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====Pafase====
====Pafase====
{{Anchor|Pafase}}
{{Anchor|Pafase}}
{{See also|Lipoprotein-associated phospholipase A2}}


Pafase, also known as rPAF-AH, was developed to treat severe [[sepsis]].<ref name="pafase">{{cite news |title=Icos Drug Pafase Hits a Dead End |work=[[The Seattle Times]] |page=D1 |date=December 20, 2002 |accessdate=January 10, 2009 |url=http://community.seattletimes.nwsource.com/archive/?date=20021220&slug=icos200}}</ref> Pafase is an [[enzyme]] made naturally by [[macrophage]]s and found in human [[blood]].<ref name="ards">{{cite news |first=Lee |last=Siegel |title=New Drug Holds Hope Against Lung Ailment |work=[[The Salt Lake Tribune]] |page=C2 |date=June 1, 2000}}</ref> The enzyme was discovered in the mid 1980s by [[graduate student]] Diana Stafforini, Steve Prescott, Guy Zimmerman, and Tom McIntyre.<ref name="ards"></ref> It inhibits a compound involved in inflammatory reactions leading to sepsis.<ref name="pafase"></ref> The [[gene]] for Pafase was discovered by Icos.<ref>{{cite journal |last=Tjoelker |first=T |coauthors=Wilder C, Eberhardt C, Stafforini DM, Dietsch G, Schimpf B, Hooper S, Le Trong H, Cousens LS, Zimmerman GA, et al |date=April 6, 1995 |title=Anti-inflammatory properties of a platelet-activating factor acetylhydrolase |journal=[[Nature (journal)|Nature]] |volume=374 |issue=6522 |pages=549&ndash;53 |pmid=7700381 |doi=10.1038/374549a0}}</ref> Early trials for sepsis showed that the drug reduced the death rate after 28&nbsp;days and patients were less likely to develop severe respiratory problems.<ref name="pafase"></ref> Icos also tested Pafase for [[acute respiratory distress syndrome]] (ARDS).<ref name="ards"></ref> In phase&nbsp;II trials for ARDS, Pafase reduced the death rate after 28&nbsp;days and reduced the chance that the [[lung]]s of the patient would fail.<ref name="ards"></ref> Icos halted development in December&nbsp;2002 when phase&nbsp;III trials for sepsis showed that the drug did not help patients survive.<ref name="pafase"></ref> In late 2006, researcher Michael Caplan planned to start clinical trials of Pafase for [[necrotizing enterocolitis]].<ref>{{cite news |first=Luke |last=Timmerman |title=Another Clinical Trial Near From Icos Pipeline |work=[[The Seattle Times]] |page=E1 |date=December 16, 2006 |accessdate=January 10, 2009 |url=http://community.seattletimes.nwsource.com/archive/?date=20061213&slug=icos130}}</ref>
Pafase, also known as rPAF-AH, was developed to treat severe [[sepsis]].<ref name="pafase">{{cite news |title=Icos Drug Pafase Hits a Dead End |work=[[The Seattle Times]] |page=D1 |date=December 20, 2002 |accessdate=January 10, 2009 |url=http://community.seattletimes.nwsource.com/archive/?date=20021220&slug=icos200}}</ref> Pafase is an [[enzyme]] made naturally by [[macrophage]]s and found in human [[blood]].<ref name="ards">{{cite news |first=Lee |last=Siegel |title=New Drug Holds Hope Against Lung Ailment |work=[[The Salt Lake Tribune]] |page=C2 |date=June 1, 2000}}</ref> The enzyme was discovered in the mid 1980s by [[graduate student]] Diana Stafforini, Steve Prescott, Guy Zimmerman, and Tom McIntyre.<ref name="ards"></ref> It inhibits a compound involved in inflammatory reactions leading to sepsis.<ref name="pafase"></ref> The [[gene]] for Pafase was discovered by Icos.<ref>{{cite journal |last=Tjoelker |first=T |coauthors=Wilder C, Eberhardt C, Stafforini DM, Dietsch G, Schimpf B, Hooper S, Le Trong H, Cousens LS, Zimmerman GA, et al |date=April 6, 1995 |title=Anti-inflammatory properties of a platelet-activating factor acetylhydrolase |journal=[[Nature (journal)|Nature]] |volume=374 |issue=6522 |pages=549&ndash;53 |pmid=7700381 |doi=10.1038/374549a0}}</ref> Early trials for sepsis showed that the drug reduced the death rate after 28&nbsp;days and patients were less likely to develop severe respiratory problems.<ref name="pafase"></ref> Icos also tested Pafase for [[acute respiratory distress syndrome]] (ARDS).<ref name="ards"></ref> In phase&nbsp;II trials for ARDS, Pafase reduced the death rate after 28&nbsp;days and reduced the chance that the [[lung]]s of the patient would fail.<ref name="ards"></ref> Icos halted development in December&nbsp;2002 when phase&nbsp;III trials for sepsis showed that the drug did not help patients survive.<ref name="pafase"></ref> Scientists at [[Northwestern University]] studied Pafase for [[necrotizing enterocolitis]],<ref>{{cite news |first=Luke |last=Timmerman |title=Another Clinical Trial Near From Icos Pipeline |work=[[The Seattle Times]] |page=E1 |date=December 16, 2006 |accessdate=January 10, 2009 |url=http://community.seattletimes.nwsource.com/archive/?date=20061213&slug=icos130}}</ref> and there is ongoing research on the enzyme for [[atherosclerosis]] at the [[University of Utah]].<ref>{{cite journal |last=Stafforini |first=Diana M |date=February 2009 |title=Biology of Platelet-activating Factor Acetylhydrolase (PAF-AH, Lipoprotein Associated Phospholipase A2) |journal=Cardiovascular Drugs and Therapy |volume=23 |issue=1 |pages=73&ndash;83 |pmid=18949548 |doi=10.1007/s10557-008-6133-8}}</ref>


====Sitaxsentan sodium and TBC3711====
====Sitaxsentan sodium and TBC3711====

Revision as of 23:00, 10 March 2009

For other uses, see ICOS (disambiguation).
ICOS Corporation
Company typePublic
IndustryBiotechnology
FoundedBothell, Washington, United States (1989 (1989))
FounderGeorge Rathmann
Robert Nowinski
Christopher Henney
DefunctJanuary 29, 2007 (2007-01-29)
FateAcquired, Dissolved
SuccessorCMC ICOS Biologics, Inc.
Headquarters
United States Bothell, Washington
,
United States
Key people
George Rathmann (Founder, CEO, Chairman)
Paul Clark (CEO, Chairman)
ProductsCialis
RevenueUS$ 71,410,000 (2005)[1]
US$ −74,242,000 (2005)[1]
US$ −74,842,000 (2005)[1]
Total assetsUS$ 241,767,000 (2005)[1]
Total equityUS$ −59,270,000 (2005)[1]
Number of employees
700 (2006)

Icos Corporation, trademarked as ICOS, was a biotechnology company based in Bothell, Washington. Icos was the largest biotechnology company in Washington.[2] It began operations in 1990 after being co-founded by George B. Rathmann, previously Chief Executive Officer (CEO) and co-founder of Amgen and a pioneer in the biotechnology industry.[3] The company's focus was developing drugs to treat inflammatory disorders.[3] During its 17-year history, Icos conducted clinical trials of many compounds in the areas of sepsis, multiple sclerosis, ischemic stroke, heart attack, pancreatitis, pulmonary arterial hypertension (PAH), chronic obstructive pulmonary disease (COPD), interstitial cystitis, psoriasis, haemorrhagic shock, sexual dysfunction, benign prostatic hyperplasia (BPH), rheumatoid arthritis, emphysema, chronic bronchitis, and acute respiratory distress syndrome (ARDS). Icos also manufactured antibodies for other biotechnology companies.

Icos is famous for developing the erectile dysfunction drug tadalafil (Cialis). The compound was discovered by GlaxoSmithKline, developed by Icos, and manufactured and marketed by a partnership between Eli Lilly and Company and Icos. Sales from Cialis, helped by the unique advertising campaign led by the Grey Worldwide Agency, brought Icos to profitability.[4] Cialis was the only drug developed by the company to be approved.[4] Eli Lilly bought Icos in 2007, laying off most of its workers.[5] CMC Biopharmaceuticals bought the remnants of Icos, keeping the remaining employees.[5]

History

Icos was founded by George Rathmann, Robert Nowinski, and Christopher Henney in 1989.[6] The name Icos comes from a shortening of the word icosahedron, a 20-sided polyhedron, because many viruses have this shape.[3] The founders raised $33 million in July 1990 from many investors, including Bill Gates.[6] Gates was the largest shareholder at the time, and owned 10 percent of the equity.[6] The company initially had temporary offices in downtown Seattle, but moved to Bothell on September 20, 1990. Icos went public on June 6, 1991, and raised $36 million.[7] George Rathmann, seen as a guiding father to Icos, left the company in February 2000, and was replaced as CEO and chairman by Paul Clark.[8] A former Icos manager has said that the company did not achieve its full potential because of Paul Clark's leadership.[4]

Cialis

Main article: Tadalafil
20 milligram Cialis tablet

Tadalafil, sold as Cialis and initially codenamed IC351, is a drug currently on the market for erectile dysfunction (ED). It is a phosphodiesterase type 5 (PDE5) inhibitor.[9] The drug has undergone clinical trials for benign prostatic hyperplasia (BPH), hypertension, and pulmonary arterial hypertension (PAH), and has also been explored as a treatment for female sexual dysfunction.[10][11] In 2006, Cialis generated $971 million in sales.[12] Revenue from Cialis gave Icos its first-ever quarterly profit in August 2006.[4]

Research and development

Tadalafil was discovered by Glaxo Wellcome (now GlaxoSmithKline) under a partnership between Glaxo and Icos to develop new drugs that began in August 1991.[13][14] The drug was originally researched as a treatment for cardiovascular diseases such as hypertension and angina, but focus quickly shifted to ED with the success of another PDE5 inhibitor sildenafil (Viagra), which had been developed by Pfizer.[13][3] Icos began research on tadalafil in 1993, and clinical trials were undertaken two years later.[9] Although Glaxo had an agreement with Icos to share profits 50/50 for drugs resulting from the partnership, Glaxo let the agreement lapse in 1996 as the drugs developed were not in the company's core markets.[3] In 1998, Icos formed a 50/50 jointly owned venture with Indianapolis-based Eli Lilly (Lilly ICOS LLC) to develop and commercialize tadalafil as Cialis.[10] The release of Cialis in the United States was delayed in April 2002 when the Food and Drug Administration (FDA) recommended that Icos perform more studies, improve labeling, and fix manufacturing issues.[9] Cialis was approved in Europe in November 2002 and in the United States a year later.[9] The drug was approved for once-daily use in Europe in June 2007 and in the United States in January 2008.[15][12]

Lawsuits with Pfizer

Pfizer and Lilly Icos have contested many lawsuits in various countries over Cialis. Pfizer was given a broad patent on PDE5 inhibitors in Britain in 1993.[16] Lilly Icos filed a complaint in a London court in September 1999, and the patent was overturned in November 2000 on the grounds that Pfizer's patent was based on information already in the public domain when the patent was issued.[16][17] In the United States, Pfizer filed suit against Lilly Icos soon after receiving a broad patent for PDE5 inhibitors in October 2002.[18] The United States Patent and Trademark Office (PTO) ordered a reexamination of the patent, and, as in Britain, the examiner found that PDE5 inhibitors were not a new invention by Pfizer, voiding the patent.[19] In Canada, Pfizer moved to block sales of Cialis, arguing that there could be consumer backlash against Pfizer should Cialis be pulled from the market as a result of an ongoing patent lawsuit.[20] A federal judge refused, saying he "cannot imagine demonstrations in the street or storming of the barricades because one impotence medicine is made unavailable."[20]

Blindness warning on label

In May 2005, the FDA began investigating reports of sudden blindness, known as non-arteritic anterior ischemic optic neuropathy (NAION), in sildenafil (Viagra) users.[21] The FDA said it had received reports of the condition, a permanent blindness in one eye, in 38 users of sildenafil and 5 users of tadalafil and vardenafil (Levitra).[21] Lilly Icos voluntarily added a warning on the label of Cialis.[21] The FDA was criticized for its handling of the matter, as an FDA safety officer had commented on unusual reports of blindness over 13 months before a journal article was published on the issue.[21] United States Senator Charles E. Grassley wrote a letter to the FDA detailing his criticism, saying that the FDA's Office of New Drugs (OND) had taken no action "despite OND's knowledge of the blindness risks since January 2004 and general agreement among FDA staff last spring that the label should be updated."[21] Grassley's letter also suggested that Pfizer resisted adding the blindness warning to Viagra's label.[21] In July 2005, the FDA said that Viagra, Levitra, and Cialis labels would all carry warnings on the risk of sudden blindness, though it was unclear whether the drugs were actually causing the blindness.[22]

Marketing

The FDA relaxed rules on prescription drug marketing in 1997, allowing advertisements directly targeting consumers.[23] Lilly Icos hired the Grey Worldwide Agency in New York, part of the Grey Global Group, to run the Cialis advertising campaign.[24] Cialis ads have been gentler and warmer than its rivals' ads to reflect the longer duration of the drug, allowing a more relaxed approach.[24] Iconic themes in Cialis ads include couples in bathtubs and the slogan "When the moment is right, will you be ready?"[24] Cialis ads were unique among the ED drugs in mentioning specifics of the drug.[25] As a result, Cialis ads were also the first to describe the side effects in an advertisement, as the FDA requires advertisements with specifics to mention side effects. One of the first Cialis ads aired at the 2004 Super Bowl.[25] Just weeks before the Super Bowl, the FDA required more possible side effects to be listed in the advertisement, including priapism.[25] Although many parents objected to the Cialis ad being aired during the Super Bowl, Janet Jackson's halftime "wardrobe malfunction" overshadowed Cialis.[25] In January 2006, the Cialis ads were tweaked, adding a doctor on screen to describe side effects and only running ads where more than 90 percent of the audience are adults, effectively ending Super Bowl ads.[23] In 2004, Lilly Icos, Pfizer, and GlaxoSmithKline spent a combined $373.1 million to advertise Cialis, Viagra, and Levitra respectively.[25] Cialis has sponsored many sports events, such as the America's Cup and the PGA Tour, once being title sponsor of the PGA Tour Western Open tournament.[26]

Drug development

Icos developed drugs to disrupt the process of inflammation in the body.[3] The research program looked first at the underlying causes of inflammation rather than at specific disorders.[3]

LeukArrest

Main article: Rovelizumab

LeukArrest, also known as rovelizumab and Hu23F2G, was developed to treat patients suffering from haemorrhagic shock.[27] The drug is a monoclonal antibody that suppresses white blood cells which become overly active during shock.[3][28] During testing the number of patients given the drug was low because LeukArrest had to be delivered within four hours of the injury and consent was required.[28] Often the patient was unconscious and relatives had to be reached to give consent.[28] In June 1998, Icos and many medical centers asked the FDA to waive consent requirements in situations where the patient was at high risk of dying and relatives could not be reached.[28] While some medical ethicists opposed waiving consent, the FDA approved the proposal in August 1998 for five medical centers.[29][30] Development of LeukArrest was halted in April 2000 when interim data from phase III clinical trials did not meet Icos's goals.[31] The company's goals for LeukArrest included reducing the chance of multiple organ failure and reducing the death-rate from shock at 28 days.[27] LeukArrest was also being tested for treating heart attack, multiple sclerosis, and stroke.[32]

Pafase

See also: Lipoprotein-associated phospholipase A2

Pafase, also known as rPAF-AH, was developed to treat severe sepsis.[33] Pafase is an enzyme made naturally by macrophages and found in human blood.[34] The enzyme was discovered in the mid 1980s by graduate student Diana Stafforini, Steve Prescott, Guy Zimmerman, and Tom McIntyre.[34] It inhibits a compound involved in inflammatory reactions leading to sepsis.[33] The gene for Pafase was discovered by Icos.[35] Early trials for sepsis showed that the drug reduced the death rate after 28 days and patients were less likely to develop severe respiratory problems.[33] Icos also tested Pafase for acute respiratory distress syndrome (ARDS).[34] In phase II trials for ARDS, Pafase reduced the death rate after 28 days and reduced the chance that the lungs of the patient would fail.[34] Icos halted development in December 2002 when phase III trials for sepsis showed that the drug did not help patients survive.[33] Scientists at Northwestern University studied Pafase for necrotizing enterocolitis,[36] and there is ongoing research on the enzyme for atherosclerosis at the University of Utah.[37]

Sitaxsentan sodium and TBC3711

In June 2000, Icos and Texas Biotechnology formed a 50/50 partnership to research endothelin antagonists for use in the areas of pulmonary hypertension and chronic heart failure.[38] Two drugs, sitaxsentan sodium and TBC3711, were tested in clinical trials under the partnership.[39] Sitaxsentan sodium was designed to treat pulmonary artery hypertension (PAH), and TBC3711 was designed to treat cardiovascular diseases such as hypertension.[40] In April 2003, Icos sold its piece of the 50/50 partnership to Texas Biotechnology for $4 million at closing and another $6 million within 18 months.[39] From the deal Texas Biotechnology got full ownership rights of sitaxsentan sodium and TBC3711.[39]

Other drugs tested in clinical trials

Icos tested many other drugs that were not approved. They are:

Manufacturing

Icos manufactured many compounds for various companies. In August 2001, Icos partnered with Seattle Genetics to manufacture a component of Seattle Genetics's lead antibody drug SGN-15.[45] In November 2001, Icos signed a production agreement with GPC Biotech to manufacture a class of GPC's antibodies.[46] In January 2002, Icos signed an agreement with Eos Biotechnology.[47] Under the agreement, Icos would produce Eos's lead monoclonal antibody candidate, and Eos would have non-exclusive rights to Icos's CHEF1 enhanced mammalian protein expression technology.[47] Eos chose Icos because of the company's ability to produce Eos's compound according to Current Good Manufacturing Practices standards.[47] Eos's antibody inhibits new blood vessel formation and was being researched as a treatment for solid tumors.[47] In October 2003, Icos partnered with Protein Design Labs (PDL) to manufacture PDL's M200 antibody.[48]

Acquisition by Eli Lilly

Eli Lilly and Company's global headquarters in Indianapolis, Indiana, United States

After Icos's experimental drugs failed in clinical trials, Eli Lilly was in a prime position to purchase the company. In October 2006, Eli Lilly announced that it had reached terms to acquire Icos for $2.1 billion, or $32 a share.[4] After receiving pressure from large institutional shareholders, as well as proxy advisory firm Institutional Shareholder Services (ISS) suggesting the deal should be rejected, Lilly increased its offer to $34 per share, a 6 percent increase.[49] Resistance to the new offer was voiced again by some large shareholders, and ISS again advised shareholders against accepting the offer, which it deemed as insufficient.[50] At a special meeting of shareholders, held on January 25, 2007, 77 percent of the shareholders voted in support of the acquisition.[51] Eli Lilly closed the transaction to acquire Icos for $2.3 billion on January 29, 2007.[52]

As a result of the acquisition, Eli Lilly gained complete ownership of Cialis and promptly shut down Icos operations and laid off Icos personnel, except for 127 employees working at the biologics facility.[44][5] Icos was the largest biotechnology company in the Pacific Northwest at the time of the acquisition, and employed approximately 700 people.[53][5] In December 2007, CMC Biopharmaceuticals A/S (CMC), a Copenhagen, Denmark based provider of contract biomanufacturing services, bought the Bothell-based biologics facility and retained the existing 127 employees.[5]

Controversy

In addition to the termination of Icos employees, other aspects of the acquisition were similarly legal but controversial, such as assertions that Icos was being sold too cheaply and that conflicts of interests existed.[54] The latter related to Icos senior executives, who – despite poor stock performance in part from failed clinical development programs and an inability to successfully license drugs over the preceding years – advocated for and were to be massively compensated upon a successful acquisition.[4]

Senior executives at Icos received cash payments worth a combined $67.8 million for selling the company to Eli Lilly.[55] Icos chairman, chief executive and president Paul Clark received a "golden parachute" worth $23.2 million in severance pay, cashed-out stock options, restricted stock awards and other bonuses for retention and closing the deal.[55] Other management packages included Executive Vice President Gary Wilcox ($8.5 million); Chief Financial Officer Michael Stein ($7.1 million); Chief Medical Officer David Goodkin ($5.9 million); Thomas St. John, Vice President, Therapeutic Development ($5.2 million); Leonard Blum, Senior Vice President, Sales & Marketing ($4.9 million); John Kliewer, Vice President, General Counsel ($4 million); Michelle Yetman, Vice President, Human Resources ($4 million); Clifford Stocks, Vice President, Business Development ($3.6 million), and Shing Chang, Senior Vice President, Drug Discovery ($1.4 million).[55]

See also

Template:Companies portal

References

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  2. ^ Cook, John (December 12, 2006). "Icos sale may cost 700 jobs". The Seattle Post-Intelligencer. p. C1. Retrieved January 17, 2009.
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  4. ^ a b c d e f Timmerman, Luke (October 18, 2006). "Icos Sale a Blow to Local Biotech". The Seattle Times. p. A1. Retrieved January 10, 2009. Cite error: The named reference "Icos sale" was defined multiple times with different content (see the help page).
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  6. ^ a b c Erickson, Jim (July 3, 1990). "Top Scientists Form Biotech Firm; Gates is Largest Shareholder as Investors Come Up With $33 Million". The Seattle Post-Intelligencer. p. A1. Retrieved January 24, 2009.
  7. ^ "Icos Offering Is A Success". The Seattle Post-Intelligencer. July 7, 1991. p. E1.
  8. ^ Lee, Tyrone (February 2, 2000). "Guiding Father of Icos Cuts Cord". The Seattle Times. p. E1. Retrieved January 10, 2009.
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  13. ^ a b Daugan, A (October 9, 2003). "The discovery of tadalafil: a novel and highly selective PDE5 inhibitor. 1: 5,6,11,11a-tetrahydro-1H-imidazo[1',5':1,6]pyrido[3,4-b]indole-1,3(2H)-dione analogues". Journal of Medicinal Chemistry. 46 (21): 4525–32. doi:10.1021/jm0300577. PMID 14521414. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
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  26. ^ Loyd, Linda (July 6, 2003). "Two Pills Look to Topple Viagra's Reign in Market; Levitra Expects Approval Next Month, Cialis Later This Year". The Philadelphia Inquirer. p. E01.
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  29. ^ Lerner, Maura (June 23, 1998). "HCMC Seeks Feedback On Plans To Test Trauma Drug; Doctors Hope to Test a Medicine That Could Save Lives of Patients Who Are Unable to Speak For Themselves". Star Tribune. p. 1A.
  30. ^ "Community consultation and public disclosure information for waiver of Informed Consent" (PDF). Food and Drug Administration. August 27, 1998. Retrieved January 12, 2009.
  31. ^ "Icos Halts Stroke-Drug Study After Late Results Disappoint". The Seattle Times. April 21, 2000. p. C6. Retrieved January 10, 2009.
  32. ^ "Icos shares tumble on phase II results of LeukArrest". Reuters Health Medical News. June 16, 1999. {{cite news}}: External link in |work= (help)
  33. ^ a b c d e "Icos Drug Pafase Hits a Dead End". The Seattle Times. December 20, 2002. p. D1. Retrieved January 10, 2009.
  34. ^ a b c d Siegel, Lee (June 1, 2000). "New Drug Holds Hope Against Lung Ailment". The Salt Lake Tribune. p. C2.
  35. ^ Tjoelker, T (April 6, 1995). "Anti-inflammatory properties of a platelet-activating factor acetylhydrolase". Nature. 374 (6522): 549–53. doi:10.1038/374549a0. PMID 7700381. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  36. ^ Timmerman, Luke (December 16, 2006). "Another Clinical Trial Near From Icos Pipeline". The Seattle Times. p. E1. Retrieved January 10, 2009.
  37. ^ Stafforini, Diana M (February 2009). "Biology of Platelet-activating Factor Acetylhydrolase (PAF-AH, Lipoprotein Associated Phospholipase A2)". Cardiovascular Drugs and Therapy. 23 (1): 73–83. doi:10.1007/s10557-008-6133-8. PMID 18949548.
  38. ^ Beason, Tyrone (June 7, 2000). "Icos teams with Texas biotech for drug trials". The Seattle Times. p. C3. Retrieved January 15, 2009.
  39. ^ a b c "Bothell biotech's partner makes additional investment". The Seattle Times. April 24, 2003. p. E3. Retrieved January 15, 2009.
  40. ^ "Web Cloaking Service Promises Anonymity". The Seattle Post-Intelligencer. December 21, 2000. p. C2.
  41. ^ "Icos Psoriasis Treatment Falls Short". Puget Sound Business Journal. June 6, 2003. Retrieved January 10, 2009.
  42. ^ a b Timmerman, Luke (January 14, 2004). "Icos chief stirs up interest in Cialis at investor event". The Seattle Times. p. E1. Retrieved January 12, 2009.
  43. ^ "Tech Briefs". The Seattle Post-Intelligencer. November 6, 2001. p. D2. Retrieved January 12, 2009.
  44. ^ a b Timmerman, Luke (December 12, 2006). "All Icos workers losing their jobs". The Seattle Times. p. C1. Retrieved January 16, 2008.
  45. ^ "Seattle Genetics Signs Development and Manufacturing Agreement with ICOS for the Monoclonal Antibody Component of SGN-15". Business Wire. August 14, 2001. Retrieved January 24, 2009.
  46. ^ "Tech Briefs". The Seattle Post-Intelligencer. November 27, 2001. p. D2. Retrieved January 17, 2009.
  47. ^ a b c d "Eos Biotechnology and ICOS Sign Manufacturing and Licensing Agreements; ICOS to Manufacture Eos' Lead Antibody Candidate Targeting Angiogenesis". PR Newswire. January 9, 2002.
  48. ^ "Icos to Manufacture Clinical Candidate for Protein Design Labs". Business Wire. October 9, 2003. Retrieved January 24, 2009.
  49. ^ "Lilly Increases Offer for Icos; Shareholders' Vote Is Put Off". The New York Times. December 19, 2006. p. C10. Retrieved January 16, 2008.
  50. ^ Timmerman, Luke (January 13, 2007). "Reject Icos offer, holders of shares advised". The Seattle Times. p. E1. Retrieved January 17, 2009.
  51. ^ James, Andrea (January 26, 2007). "Icos voters approve buyout by Eli Lilly". The Seattle Post-Intelligencer. p. C1. Retrieved January 17, 2009.
  52. ^ "Eli Lilly completes Icos takeover". The Seattle Times. January 30, 2007. p. C1. Retrieved January 17, 2009.
  53. ^ Cook, John (October 20, 2006). "Icos' gain is Seattle's loss". The Seattle Post-Intelligencer. p. C1. Retrieved January 17, 2009.
  54. ^ Timmerman, Luke (November 7, 2006). "Proposed Icos sale gets more criticism: Payouts for execs called "overkill"". The Seattle Times. p. C1. Retrieved January 16, 2008.
  55. ^ a b c Timmerman, Luke (November 2, 2006). "Icos leaders to get $68 million from company's sale". The Seattle Times. p. C1. Retrieved January 16, 2008.

External links

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