| Isis Pharmaceuticals' 2014 Annual Report | I |
| Chairman’s Letter | II |
| Form 10-K | V |
| Forward-Looking Statements | 1 |
| Trademarks | 1 |
| Corporate Information | 1 |
| Part I | 3 |
| Part II | 65 |
| 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities | 65 |
| 6. Selected Financial Data | 66 |
| 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations | 66 |
| 7A. Quantitative and Qualitative Disclosures About Market Risk | 88 |
| 8. Financial Statements and Supplementary Data | 88 |
| 9. Changes in and Disagreements With Accountants on Accounting and Financial Disclosure | 88 |
| 9A. Controls and Procedures | 88 |
| 9B. Other Information | 91 |
| Part III | 91 |
| 10. Directors, Executive Officers and Corporate Governance | 91 |
| 11. Executive Compensation | 93 |
| 12. Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters | 120 |
| 13. Certain Relationships and Related Transactions, and Director Independence | 123 |
| 14. Principal Accounting Fees and Services | 124 |
| Part IV | 126 |
| Corporate Information | 185 |