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CONSOLIDATED STATEMENTS OF CASH FLOWS - USD ($) $ in Thousands | 3 Months Ended | 12 Months Ended
--- | --- | ---
Dec. 31, 2022 | Dec. 31, 2021 | Mar. 31, 2020 | Dec. 31, 2022 | Dec. 31, 2021 | Dec. 31, 2020 | Dec. 31, 2019
Operating activities: |  |  |  |  |  |  |  |
Net loss | $ (52,430) | [1] | $ 224,613 |  | $ (269,722) | $ (28,597) | $ (479,743) |
Adjustments to reconcile net loss to net cash provided by (used in) operating activities: |  |  |  |  |  |  |  |
Depreciation |  |  |  |  | 14,328 | 15,487 | 13,365 |
Amortization of right-of-use operating lease assets |  |  |  |  | 5,362 | 1,721 | 1,731 |
Amortization of other assets |  |  |  |  | 2,415 | 2,352 | 2,064 |
Amortization of premium on investments, net |  |  |  |  | 7,389 | 17,776 | 11,521 |
Amortization of debt issuance costs |  |  |  |  | 5,373 | 4,958 | 3,255 |
Stock-based compensation expense |  |  |  |  | 100,264 | 120,678 | 230,117 |
Loss on early retirement of debt |  |  |  |  | 0 | 8,627 | 0 |
Non-cash losses related to disposal of property, plant and equipment |  |  |  |  | 531 | 0 | 0 |
Gain on sale of real estate assets | (150,100) |  |  |  | (150,135) | 0 | 0 |
Gain on investments |  |  |  |  | 224 | (1,092) | (16,540) |
Deferred income taxes, including changes in valuation allowance |  |  |  |  | 0 | 0 | 341,729 |
Non-cash losses related to other assets |  |  |  |  | 2,030 | 2,707 | 1,948 |
Changes in operating assets and liabilities: |  |  |  |  |  |  |  |
Contracts receivable |  |  |  |  | 36,358 | 14,308 | (13,170) |
Inventories |  |  |  |  | 2,773 | (2,841) | (1,261) |
Other current and long-term assets |  |  |  |  | (24,682) | (877) | (9,975) |
Long-term income taxes receivable (payable) |  |  |  |  | 0 | 1,008 | (89) |
Accounts payable |  |  |  |  | 1,094 | (6,000) | (2,755) |
Income taxes |  |  |  |  | 6,213 | (1,288) | (31,190) |
Accrued compensation |  |  |  |  | 10,368 | (26,918) | 28,371 |
Accrued liabilities and other current liabilities |  |  |  |  | 46,695 | (8,381) | 32,424 |
Deferred contract revenue |  |  |  |  | (71,248) | (82,829) | (75,910) |
Net cash provided by (used in) operating activities |  |  |  |  | (274,370) | 30,799 | 35,892 |
Investing activities: |  |  |  |  |  |  |  |
Purchases of short-term investments |  |  |  |  | (1,485,772) | (1,124,193) | (1,570,410) |
Proceeds from sale of short-term investments |  |  |  |  | 989,152 | 1,344,185 | 1,885,935 |
Purchases of property, plant and equipment |  |  |  |  | (15,721) | (11,955) | (35,120) |
Proceeds from sale of real estate assets |  |  |  |  | 254,083 | 0 | 0 |
Acquisition of licenses and other assets, net |  |  |  |  | (4,378) | (5,946) | (5,928) |
Purchases of strategic investments |  |  |  |  | 0 | (7,185) | 0 |
Net cash provided by (used in) investing activities |  |  |  |  | (262,636) | 194,906 | 274,477 |
Financing activities: |  |  |  |  |  |  |  |
Proceeds from equity, net |  |  |  |  | 6,373 | 11,565 | 52,036 |
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options |  |  |  |  | (10,953) | (16,725) | (13,411) |
Proceeds from the issuance of 0 percent convertible senior notes |  |  |  |  | 0 | 632,500 | 0 |
Royalty monetization issuance costs |  |  |  |  | (29) | 0 | 0 |
0 percent convertible senior notes issuance costs |  |  |  |  | 0 | (15,609) | 0 |
Repurchase of $247.9 million principal amount of 1 percent convertible senior notes |  |  |  |  | 0 | (256,963) | 0 |
Repayment of remaining principal amount of 1 percent convertible senior notes at maturity |  |  |  |  | 0 | (61,967) | 0 |
Proceeds from issuance of warrants |  |  |  |  | 0 | 89,752 | 0 |
Purchase of note hedges |  |  |  |  | 0 | (136,620) | 0 |
Repurchases and retirements of common stock |  |  |  | $ (90,500) | 0 | 0 | (90,548) | $ (34,400)
Principal payments on debt |  |  |  |  | (50,686) | 0 | 0 |
Purchase of noncontrolling interest of Akcea Therapeutics, Inc., including cash payments for cancellation of Akcea Therapeutics, Inc. equity awards |  |  |  |  | 0 | 0 | (544,686) |
Net cash provided by (used in) financing activities |  |  |  |  | (55,295) | 245,933 | (596,609) |
Effects of exchange rates on cash |  |  |  |  | (418) | (111) | 617 |
Net increase (decrease) in cash and cash equivalents |  |  |  |  | (592,719) | 471,527 | (285,623) |
Cash and cash equivalents at beginning of year |  |  |  | $ 683,287 | 869,191 | 397,664 | 683,287 |
Cash and cash equivalents at end of year | $ 276,472 |  | $ 869,191 |  | 276,472 | 869,191 | 397,664 | $ 683,287
Supplemental disclosures of cash flow information: |  |  |  |  |  |  |  |
Interest paid |  |  |  |  | 2,898 | 4,778 | 6,247 |
Income taxes paid |  |  |  |  | 5,010 | 38 | 25,855 |
Supplemental disclosures of non-cash investing and financing activities: |  |  |  |  |  |  |  |
Right-of-use assets obtained in exchange for lease liabilities |  |  |  |  | 168,931 | 6,641 | 2,149 |
Amounts accrued for capital and patent expenditures |  |  |  |  | $ 4,767 | $ 705 | $ 4,059 |
[1] | Our net loss for the three months ended December 31, 2022 includes the $150.1 million gain we recognized from the sale and leaseback transaction for our headquarters in Carlsbad, California.

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- Definition The cash outflow to repay long-term debt that is wholly or partially secured by collateral. Excludes repayments of tax exempt secured debt. + References Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef -Publisher FASB -Name Accounting Standards Codification -Topic 230 -SubTopic 10 -Section 45 -Paragraph 15 -Subparagraph (b) -URI https://asc.fasb.org/extlink&oid=126954810&loc=d3e3291-108585 + Details
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- Definition Amount of increase in right-of-use asset obtained in exchange for operating lease liability. + References Reference 1: http://www.xbrl.org/2003/role/exampleRef -Publisher FASB -Name Accounting Standards Codification -Topic 842 -SubTopic 20 -Section 55 -Paragraph 53 -URI https://asc.fasb.org/extlink&oid=123414884&loc=SL77918982-209971 Reference 2: http://www.xbrl.org/2003/role/disclosureRef -Publisher FASB -Name Accounting Standards Codification -Topic 842 -SubTopic 20 -Section 50 -Paragraph 4 -Subparagraph (g)(2) -URI https://asc.fasb.org/extlink&oid=128292326&loc=SL77918686-209980 + Details
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- Definition Amount of gain (loss) on sale and leaseback transaction from transfer of asset accounted for as sale. + References Reference 1: http://www.xbrl.org/2003/role/disclosureRef -Publisher FASB -Name Accounting Standards Codification -Topic 842 -SubTopic 40 -Section 50 -Paragraph 2 -Subparagraph (b) -URI https://asc.fasb.org/extlink&oid=128295416&loc=SL77919786-209982 Reference 2: http://www.xbrl.org/2003/role/exampleRef -Publisher FASB -Name Accounting Standards Codification -Topic 842 -SubTopic 20 -Section 55 -Paragraph 53 -URI https://asc.fasb.org/extlink&oid=123414884&loc=SL77918982-209971 Reference 3: http://www.xbrl.org/2003/role/disclosureRef -Publisher FASB -Name Accounting Standards Codification -Topic 842 -SubTopic 20 -Section 50 -Paragraph 4 -Subparagraph (f) -URI https://asc.fasb.org/extlink&oid=128292326&loc=SL77918686-209980 + Details
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- Definition Amount of noncash expense for share-based payment arrangement. + References Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef -Publisher FASB -Name Accounting Standards Codification -Topic 230 -SubTopic 10 -Section 45 -Paragraph 28 -Subparagraph (a) -URI https://asc.fasb.org/extlink&oid=126954810&loc=d3e3602-108585 + Details
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