CONSOLIDATED STATEMENTS OF CASH FLOWS - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Operating activities:
Net income (loss)	$ (28,597)	$ (479,743)	$ 287,259
Adjustments to reconcile net income (loss) to net cash used in operating activities:
Depreciation	15,487	13,365	12,540
Amortization of right-of-use operating lease assets	1,721	1,731	1,542
Amortization of patents	2,352	2,064	1,912
Amortization of premium (discount) on investments, net	17,776	11,521	(7,485)
Amortization of debt issuance costs	4,958	3,255	2,945
Stock-based compensation expense	120,678	230,117	146,574
Loss on early retirement of debt	8,627	0	66,196
Gain on investments	(1,092)	(16,540)	(192)
Deferred income taxes, including changes in valuation allowance	0	341,729	911
Non-cash losses related to patents	2,707	1,948	2,226
Changes in operating assets and liabilities:
Contracts receivable	14,308	(13,170)	(47,674)
Inventories	(2,841)	(1,261)	(5,411)
Other current and long-term assets	(877)	(9,975)	(44,659)
Long-term income taxes receivable (payable)	1,008	(89)	8,418
Accounts payable	(6,000)	(2,755)	(16,343)
Income taxes	(1,288)	(31,190)	31,656
Accrued compensation	(26,918)	28,371	8,089
Accrued liabilities and other current liabilities	(8,381)	32,424	16,406
Deferred contract revenue	(82,829)	(75,910)	(119,283)
Net cash used in operating activities	30,799	35,892	345,627
Investing activities:
Purchases of short-term investments	(1,124,193)	(1,570,410)	(1,946,726)
Proceeds from sale of short-term investments	1,344,185	1,885,935	1,951,734
Purchases of property, plant and equipment	(11,955)	(35,120)	(30,905)
Acquisition of licenses and other assets, net	(5,946)	(5,928)	(5,377)
Purchases of strategic investments	(7,185)	0	(10,000)
Net cash provided by (used in) investing activities	194,906	274,477	(41,274)
Financing activities:
Proceeds from equity, net	11,565	52,036	119,657
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options	(16,725)	(13,411)	(19,242)
Repurchase of $247.9 million principal amount of 1 percent convertible senior notes	(256,963)	0	0
Repayment of remaining principal amount of 1 percent convertible senior notes at maturity	(61,967)	0	0
Proceeds from issuance of warrants	89,752	0	56,110
Purchase of note hedges	(136,620)	0	(108,684)
Repurchases and retirements of common stock	0	(90,548)	(34,392)
Purchase of noncontrolling interest of Akcea Therapeutics, Inc., including cash payments for cancellation of Akcea Therapeutics, Inc. equity awards	0	(544,686)	0
Principal payments on line of credit	0	0	(12,500)
Net cash provided by (used in) financing activities	245,933	(596,609)	100,021
Effects of exchange rates on cash	(111)	617	93
Net increase (decrease) in cash and cash equivalents	471,527	(285,623)	404,467
Cash and cash equivalents at beginning of year	397,664	683,287	278,820
Cash and cash equivalents at end of year	869,191	397,664	683,287
Supplemental disclosures of cash flow information:
Interest paid	4,778	6,247	9,870
Income taxes paid	38	25,855	9,041
Supplemental disclosures of non-cash investing and financing activities:
Right-of-use assets obtained in exchange for lease liabilities	6,641	2,149	14,178
Amounts accrued for capital and patent expenditures	705	4,059	3,126
0.125 percent convertible senior notes principal issued related to our December 2019 debt exchange/issuance	0	0	439,326
1 percent convertible senior notes principal extinguished related to our December 2019 debt exchange	0	0	375,590
0 Percent Convertible Senior Notes [Member]
Financing activities:
Proceeds from the issuance of convertible senior notes	632,500	0	0
Convertible senior notes issuance costs	(15,609)	0	0
0.125 Percent Convertible Senior Notes [Member]
Financing activities:
Proceeds from the issuance of convertible senior notes	0	0	109,500
Convertible senior notes issuance costs	$ 0	$ 0	$ (10,428)