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Employee service share based compensation nonvested awards compensation cost expected to be recognized year three.

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Employee service share based compensation nonvested awards compensation cost expected to be recognized year two.

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Employee service share-based compensation nonvested awards compensation cost expected to be recognized next year.

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Represents percentage of common stock shares beginning.

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Amount of expense for award under share-based payment arrangement. Excludes amount capitalized.

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Amount of cost not yet recognized for nonvested award under share-based payment arrangement.

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Weighted average purchase price of capital shares purchased through an employee stock ownership plan.

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Period over which grantee's right to exercise award under share-based payment arrangement is no longer contingent on satisfaction of service or performance condition, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days. Includes, but is not limited to, combination of market, performance or service condition.

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The weighted average fair value at grant date for nonvested equity-based awards issued during the period on other than stock (or unit) option plans (for example, phantom stock or unit plan, stock or unit appreciation rights plan, performance target plan).

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The estimated dividend rate (a percentage of the share price) to be paid (expected dividends) to holders of the underlying shares over the option's term.

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The highest quantity of shares an employee can purchase under the plan per period.

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Number of shares authorized for issuance under share-based payment arrangement.

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The difference between the maximum number of shares (or other type of equity) authorized for issuance under the plan (including the effects of amendments and adjustments), and the sum of: 1) the number of shares (or other type of equity) already issued upon exercise of options or other equity-based awards under the plan; and 2) shares (or other type of equity) reserved for issuance on granting of outstanding awards, net of cancellations and forfeitures, if applicable.

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Amount of accumulated difference between fair value of underlying shares on dates of exercise and exercise price on options exercised (or share units converted) into shares.

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Gross number of share options (or share units) granted during the period.

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The weighted average grant-date fair value of options granted during the reporting period as calculated by applying the disclosed option pricing methodology.

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Number of fully vested and expected to vest options outstanding that can be converted into shares under option plan. Includes, but is not limited to, unvested options for which requisite service period has not been rendered but that are expected to vest based on achievement of performance condition, if forfeitures are recognized when they occur.

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Weighted-average exercise price, at which grantee can acquire shares reserved for issuance, for fully vested and expected to vest options outstanding. Includes, but is not limited to, unvested options for which requisite service period has not been rendered but that are expected to vest based on achievement of performance condition, if forfeitures are recognized when they occur.

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Percentage of vesting of award under share-based payment arrangement.

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Period from grant date that an equity-based award expires, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.

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Amount of difference between fair value of the underlying shares reserved for issuance and exercise price of vested portions of options outstanding and currently exercisable.

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Weighted average remaining contractual term for vested portions of options outstanding and currently exercisable or convertible, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.

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Weighted average remaining contractual term for fully vested and expected to vest options outstanding, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days. Includes, but is not limited to, unvested options for which requisite service period has not been rendered but that are expected to vest based on achievement of performance condition, if forfeitures are recognized when they occur.

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Fair value of options vested. Excludes equity instruments other than options, for example, but not limited to, share units, stock appreciation rights, restricted stock.

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Number of shares issued during the period as a result of an employee stock purchase plan.

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Note 12 - Stock-based Compensation (Details Textual) - USD ($) $ / shares in Units, $ in Thousands	1 Months Ended			12 Months Ended
	Dec. 31, 2019	Dec. 31, 2014	Aug. 31, 2013	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019	Dec. 31, 2018
Share-based Payment Arrangement, Expense				$ 34,640	$ 14,794	$ 17,719
Share-based Compensation Arrangement by Share-based Payment Award, Options, Grants in Period, Gross (in shares)				7,756,000
Share-based Compensation Arrangement by Share-based Payment Award, Options, Grants in Period, Weighted Average Grant Date Fair Value (in dollars per share)				$ 3.31
Share-based Payment Arrangement, Nonvested Award, Cost Not yet Recognized, Amount, Total				$ 107,852
Employee Service Share-based Compensation, Nonvested Awards, Compensation Cost Expected to be Recognized Next Year				35,060
Employee Service Share-based Compensation, Nonvested Awards, Compensation Cost Expected to be Recognized Year Two				30,375
Employee Service Share-based Compensation, Nonvested Awards, Compensation Cost Expected to be Recognized Year Three				27,607
Employee Service Share-based Compensation, Nonvested Awards, Compensation Cost Expected to be Recognized Year Four				$ 14,810
Stock Issued During Period, Shares, Employee Stock Purchase Plans (in shares)				321,000	246,000	115,000
Share-based Payment Arrangement, Option [Member] \| Non-employee Directors [Member]
Share-based Compensation Arrangement by Share-based Payment Award, Award Vesting Period (Year)				1 year
Incentive Plan [Member]
Share-based Payment Arrangement, Expense				$ 27,062	$ 12,938	$ 17,164
Share-based Compensation Arrangement by Share-based Payment Award, Options, Grants in Period, Weighted Average Grant Date Fair Value (in dollars per share)				$ 7.93	$ 5.48	$ 2.63
Share-based Compensation Arrangement by Share-based Payment Award, Options, Exercises in Period, Intrinsic Value				$ 25,484	$ 1,562	$ 1,127
Share-based Compensation Arrangement by Share-based Payment Award, Number of Shares Available for Grant (in shares)	968,000			3,651,000	4,592,000	968,000	805,000
Incentive Plan [Member] \| Share-based Payment Arrangement, Option [Member] \| Maximum [Member]
Share-based Compensation Arrangement by Share-based Payment Award, Options, Exercisable, Weighted Average Remaining Contractual Term (Year)				10 years
Incentive Plan [Member] \| Share-based Payment Arrangement, Option [Member] \| Vest 25% Each Year Until Fully Vested [Member]
Share-based Compensation Arrangement by Share-based Payment Award, Award Vesting Rights, Percentage				25.00%
Share-based Compensation Arrangement by Share-based Payment Award, Award Vesting Period (Year)				4 years
Incentive Plan [Member] \| Share-based Payment Arrangement, Option [Member] \| Thirty-six Equal Monthly Installments [Member] \| Non-employee Directors [Member]
Share-based Compensation Arrangement by Share-based Payment Award, Award Vesting Period (Year)				3 years
Incentive Plan [Member] \| Performance Shares [Member] \| August 2013 [Member]
Share-based Payment Arrangement, Expense					$ 1,768
Incentive Plan [Member] \| Performance Shares [Member] \| December 2019 [Member]
Share-based Payment Arrangement, Expense					684
Incentive Plan [Member] \| Performance Shares [Member] \| Vest Upon Successful Completion of Specific Development Milestones [Member]
Share-based Compensation Arrangement by Share-based Payment Award, Award Vesting Rights, Percentage	100.00%	85.00%	100.00%
Share-based Compensation Arrangement by Share-based Payment Award, Options, Grants in Period, Gross (in shares)	315,000	1,250,000	1,032,000
Incentive Plan [Member] \| Restricted Stock Units (RSUs) [Member]
Share-based Compensation Arrangement by Share-based Payment Award, Equity Instruments Other than Options, Grants in Period, Weighted Average Grant Date Fair Value (in dollars per share)				$ 11.36
Inducement Plan [Member]
Share-based Payment Arrangement, Expense				$ 6,055	$ 1,494	$ 323
Share-based Compensation Arrangement by Share-based Payment Award, Award Vesting Period (Year)				4 years
Share-based Compensation Arrangement by Share-based Payment Award, Options, Grants in Period, Weighted Average Grant Date Fair Value (in dollars per share)				$ 9.65	$ 2.73	$ 2.41
Share-based Compensation Arrangement by Share-based Payment Award, Expiration Period (Year)				10 years
Share-based Compensation Arrangement by Share-based Payment Award, Options, Exercises in Period, Intrinsic Value				$ 6,700	$ 0
Share-based Compensation Arrangement by Share-based Payment Award, Number of Shares Available for Grant (in shares)				900,000	229,000
Inducement Plan [Member] \| Vest 25% Each Year Until Fully Vested [Member]
Share-based Compensation Arrangement by Share-based Payment Award, Award Vesting Rights, Percentage				25.00%
Inducement Plan [Member] \| Share-based Payment Arrangement, Option [Member]
Share-based Compensation Arrangement by Share-based Payment Award, Fair Value Assumptions, Expected Dividend Rate				0.00%
Employee Stock Purchase Plan [Member]
Share-based Payment Arrangement, Expense				$ 1,523	$ 362	$ 232
Share-based Compensation Arrangement by Share-based Payment Award, Equity Instruments Other than Options, Grants in Period, Weighted Average Grant Date Fair Value (in dollars per share)				$ 2.80	$ 1.47	$ 2.01
Share-based Compensation Arrangement by Share-based Payment Award, Number of Shares Authorized (in shares)				7,975,000
Share-based Compensation Arrangement by Share-based Payment Award, Number of Shares Available for Grant (in shares)				6,052,000
Percentage of Salary to Purchase Common Stock, Maximum				15.00%
Percentage of Common Stock Shares, Beginning				85.00%
Percentage of Common Stock Shares, Ending				85.00%
Share-based Compensation Arrangement by Share-based Payment Award, Maximum Number of Shares Per Employee (in shares)				3,000
Share-based Compensation Arrangement by Share-based Payment Award, Maximum Number of Shares Per Employee, Amount				$ 25
Employee Stock Ownership Plan (ESOP), Weighted Average Purchase Price of Shares Purchased (in dollars per share)				$ 6.20	$ 2.56	$ 3.51
Incentive Plan and Inducement Plan [Member]
Share-based Compensation Arrangement by Share-based Payment Award, Options, Exercisable, Weighted Average Remaining Contractual Term (Year)				5 years 8 months 12 days
Share-based Compensation Arrangement by Share-based Payment Award, Fair Value Assumptions, Expected Dividend Rate				0.00%	0.00%	0.00%
Share-based Compensation Arrangement by Share-based Payment Award, Options, Exercisable, Intrinsic Value				$ 116,811
Share-based Compensation Arrangement by Share-based Payment Award, Options, Vested in Period, Fair Value				$ 23,395	$ 18,739	$ 12,499
Share-based Compensation Arrangement by Share-based Payment Award, Options, Vested and Expected to Vest, Outstanding, Number (in shares)				30,268
Share-based Compensation Arrangement by Share-based Payment Award, Options, Vested and Expected to Vest, Outstanding, Weighted Average Exercise Price (in dollars per share)				$ 7.64
Share-based Compensation Arrangement by Share-based Payment Award, Options, Vested and Expected to Vest, Outstanding, Weighted Average Remaining Contractual Term (Year)				7 years 4 months 24 days