CONSOLIDATED STATEMENTS OF CASH FLOWS - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2015	Dec. 31, 2014	Dec. 31, 2013
Operating activities:
Net loss	$ (88,278)	$ (38,984)	$ (60,644)
Adjustments to reconcile net loss to net cash provided by operating activities:
Depreciation	6,984	6,380	6,591
Amortization of patents	1,381	1,142	1,184
Amortization of licenses	1,873	1,882	2,007
Amortization of premium on investments, net	7,812	7,470	5,572
Amortization of debt issuance costs	1,133	595	415
Amortization of long-term financing liability for leased facility	6,665	6,622	6,567
Share-based compensation expense	59,314	31,383	11,418
Gain on investment in Regulus Therapeutics Inc.	(20,211)	(19,902)	0
Loss on early retirement of debt	0	8,292	0
Gain on investments, net	(75)	(1,256)	(2,378)
Non-cash losses related to patents, licensing and property, plant and equipment	1,881	1,305	6,306
Tax benefit from other unrealized gains on securities	0	(12,835)	(5,914)
Changes in operating assets and liabilities:
Contracts receivable	(7,453)	7,199	(10,580)
Inventories	(609)	1,743	(1,912)
Other current and long-term assets	(4,319)	(1,750)	(1,091)
Accounts payable	9,211	4,824	66
Income taxes	0	(4,034)	0
Accrued compensation	3,763	134	4,290
Deferred rent	205	153	217
Accrued liabilities	(2,345)	8,358	6,691
Deferred contract revenue	22,118	(11,415)	88,344
Net cash provided by operating activities	21,125	6,285	63,493
Investing activities:
Purchases of short-term investments	(493,467)	(391,883)	(425,554)
Proceeds from the sale of short-term investments	419,584	294,727	172,762
Purchases of property, plant and equipment	(7,692)	(7,518)	(1,552)
Acquisition of licenses and other assets, net	(4,056)	(3,586)	(3,810)
Proceeds from the sale of Regulus Therapeutics, Inc.	25,527	22,949	0
Proceeds from the sale of strategic investments	52	2,463	2,428
Net cash used in investing activities	(60,052)	(82,848)	(255,726)
Financing activities:
Proceeds from equity awards	24,888	23,071	62,958
Proceeds from issuance of 1 percent convertible senior notes, net of issuance costs	0	487,035	0
Repurchase of $140 million principal amount of the 2 3/4 percent convertible senior notes	0	(441,394)	0
Proceeds from borrowing on line of credit facility	8,500	0	0
Proceeds from public common stock offering	0	0	173,292
Proceeds from equipment financing arrangement	0	0	2,513
Excess tax benefits from share-based compensation awards	396	1,463	0
Principal payments on debt and capital lease obligations	(9,058)	(10,587)	(11,039)
Net cash provided by financing activities	24,726	59,588	227,724
Net (decrease) increase in cash and cash equivalents	(14,201)	(16,975)	35,491
Cash and cash equivalents at beginning of year	142,998	159,973	124,482
Cash and cash equivalents at end of year	128,797	142,998	159,973
Supplemental disclosures of cash flow information:
Interest paid	6,800	6,353	6,000
Supplemental disclosures of non-cash investing and financing activities:
Amounts accrued for capital and patent expenditures	1,162	2,151	704
2 3/4 Percent Convertible Senior Notes [Member]
Adjustments to reconcile net loss to net cash provided by operating activities:
Amortization of convertible notes discount	2,347	6,723	6,344
1 Percent Convertible Senior Notes [Member]
Adjustments to reconcile net loss to net cash provided by operating activities:
Amortization of convertible notes discount	$ 19,728	$ 2,256	$ 0