7. Income Taxes

For the years ended December 31, 2015, 2014 and 2013 there was no provision for income taxes due to taxable losses generated, fully offset by a valuation allowance.

The significant components of the Company's deferred income tax assets (liabilities) were as follows (in thousands):

	December 31,
	2015			2014
Deferred income tax assets:
Federal U.S. net operating loss carryforward	$	57,949		$	55,358
State net operating loss carryforward		3,907			3,723
Research and development credit, net		10,278			7,177
Orphan drug credit, net		19,284			19,287
Deferred rent		2,947			4,069
Deferred revenue		6,632			3,989
Depreciation		1,597			1,337
Other		2,532			962
Gross deferred income tax assets		105,126			95,902
Valuation allowance		(104,399	)		(94,297	)
Net deferred income tax assets		727			1,605

Deferred income tax liabilities:
Prepaid expenditures		(727	)		(1,605	)
Gross deferred income tax liabilities		(727	)		(1,605	)
Net deferred income tax asset/(liability)	$	—		$	—

The Company recognizes valuation allowances to reduce deferred tax assets to the amount that is more likely than not to be realized. In assessing the likelihood of realization, management considers (i) future reversals of existing taxable temporary differences; (ii) future taxable income exclusive of reversing temporary difference and carryforwards; (iii) taxable income in prior carryback years if carryback is permitted under applicable tax law; and (iv) tax planning strategies. The Company's net deferred income tax asset is not more likely than not to be utilized due to the lack of sufficient sources of future taxable income and cumulative book losses which have resulted over the years. The net increase in the valuation allowance in 2015 is due to the fact the Company generated research and development and orphan drug credits and NOL carryforwards which increased the net deferred tax asset.

As of December 31, 2015, the Company has U.S. federal and state NOL carryforwards of approximately $165.6 million that will expire in various years beginning in 2020 through 2035. In addition, the Company has U.S. federal tax credits of $29.3 million which will expire in various years beginning in 2020 through 2035.

The use of the Company's U.S. federal NOL and tax credit carryforwards in future years are restricted due to changes in the Company's ownership and tax attributes acquired through the Company's acquisitions. As of December 31, 2015, $13.5 million of the Company's US Federal NOLs are limited for use over the years 2016 – 2028 in which a range of such amounts could be utilized on an annual basis of $0.2 million to $1.4 million. The remaining $152.1 million of NOLs is not limited and can be offset against future taxable income. Additionally, approximately $14.7 million of NOLs will be recognized as a benefit through additional-paid-in-capital when realized. Further, despite the NOL and credit carryforwards, the Company may have a future tax liability due to an alternative minimum tax or state tax requirements in which net operating losses do not exist.

The reconciliation of the reported estimated income tax benefit to the amount that would result by applying the U.S. federal statutory tax rate to the net income is as follows (in thousands):

	Year Ended December 31,
	2015			2014			2013

United States federal tax at statutory rate	$	(7,049	)	$	(13,410	)	$	(91	)
State taxes (net of federal benefit)		(897	)		(1,608	)		609
Deferred income tax adjustments		661			—			(855	)
Deferred state blended rate adjustments		(493	)		3,034			(344	)
Research credit, net		(3,296	)		(2,228	)		(226	)
Transaction cost deduction		—			(379	)		—
Transaction cost deduction - prior year adjustment		—			(564	)		—
Orphan drug credit, net		(106	)		(139	)		(843	)
Other permanent items		(25	)		(382	)		3
Equity-based compensation		1,102			756			241
Fair value adjustment of preferred stock warrant liability		—			—			219
Change in valuation allowance		10,103			14,920			1,287
Income tax expense/(benefit)	$	—		$	—		$	—

A reconciliation of the beginning and ending amount of gross unrecognized tax benefits is as follows (in thousands):

	Year Ended December 31,
	2015			2014			2013

Beginning balance		$	2,047		$	1,708		$	1,592
Increases/(decreases) for current year tax positions			357			242			116
Increases/(decreases) for prior year tax positions			21			97			—
Decreases as a result of expiration of statute of limitations			—			—			—
Ending balance		$	2,425		$	2,047		$	1,708

As of December 31, 2015 and 2014, of the total gross unrecognized tax benefits, approximately $2.0 million and $1.7 million would favorably impact the Company's effective income tax rate, respectively. Although, due to the Company's determination that the deferred income tax asset would not more likely than not be realized, a valuation allowance would be recorded, therefore, zero net impact would result within the Company's effective income tax rate. The Company's uncertain income tax position liability has been recorded to deferred income taxes to offset the tax attribute carryforward amounts.

For the years ended December 31, 2015, 2014 and 2013, the Company has not recognized any interest or penalties related to the uncertain income tax positions due to the fact such position is related to tax attribute carryforwards which have not yet been utilized. The Company does not expect its unrecognized income tax position to significantly decrease within the next twelve months.

The Company's U.S. Federal and state income tax returns from 2001 forward remain open to examination due to the carryover of unused net operating losses and tax credits.