Can you please find?

Net cash provided by operating activities minus cash payments earmarked for investments in plant assets

I need the calculations as well.

The Consolidated Statement of Cash Flow for the company is attached.

Thank you

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-K (Mark One) ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2015 or TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File No. 0-19731 GILEAD SCIENCES, INC. (Exact name of registrant as specified in its charter) Delaware 94-3047598 (State or Other Jurisdiction of Incorporation or Organization) (I.R.S. Employer Identification No.) 333 Lakeside Drive, Foster City, California 94404 (Address of principal executive offices) (Zip Code) Registrant's telephone number, including area code: 650-574-3000 SECURITIES REGISTERED PURSUANT TO SECTION 12(b) OF THE ACT: Title of each class Name of each exchange on which registered Common Stock, $0.001 par value per share The Nasdaq Global Select Market SECURITIES REGISTERED PURSUANT TO SECTION 12(g) OF THE ACT: NONE Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes No Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act. Yes No Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days. Yes No Indicate by check mark whether the registrant has submitted electronically and posted on its corporate Web site, if any, every Interactive Data File required to be submitted and posted pursuant to Rule 405 of Regulation S-T ( 232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit and post such files). Yes No Indicate by check mark if disclosure of delinquent filers pursuant to Item 405 of Regulation S-K ( 229.405) is not contained herein, and will not be contained, to the best of registrant's knowledge, in definitive proxy or information statements incorporated by reference in Part III of this Form 10K or any amendment to this Form 10-K. Indicate by check mark whether registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, or a smaller reporting company. See the definitions of \"large accelerated filer,\" \"accelerated filer\" and \"smaller reporting company\" in Rule 12b-2 of the Exchange Act. (Check one): Large accelerated filer Accelerated filer Non-Accelerated filer Smaller reporting company (Do not check if a smaller reporting company) Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act). Yes No The aggregate market value of the voting and non-voting common equity held by non-affiliates of the registrant based upon the closing price of its Common Stock on the Nasdaq Global Select Market on June 30, 2015 was $140,034,139,655.* The number of shares outstanding of the registrant's Common Stock on February 12, 2016 was 1,366,845,691. DOCUMENTS INCORPORATED BY REFERENCE Specified portions of the registrant's proxy statement, which will be filed with the Commission pursuant to Regulation 14A in connection with the registrant's 2016 Annual Meeting of Stockholders, to be held on May 11, 2016, are incorporated by reference into Part III of this Report. * Based on a closing price of $117.08 per share on June 30, 2015. Excludes 276,651,262shares of the registrant's Common Stock held by executive officers, directors and any stockholders whose ownership exceeds 5% of registrant's common stock outstanding at June 30, 2015. Exclusion of such shares should not be construed to indicate that any such person possesses the power, direct or indirect, to direct or cause the direction of the management or policies of the registrant or that such person is controlled by or under common control with the registrant. GILEAD SCIENCES, INC. 2015 Form 10-K Annual Report Table of Contents PART I Item 1 Item 1A Item 1B Item 2 Item 3 Item 4 Business Risk Factors Unresolved Staff Comments Properties Legal Proceedings Mine Safety Disclosures 3 27 44 44 44 44 PART II Item 5 Market for Registrant's Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities Item 6 Selected Financial Data Item 7 Management's Discussion and Analysis of Financial Condition and Results of Operations 44 46 47 Item 7A Quantitative and Qualitative Disclosures about Market Risk Item 8 Financial Statements and Supplementary Data Item 9 Changes in and Disagreements with Accountants on Accounting and Financial Disclosure 61 64 107 Item 9A Controls and Procedures Item 9B Other Information 107 109 PART III Item 10 Directors, Executive Officers and Corporate Governance Item 11 Executive Compensation Item 12 Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters Item 13 Certain Relationships and Related Transactions, and Director Independence Item 14 Principal Accountant Fees and Services 109 109 109 109 109 PART IV Item 15 Exhibits and Financial Statement Schedules 109 SIGNATURES 114 We own or have rights to various trademarks, copyrights and trade names used in our business, including the following: GILEAD , GILEAD SCIENCES , AMBISOME , CAYSTON , COMPLERA , EMTRIVA , EVIPLERA , GENVOYA , HARVONI , HEPSERA , LETAIRIS , RANEXA , RAPISCAN , SOVALDI , STRIBILD , TRUVADA , TYBOST , VIREAD , VITEKTA , VOLIBRIS , and ZYDELIG . ATRIPLA is a registered trademark belonging to Bristol-Myers Squibb & Gilead Sciences, LLC. LEXISCAN is a registered trademark belonging to Astellas U.S. LLC. MACUGEN is a registered trademark belonging to Eyetech, Inc. SUSTIVA is a registered trademark of Bristol-Myers Squibb Pharma Company. TAMIFLU is a registered trademark belonging to Hoffmann-La Roche Inc. This report also includes other trademarks, service marks and trade names of other companies. This Annual Report on Form 10-K, including the section entitled \"Management's Discussion and Analysis of Financial Condition and Results of Operations,\" contains forward-looking statements regarding future events and our future results that are subject to the safe harbors created under the Securities Act of 1933, as amended (the Securities Act), and the Securities Exchange Act of 1934, as amended (the Exchange Act). Words such as \"expect,\" \"anticipate,\" \"target,\" \"goal,\" \"project,\" \"hope,\" \"intend,\" \"plan,\" \"believe,\" \"seek,\" \"estimate,\" \"continue,\" \"may,\" \"could,\" \"should,\" \"might,\" variations of such words and similar expressions are intended to identify such forward-looking statements. In addition, any statements other than statements of historical fact are forward-looking statements, including statements regarding overall trends, operating cost and revenue trends, liquidity and capital needs and other statements of expectations, beliefs, future plans and strategies, anticipated events or trends and similar expressions. We have based these forward-looking statements on our current expectations about future events. These statements are not guarantees of future performance and involve risks, uncertainties and assumptions that are difficult to predict. Our actual results may differ materially from those suggested by these forward-looking statements for various reasons, including those identified in Part I, Item 1A of this Form 10-K under the heading \"Risk Factors.\" Given these risks and uncertainties, you are cautioned not to place undue reliance on forward-looking statements. The forward-looking statements included in this report are made only as of the date hereof. Except as required under federal securities laws and the rules and regulations of the Securities and Exchange Commission (SEC), we do not undertake, and specifically decline, any obligation to update any of these statements or to publicly announce the results of any revisions to any forward-looking statements after the distribution of this report, whether as a result of new information, future events, changes in assumptions or otherwise. 2 PART I ITEM BUSINESS 1. Overview Gilead Sciences, Inc. (Gilead, we or us), incorporated in Delaware on June 22, 1987, is a research-based biopharmaceutical company that discovers, develops and commercializes innovative medicines in areas of unmet medical need. With each new discovery and investigational drug candidate, we strive to transform and simplify care for people with life-threatening illnesses around the world. Gilead's primary areas of focus include human immunodeficiency virus (HIV), liver diseases such as chronic hepatitis C virus (HCV) infection and chronic hepatitis B virus (HBV) infection, cardiovascular, hematology/oncology and inflammation/respiratory. We have operations in more than 30 countries worldwide, with headquarters in Foster City, California. We continue to add to our existing portfolio of products through our internal discovery and clinical development programs and through a product acquisition and inlicensing strategy. 2015 Highlights Over the past year, we worked to bring best-in-class drugs to market that advance the standard of care by offering enhanced modes of delivery, more convenient treatment regimens, improved resistance profiles, reduced side effects and greater efficacy. In the HIV area, we received approval from U.S. Food and Drug Administration (FDA) and the European Commission of Genvoya (elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg or E/C/F/TAF), a once-daily single tablet regimen for the treatment of HIV-1 infection. Two other TAF-based regimens are currently under evaluation by FDA and the European Medicines Agency (EMA). The first is an investigational, fixed-dose combination of emtricitabine 200 mg and tenofovir alafenamide 25 or 10 mg (F/TAF) for use in combination with other antiretroviral agents. The second is an investigational, once-daily single tablet regimen that combines emtricitabine 200 mg, tenofovir alafenamide 25 mg and rilpivirine 25 mg (R/F/TAF). In the liver diseases area, we received approval from FDA to expand the use of Harvoni in patients with genotype 4, 5 and 6 chronic HCV infection and in patients co-infected with HIV. In addition, Harvoni plus ribavirin (RBV) for 12 weeks was approved as an alternate therapy to 24 weeks of Harvoni for treatment-experienced, genotype 1 patients with cirrhosis. We also submitted marketing applications to FDA and the EMA for the approval of a once-daily fixed-dose combination of sofosbuvir (SOF), approved as Sovaldi in December 2013, and velpatasvir (VEL), an investigational pan-genotypic NS5A inhibitor, for the treatment of chronic genotype 1-6 HCV. If approved, SOF/VEL would become the first pan-genotypic, all-oral single tablet regimen for the treatment of HCV and would complement our current HCV portfolio of Sovaldi and Harvoni, offering high cure rates and the potential to simplify treatment and eliminate the need for HCV genotype testing. In the hematology/oncology area, we submitted supplemental new drug applications to FDA and the EMA for approval of Zydelig (idelalisib) in combination with ofatumumab in previously-treated patients with chronic lymphocytic leukemia (CLL). Zydelig was originally approved in combination with rituximab for the treatment of certain patients with CLL, small lymphocytic lymphoma and follicular lymphoma, the most common type of indolent non-Hodgkin's lymphoma (iNHL). We also advanced our research and development pipeline, with 180 active clinical studies at the end of 2015, of which 61 were Phase 3 clinical trials. In addition to advancing treatment options across therapeutic areas, we also enabled access to our medications for people who need them around the world. During 2015, we expanded our generic licensing agreements with our India-based manufacturing partners to include SOF/VEL, once approved, for distribution in developing countries. A pan-genotypic therapeutic option for the treatment of HCV is particularly important for developing countries, where genotype testing is often unreliable or not readily available. We also expanded the geographic scope of our licensing agreements with our India-based manufacturing partners to include 101 developing countries. In 2015, we also updated our tiered pricing strategy to make our branded HCV medicines available at a significantly reduced public/government price in all of these 101 countries. By making our pricing in these countries clear and transparent, we hope to facilitate planning and encourage a meaningful public health response to HCV. HIV Program Our goal is to ensure that all HIV patients can choose a single tablet regimen that is right for them. Single tablet regimens allow patients to adhere to a fully suppressive course of therapy more easily and consistently, which is critical for the successful management of the disease. HIV patients are living longer, thus facing additional health challenges to those experienced by newly diagnosed patients. We are motivated to continue improving on existing treatment options. The need for efficacy together with improved long-term safety has driven our development programs and the design of the studies we have completed and those that are planned. We look forward to introducing this new generation of TAF single tablet regimens that we have created to address the evolving needs of people living with HIV. TAF is a novel targeted prodrug of tenofovir that has demonstrated high antiviral efficacy similar to and at a dose less than one-tenth that of Viread (tenofovir disoproxil fumarate, TDF), as well as 3 improvement in surrogate laboratory markers of renal and bone safety as compared in clinical trials to TDF in combination with other antiretroviral agents. With the launch of our first TAF-based regimen, Genvoya, we now have four single tablet regimens available for the treatment of HIV. Marketing approvals for two additional TAF-based product candidates, F/TAF and R/F/TAF, are pending in the United States and European Union. Our product candidate R/F/TAF has been assigned an approval date under the Prescription Drug User Fee Act (PDUFA) of March 1, 2016 and a European Commission decision is expected in the third quarter of 2016. F/TAF has been assigned a PDUFA date of April 7, 2016 and a European Commission decision is expected in the second quarter of 2016. Emtricitabine and TAF are from Gilead and rilpivirine is from Janssen Sciences Ireland UC (Janssen). In addition, we are investigating two additional TAF-based single tablet regimens; TAF, emtricitabine and GS-9883, our proprietary integrase inhibitor currently in Phase 3 clinical studies; and TAF, emtricitabine, cobicistat and Janssen's darunavir (D/C/F/TAF), which is being developed and commercialized by Janssen. Liver Diseases Our goal is to advance the treatment options and standard of care for the underserved HCV market. With the approval of Sovaldi, compared to the prior standard of care of up to 48 weeks, the duration of treatment has been shortened to as few as 12 weeks and the need for peg-interferon (peg-IFN) injections in certain viral genotype populations has been reduced or eliminated completely. In 2014, we received FDA and European Commission approval of Harvoni, the first once-daily single tablet regimen for the treatment of HCV genotype 1 infected patients, the most prevalent genotype in the United States. We received approval of Harvoni in Japan in 2015. Harvoni combines the NS5A inhibitor ledipasvir with sofosbuvir and is indicated for an eight, 12 or 24 week treatment duration depending on prior treatment history, cirrhosis status and baseline viral load and eliminates the need for peg-IFN and RBV, which can be challenging to take and tolerate. In 2015, FDA expanded the use of Harvoni to include patients with genotype 4, 5 and 6 chronic HCV infection and in patients co-infected with HIV. In addition, Harvoni plus ribavirin for 12 weeks was approved as an alternate therapy to 24 weeks of Harvoni for treatment-experienced, genotype 1 patients with cirrhosis. Our long term goal is to develop an oral therapy for all HCV patients across genotypes. In the fourth quarter of 2015, we submitted marketing applications to FDA and the EMA for the approval of a once-daily fixed-dose combination of SOF/VEL for the treatment of chronic genotype 1-6 HCV. In the fourth quarter of 2015, we also initiated Phase 3 clinical trials evaluating the once-daily fixed-dose combination of SOF, VEL and GS-9857, an investigational NS3 protease inhibitor, for the treatment of chronic genotype 16 HCV. We are evaluating TAF for the treatment of chronic HBV infection and based on data from two Phase 3 clinical trials, we filed marketing applications to FDA and the EMA in the first quarter of 2016. We are also conducting Phase 2 clinical trials of GS-9620, an oral TLR-7 agonist, and GS-4774, a Tarmogen T cell immunity stimulator, for the treatment of HBV. We are evaluating simtuzumab, a monoclonal antibody, for the treatment of nonalcoholic steatohepatitis (NASH) and primary sclerosing cholangitis in Phase 2 clinical trials. We are also evaluating GS-4977, an ASK-1 inhibitor, for NASH in Phase 2 clinical trials. We are also evaluating GS-9674, a FXR Agonist, for NASH in Phase 1 clinical trials. Cardiovascular In 2015, we received FDA approval of the use of Letairis (ambrisentan) in combination with tadalafil for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to reduce the risks of disease progression and hospitalization for worsening PAH, and to improve exercise ability. Letairis is an endothelin receptor antagonist that was first approved in 2007 in the United States as monotherapy for PAH to improve exercise ability and delay clinical worsening. Tadalafil is a PDE5 inhibitor that was initially approved for PAH in the United States in 2009 to improve exercise ability. Eleclazine, formerly known as GS-6615, a late sodium channel inhibitor, is being evaluated in Phase 3 clinical trials for the treatment of Long QT-3 Syndrome. Eleclazine is also being evaluated in Phase 2 clinical trials for the treatment of hypertrophic cardiomyopathy and ventricular tachycardia/ventricular fibrillation. We are also evaluating GS-4977, an ASK-1 inhibitor, for pulmonary arterial hypertension in Phase 2 clinical trials. Hematology/Oncology In the oncology area, we are seeking to expand the use of Zydelig (idelalisib), a first-in-class PI3K delta inhibitor, for the treatment of patients with certain blood cancers. In 2015, we submitted supplemental new drug applications with FDA and the EMA for approval of Zydelig in combination with ofatumumab in previously-treated patients with CLL. Idelalisib is in Phase 3 clinical trials for the treatment of patients with frontline and relapsed refractory CLL and relapsed refractory 4 iNHL. We plan to submit supplemental regulatory filings with FDA and the EMA for approval of Zydelig in combination with bendamustine and rituximab for patients with previously treated CLL in the second quarter of 2016. In the fourth quarter of 2015, we initiated Phase 3 clinical trials evaluating GS-5745, a MMP9 mAb inhibitor, for the treatment of gastric cancer. We are also conducting Phase 3 clinical trials evaluating momelotinib for the treatment of myleofibrosis and pancreatic cancer. Inflammation/Respiratory In the inflammation/respiratory area, we advanced several product candidates in clinical trials. Presatovir, formerly known as GS-5806, a fusion inhibitor, is currently in Phase 2 clinical trials for the treatment of respiratory syncytial virus. GS-5745, a MMP9 mAb inhibitor, is being evaluated in Phase 2 clinical trials for ulcerative colitis and Crohn's disease. Filgotinib, a JAK1 inhibitor, is being evaluated in Phase 2 clinical trials for rheumatoid arthritis and Crohn's disease. Our Products HIV Genvoya is an oral formulation dosed once a day for the treatment of HIV-1 infection in adults. Genvoya is our fourth complete single tablet regimen for the treatment of HIV and is a fixed-dose combination of our antiretroviral medicines, Vitekta (elvitegravir 85 mg and 150 mg), Tybost (cobicistat), Emtriva (emtricitabine) and TAF 10 mg. Genvoya was approved by FDA and the European Commission in November 2015. Stribild is an oral formulation dosed once a day for the treatment of HIV-1 infection in treatment-naive adults. Stribild is our third complete single tablet regimen for the treatment of HIV and is a fixed-dose combination of our antiretroviral medications, Vitekta, Tybost, Viread and Emtriva. Complera/Eviplera is an oral formulation dosed once a day for the treatment of HIV-1 infection in adults. The product, marketed in the United States as Complera and in Europe as Eviplera, is our second complete single tablet regimen for the treatment of HIV and is a fixed-dose combination of our antiretroviral medications, Viread and Emtriva, and Janssen's non-nucleoside reverse transcriptase inhibitor, Edurant (rilpivirine). Atripla is an oral formulation dosed once a day for the treatment of HIV infection in adults. Atripla is our first single tablet regimen for HIV intended as a stand-alone therapy or in combination with other antiretrovirals. It is a fixeddose combination of our antiretroviral medications, Viread and Emtriva, and Bristol-Myers Squibb Company's (BMS's) non-nucleoside reverse transcriptase inhibitor, Sustiva (efavirenz). Truvada (emtricitabine and tenofovir disoproxil fumarate) is an oral formulation dosed once a day as part of combination therapy to treat HIV infection in adults. It is a fixed-dose combination of our antiretroviral medications, Viread and Emtriva. FDA also approved Truvada, in combination with safer sex practices, to reduce the risk of sexually acquired HIV1 infection in adults at high risk; a strategy called pre-exposure prophylaxis (PrEP). Viread is an oral formulation of a nucleotide analog reverse transcriptase inhibitor, dosed once a day as part of combination therapy to treat HIV infection in patients two years of age and older. The European Commission also approved the use of Viread in combination with other antiretroviral agents for the treatment of HIV-1 infected adolescent patients aged two to less than 18 years with nucleoside reverse transcriptase inhibitor resistance or toxicities precluding the use of first-line pediatric agents. Viread is also approved for the treatment of chronic HBV. Emtriva is an oral formulation of a nucleoside analog reverse transcriptase inhibitor, dosed once a day as part of combination therapy to treat HIV infection in adults. In the United States and Europe, Emtriva is also available as an oral solution approved as part of combination therapy to treat HIV infection in children. Tybost isa pharmacokinetic enhancer dosed once a day that boosts blood levels of certain HIV medicines. Tybost is indicated as a boosting agent for the HIV protease inhibitors atazanavir and darunavir as part of antiretroviral combination therapy in adults with HIV-1 infection. Vitekta is an oral formulation of an integrase inhibitor, dosed once a day as part of combination therapy to treat HIV infection in adults without known mutations associated with resistance to elvitegravir, the active ingredient of Vitekta. Vitekta is indicated for use as part of HIV treatment regimens that include a ritonavir-boosted protease inhibitor. 5 Liver Diseases Harvoni is an oral formulation of the NS5A inhibitor with a nucleotide analog polymerase inhibitor dosed once a day for the treatment of genotypes 1, 4, 5 and 6, HCV/HIV-1 co-infection, HCV genotype 1 and 4 liver transplant recipients, and genotype 1-infected patients with decompensated cirrhosis. In Europe, Harvoni is also indicated for certain patients with HCV genotype 4 infection, HCV genotype 3 infection with cirrhosis and/or prior treatment failure and those with HCV/HIV-1 co-infection. Sovaldi is an oral formulation of a nucleotide analog polymerase inhibitor dosed once a day for the treatment of HCV as a component of a combination antiviral treatment regimen. Sovaldi's efficacy has been established in patients with HCV genotypes 1, 2, 3 or 4 infection (in United States and Europe) and genotypes 5 and 6 infection (in Europe), including those with hepatocellular carcinoma meeting Milan criteria (awaiting liver transplantation) and those with HCV/HIV-1 coinfection. Viread is an oral formulation of a nucleotide analog reverse transcriptase inhibitor, dosed once a day for the treatment of chronic HBV in adults with compensated and decompensated liver disease. We licensed to GlaxoSmithKline Inc. (GSK) the rights to commercialize Viread for the treatment of chronic HBV in China, Japan and Saudi Arabia. In 2012, the European Commission approved the use of Viread for the treatment of chronic HBV infection in adolescent patients aged 12 to less than 18 years with compensated liver disease and evidence of immune active disease. Viread is also approved for the treatment of HIV infection. Hepsera (adefovir dipivoxil) is an oral formulation of a nucleotide analog polymerase inhibitor, dosed once a day to treat chronic HBV in patients 12 years of age and older. We licensed to GSK the rights to commercialize Hepsera for the treatment of chronic HBV in Asia Pacific, Latin America and certain other territories. Cardiovascular Letairis (ambrisentan) is an oral formulation of an endothelin receptor antagonist (ERA) indicated for the treatment of pulmonary arterial hypertension (PAH) (World Health Organization (WHO) Group 1) in patients with WHO Class II or III symptoms to improve exercise capacity and delay clinical worsening. We sublicensed to GSK the rights to ambrisentan, marketed by GSK as Volibris (ambrisentan), for PAH in territories outside of the United States. Ranexa(ranolazine) is an extended-release tablet for the treatment of chronic angina. We have licensed to Menarini International Operations Luxembourg SA the rights to Ranexa in territories outside of the United States. Lexiscan/Rapiscan (regadenoson) injection is indicated for use as a pharmacologic stress agent in radionuclide myocardial perfusion imaging (MPI), a test that detects and characterizes coronary artery disease, in patients unable to undergo adequate exercise stress. Astellas US LLC (Astellas) has exclusive rights to manufacture and sell regadenoson under the name Lexiscan in the United States. Rapidscan Pharma Solutions, Inc. (RPS) holds the exclusive right to manufacture and sell regadenoson under the name Rapiscan in Europe and certain territories outside the United States. We receive royalties from Astellas and RPS for sales in these territories. Hematology/Oncology Zydelig is a first-in-class PI3K delta inhibitor for the treatment of certain blood cancers. In the United States, Zydelig is approved in combination with rituximab for patients with relapsed chronic lymphocytic leukemia (CLL) for whom rituximab alone would be considered appropriate therapy and as monotherapy for patients with relapsed follicular B-cell non-Hodgkin lymphoma (FL) and small lymphocytic lymphoma (SLL) who have received at least two prior systemic therapies. In the European Union, Zydelig is approved for the treatment of CLL and FL. Inflammation/Respiratory Cayston (aztreonam for inhalation solution) is an inhaled antibiotic for the treatment of respiratory systems in cystic fibrosis (CF) patients seven years of age and older with Pseudomonas aeruginosa (P. aeruginosa) . Tamiflu (oseltamivir phosphate) is an oral antiviral available in capsule form for the treatment and prevention of influenza A and B. Tamiflu is approved for the treatment of influenza in children and adults in more than 60 countries, including the United States, Japan and the European Union. Tamiflu is also approved for the prevention of influenza in children and adults in the United States, Japan and the European Union. We developed Tamiflu with F. Hoffmann-La Roche Ltd (together with Hoffmann-La Roche Inc., Roche). Roche has the 6 exclusive right to manufacture and sell Tamiflu worldwide, subject to its obligation to pay us royalties based on a percentage of the net sales of Tamiflu. Other AmBisome(amphotericin B liposome for injection) is a proprietary liposomal formulation of amphotericin B, an antifungal agent to treat serious invasive fungal infections caused by various fungal species in adults. Our corporate partner, Astellas Pharma US, Inc., promotes and sells AmBisome in the United States and Canada, and we promote and sell AmBisome in Europe, Australia and New Zealand. Macugen (pegaptanib sodium injection) is an intravitreal injection of an anti-angiogenic oligonucleotide for the treatment of neovascular age-related macular degeneration. Macugen was developed by Eyetech Inc. (Eyetech) using technology licensed from us and is now promoted in the United States by Valeant Pharmaceuticals, Inc. (Valeant), which acquired Eyetech in 2012. Valeant holds the exclusive rights to manufacture and sell Macugen in the United States, and Pfizer Inc. (Pfizer) holds the exclusive right to manufacture and sell Macugen in the rest of the world. We receive royalties from Valeant and Pfizer based on worldwide sales of Macugen. Sales of our antiviral products, which include products in our HIV and liver diseases areas described above, were $30.2 billion in 2015, $22.8 billion in 2014 and $9.3 billion in 2013 and represented 93% of our total revenues in 2015, 92% of our total revenues in 2014 and 83% of our total revenues in 2013. Sales of our other products were $1.9 billion in 2015, $1.7 billion in 2014 and $1.5 billion in 2013 and represented 6% of our total revenues in 2015, 7% of our total revenues in 2014 and 13% of our total revenues in 2013. See Item 7, Management's Discussion and Analysis and Item 8, Note 15 Segment Information in our Consolidated Financial Statements included in this Annual Report on Form 10-K for further information related to sales by product. Commercialization and Distribution We have U.S. and international commercial sales operations, with marketing subsidiaries in over 30 countries. Our products are marketed through our commercial teams and/or in conjunction with third-party distributors and corporate partners. Our commercial teams promote our products through direct field contact with physicians, hospitals, clinics and other healthcare providers. We generally grant our third-party distributors the exclusive right to promote our product in a territory for a specified period of time. Most of our agreements with these distributors provide for collaborative efforts between the distributor and Gilead in obtaining and maintaining regulatory approval for the product in the specified territory. We sell and distribute Harvoni, Sovaldi, Truvada, Atripla, Stribild, Complera, Viread, Genvoya, Emtriva, Tybost, Vitekta, Ranexa, AmBisome, Zydelig and Hepsera in the United States exclusively through the wholesale channel. Our product sales to three large wholesalers, Cardinal Health, Inc., McKesson Corporation and AmerisourceBergen Corporation, each accounted for more than 10% of total revenues for each of the years ended December 31, 2015, 2014 and 2013. On a combined basis, in 2015, these wholesalers accounted for approximately 89% of our product sales in the United States and approximately 58% of our total worldwide revenues. Letairis and Cayston are distributed exclusively by specialty pharmacies. These specialty pharmacies dispense medications for complex or chronic conditions that require a high level of patient education and ongoing counseling. We sell and distribute Harvoni, Sovaldi, Truvada, Atripla, Stribild, Eviplera, Viread, Emtriva, Tybost, Vitekta, Genvoya, Ranexa, AmBisome, Zydelig and Hepsera in Europe and countries outside the United States where the product is approved, either through our commercial teams, thirdparty distributors or corporate partners. U.S. Patient Access We make it a priority to increase access to our medicines for people who can benefit from them, regardless of their ability to pay. In the United States, our U.S. patient assistance programs help make our therapies accessible for uninsured individuals and those who need financial assistance. We also support programs for those unable to afford the co-payments associated with health insurance programs. Half of all patients taking our HIV medicines in the United States already receive them through federal and state programs at substantially discounted prices. We have a long history of working with state AIDS Drug Assistance Programs (ADAPs) to provide lower pricing for our HIV medicines. The price freeze we instituted for ADAPs in 2008 was extended in 2013 through the end of 2016, providing important support to these critical programs as they evolve in the changing U.S. healthcare environment. 7 Access in the Developing World Through the Gilead Access Program, established in 2003, certain of our products for HIV/AIDS, viral hepatitis and visceral leishmaniasis are available at substantially reduced prices in the developing world. We work with a network of regional business partners, generic licensing partners, the Medicines Patent Pool and other stakeholders to expand treatment globally. We have also entered into a number of collaborations related to access to our products in the developing world, which include: Licenses with Generic Manufacturers. We have entered into non-exclusive license agreements with Indian generic manufacturers, granting them rights to produce and distribute generic versions of TDF, emtricitabine, cobicistat, elvitegravir, including generic versions of combination product containing cobicistat, elvitegravir, TDF and emtricitabine for the treatment of HIV infection to low income countries around the world, which include India and many countries in our Gilead Access Program. We also included in these non-exclusive license agreements the ability to manufacture and distribute generic versions of TDF for the treatment of HBV in the same countries where they are authorized to sell generic versions of TDF for HIV. In 2014, we granted certain of our Indian partners direct licenses to produce and distribute generic TAF in the developing world, including single tablet regimens containing emtricitabine and fixed-dose combinations of TAF and emtricitabine co-formulated with our other HIV medicines. We also entered into collaborations with our Indian partners to produce and distribute generic versions in low-income countries and lower-middle income countries. In early 2015, we expanded our collaborations to allow our Indian partners to manufacture VEL and the single tablet regimen of SOF/VEL, once approved. Medicines Patent Pool (the MPP). In 2011, we entered into an agreement with the MPP, an organization that was established by the United Nations to increase global access to high-quality, low-cost antiretroviral therapy through the sharing of patents. We granted the MPP a non-exclusive license to identify generic pharmaceutical manufacturers in India who specialize in high-quality production of generic medicines and granted sublicenses to those Indian manufacturers to manufacture and distribute generic versions of our antiretrovirals in the developing world. Sublicensees through the MPP will be free to develop combination products and pediatric formulations of our HIV medicines. We also granted the MPP the right to grant sublicenses to generic versions of elvitegravir and cobicistat, the single tablet regimen consisting of elvitegravir, cobicistat, TDF and emtricitabine and TAF for HIV and HBV to developing countries, contingent on the medicine's U.S. regulatory approval. Special Partnerships. We work with national governments and local organizations to increase access to our HIV and HCV medicines and strengthen healthcare systems. For example, we have established an agreement with the National AIDS Program of Myanmar to donate a generic version of our Atripla to 2,000 people living with HIV in the country, as well as provide HIV educational activities and financial support to strengthen the country's health system. In Tanzania, we launched an HIV \"test-and-treat\" demonstration project with the Holy See's Good Samaritan Foundation. The program's goal is to enable screening of 120,000 patients for HIV and provide HIV therapy to 20,000 HIV-positive individuals over five years. In Egypt, we have agreed to provide Sovaldi and Harvoni to the Egyptian Ministry of Health at a significantly reduced price. In addition, in partnership with the Ministry of Health, we invest in local HCV medical education and prevention efforts, as well as screening and patient awareness initiatives. In Georgia, we established an agreement with the Ministry of Labor, Health and Social Affairs of Georgia to help eliminate HCV in the country. The project aims to reduce the number of Georgians infected with HCV and lower the rate of new infections through universal screening, treatment, prevention and surveillance. Competition Our marketed products target a number of areas, including HIV, liver diseases, hematology/oncology, cardiovascular, inflammation/respiratory and other diseases. There are many commercially available products for the treatment of these diseases. We face significant competition from large global pharmaceutical and biotechnology companies, specialized pharmaceutical firms and generic drug manufacturers. Our products compete with other available products based primarily on efficacy, safety, tolerability, acceptance by doctors, ease of patient compliance, ease of use, price, insurance and other reimbursement coverage, distribution and marketing. 8 Our HIV Products The HIV landscape is becoming more competitive and complex as treatment trends continue to evolve. A growing number of HIV drugs are currently sold or are in advanced stages of clinical development. Competition from current and expected competitors may erode the revenues we receive from sales of our HIV products. Our HIV products compete primarily with products from ViiV Healthcare (ViiV), which markets fixed-dose combination products that compete with Genvoya, Stribild, Complera/Eviplera, Atripla and Truvada. For example, two products marketed by ViiV, Tivicay (dolutegravir), an integrase inhibitor, and Triumeq (dolutegravir/abacavir/lamivudine), a single tablet antiretroviral regimen, could adversely impact sales of our HIV products. In addition, ViiV's lamivudine competes with emtricitabine, the active pharmaceutical ingredient of Emtriva and a component of Genvoya, Stribild, Complera/Eviplera, Atripla and Truvada. For Tybost, we compete with ritonavir, marketed by AbbVie Inc. (AbbVie). We also face competition from generic HIV products. Generic versions of lamivudine and Combivir (lamivudine and zidovudine) are available in the United States and certain other countries. Generic versions of Sustiva (efavirenz), a component of our Atripla, are now available in Canada and Europe and we anticipate competition from generic efavirenz in the United States in December 2017. We have observed some pricing pressure related to the Sustiva component of our Atripla sales. Our Liver Diseases Products Our HCV products, Harvoni and Sovaldi, compete with Viekira Pak (ombitasvir, paritaprevir and ritonavir tablets co-packaged with dasabuvir tablets) marketed by AbbVie, Zepatier (elbasvir and grazoprevir) marketed by Merck & Co. Inc. (Merck), Daklinza (daclastavir) marketed by Bristol-Myers Squibb Company (BMS) and Olysio (simeprevir) marketed by Janssen Therapeutics. Our HBV products, Viread and Hepsera, face competition from existing and expected therapies for treating patients with HBV. Our HBV products face competition from Baraclude (entecavir), an oral nucleoside analog marketed by BMS, as well as generic entecavir. Our HBV products also compete with Tyzeka/Sebivo (telbivudine), an oral nucleoside analog marketed by Novartis Pharmaceuticals Corporation (Novartis). Our Cardiovascular Products Letairis competes with Tracleer (bosentan) and Opsumit (macitentan) marketed by Actelion Pharmaceuticals US, Inc. and also with Adcirca (tadalafil) marketed by United Therapeutics Corporation and Pfizer Inc. (Pfizer). Ranexa competes predominantly with generic compounds from three distinct classes of drugs for the treatment of chronic angina in the United States, including generic and/or branded beta-blockers, calcium channel blockers and long-acting nitrates. In addition, surgical treatments and interventions such as coronary artery bypass grafting and percutaneous coronary intervention can be another option for angina patients, which may be perceived by healthcare practitioners as preferred methods to treat the cardiovascular disease that underlies and causes angina. There are numerous marketed generic and/or branded pharmacologic stress agents that compete with Lexiscan/Rapiscan. Our Hematology/Oncology Products Zydelig competes with Imbruvica (ibrutinib) marketed by Pharmacyclics, Inc., Gazyva (obinutuzumab) marketed by Genentech (a member of the Roche Group) and Treanda (bendamustine hydrochloride) marketed by Cephalon, Inc. Our Inflammation/Respiratory Products Cayston competes primarily with Tobi (tobramycin inhalation solution), an inhaled medication marketed by Novartis for the treatment of cystic fibrosis patients whose lungs contain P. aeruginosa , a bacterial infection. Tamiflu competes with Relenza (zanamivir), an influenza neuraminidase inhibitor marketed by GlaxoSmithKline, and products sold by generic competitors. 9 Our Other Products AmBisome competes with Vfend (voriconazole) marketed by Pfizer and caspofungin, a product developed by Merck that is marketed as Cancidas in the United States and as Caspofungin elsewhere. AmBisome also competes with other lipid-based amphotericin B products, including Abelcet (amphotericin B lipid complex injection), sold by Enzon Pharmaceuticals, Inc. in the United States, Canada and Japan and by Zeneus Pharma Ltd. in Europe; Amphotec (amphotericin B cholesteryl sulfate complex for injection), sold by Three Rivers Pharmaceuticals, LLC worldwide; and Anfogen (amphotericin B liposomal), sold by Genpharma, S.A. in Argentina. BMS and numerous generic manufacturers sell conventional amphotericin B, which also competes with AmBisome. In addition, we are aware of at least three lipid formulations that claim similarity to AmBisome becoming available outside of the United States. These formulations may reduce market demand for AmBisome. Furthermore, the manufacture of lipid formulations of amphotericin B is very complex, and if any of these formulations are found to be unsafe, sales of AmBisome may be negatively impacted by association. In addition, a number of companies are pursuing the development of technologies which are competitive with our existing products or research programs. These competing companies include specialized pharmaceutical firms and large pharmaceutical companies acting either independently or together with other pharmaceutical companies. Furthermore, academic institutions, government agencies and other public and private organizations conducting research may seek patent protection and may establish collaborative arrangements for competitive products and programs. If any of these competitors gain market share on our products, it could adversely affect our results of operations and stock price. Collaborative Relationships As part of our business strategy, we establish collaborations with other companies, universities and medical research institutions to assist in the clinical development and/or commercialization of certain of our products and product candidates and to provide support for our research programs. We also evaluate opportunities for acquiring products or rights to products and technologies that are complementary to our business from other companies, universities and medical research institutions. For more information regarding certain of these relationships, including their ongoing financial and accounting impact on our business, see Item 8, Note 9 Collaborative Arrangements in our Consolidated Financial Statements included in this Annual Report on Form 10-K. Commercial Collaborations Although we currently have a number of collaborations with corporate partners for the manufacture, sale, distribution and/or marketing of our products in various territories worldwide, the following commercial collaborations are those that are most significant to us from a financial statement perspective and where significant ongoing collaboration activity exists. BMS. In 2004, we entered into a collaboration arrangement with BMS to develop and commercialize a single tablet regimen containing our Truvada and BMS's Sustiva (efavirenz) in the United States. This combination was approved for use in the United States in 2006 and is sold under the brand name Atripla. We and BMS structured this collaboration as a joint venture that operates as a limited liability company named Bristol-Myers Squibb & Gilead Sciences, LLC, which we consolidate. We and BMS granted royalty-free sublicenses to the joint venture for the use of our respective company owned technologies and, in return, were granted a license by the joint venture to use any intellectual property that results from the collaboration. In 2006, we and BMS amended the joint venture's collaboration agreement to allow the joint venture to sell Atripla in Canada. The economic interests of the joint venture held by us and BMS (including share of revenues and out-of-pocket expenses) are based on the portion of the net selling price of Atripla attributable to efavirenz and Truvada. Since the net selling price for Truvada may change over time relative to the net selling price of efavirenz, both our and BMS's respective economic interests in the joint venture may vary annually. We and BMS shared marketing and sales efforts. Starting in 2011, except for a limited number of activities that are jointly managed, the parties no longer coordinate detailing and promotional activities in the United States, and the parties have reduced their joint promotional efforts since we launched Complera in August 2011 and Stribild in August 2012. Efavirenz purchased by the joint venture from BMS at BMS's estimated net selling price of efavirenz is included in inventories on our Consolidated Balance Sheets as of December 31, 2015 and 2014.The agreement will continue until terminated by the mutual agreement of the parties. In addition, either party may terminate the other party's participation in the collaboration within 30 days after the launch of at least one generic version of such other party's single agent products (or the double agent products). The terminating party then has the right to continue to sell Atripla and become the continuing party, but will be obligated to pay the terminated party certain royalties for a three-year period following the effective date of the termination. In 2007, Gilead Sciences Ireland Unlimited Company, our wholly-owned subsidiary, and BMS entered into a collaboration agreement under which we and BMS commercialize and distribute Atripla in the European Union, Iceland, Liechtenstein, Norway and Switzerland (collectively, the European Territory). The parties formed a 10 limited liability company which we consolidate, to manufacture Atripla for distribution in the European Territory using efavirenz that it purchases from BMS at BMS's estimated net selling price of efavirenz in the European Territory. Starting in 2012, except for a limited number of activities that are jointly managed, the parties no longer coordinate detailing and promotional activities in the region. Efavirenz purchased from BMS at BMS's estimated net selling price of efavirenz in the European Territory is included in inventories on our Consolidated Balance Sheets as of December 31, 2015 and 2014. The agreement will terminate upon the expiration of the last-to-expire patent which affords market exclusivity to Atripla or one of its components in the European Territory. In addition, either party may terminate the agreement for any reason and such termination will be effective two calendar quarters after notice of termination. The non-terminating party has the right to continue to sell Atripla and become the continuing party, but will be obligated to pay the terminating party certain royalties for a three-year period following the effective date of the termination. In the event the continuing party decides not to sell Atripla, the effective date of the termination will be the date Atripla is withdrawn in each country or the date on which a third party assumes distribution of Atripla, whichever is earlier. Janssen. In 2009, we entered into a collaboration agreement with Janssen to develop and commercialize a fixed-dose combination of our Truvada and Janssen's rilpivirine. The agreement was amended in 2011, 2013 and 2014. The combination was approved in the United States and European Union in 2011 and is sold under the brand name Complera in the United States and Eviplera in the European Union. The 2014 amendment expanded the collaboration to include another single tablet regimen containing Janssen's rilpivirine and our emtricitabine and tenofovir alafenamide (R/F/TAF). Under the agreement, Janssen granted us an exclusive license to Complera/Eviplera and R/F/TAF worldwide but has the right to distribute both combination products in 18 countries including Mexico, Russia and Japan. Neither party is restricted from combining its drugs with any other drug products except those which are similar to the components of Complera/Eviplera and R/F/TAF. We are responsible for manufacturing Complera/Eviplera and R/F/TAF and have the lead role in registration, distribution and commercialization of both products except in the countries where Janssen distributes. Janssen has exercised a right to co-detail the combination product in some of the countries where Gilead is the selling party. The selling party sets the price of the products and the parties share revenues based on the ratio of the net selling prices of the party's component(s), subject to certain restrictions and adjustments. We retain a specified percentage of Janssen's share of revenues, up to 30% in major markets. Either party may terminate the collaboration agreement with respect to a product and a country if the product is withdrawn from the market in such country or with respect to a product in all countries if the other party materially breaches the agreement with respect to a product. The agreement and the parties' obligation to share revenues will expire on a product-by-product and country-by-country basis as Janssen patents providing exclusivity for the product expire or, if later, on the tenth anniversary of the commercial launch for such product. We may terminate the agreement without cause with respect to the countries where we sell the products in which case Janssen has the right to become the selling party for such country if the product has launched but has been on the market for fewer than 10 years. Japan Tobacco. In 2005, Japan Tobacco Inc. (Japan Tobacco) granted us exclusive rights to develop and commercialize elvitegravir, a novel HIV integrase inhibitor, in all countries of the world, excluding Japan, where Japan Tobacco retained such rights. Under the agreement, we are responsible for seeking regulatory approval in our territories and are required to use diligent efforts to commercialize elvitegravir for the treatment of HIV infection. We bear all costs and expenses associated with such commercialization efforts. We received approval of Stribild (an elvitegravir-containing product) from FDA in August 2012 and from the European Commission in May 2013. We received approval of Genvoya (an elvitegravir-containing product) from FDA and the European Commission in November 2015. The agreement and our obligation to pay royalties to Japan Tobacco will terminate on a product-by-product basis as patents providing exclusivity for the product expire or, if later, on the tenth anniversary of commercial launch for such product. We may terminate the agreement for any reason in which case the license granted by Japan Tobacco to us would terminate. Either party may terminate the agreement in response to a material breach by the other party. Research Collaborations We have a number of collaborations with partners for the research and development (R&D) of certain compounds and drug candidates. None of our research collaborations are significant to us from a financial statement perspective. 11 Research and Development Our R&D philosophy and strategy is to develop best-in-class drugs that improve safety or efficacy for unmet medical needs. We intend to continue committing significant resources to internal R&D opportunities and external business development activity. Our product development efforts cover a wide range of medical conditions, including HIV/AIDS and liver diseases such as HBV and HCV, inflammation/oncology and serious cardiovascular and respiratory conditions. We have research scientists in Foster City, Fremont, San Dimas and Oceanside, California; Seattle, Washington; and Alberta, Canada engaged in the discovery and development of new molecules and technologies that we hope will lead to the approval of new medicines addressing unmet needs. The development of our product candidates is subject to various risks and uncertainties. These risks and uncertainties include our ability to enroll patients in clinical trials, the possibility of unfavorable results of our clinical trials, the need to modify or delay our clinical trials or to perform additional trials and the risk of failing to obtain regulatory approvals. As a result, our product candidates may never be successfully commercialized. Drug development is inherently risky and many product candidates fail during the drug development process. Below is a summary of our key product candidates and their corresponding current stages of development. Product Candidates for the Treatment of HIV Product Candidates Marketing Applications Pending Fixed-dose co-formulation of emtricitabine and TAF (F/TAF) Single tablet regimen of emtricitabine, rilpivirine and TAF (R/F/TAF) Description A fixed-dose co-formulation of emtricitabine and TAF is being evaluated for the treatment of HIV infection. Under an agreement with Janssen, a single tablet regimen of emtricitabine, rilpivirine and TAF is being evaluated for the treatment of HIV infection. Product in Phase 3 Single tablet regimen of GS-9883 (non- A single tablet regimen of GS-9883 and F/TAF is being evaluated for the treatment of HIV boosted integrase inhibitor) and F/TAF infection. Product in Phase 1 GS-9620 GS-9620, a TLR-7 agonist, is being evaluated for the treatment of HIV infection. Product Candidates for the Treatment of Liver Diseases Product Candidates Description Market Applications Pending Single tablet regimen of sofosbuvir (SOF) and velpatasvir (VEL) TAF A single tablet regimen of sofosbuvir and velpatasvir, a nucleotide NS5B inhibitor/pangenotypic NS5A inhibitor, is being evaluated for the treatment of HCV. TAF is a nucleotide reverse transcriptase inhibitor being evaluated for the treatment of HBV. Product in Phase 3 Single tablet regimen of GS-9857 and SOF/VEL A single tablet regimen of GS-9857, a pan-genotypic NS3 protease inhibitor, and SOF/VEL is being evaluated for the treatment of HCV. Products in Phase 2 GS-4774 GS-9620 Simtuzumab GS-4997 GS-4774, a Tarmogen T cell immunity stimulator, is being evaluated for the treatment of HBV. GS-9620 is being evaluated for the treatment of HBV. Simtuzumab, a monoclonal antibody, is being evaluated for the treatment of NASH and primary sclerosing cholangitis. GS-4997, an ASK-1 inhibitor, is being evaluated for the treatment of diabetic nephropathy and NASH. 12 Product Candidates for the Treatment of Cardiovascular Diseases Product Candidates Product in Phase 3 Eleclazine Products in Phase 2 Eleclazine GS-4997 Description Eleclazine, a late sodium current inhibitor, is being evaluated for the treatment of Long QT3 Syndrome. Eleclazine is being evaluated for the treatment of hypertrophic cardiomyopathy and ventricular tachycardia/ventricular fibrillation. GS-4997 is being evaluated for the treatment of pulmonary arterial hypertension. Product Candidates for the Treatment of Hematology/Oncology Product Candidates Products in Phase 3 Idelalisib Momelotinib GS-5745 Products in Phase 2 Entospletinib Idelalisib Products in Phase 1 GS-4059 GS-5745 GS-5829 Description Idelalisib, a PI3K delta inhibitor, is being evaluated for the treatment of frontline and relapsed refractory CLL and relapsed refractory iNHL. Momelotinib, a JAK inhibitor, is being evaluated for the treatment of myelofibrosis and pancreatic cancer. GS-5745, a MMP9 maB inhibitor, is being evaluated for the treatment of gastric cancer. Entospletinib, a spleen tyrosine kinase (Syk) inhibitor, is being evaluated for the treatment of hematological malignancies. Idelalisib is being evaluated for the treatment of frontline iNHL. GS-4059, a Bruton's tyrosine kinase inhibitor, is being evaluated for the treatment of B-cell malignancies. GS-5745 is being evaluated for the treatment of solid tumors. GS-5829, a bromodomain and extra-terminal (BET) inhibitor, is being evaluated for the treatment of solid tumors. Product Candidates for the Treatment of Inflammation/Respiratory Diseases Product Candidates Description Products in Phase 2 Filgotinib GS-5745 Presatovir Products in Phase 1 GS-5745 GS-9876 Filgotinib, a JAK1-selective inhibitor, is being evaluated for the treatment of rheumatoid arthritis and Crohn's Disease. GS-5745 is being evaluated for the treatment of ulcerative colitis and Crohn's Disease. Presatovir, a fusion inhibitor, is being evaluated for the treatment of respiratory syncytial virus. GS-5745 is being evaluated for the treatment of chronic obstructive pulmonary disease and rheumatoid arthritis. GS-9876, a Syk inhibitor, is being evaluated for the treatment of rheumatoid arthritis. 13 Other Product Candidates Product Candidates Product in Phase 2 GS-4997 Product in Phase 1 GS-5734 Description GS-4997 is being evaluated for the treatment of Diabetic Nephropathy. GS-5734, a nucleotide prodrug, is being evaluated for the treatment of Ebola. In total, our R&D expenses were $3.0 billion for 2015, $2.9 billion for 2014 and $2.1 billion for 2013. In addition to our internal discovery and clinical development programs, we seek to add to our portfolio of products through product acquisitions, licenses and collaborations. We entered into a license and collaboration agreement with Galapagos NV (Galapagos), a clinical-stage biotechnology company based in Belgium, for the development and commercialization of filgotinib, a JAK1-selective inhibitor being investigated for inflammatory disease indications. The agreement became effective on January 19, 2016. Phase 3 trials in rheumatoid arthritis and Crohn's Disease are expected to start in 2016. Patents and Proprietary Rights U.S. and European Patent Expiration We have a number of U.S. and foreign patents, patent applications and rights to patents related to our compounds, products and technology, but we cannot be certain that issued patents will be enforceable or provide adequate protection or that pending patent applications will result in issued patents. The following table shows the estimated expiration dates (including Patent Term Extension, Supplementary Protection Certificates and/or Pediatric exclusivity where granted) in the United States and Europe for the primary (typically compound) patents for our Phase 3 product candidates. Patents do not cover the ranolazine compound, the active ingredient of Ranexa. Instead, when it was discovered that only a sustained-release formulation of ranolazine would achieve therapeutic plasma levels, patents were obtained on those formulations and the characteristic plasma levels they achieve. For our product candidates that are single tablet regimens, the estimated patent expiration date provided corresponds to the latest expiring compound patent for one of the active ingredients in the single tablet regimen. Phase 3 Product Candidates Product Candidates for the Treatment of HIV Single tablet regimen of emtricitabine and TAF Single tablet regimen of darunavir, cobicistat, emtricitabine and TAF Single tablet regimen of emtricitabine, rilpivirine and TAF Single tablet regimen of GS-9883 and F/TAF Product Candidates for the Treatment of Liver Diseases Single tablet regimen of sofosbuvir and velpatasvir for the treatment of HCV Single tablet regimen of sofosbuvir, velpatasvir and GS-9857 for the treatment of HCV Single agent TAF for the treatment of HBV Product Candidates for the Treatment of Oncology/Inflammation Idelalisib for the treatment of frontline and relapsed refractory CLL and relapsed refractory iNHL. Momelotinib for the treatment of myelofibrosis and pancreatic cancer GS-5745 for the treatment of gastric cancer Product Candidates for the Treatment of Cardiovascular Diseases Eleclazine (formerly known as GS-6615) for the treatment of LQT-3 Syndrome Patent Expiration U.S. 2022 2029 2022 2033 E.U. 2021 2027 2022 (2033) 2032 (2033) 2022 2032 (2033) 2021 2025 2030 2031 (2025) 2028 (2031) 2032 (2032) Dates in parentheses reflect the estimated expiration date of patents which may issue from currently pending applications. The estimated expiration dates do not include any potential additional exclusivity (e.g., patent term extension, supplementary protection certificates or pediatric exclusivity) that has not yet been granted. 14 The following table shows the actual or estimated expiration dates (including Patent Term Extension, Supplementary Protection Certificates and/or Pediatric exclusivity where granted) in the United States and Europe for the primary (typically compound) patents for our marketed products. For our product that are fixed-dose combinations or single tablet regimens (e.g., Truvada, Atripla, Complera/Eviplera, Stribild and Genvoya), the estimated patent expiration dates provided correspond to the latest expiring compound patent for one of the active ingredients in the single tablet regimen. Products Patent Expiration U.S. 2014 Hepsera AmBisome Macugen Tamiflu Letairis Viread E.U. 2016 2008 2017 2016 2020 2017 Ranexa 2016 2017 2017 2018 2018* 2019** Atripla Cayston 2021 2021 2017 2021 Emtriva 2021 2016 Truvada Lexiscan 2021 2022 2017 2025 Complera/Eviplera Vitekta Zydelig Sovaldi Stribild Genvoya Tybost Harvoni 2022 2023 2025 2029 2029 2029 2029 2030 2022 2028 (2025) 2028 2028 2028 2027 2030 2023 Dates in parentheses reflect the estimated expiration date of patents which may issue from currently pending applications. The estimated expiration dates do not include any potential additional exclusivity (e.g., patent term extension, supplementary protection certificates or pediatric exclusivity) that has not yet been granted. * In 2013, Gilead and Teva Pharmaceuticals (Teva) reached an agreement in principle to settle the ongoing patent litigation concerning the four patents that protect tenofovir disoproxil fumarate in our Viread, Truvada and Atripla products. Under the agreement, Teva will be allowed to launch a generic version of Viread on December 15, 2017. ** In 2013, Gilead and Lupin Limited (Lupin) reached an agreement to settle the patent litigation prior to issuance of the court's decision. Under the agreement, Lupin will be allowed to launch a generic version of Ranexa on February 27, 2019. Patent Protection and Certain Challenges Patents and other proprietary rights are very important to our business. If we have a properly drafted and enforceable patent, it can be more difficult for our competitors to use our technology to create competitive products and more difficult for our competitors to obtain a patent that prevents us from using technology we create. As part of our business strategy, we actively seek patent protection both in the United States and internationally and file additional patent applications, when appropriate, to cover improvements in our compounds, products and technology. Patents covering certain of the active pharmaceutical ingredients of Truvada, Atripla, Stribild, Complera/Eviplera, Genvoya, Vitekta, Emtriva, Letairis, and Hepsera are held by third parties. We acquired exclusive rights to these patents in the agreements we have with these parties. Patents do not cover the ranolazine compound, the