our pipeline of antibody-based product candidates target a number of potential indications including al amyloidosis ( neod001 ) , parkinson 's disease and other related synucleinopathies ( prx002 ) , inflammatory diseases including psoriasis and psoriatic arthritis ( prx003 ) and attr amyloidosis ( prx004 ) . the company continues discovery of additional novel therapeutic candidates where our deep scientific understanding of disease pathology can be leveraged . we are a public limited company formed under the laws of ireland . we separated from elan corporation , plc ( “ elan ” ) on december 20 , 2012. after the separation from elan , and the related distribution of the company 's ordinary shares to elan 's shareholders , our ordinary shares began trading on the nasdaq global market under the symbol “ prta ” on december 21 , 2012 and currently trade on the nasdaq global select market . 45 recent developments neod001 for the potential treatment of al amyloidosis neod001 is an investigational monoclonal antibody that targets circulating misfolded soluble light chain and deposited insoluble amyloid for the potential treatment of al amyloidosis . results from the dose-escalation portion ( n=27 ) of the phase 1/2 clinical study of neod001 in patients with al amyloidosis and persistent organ dysfunction were published in the journal of clinical oncology in february 2016. in july 2016 , we presented positive interim data from the phase 1/2 clinical study from patients in both the dose escalation and expansion phases ( n=69 ) at the international symposium on amyloidosis ( isa ) ; and in december 2016 , results from the completed study were presented in an oral session at the american society of hematology ( ash ) annual meeting . results from this phase 1/2 study demonstrated that neod001 was safe and well-tolerated in patients with al amyloidosis and persistent organ dysfunction . the analysis showed that a total of 69 patients across the dose-escalation and expansion portions of the study received more than 990 infusions of up to 24 mg/kg , with a mean treatment duration of 12.8 months . in a best response analysis of patients in the phase 1/2 study who received neod001 , 53 % or 19 of 36 total cardiac-evaluable patients demonstrated a cardiac response , defined as more than 30 % and 300 pg/ml decrease in levels of nt-probnp . these cardiac best response rates compared favorably to cardiac response rates of 0 % to 15 % from available published historical data in patients previously treated with plasma cell directed therapy , and were consistent with the best response rate of 57 % , or 8 of 14 cardiac-evaluable patients , reported in the interim analysis of the dose escalation phase ( n=27 ) of the neod001 phase 1/2 study published in the journal of clinical oncology in february 2016. in a best response analysis of patients in the phase 1/2 study who received neod001 , 64 % , or 23 of 36 total renal-evaluable patients , demonstrated a renal response , defined as a 30 % decrease in proteinuria ( a renal function biomarker ) in the absence of estimated glomerular filtration rate ( egfr ) worsening . these renal best response rates compared favorably to renal response rates of 17 % to 29 % from published historical data in patients previously treated with plasma cell directed therapy , and were consistent with the best response rate of 60 % , or 9 of 15 renal-evaluable patients , reported in the interim analysis of the dose-escalation phase ( n=27 ) of the neod001 phase 1/2 study published in the journal of clinical oncology in february 2016. in addition , an improvement in peripheral neuropathy in patients in the prospectively defined peripheral neuropathy expansion cohort was demonstrated by a mean 35 % ( median 23 % ) decrease in the neuropathy impairment score-lower limb ( “ nis-ll ” ) measured at month 10 , indicating improvement to a third organ system in neod001-treated patients . complete resolution of peripheral neuropathy , as measured by nis-ll , was achieved in two patients in this cohort . improvements in patient nis-ll scores resulted in a response rate of 82 % or 9 of 11 patients in the peripheral neuropathy expansion cohort of the phase 1/2 study . a response on the nis-ll is defined as a less than 2-point increase on the 88-point scale . in august 2016 , we published a study in the journal amyloid that further supports neod001 's proposed mechanism of action and features preclinical data demonstrating the binding and phagocytosis clearance properties of neod001 and the related murine form of the antibody in tissue samples from multiple organs of patients with al amyloidosis . prx002 for the potential treatment of parkinson 's disease and other synucleinopathies prx002 is an investigational monoclonal antibody targeting alpha-synuclein designed to slow the progressive neurodegeneration associated with synuclein misfolding and or the cell-to-cell transmission of the pathogenic forms of synuclein in parkinson 's disease and other synucleinopathies . prx002 , also known as rg7935 , is the focus of a worldwide collaboration between prothena and roche . in november 2016 , we announced data from a phase 1b multiple ascending dose study of prx002 in patients with parkinson 's disease that was designed to assess the safety , tolerability , pharmacokinetics and immunogenicity of prx002 . the 80 patients with parkinson 's disease in this phase 1b double-blind , placebo-controlled , multiple ascending dose study were randomized into six escalating dose cohorts to receive prx002 or placebo ( 2:1 randomization for 0.3 , 1 , 3 or 10 mg/kg , and 3:1 randomization for 30 or 60 mg/kg ) . all dose levels of prx002 were found to have an acceptable safety and tolerability profile in patients with parkinson 's disease , meeting the primary objective of the study . story_separator_special_tag share-based awards , including stock options , are measured at fair value as of the grant date and recognized to expense over the requisite service period ( generally the vesting period ) , which we have elected to amortize on a straight-line basis . since share-based compensation expense is based on awards ultimately expected to vest , it has been reduced by an estimate for future forfeitures . forfeitures are estimated based on expected turnover and historical experience . we estimate forfeitures at the time of grant and revise our estimate , if necessary , in subsequent periods . we estimate the fair value of options granted using the black-scholes option valuation model . significant judgment is required in determining the proper assumptions used in these models . the assumptions used include the risk free interest rate , expected term , expected volatility and expected dividend yield . we base our assumptions on historical data when available or when not available , on a peer group of companies . prior to 2015 , the expected volatility was based on historical stock volatilities of several of our publicly traded comparable companies over a period equal to the expected life of the options , as we did not have a long enough trading history to use the volatility of our own ordinary shares . starting in 2015 , the expected volatility was based on a combination of historical volatility for our shares and the historical volatilities of several of our publicly traded comparable companies . these peer companies are publicly traded , have similar industry , life cycle , revenue and market capitalization . in addition , since we do not have sufficient historical employee share option exercise data , the simplified method has been used to estimate the expected life of all options . these assumptions consist of estimates of future market conditions , which are inherently uncertain , and therefore subject to our judgment and therefore any changes in assumptions could significantly impact the future grant date fair value of share-based awards . total share-based compensation expense for the years ended december 31 , 2016 , 2015 and 2014 was $ 24.9 million , $ 10.4 million , and $ 5.6 million , respectively . the information contained in note 2 to the consolidated financial statements under the heading “ recent accounting pronouncements ” is hereby incorporated by reference into this part ii , item 7. results of operations comparison of years ended december 31 , 2016 , 2015 and 2014 revenue replace_table_token_3_th total revenue was $ 1.1 million , $ 1.6 million and $ 50.9 million for the years ended december 31 , 2016 , 2015 and 2014 , respectively . collaboration revenue includes reimbursements under our license agreement with roche , which became effective january 2014 . the portion of the amounts recognized as collaboration revenue for the milestone and the development reimbursements 50 were based on the relative selling price method in applying multiple element accounting . see note 8 to the consolidated financial statements “ roche license agreement ” for more information . collaboration revenue for the year ended december 31 , 2016 consisted of reimbursement for research service of $ 1.1 million . collaboration revenue for the year ended december 31 , 2015 consisted of the following amounts from roche under the license agreement : reimbursement for development costs of $ 5.1 million ( of which $ 0.2 million was recognized as collaboration license revenue ) and reimbursement for research services of $ 1.4 million . conversely , collaboration revenue for the year ended december 31 , 2014 consisted of the following amounts : a one-time , non-refundable , non-creditable upfront payment of $ 30.0 million ( which was recognized as collaboration license revenue ) , a clinical milestone payment from roche of $ 15.0 million ( of which $ 13.3 million was recognized as collaboration revenue ) , reimbursement for development costs of $ 6.0 million ( of which $ 5.3 million was recognized as collaboration license revenue ) and reimbursement for research services of $ 1.7 million . related-party revenue for the year ended december 31 , 2014 was comprised of fees earned from the provision of research and development services to elan . total related-party revenue decreased by $ 142,000 , or 21 % , during the year ended december 31 , 2014 , compared to the corresponding period of the prior year . since our research and development services agreement with elan terminated in december 2014 , we did not have any related-party revenue in the years ended december 31 , 2016 and 2015. operating expenses replace_table_token_4_th total operating expenses consist of research and development ( `` r & d `` ) expenses and general and administrative ( `` g & a `` ) expenses . our operating expenses for the years ended december 31 , 2016 , 2015 and 2014 were $ 160.6 million , $ 81.5 million , and $ 57.5 million , respectively . our r & d expenses primarily consist of personnel costs and related expenses , including share-based compensation , external costs associated with preclinical activities and drug development related to our drug programs , including neod001 , prx002 , prx003 , prx004 , our discovery programs , and in 2014 included cost of providing research services to elan . pursuant to our license agreement with roche , we make payments to roche for our share of the development expenses incurred by roche related to prx002 program , which is included in our r & d expense . we also recorded reimbursements from roche for development and supply services based on the relative percentages as an offset to r & d expense . our g & a expenses primarily consist of professional service expenses and personnel costs and related expenses , including share-based compensation . research and development expenses our r & d expenses increased by $ 61.1 million , or 105 % , for the

net cash used in operating activities was $ 117.3 million for the year ended december 31 , 2016 , primarily due to use of $ 160.6 million for operating expenses ( adjusted to exclude non-cash charges ) , which was partially offset by an increase in accounts payable and accrued liabilities . net cash used in operating activities was $ 62.5 million for the year ended december 31 , 2015 , primarily due to use of $ 81.5 million for operating expenses ( adjusted to exclude non-cash charges ) , which was partially offset by an increase in accrued liabilities . net cash used in operating activities was $ 0.7 million for the year ended december 31 , 2014 , primarily due to receipt of the upfront payment of $ 30.0 million , the clinical milestone payment of $ 15.0 million and reimbursement for research and development costs of $ 7.0 million from roche , recognized as revenue , offset by $ 57.5 million in expenses ( adjusted to exclude non-cash charges ) and increases in accrued liabilities . cash used in investing activities net cash used in investing activities was $ 16.6 million , $ 1.4 million and $ 0.5 million for the years ended december 31 , 2016 , 2015 and 2014 , respectively .


 Write a concise suspicious activity report of the following text delimited by triple backquotes. Return your response as a formal report which covers the key points highlighting the location,dates,entity names and account holder information in chronological order of the text.
     ```net cash used in operating activities was $ 117.3 million for the year ended december 31 , 2016 , primarily due to use of $ 160.6 million for operating expenses ( adjusted to exclude non-cash charges ) , which was partially offset by an increase in accounts payable and accrued liabilities . net cash used in operating activities was $ 62.5 million for the year ended december 31 , 2015 , primarily due to use of $ 81.5 million for operating expenses ( adjusted to exclude non-cash charges ) , which was partially offset by an increase in accrued liabilities . net cash used in operating activities was $ 0.7 million for the year ended december 31 , 2014 , primarily due to receipt of the upfront payment of $ 30.0 million , the clinical milestone payment of $ 15.0 million and reimbursement for research and development costs of $ 7.0 million from roche , recognized as revenue , offset by $ 57.5 million in expenses ( adjusted to exclude non-cash charges ) and increases in accrued liabilities . cash used in investing activities net cash used in investing activities was $ 16.6 million , $ 1.4 million and $ 0.5 million for the years ended december 31 , 2016 , 2015 and 2014 , respectively .
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 Suspicious Activity Report : our pipeline of antibody-based product candidates target a number of potential indications including al amyloidosis ( neod001 ) , parkinson 's disease and other related synucleinopathies ( prx002 ) , inflammatory diseases including psoriasis and psoriatic arthritis ( prx003 ) and attr amyloidosis ( prx004 ) . the company continues discovery of additional novel therapeutic candidates where our deep scientific understanding of disease pathology can be leveraged . we are a public limited company formed under the laws of ireland . we separated from elan corporation , plc ( “ elan ” ) on december 20 , 2012. after the separation from elan , and the related distribution of the company 's ordinary shares to elan 's shareholders , our ordinary shares began trading on the nasdaq global market under the symbol “ prta ” on december 21 , 2012 and currently trade on the nasdaq global select market . 45 recent developments neod001 for the potential treatment of al amyloidosis neod001 is an investigational monoclonal antibody that targets circulating misfolded soluble light chain and deposited insoluble amyloid for the potential treatment of al amyloidosis . results from the dose-escalation portion ( n=27 ) of the phase 1/2 clinical study of neod001 in patients with al amyloidosis and persistent organ dysfunction were published in the journal of clinical oncology in february 2016. in july 2016 , we presented positive interim data from the phase 1/2 clinical study from patients in both the dose escalation and expansion phases ( n=69 ) at the international symposium on amyloidosis ( isa ) ; and in december 2016 , results from the completed study were presented in an oral session at the american society of hematology ( ash ) annual meeting . results from this phase 1/2 study demonstrated that neod001 was safe and well-tolerated in patients with al amyloidosis and persistent organ dysfunction . the analysis showed that a total of 69 patients across the dose-escalation and expansion portions of the study received more than 990 infusions of up to 24 mg/kg , with a mean treatment duration of 12.8 months . in a best response analysis of patients in the phase 1/2 study who received neod001 , 53 % or 19 of 36 total cardiac-evaluable patients demonstrated a cardiac response , defined as more than 30 % and 300 pg/ml decrease in levels of nt-probnp . these cardiac best response rates compared favorably to cardiac response rates of 0 % to 15 % from available published historical data in patients previously treated with plasma cell directed therapy , and were consistent with the best response rate of 57 % , or 8 of 14 cardiac-evaluable patients , reported in the interim analysis of the dose escalation phase ( n=27 ) of the neod001 phase 1/2 study published in the journal of clinical oncology in february 2016. in a best response analysis of patients in the phase 1/2 study who received neod001 , 64 % , or 23 of 36 total renal-evaluable patients , demonstrated a renal response , defined as a 30 % decrease in proteinuria ( a renal function biomarker ) in the absence of estimated glomerular filtration rate ( egfr ) worsening . these renal best response rates compared favorably to renal response rates of 17 % to 29 % from published historical data in patients previously treated with plasma cell directed therapy , and were consistent with the best response rate of 60 % , or 9 of 15 renal-evaluable patients , reported in the interim analysis of the dose-escalation phase ( n=27 ) of the neod001 phase 1/2 study published in the journal of clinical oncology in february 2016. in addition , an improvement in peripheral neuropathy in patients in the prospectively defined peripheral neuropathy expansion cohort was demonstrated by a mean 35 % ( median 23 % ) decrease in the neuropathy impairment score-lower limb ( “ nis-ll ” ) measured at month 10 , indicating improvement to a third organ system in neod001-treated patients . complete resolution of peripheral neuropathy , as measured by nis-ll , was achieved in two patients in this cohort . improvements in patient nis-ll scores resulted in a response rate of 82 % or 9 of 11 patients in the peripheral neuropathy expansion cohort of the phase 1/2 study . a response on the nis-ll is defined as a less than 2-point increase on the 88-point scale . in august 2016 , we published a study in the journal amyloid that further supports neod001 's proposed mechanism of action and features preclinical data demonstrating the binding and phagocytosis clearance properties of neod001 and the related murine form of the antibody in tissue samples from multiple organs of patients with al amyloidosis . prx002 for the potential treatment of parkinson 's disease and other synucleinopathies prx002 is an investigational monoclonal antibody targeting alpha-synuclein designed to slow the progressive neurodegeneration associated with synuclein misfolding and or the cell-to-cell transmission of the pathogenic forms of synuclein in parkinson 's disease and other synucleinopathies . prx002 , also known as rg7935 , is the focus of a worldwide collaboration between prothena and roche . in november 2016 , we announced data from a phase 1b multiple ascending dose study of prx002 in patients with parkinson 's disease that was designed to assess the safety , tolerability , pharmacokinetics and immunogenicity of prx002 . the 80 patients with parkinson 's disease in this phase 1b double-blind , placebo-controlled , multiple ascending dose study were randomized into six escalating dose cohorts to receive prx002 or placebo ( 2:1 randomization for 0.3 , 1 , 3 or 10 mg/kg , and 3:1 randomization for 30 or 60 mg/kg ) . all dose levels of prx002 were found to have an acceptable safety and tolerability profile in patients with parkinson 's disease , meeting the primary objective of the study . story_separator_special_tag share-based awards , including stock options , are measured at fair value as of the grant date and recognized to expense over the requisite service period ( generally the vesting period ) , which we have elected to amortize on a straight-line basis . since share-based compensation expense is based on awards ultimately expected to vest , it has been reduced by an estimate for future forfeitures . forfeitures are estimated based on expected turnover and historical experience . we estimate forfeitures at the time of grant and revise our estimate , if necessary , in subsequent periods . we estimate the fair value of options granted using the black-scholes option valuation model . significant judgment is required in determining the proper assumptions used in these models . the assumptions used include the risk free interest rate , expected term , expected volatility and expected dividend yield . we base our assumptions on historical data when available or when not available , on a peer group of companies . prior to 2015 , the expected volatility was based on historical stock volatilities of several of our publicly traded comparable companies over a period equal to the expected life of the options , as we did not have a long enough trading history to use the volatility of our own ordinary shares . starting in 2015 , the expected volatility was based on a combination of historical volatility for our shares and the historical volatilities of several of our publicly traded comparable companies . these peer companies are publicly traded , have similar industry , life cycle , revenue and market capitalization . in addition , since we do not have sufficient historical employee share option exercise data , the simplified method has been used to estimate the expected life of all options . these assumptions consist of estimates of future market conditions , which are inherently uncertain , and therefore subject to our judgment and therefore any changes in assumptions could significantly impact the future grant date fair value of share-based awards . total share-based compensation expense for the years ended december 31 , 2016 , 2015 and 2014 was $ 24.9 million , $ 10.4 million , and $ 5.6 million , respectively . the information contained in note 2 to the consolidated financial statements under the heading “ recent accounting pronouncements ” is hereby incorporated by reference into this part ii , item 7. results of operations comparison of years ended december 31 , 2016 , 2015 and 2014 revenue replace_table_token_3_th total revenue was $ 1.1 million , $ 1.6 million and $ 50.9 million for the years ended december 31 , 2016 , 2015 and 2014 , respectively . collaboration revenue includes reimbursements under our license agreement with roche , which became effective january 2014 . the portion of the amounts recognized as collaboration revenue for the milestone and the development reimbursements 50 were based on the relative selling price method in applying multiple element accounting . see note 8 to the consolidated financial statements “ roche license agreement ” for more information . collaboration revenue for the year ended december 31 , 2016 consisted of reimbursement for research service of $ 1.1 million . collaboration revenue for the year ended december 31 , 2015 consisted of the following amounts from roche under the license agreement : reimbursement for development costs of $ 5.1 million ( of which $ 0.2 million was recognized as collaboration license revenue ) and reimbursement for research services of $ 1.4 million . conversely , collaboration revenue for the year ended december 31 , 2014 consisted of the following amounts : a one-time , non-refundable , non-creditable upfront payment of $ 30.0 million ( which was recognized as collaboration license revenue ) , a clinical milestone payment from roche of $ 15.0 million ( of which $ 13.3 million was recognized as collaboration revenue ) , reimbursement for development costs of $ 6.0 million ( of which $ 5.3 million was recognized as collaboration license revenue ) and reimbursement for research services of $ 1.7 million . related-party revenue for the year ended december 31 , 2014 was comprised of fees earned from the provision of research and development services to elan . total related-party revenue decreased by $ 142,000 , or 21 % , during the year ended december 31 , 2014 , compared to the corresponding period of the prior year . since our research and development services agreement with elan terminated in december 2014 , we did not have any related-party revenue in the years ended december 31 , 2016 and 2015. operating expenses replace_table_token_4_th total operating expenses consist of research and development ( `` r & d `` ) expenses and general and administrative ( `` g & a `` ) expenses . our operating expenses for the years ended december 31 , 2016 , 2015 and 2014 were $ 160.6 million , $ 81.5 million , and $ 57.5 million , respectively . our r & d expenses primarily consist of personnel costs and related expenses , including share-based compensation , external costs associated with preclinical activities and drug development related to our drug programs , including neod001 , prx002 , prx003 , prx004 , our discovery programs , and in 2014 included cost of providing research services to elan . pursuant to our license agreement with roche , we make payments to roche for our share of the development expenses incurred by roche related to prx002 program , which is included in our r & d expense . we also recorded reimbursements from roche for development and supply services based on the relative percentages as an offset to r & d expense . our g & a expenses primarily consist of professional service expenses and personnel costs and related expenses , including share-based compensation . research and development expenses our r & d expenses increased by $ 61.1 million , or 105 % , for the

