAND CASES)

Figure 18. PREVALENCE OF RETINAL DISORDERS, 2000-2007 (THOUSAND CASES)

Table 54. MARKET FOR RETINAL DISORDERS THERAPEUTICS IN THE U.S., THROUGH 2007 ($ BILLIONS)

AGE-RELATED MACULAR DEGENERATION (AMD)
Table 55. COST OF AGE-RELATED MACULAR DEGENERATION THERAPEUTICS IN THE U.S., THROUGH 2007 ($/PATIENT/YEAR)

Table 56. MARKET FOR AGE-RELATED MACULAR DEGENERATION THERAPEUTICS IN THE U.S., THROUGH 2007 ($ BILLIONS)

DIABETIC RETINOPATHY (DR)
Table 57. COST OF DIABETIC RETINOPATHY THERAPEUTICS IN THE U.S., THROUGH 2007 ($/PATIENT/YEAR)

Table 58. MARKET FOR DIABETIC RETINOPATHY THERAPEUTICS IN THE U.S., THROUGH 2007 ($ BILLIONS)

PROLIFERATIVE VITREORETINOPATHY (PVR)
Table 59. COST OF PROLIFERATIVE VITREORETINOPATHY THERAPEUTICS IN THE U.S., THROUGH 2007 ($/PATIENT/YEAR)

Table 60. MARKET FOR PROLIFERATIVE VITREORETINOPATHY THERAPEUTICS IN THE U.S., THROUGH 2007 ($ BILLIONS)

POTENTIAL MARKETS FOR ANTISENSE THERAPEUTICS
CANCER

Cancer (Continued)
RESTENOSIS
Table 62. ANTISENSE ANTI-RESTENOSIS THERAPEUTICS MARKET, 2007 ($ MILLIONS)
TYPE 2 DIABETES
IMMUNOLOGICAL DISORDERS
Table 63. ANTISENSE IMMUNOLOGICAL DISORDER THERAPEUTICS MARKETS, 2007 ($ MILLIONS)
INFECTIOUS DISEASES
Table 64. ANTISENSE INFECTIOUS DISEASE THERAPEUTICS MARKET, 2007 ($ MILLIONS)
POLYCYSTIC KIDNEY DISEASE
Table 65. ANTISENSE POLYCYSTIC KIDNEY DISEASE THERAPEUTICS MARKET, 2007 ($ MILLIONS)
RETINAL DISORDERS
Table 66. ANTISENSE RETINAL DISORDERS THERAPEUTICS MARKET, 2007 ($ MILLIONS)
TOTAL POTENTIAL MARKET FOR ANTISENSE THERAPEUTICS
Table 67. POTENTIAL MARKET FOR ANTISENSE THERAPEUTICS, 2007 ($ MILLIONS)

NEW DEVELOPMENTS IN ANTISENSE TECHNOLOGY
THERAPEUTIC DISCOVERY, TARGET VALIDATION, AND GENE FUNCTION
Table 68. DEVELOPER OF DRUG DISCOVERY ANTISENSE APPLICATIONS
PATENTS
PATENT CATEGORIES
Chemistry
Drug Discovery
Table 69. U.S. ANTISENSE AND RELATED TECHNOLOGY PATENTS
Therapeutics
Other

ANTISENSE INDUSTRY STRUCTURE
WORLDWIDE DISTRIBUTION OF ANTISENSE THERAPEUTICS DEVELOPERS
Table 70. COMPANIES DEVELOPING ANTISENSE PRODUCTS

Table 70. (CONTINUED) Figure 19. WORLDWIDE DISTRIBUTION OF DEVELOPERS OF ANTISENSE THERAPEUTICS, 2002 (%)

APPLICATION OF ANTISENSE THERAPEUTICS
Figure 20. DISTRIBUTION OF ANTISENSE THERAPEUTICS BY APPLICATION, 2002 (%)

Table 71. APPLICATIONS FOR ANTISENSE THERAPEUTICS

DEVELOPMENT AND REGULATORY ENVIRONMENT OF ANTISENSE THERAPEUTICS
DEVELOPMENT OF THERAPEUTIC AGENTS
Table 72. DEVELOPMENT STAGES OF THERAPEUTIC AGENTS
The Development of Therapeutic Agents
Research and Discovery
Preclinical Development
Phase I Clinical Trials
Phase II Clinical Trials
Phase III Clinical Trials
Approval Phase
ANTISENSE THERAPEUTIC DEVELOPMENT
Figure 21. DISTRIBUTION OF ANTISENSE PRODUCTS DEVELOPMENT STAGE (%)

Figure 21. (CONTINUED) Table 73. STAGE OF DEVELOPMENT OF ANTISENSE PRODUCTS

Table 73. (CONTINUED)

STRATEGIC ALLIANCES AND PARTNERSHIP
ANGIOGENE INC.
Abbott Vascular
ANTISENSE PHARMA
Biognostik GmbH
ANTISENSE THERAPEUTICS
Isis Pharmaceuticals
Murdoch Children's Research Institute
AVI BIOPHARMA
Medtronic
Exelixis Inc.
EPIGENESIS PHARMACEUTICAL
Taisho Pharmaceuticals
Chiesi Farmaceutici S.P.A.
Hybridon
GENTA
Aventis
HYBRIDON
Epigenesis Pharmaceuticals
MethylGene
Micrologix Biotech
OriGenix Technologies
IMMUSOL
Chugai Pharma USA LLC
Vertex Pharmaceuticals
Novartis
ISIS PHARMACEUTICALS
Abbott Laboratories
Amgen Inc.
Celera Genomic Group
Elan Partnerships
Novartis Ophthalmic
METHYLGENE INC.
MGI Pharma
ONCOGENEX TECHNOLOGIES
Isis Pharmaceuticals
ORIGENIX TECHNOLOGY
RIBOZYME PHARMACEUTICALS
Archemix
STRATEGIES OF LEADING ANTISENSE COMPANIES

AEGERA THERAPEUTICS INC.
ANGIOGENE INC.
ANTISENSE PHARMA GMBH
ANTISENSE THERAPEUTICS LTD.
ATUGEN AG
AVI BIOPHARMA
BENITEC AUSTRALIA LIMITED
BIOGNOSTIK GMBH
ENZO THERAPEUTICS
EPIGENESIS PHARMACEUTICALS
EXEGENICS INC.
GENTA INC.
HYBRIDON INC.
IMMUSOL INC.
INEX PHARMACEUTICAL CORP.
ISIS PHARMACEUTICALS
LORUS THERAPEUTICS INC.
METHYLGENE INC.
MICROLOGIX BIOTECH INC.
NEOPHARM INC.
ONCOGENEX TECHNOLOGIES
ORIGENIX TECHNOLOGIES
PANACEA PHARMACEUTICALS
PATHECO A/S
RIBOZYME PHARMACEUTICALS INC.
SEQUITUR INC.
SALUS THERAPEUTICS
SALUS THERAPEUTICS (CONTINUED)

Table 74. COMPANY AND TYPE OF ANTISENSE PRODUCTS

PATENT SUMMARIES
AEGERA THERAPEUTICS
Table 75. ANTISENSE PATENT PORTFOLIO OF AEGERA THERAPEUTICS
ANGIOGENE INC.
Table 76. ANTISENSE PATENT PORTFOLIO OF ANGIOGENE
ANTISENSE PHARMA
Table 77. ANTISENSE PATENT PORTFOLIO OF ANTISENSE PHARMA
AVI BIOPHARMA
Table 78. ANTISENSE PATENT PORTFOLIO OF AVI BIOPHARMA Table 78. (CONTINUED)
EPIGENESIS PHARMACEUTICALS
Table 79. ANTISENSE PATENT PORTFOLIO OF EPIGENESIS
GENTA INC.
Table 80. ANTISENSE PATENT PORTFOLIO OF GENTA Table 80. (CONTINUED)
HYBRIDON INC.
Table 81. ANTISENSE PATENT PORTFOLIO OF HYBRIDON Table 81. (CONTINUED)
IMMUSOL INC.

ISIS PHARMACEUTICALS
Table 83. ANTISENSE PATENT PORTFOLIO OF ISIS PHARMACEUTICALS
LORUS THERAPEUTICS
Table 84. ANTISENSE PATENT PORTFOLIO OF LORUS THERAPEUTICS
METHYLGENE INC.
Table 85. ANTISENSE PATENT PORTFOLIO OF METHYLGENE Table 85. (CONTINUED)
RIBOZYME PHARMACEUTICALS
Table 86. ANTISENSE PATENT PORTFOLIO OF RIBOZYME PHARMACEUTICALS

LIST OF TABLES

Table 1 ANTISENSE PRODUCTS FOR TREATMENT OF CANCER

Table 2 ANTISENSE PRODUCTS FOR TREATMENT OF RESTENOSIS

Table 3 ANTISENSE PRODUCTS FOR TREATMENT OF TYPE 2 DIABETES

Table 4 ANTISENSE PRODUCTS FOR TREATMENT OF IMMUNOLOGICAL DISORDERS

Table 5 ANTISENSE PRODUCTS FOR TREATMENT OF INFECTIOUS DISEASES

Table 6 ANTISENSE PRODUCTS FOR TREATMENT OF RETINAL DISORDERS

Table 7 CLINICAL TRIAL STATUS OF ANTISENSE THERAPEUTIC ONCOMYC

Table 8 CLINICAL TRIAL STATUS OF ANTISENSE THERAPEUTIC GENASENSE™

Table 9 CLINICAL TRIAL STATUS OF ANTISENSE THERAPEUTIC GEM®231

Table 10 CLINICAL TRIAL STATUS OF ANTISENSE THERAPEUTIC AFFINITAC™

Table 11 CLINICAL TRIAL STATUS OF ANTISENSE THERAPEUTIC ALICAFORSEN

Table 12 CLINICAL TRIAL STATUS OF ANTISENSE THERAPEUTIC ISIS 2503

Table 13 CLINICAL TRIAL STATUS OF ANTISENSE THERAPEUTIC ISIS 104828

Table 14 CLINICAL TRIAL STATUS OF ANTISENSE THERAPEUTIC GTI 2040

Table 15 CLINICAL TRIAL STATUS OF ANTISENSE THERAPEUTIC OGX-011

Table 16 CLINICAL TRIAL STATUS OF ANTISENSE THERAPEUTIC ANGIOZYME®

Table 17 INCIDENCE OF CANCER IN THE U.S., THROUGH 2007 (NUMBER OF CASES)

Table 18 MARKET FOR CANCER THERAPEUTICS IN THE U.S., THROUGH 2007 ($ BILLIONS)

Table 19 COST OF CANCER THERAPEUTICS IN THE U.S., THROUGH 2007 ($/PATIENT/YEAR)

Table 20 STENTS USED IN ANGIOPLASTY PROCEDURES, THROUGH 2007 (MILLIONS OF UNITS)

Table 21 COST OF STENTS IN THE U.S., THROUGH 2007 ($/STENT)

Table 22 MARKET FOR STENTS IN THE U.S., THROUGH 2007 ($ BILLIONS)

Table 23 PREVALENCE OF TYPE 2 DIABETES, THROUGH 2007 (THOUSANDS OF CASES)

Table 24 COST OF TYPE 2 DIABETES THERAPEUTICS IN THE U.S., THROUGH 2007 ($/PATIENT/YEAR)

Table 25 MARKET FOR TYPE 2 DIABETES THERAPEUTICS IN THE U.S., THROUGH 2007 ($ BILLIONS)

Table 26 PREVALENCE OF IMMUNOLOGICAL DISORDERS POTENTIAL TREATED WITH ANTISENSE THERAPEUTICS, THROUGH 2007 (THOUSAND CASES)

Table 27 MARKET FOR THERAPEUTICS FOR IMMUNOLOGICAL DISORDERS, THROUGH 2007 ($ BILLIONS)

Table 28 COST OF ASTHMA THERAPEUTICS IN THE U.S., THROUGH 2007 ($/PATIENT/YEAR)

Table 29 MARKET FOR ASTHMA THERAPEUTICS IN THE U.S., THROUGH 2007 ($ BILLIONS)

Table 30 COST OF CROHN'S DISEASE AND ULCERATIVE COLITIS THERAPEUTICS IN THE U.S., THROUGH 2007 ($/PATIENT/YEAR)

Table 31 MARKET FOR CROHN'S DISEASE AND ULCERATIVE COLITIS THERAPEUTICS IN THE U.S., THROUGH 2007 ($ BILLIONS)

Table 32 COST OF MULTIPLE SCLEROSIS THERAPEUTICS IN THE U.S., THROUGH 2007 ($/PATIENT/YEAR)

Table 33 MARKET FOR MULTIPLE SCLEROSIS THERAPEUTICS IN THE U.S., THROUGH 2007 ($ BILLIONS)

Table 34 COST OF PSORIASIS THERAPEUTICS IN THE U.S., THROUGH 2007 ($/PATIENT/YEAR)

Table 35 MARKET FOR PSORIASIS THERAPEUTICS IN THE U.S., THROUGH 2007 ($ BILLIONS)

Table 36 COST OF RHEUMATOID ARTHRITIS THERAPEUTICS IN THE U.S., THROUGH 2007 ($/PATIENT/YEAR)

Table 37 MARKET FOR RHEUMATOID ARTHRITIS THERAPEUTICS IN THE U.S., THROUGH 2007 ($ BILLIONS)

Table 38 PREVALENCE OF VIRAL DISEASES POTENTIALLY TREATED WITH ANTISENSE THERAPEUTICS, THROUGH 2007 (THOUSANDS OF CASES)

Table 39 MARKET FOR INFECTIOUS DISEASE THERAPEUTICS, THROUGH 2007 ($ BILLIONS)

Table 40 COST OF CMV RETINITIS THERAPEUTICS IN THE U.S., THROUGH 2007 ($/PATIENT/YEAR)

Table 41 MARKET FOR CMV RETINITIS THERAPEUTICS IN THE U.S., THROUGH 2007 ($ MILLIONS)

Table 42 COST OF HBV INFECTIONS AND CHRONIC DISEASE THERAPEUTICS IN THE U.S., THROUGH 2007 ($/PATIENT/YEAR)

Table 43 MARKET FOR HBV INFECTIONS AND CHRONIC DISEASE THERAPEUTICS IN THE U.S., THROUGH 2007 ($ BILLIONS)

Table 44 COST OF HCV INFECTIONS AND CHRONIC DISEASE THERAPEUTICS IN THE U.S., THROUGH 2007 ($/PATIENT/YEAR)

Table 45 MARKET FOR HCV INFECTIONS AND CHRONIC DISEASE THERAPEUTICS IN THE U.S., THROUGH 2007 ($ BILLIONS)

Table 46 COST OF HIV INFECTIONS THERAPEUTICS IN THE U.S., THROUGH 2007 ($/PATIENT/YEAR)

Table 47 MARKET FOR HIV INFECTIONS THERAPEUTICS IN THE U.S., THROUGH 2007 ($ BILLIONS)

Table 48 COST OF HPV INFECTIONS THERAPEUTICS IN THE U.S., THROUGH 2007 ($/PATIENT/YEAR)

Table 49 MARKET FOR HPV INFECTIONS THERAPEUTICS IN THE U.S., THROUGH 2007 ($ BILLIONS)

Table 50 PREVALENCE OF POLYCYSTIC KIDNEY DISEASE, THROUGH 2007 (CASES)

Table 51 COST OF POLYCYSTIC KIDNEY DISEASE THERAPEUTICS IN THE U.S., THROUGH 2007 ($/PATIENT/YEAR)

Table 52 MARKET FOR POLYCYSTIC KIDNEY DISEASE THERAPEUTICS IN THE U.S., THROUGH 2007 ($ BILLIONS)

Table 53 PREVALENCE OF RETINAL DISORDERS, THROUGH 2007 (THOUSAND CASES)

Table 54 MARKET FOR RETINAL DISORDERS THERAPEUTICS IN THE U.S., THROUGH 2007 ($ BILLIONS)

Table 55 COST OF AGE-RELATED MACULAR DEGENERATION THERAPEUTICS IN THE U.S., THROUGH 2007 ($/PATIENT/YEAR)

Table 56 MARKET FOR AGE-RELATED MACULAR DEGENERATION THERAPEUTICS IN THE U.S., THROUGH 2007 ($ BILLIONS)

Table 57 COST OF DIABETIC RETINOPATHY THERAPEUTICS IN THE U.S., THROUGH 2007 ($/PATIENT/YEAR)

Table 58 MARKET FOR DIABETIC RETINOPATHY THERAPEUTICS IN THE U.S., THROUGH 2007 ($ BILLIONS)

Table 59 COST OF PROLIFERATIVE VITREORETINOPATHY THERAPEUTICS IN THE U.S., THROUGH 2007 ($/PATIENT/YEAR)

Table 60 MARKET FOR PROLIFERATIVE VITREORETINOPATHY THERAPEUTICS IN THE U.S., THROUGH 2007 ($ BILLIONS)

Table 61 ANTISENSE CANCER THERAPEUTICS MARKET, 2007 ($ MILLIONS)

Table 62 ANTISENSE ANTI-RESTENOSIS THERAPEUTICS MARKET, 2007 ($ MILLIONS)

Table 63 ANTISENSE IMMUNOLOGICAL DISORDER THERAPEUTICS MARKETS, 2007 ($ MILLIONS)

Table 64 ANTISENSE INFECTIOUS DISEASE THERAPEUTICS MARKET, 2007 ($ MILLIONS)

Table 65 ANTISENSE POLYCYSTIC KIDNEY DISEASE THERAPEUTICS MARKET, 2007 ($ MILLIONS)

Table 66 ANTISENSE RETINAL DISORDERS THERAPEUTICS MARKET, 2007 ($ MILLIONS)

Table 67 POTENTIAL MARKET FOR ANTISENSE THERAPEUTICS, 2007 ($ MILLIONS)

Table 68 DEVELOPER OF DRUG DISCOVERY ANTISENSE APPLICATIONS

Table 69 U.S. ANTISENSE AND RELATED TECHNOLOGY PATENTS

Table 70 COMPANIES DEVELOPING ANTISENSE PRODUCTS

Table 71 APPLICATIONS FOR ANTISENSE THERAPEUTICS

Table 72 DEVELOPMENT STAGES OF THERAPEUTIC AGENTS

Table 73 STAGE OF DEVELOPMENT OF ANTISENSE PRODUCTS

Table 74 COMPANY AND TYPE OF ANTISENSE PRODUCTS

Table 75 ANTISENSE PATENT PORTFOLIO OF AEGERA THERAPEUTICS

Table 76 ANTISENSE PATENT PORTFOLIO OF ANGIOGENE

Table 77 ANTISENSE PATENT PORTFOLIO OF ANTISENSE PHARMA

Table 78 ANTISENSE PATENT PORTFOLIO OF AVI BIOPHARMA

Table 79 ANTISENSE PATENT PORTFOLIO OF EPIGENESIS

Table 80 ANTISENSE PATENT PORTFOLIO OF GENTA

Table 81 ANTISENSE PATENT PORTFOLIO OF HYBRIDON

Table 82 ANTISENSE PATENT PORTFOLIO OF IMMUSOL

Table 83 ANTISENSE PATENT PORTFOLIO OF ISIS PHARMACEUTICALS

Table 84 ANTISENSE PATENT PORTFOLIO OF LORUS THERAPEUTICS

Table 85 ANTISENSE PATENT PORTFOLIO OF METHYLGENE

Table 86 ANTISENSE PATENT PORTFOLIO OF RIBOZYME PHARMACEUTICALS

LIST OF FIGURES

Figure 1 SIGNALING TO BEGIN EXPRESSION OF A GENE

Figure 2 UNWINDING AND SEPARATION OF DNA STRANDS

Figure 3 RNA TRANSCRIPTION

Figure 4 RNA SPLICING

Figure 5 TRANSLATION OF A PROTEIN

Figure 6 HYBRIDIZATION OF ANTISENSE OLIGO TO MRNA

Figure 7 HYBRIDIZED OLIGO INTERFERES WITH SPLICING

Figure 8 ANTISENSE OLIGO INHIBITION OF RIBOSOMES

Figure 9 RNASE H DIGESTION OF RNA-DNA DUPLEX

Figure 10 STRUCTURE OF DNA AND RNA

Figure 11 FIRST GENERATION OF ANTISENSE MOLECULES

Figure 12 SECOND GENERATION ANTISENSE MODIFICATIONS

Figure 13 RIBOZYMES

Figure 14 NUMBER OF ANTISENSE SCIENTIFIC PUBLICATIONS, 1973-2002

Figure 15 INCIDENCE OF TYPES OF CANCERS, 2002, 2002 AND 2007 (NUMBER OF CASES)

Figure 16 PREVALENCE OF IMMUNOLOGICAL DISORDERS, 2002, 2002 AND 2007 (THOUSAND CASES)

Figure 17 PREVALENCE OF VIRAL DISEASE, 2000, 2002 AND 2007 (THOUSAND CASES)

Figure 18 PREVALENCE OF RETINAL DISORDERS, 2000, 2002 AND 2007 (THOUSAND CASES)

Figure 19 WORLDWIDE DISTRIBUTION OF DEVELOPERS OF ANTISENSE THERAPEUTICS, 2002 (%)

Figure 20 DISTRIBUTION OF ANTISENSE THERAPEUTICS BY APPLICATION, 2002 (%)

Figure 21 DISTRIBUTION OF ANTISENSE PRODUCTS DEVELOPMENT STAGE (%)