CONSOLIDATED STATEMENTS OF CASH FLOWS - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2016	Dec. 31, 2015	Dec. 31, 2014
Operating activities:
Net loss	$ (86,556)	$ (88,278)	$ (38,984)
Adjustments to reconcile net loss to net cash provided by (used in) operating activities:
Depreciation	7,481	6,984	6,380
Amortization of patents	1,552	1,381	1,142
Amortization of licenses	0	1,873	1,882
Amortization of premium on investments, net	6,813	7,812	7,470
Amortization of debt issuance costs	1,225	1,133	595
Amortization of long-term financing liability for leased facility	6,693	6,665	6,622
Share-based compensation expense	72,108	59,314	31,383
Gain on investment in Regulus Therapeutics Inc.	0	(20,211)	(19,902)
Loss on early retirement of debt	3,983	0	8,292
Gain on investments, net	(56)	(75)	(1,256)
Non-cash losses related to patents, licensing and property, plant and equipment	2,297	1,881	1,305
Tax benefit from other unrealized gains on securities	0	0	(12,835)
Changes in operating assets and liabilities:
Contracts receivable	(96,687)	(7,453)	7,199
Inventories	(590)	(609)	1,743
Other current and long-term assets	1,659	(4,319)	(1,750)
Accounts payable	(10,677)	9,211	4,824
Income taxes	1,069	0	(4,034)
Accrued compensation	8,121	3,763	134
Deferred rent	125	205	153
Accrued liabilities	4,595	(2,345)	8,358
Deferred contract revenue	(59,150)	22,118	(11,415)
Net cash provided by (used in) operating activities	(112,105)	21,125	6,285
Investing activities:
Purchases of short-term investments	(300,912)	(493,467)	(391,883)
Proceeds from the sale of short-term investments	364,572	419,584	294,727
Purchases of property, plant and equipment	(7,107)	(7,692)	(7,518)
Acquisition of licenses and other assets, net	(4,421)	(4,056)	(3,586)
Proceeds from the sale of Regulus Therapeutics, Inc.	4,467	25,527	22,949
Proceeds from the sale of strategic investments	0	52	2,463
Net cash provided by (used in) investing activities	56,599	(60,052)	(82,848)
Financing activities:
Proceeds from equity, net	12,599	24,888	23,071
Proceeds from issuance of 1 percent convertible senior notes, net of issuance costs	0	0	487,035
Repurchase of $140 million of the principal amount of the 2 3/4 percent convertible senior notes	0	0	(441,394)
Proceeds from borrowing on line of credit facility	4,000	8,500	0
Excess tax benefits from share-based compensation awards	1,861	396	1,463
Principal payments on debt and capital lease obligations	(7,066)	(9,058)	(10,587)
Net cash provided by financing activities	11,394	24,726	59,588
Net decrease in cash and cash equivalents	(44,112)	(14,201)	(16,975)
Cash and cash equivalents at beginning of year	128,797	142,998	159,973
Cash and cash equivalents at end of year	84,685	128,797	142,998
Supplemental disclosures of cash flow information:
Interest paid	7,313	6,800	6,353
Supplemental disclosures of non-cash investing and financing activities:
Amounts accrued for capital and patent expenditures	3,439	1,162	2,151
1 percent convertible senior notes principal issued related to our December 2016 debt exchange	185,450	0	0
2 3/4 percent convertible senior notes principal extinguished related to our December 2016 debt exchange	61,099	0	0
2 3/4 Percent Convertible Senior Notes [Member]
Adjustments to reconcile net loss to net cash provided by (used in) operating activities:
Amortization of senior convertible notes discount	2,564	2,347	6,723
1 Percent Convertible Senior Notes [Member]
Adjustments to reconcile net loss to net cash provided by (used in) operating activities:
Amortization of senior convertible notes discount	$ 21,326	$ 19,728	$ 2,256