로이터통신 Tue Jul 30, 2013 2:48pm IST
http://in.reuters.com/article/2013/07/30/novartis-gilenya-idINL6N0G02A52013073

* Patient took Novartis’ Gilenya MS pill

* Developed progressive viral disease

* First incidence in 71,000 patients

* Gilenya facing competition from Biogen’s Tecfidera

ZURICH, July 30 (Reuters) – A patient taking Novartis’ multiple sclerosis pill Gilenya developed a rare and potentially fatal viral disease, the Swiss drugmaker said on Tuesday, an unexpected setback as it faces growing competition from new oral treatments.

Gilenya is one of Novartis’ big new drug hopes, growing 66 percent in the second quarter to $468 million. But the drug faces competition from new medicines such as Biogen Idec’s Tecfidera.

Novartis said it had been informed of a case of progressive multifocal leukoencephalopathy (PML) in a patient who had been taking Gilenya for MS for seven months.

It said it was working with the reporting physician to understand all possible contributing factors, including those beyond treatment, given several atypical features of the case.

“The course of the underlying neurological disease was rapid with some atypical findings for MS on the MRI scans of the brain and spinal cord, as well as some unusual clinical features,” Novartis said in a statement.

Novartis said all previously reported cases of PML among the approximately 71,000 patients treated with Gilenya thus far had been attributed to prior treatment with Biogen Idec’s Tysabri, which bears a known risk of PML.

Deutsche bank analyst Tim Race said the case may provoke some concerns about Gilenya’s future growth potential. But he noted the incidence of reported PML cases for Gilenya has so far been extremely low.

“By the time there was a similar level of patient experience with Tysabri there had been 298 cases reported. Thus, even if the risk proves to be real it is likely to be of a very different order of magnitude,” Race said in a note.

Shares in Novartis were trading down 0.8 percent at 66.10 Swiss francs by 0904 GMT, compared to a 0.4 percent weaker European healthcare sector.

=============

노바티스 ‘길레니아’ 복용자, PML 발생 보고
치명적 바이러스 질환.. 발생 원인 조사 중

데일리팜 2013-07-31 08:05:57
http://www.dailypharm.com/Users/News/NewsView.html?ID=173758
노바티스는 다발성 경화증 치료제인 ‘길레니아(Gilenya)’를 복용한 환자에서 드물고 잠재적으로 치명적인 바이러스 질환이 발생했다고 30일 밝혔다.

길레니아는 노바티스가 기대하는 약물 중 하나. 그러나 바이오겐의 ‘텍피데라(Tecfidera)’와 경쟁으로 영향이 있을 것으로 전망된다.

노바티스는 7개월간 길레니아를 복용한 환자에서 진행성 다소성 백질뇌염(progressive multifocal leukoencephalopathy, PML)이 발생했다고 말했다.

현재 노바티스는 치료제를 포함해 질병의 발생 원인이 될 수 있는 모든 인자에 대해 조사를 벌이고 있는 중이라고 말했다.

지금까지 노바티스는 길레니아로 치료를 받던 7만1000명 중 PML이 발생이 보고된 경우는 PML 위험성이 있는 ‘티사브리(Tysabri)’로 이전에 치료를 받았기 때문이라고 설명해왔다.

분석가들은 길레니아의 부작용에 대한 우려가 입증될 경우 길레니아의 성장세가 정체될 수 있다며 우려를 나타냈다.

====================

July 19, 2013 Shelley Wood
http://www.theheart.org/article/1561843.do?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+Theheartorg+%28theheart.org%29

Kyoto, Japan - The past week has seen a number of new twists in the tale of a prominent Japanese cardiologist accused of fabricating and manipulating data and images for cardiology research later published in a range of cardiology journals.

Last year, the American Heart Association (AHA) issued a notice of concern about five papers appearing in three AHA-published journals—Circulation, Circulation Research, andHypertension—between 2001 and 2004, as reported by heartwire.

Dr Hiroaki Matsubara

Concerns about Dr Hiroaki Matsubara ultimately spread to the Kyoto Heart Study, the >3000 patient, postmarketing study Matsubara presented to some fanfare at the European Society of Cardiology 2009 Congress and subsequently published in the European Heart Journal(EHJ). The EHJ later retracted that article, a move the AHA opted to follow this May after concluding its review of the studies published in a number of the association’s journals. Matsubara resigned from his post at Kyoto Prefectural University earlier this year.

Last Friday, Japan’s minister of health, Norihisa Tamura, as well as university officials at Kyoto Prefectural University announced that the Kyoto Heart Study data were “very likely” fabricated, according to AFP. “Incomplete” patient data were used in the study, which concluded the blood-pressure drug could also reduce other cardiovascular end points via mechanisms unrelated to blood-pressure lowering. Had “complete patient records” been used, the study would have reached “a different conclusion,” the university concluded.

Finally, it has also emerged that two Novartis employees were involved in the conduct and analysis of the Kyoto Heart Study and a second investigator-initiated trial, the Jikei Heart study, although their participation was not acknowledged in publications and presentations of the data. Those employees are no longer with Novartis.

Novartis has issued a statement saying that it had launched a third-party investigation into allegations of conflict of interest (COI) relating to the two Novartis employees back in April.

“At the time these Japanese valsartan [investigator-initiated trials] IITs started between 2001 and 2004, there were no specific guidelines for COI in IITs,” the statement reads. “The former employees and their managers misunderstood the appropriate level of involvement in IITs of employees of a pharmaceutical company. However, there are now COI guidelines for in place across the industry, which are followed by all Novartis Pharma Japan employees.”

In June, after its investigation concluded, the company implemented “preventive and corrective measures . . . to address the causes identified in the third-party investigation, demonstrating our social and ethical accountability,” the statement notes.

According to AFP, Novartis has also stressed that the university “was not able to conclude that there was intentional wrongdoing” and that it remains possible that the “inconsistencies” may have been unintentional.

The retractions, Matsubara’s resignation, the Novartis announcement, and other details have been followed in detail on blog sites Retraction Watch and Cardiobrief, as well as onPharmaTimes.

========

Shelley Wood Managing Editor | shelley@theheart.org
Follow @shelleywood2 on Twitter

Shelley Wood joined theheart.org as a medical journalist in 2000. Born and bred in Vancouver, BC, Shelley did her bachelor’s degree at McGill University in Montreal, QC and the University of Cape Town, South Africa, and then completed her graduate degree in journalism at the University of British Columbia, specializing in health reporting. In January 2009, she took over as managing editor for heartwire.

Shelley was awarded the National Institute for Health Care Management (NIHCM) Print Journalism Award in 2009 for her series, The Myxo ring mix-up. In 2010, she led theheart.org team to win the Online News Association Online Journalism Award in the category of Specialty Site Journalism (Independent). She lives in the Okanagan Valley – between the Coastal and Rocky Mountain ranges – in Kelowna, BC.

==================

노바티스 직원, 디오반 효능 조작 관여 탄로
코메디닷컴 2013.07.30 10:57 수정 2013.07.31 16:56
http://www.kormedi.com/news/article/1207334_2892.html

최근 글로벌 제약사 노바티스 직원이 일본의 저명한 심장병 전문의 마쓰바라 히로아키 교수의 임상 데이터 조작 사건에 연루된 것으로 알려지면서 파장이 커지고 있다고 의학정보사이트 ‘The Heart Org’는 지난 19일 보도했다.

미국심장학회(AHA, American Heart Association)는 지난 2001년부터 2004년까지 학회가 발행하는 3개 저널(Circulation, Circulation Research, Hypertension)에 실린 마쓰바라 교수의 논문(5편)이 임상 데이터와 이미지의 조작과 관련이 있다며 우려를 표명해 왔다.

유럽심장학회지(EHJ)는 마쓰바라 교수가 유럽심장학회(2009년) 회의에서 발표하고 이 저널에 게재한 고혈압 치료제 디오반(성분명: 발사르탄)의 ‘시판 후 연구’ 등의 논문을 이미 철회한 바 있다. 이어 AHA도 논란 끝에 여러 저널에 실린 마쓰바라 교수의 논문들을 지난 5월에 취소키로 결정했다.

마쓰바라 교수의 연구결과에 대한 이같은 우려는 일본 내에서도 증폭되고 있다. AFP통신에 따르면 지난 26일 교토 부립의과대학(KPUM)측과 일본 후생노동성이 마쓰바라 교수의 ‘교토 심장 연구(Kyoto Heart Study)’ 자료가 조작됐을 가능성이 매우 높다고 발표했다.

이 연구는 불완전한 환자 자료를 인용해 혈압약인 ‘디오반’이 혈압강하와 관련 없는 기전으로 다른 심혈관 질환에서 효과를 보였다고 발표한 바 있다. KPUM은 “이 논문이 온전한 환자 자료를 사용했다면 다른 결론을 내렸을 것”이라고 밝혔다.

대학 측은 또 데이터에 문제가 있었던 만큼 디오반이 다른 혈압약에 비해 뇌졸중, 협심증 등을 줄이는 효과가 있다는 연구진의 결론에는 오류가 있을 가능성이 크다고 밝혔다.

더욱 논란이 일고 있는 것은 2명의 노바티스 직원이 ‘교토 심장 연구’와 연구자 주도 임상시험(이하 IIT)인 ‘지케이 심장 연구(Jikei Heart Study)’의 실행과 분석에 관여했다는 사실이 드러난 것이다. 이들은 그럼에도 논문 출판과 발표에 연구 참여자로 공식 참여하지 않아 논란의 소지를 제공했다. 이들 직원은 현재 노바티스를 퇴사한 상태이다.

노바티스는 이번 논란과 관련해 제3의 기관에 의해 지난 4월부터 조사에 착수했다는 성명서를 발표하기도 했다.

노바티스는 “지난 2001년부터 2004년 사이 일본에서 디오반(성분명:발사르탄) IIT가 시작될 무렵, IIT의 이해충돌(COI) 관련해 구체적인 가이드라인이 존재하지 않았다”고 밝히며 “제약회사의 직원들이 어느 선까지 IIT에 관여하는 게 적절한가에 대한 이해가 부족했다”고 전했다. 이어 “현재는 업계 전반에 걸쳐 COI 가이드라인이 자리를 잡았으며, 모든 노바티스의 일본 직원들은 이를 잘 따르고 있다”고 말했다.

===================

日, 의대서 혈압강하제 임상 데이터 조작 파문

도쿄|서의동 특파원 phil21@kyunghyang.com

경향신문 2013-07-31 11:35:04ㅣ
http://news.khan.co.kr/kh_news/khan_art_view.html?artid=201307311135041&code=970203

스위스 제약사 노바티스의 일본법인이 취급하는 고혈압 치료제 디오반에 대해 일본의 의과대학이 실시한 임상연구 데이터가 인위적으로 조작된 것으로 드러났다.

도쿄 지케이카이(滋惠會)의대 조사위원회는 30일 이 대학 연구팀이 실행한 혈압강하제 디오반(성분 발사르탄) 임상 연구 논문에서 “노바티스 전 직원의 관여 등을 통해 데이터가 인위적으로 조작된 사실이 인정돼 논문을 철회키로 했다”고 발표했다. 지케이카이 의대조사에 따르면 대학이 보유하고 있는 671인분의 데이터와 최종통계를 비교한 결과 86건에서 혈압치가 다른 것으로 나타났다. 다만, 조작은 통계해석의 단계에서 벌어진 것으로 보여 “대학의 연구자가 간여한 것이 아니라 노바티스의 전 사원이 조작했다”고 대학측은 판단했다.

지케이카이 대학의 임상연구는 고혈압 환자 3081명을 대상으로 실시돼 디오반이 뇌졸중과 협심증을 예방하는 데 효과가 높다는 논문을 2007년 이 대학 연구진이 영국 의학지에 발표하기도 했으나 대학측은 데이터 조작이 밝혀짐에 따라 논문을 철회하기로 했다.

일본에서 디오반 임상연구는 지케이카이 의대, 교토(京都)부립 의과대학, 나고야(名古屋)대, 지바(千葉)대 등 5개 대학에서 실시됐으며 지케이카이 의대와 교토부립 의대의 연구 논문을 노바티스측이 홍보에 사용해 왔다. 디오반은 세계 판매량 1위의 혈압강하제다.

앞서 교토부립 의대도 지난 11일 이 대학의 마쓰바라 히로아키(松原弘明) 전 교수가 실시한 디오반 임상 연구에서 데이터 조작이 이뤄진 것으로 드러나 파문을 일으켰다. 노바스티측은 교토부립 의대 연구에 자사 직원을 참가시키고 연구진에 1억엔 규모의 기부금을 제공한 것으로 알려졌다.

================

Retraction Watch

Recent examples of the use of compulsory licenses on patents[1]

KEI Research Note 2007:2

1). That it has suffered an irreparable injury;

2). That other possible legal remedies, including the payment of royalties, are inadequate to compensate for that injury;

3). That considering the balance of hardships between the plaintiff and defendant, a remedy in equity is warranted; and

4) That the public interest would not be disserved by a permanent injunction.

Defendant [Abbott] made an effort to show through cross examination of plaintiff’s witnesses that it would be risky to public health to enjoin defendant from the market both because reliance on one major manufacturer was risky in and of itself and because plaintiff’s manufacturing facility had quality control problems with another product over a period of years.

In order to prevent the statement from providing a hollow right, the concept of promoting access to medicines for all must include providing access to the diagnostic procedures necessary to determine when and which medicines to provide. The federal government should, therefore, amend the Patent Act to specifically allow the potential for compulsory licensing of patents relating to the provision of genetic diagnostic and screening tests should this power be necessary.

1. The intellectual property right should constitute, upstream, an indispensable factor in the downstream supply of a (secondary) product.
   
2. The potential licensee should intend to produce new goods or services not offered by the owner of the right, and for which there is a potential consumer demand.
   
3. The refusal should not be justified by objective reasons.
   
4. The refusal should be of such a nature that it reserves for the owner of the right the market for the provision of the product, by eliminating all competition on that market.
   

1. There are no limits on the scope of diseases. It extends to all medicinal products as defined in Article 1(2) of Directive 2001/83/EC on medicinal products for human use (1), active ingredients and diagnostic kits ex vivo.
   
2. The compulsory licenses are mandatory: “Member States shall grant a compulsory licence to any person making an application in accordance with Article 6 and subject to the conditions set out in Articles 6 to 10.”
   
3. Prior negotiation with right owners is waived “in situations of national emergency or other circumstances of extreme urgency or in cases of public non-commercial.” In these cases, “the remuneration shall be a maximum of 4 % of the total price to be paid by the importing country.” In other cases, remuneration may consider “humanitarian or noncommercial circumstances relating to the issue of the licence.”
   
4. The “safety and efficacy of medicinal products” may be evaluated through evaluation of “the scientific opinion procedure as provided for under Article 58 of Regulation (EC) No 726/2004, or . . . any similar procedures under national law, such as scientific opinions or export certificates intended exclusively for markets outside the Community.”
   
5. In Article 18.2, when compulsory licenses to data are issued under this regulation, EU “protection periods” for test data “shall not apply.” This waiver of data exclusivity for a case involving a compulsory license is quite important. Note that the remuneration for the patent is the sole remuneration in such cases.

Where the interests of public health demand, and in the absence of a voluntary agreement with the patent holder, the minister responsible for industrial property, may, by order of the minister responsible for public health, request ex officio licenses in accordance with Article L. 613-17 for any patent granted for:

a) a medicine, a medical device, a medical device for in vitro diagnosis, a related therapeutic product;

b) processes for obtaining them, [or] for products necessary in obtaining such medicines or for processes for manufacturing such products

c) a diagnostic method ex vivo.

F. Belgium

Belgium modified its patent law in 2005, creating a new compulsory cross-license for biotechnology inventions, and also a new compulsory license for public health purposes.[31]

G. Italy

1. Sorin/Chrion dispute

On 14 June 1994, Sorin Biomedica S.p.A. filed a lawsuit with the Court of Milan, Italy against Chiron Corporation and Ortho Diagnostic Systems S.p.A. for a declaration of nullity and noninfringement of the Italian counterpart to Chiron’s European Patent 0 318 216 (the ” ’216 patent”). Sorin additionally filed a request with the Italian Ministry of Industry, Commerce and Artisanship (“ICA”) for compulsory license to the ’216 patent. Chiron filed a counterclaim and sought a finding that the patent is valid and infringed by Sorin. The ICA suspended Sorin’s request for compulsory license pending the outcome of the litigation.

2. Merck antibiotic (Imipenem Cilastatina) patents

On 23 February 2005, the Autorità garante della concorrenza e del mercato (the AGCM) opened an investigation into abuses of a dominant position by refusals to license rights to active pharmaceutical products by two large pharmaceutical companies — GlaxoSmithKline and Merck & Co Inc (Cases A363 and A364).

On 21 June 2005, the AGCM ordered a compulsory license for Merck patents on antibiotics that use the active ingredients Imipenem Cilastatina.

3. Glaxo patents on migraine drug

On 8 February 2006, the AGCM closed the investigation into the Glaxo Group’s refusal to grant a licence to Fabbrica Italiana Sintetici SpA (FIS), a chemical company, for the manufacture in Italy of an active ingredient, Sumatriptan Succinate, used in the production of migraine medicines. According to the AGCM press release, “To remedy the earlier refusal to license, Glaxo granted the licences originally requested by FIS, but also set conditions such as to allow the time to be made up which had been lost because of the original refusal. Those conditions include the granting of a number of additional procedural licences, whereby Glaxo has allowed FIS to save the time otherwise required to research and test an efficient manufacturing process for Sumatriptan Succinate. FIS will thus be enabled to offer the active ingredient to manufacturers of generics as early as if Glaxo had never refused the original request for a licence.”[32] The AGCM sought to prevent delays in bringing generic pharmaceuticals to market, thus paving the way for substantial price reductions. FIS initially used the compulsory license entirely for the export market, supplying generic firms that were selling products in markets outside of Italy (such as Spain), where the patents had expired. It did so outside of the framework of the WTO 30 August 2003 decision on exports on medicines manufactured under a compulsory license, which Spain and other EU members had “opted out” as an importer. This was possible in part because the TRIPS waives all restrictions on exports in cases where the licenses were issued to remedy to anticompetitive practices.

4. Merck patents on prostate and male-pattern baldness drug

On 21 March 2007, the AGCM required Merck to “grant free licences to allow the manufacture and sale in Italy of the active ingredient Finasteride and related generic drugs two years before the 2009 expiration of the Complementary Protection Certificate.”[33] Finasteride is the active ingredient of a drug marketed initially under the brand name Proscar and Propecia. It is used to treat hypertrophy of the prostate, cancer of the prostrate, and male-pattern baldness. The Merck royalty free compulsory licenses were remedies to Merck’s earlier refusal to license the patents to Italian manufactures of active pharmaceutical ingredients. Again, the licenses anticipate exports to “other European countries.”


IV. ASIA


A. China

In 2005, China used the threat to a compulsory license to obtain voluntary licenses to manufacture generic Tamiflu.

B. India

In February 2005, India amended its patent law, to provide for patent protection for pharmaceutical inventions. The legislation created a mandatory compulsory license for products that were already manufactured and marketed in India. The new provision was added under Section 11 A of the Indian Patent Act read as follows::

“(7) On and from the date of publication of the application for patent and until the date of grant of a patent in respect of such application, the applicant shall have the like privileges and rights as if a patent for the invention had been granted on the date of publication of the application:

Provided that the applicant shall not be entitled to institute any proceedings for infringement until the patent has been granted:

Provided further that the rights of a patentee in respect of applications made under sub-section (2) of section 5 before the 1st day of January, 2005 shall accrue from the date of grant of the patent:

Provided also that after a patent is granted in respect of applications made under sub-section (2) of section 5, the patent-holder shall only be entitled to receive reasonable royalty from such enterprises which have made significant investment and were producing and marketing the concerned product prior to the 1st day of January, 2005 and which continue to manufacture the product covered by the patent on the date of grant of the patent and no infringement proceedings shall be instituted against such enterprises[34].” [Emphasis added]

C. Indonesia

On October 5, 2004, Indonesia issued a government use compulsory license to manufacture generic versions of two HIV-AIDS drugs, lamivudine and nevirapine, until the end of the patent term in 2011 and 2012 respectively. The license includes a royalty rate of 0.5% of the net selling value[35]. Production of the ARVs has started by PT Kimia Farma.

In March 2007, Indonesia reportedly issued a compulsory license for patents on the AIDS drug efavirenz.

D. Malaysia

On September 29, 2004, the Malaysian Minister of Domestic Trade and Consumer Affairs issued a two-year government use compulsory license to import from India didanosine (ddI), zidovudine (AZT) and lamivudine+zidovidine (Combivir) [36]. The Ministry of Health proposed a royalty rate of 4% of the value of the generic product.

E. Korea

On January 30, 2002, the People’s Health Coalition for Equitable Society, the Association of Physicians for Humanism, and the Korean Pharmacists for Democratic Society jointly filed for a compulsory license for Glivec, a drug to treat chronic myelogenous leukemia (CML), and gastrointestinal stromal tumor (GIST). The request was rejected[37].

In October 2005, the Korea Food and Drug Administration (KFDA) announced it was considering a compulsory license for the manufacture of generic versions of Tamiflu.[38]

F. Taiwan

On July 26, 2004, the Taiwan Intellectual Property Office (TIPO) issued a compulsory license to Gigastorage for 5 patents related to CD-R of Phillips. The term of the license is through the expiration of the patent terms.

In November 2005, Taiwan issued a compulsory license for patents needed to manufacture and sell generic versions of Tamiflu.[39] According to this report by Deutsche Presse-Agentur dpa:

The Intellectual Property Office (IPO) granted compulsory licensing to Taiwan pharmaceutical companies after talks with Roche and Gilead Science – the U.S. developer of Tamiflu – broke down. ‘Roche and Gilead insisted they can supply enough Tamiflu if bird flu erupts in Taiwan. Our argument was: When there is a bird flu pandemic, millions of people will be hospitalized or dead, and some countries might confiscate Tamiflu or ban its export. We cannot gamble our people’s lives on their unreliable promise,’ Lai Chin-hsiang, secretary-general of the Department of Health (DOH), told Deutsche Presse-Agentur dpa. Under the compulsory license, valid until December 31, 2007, Taiwan drug firms can make Tamiflu for domestic use and should use it only when there is a shortage of supply from Roche.[40]


G. Thailand

On November 29, 2006, the Thailand Ministry of Health announced a government use compulsory license to import (from India) and locally produce efavirenz until 2011. [41] The proposed royalty was 0.5 percent of the price of the generic product, a figure that is subject to additional negotiations with the patent owner.

On January 25, 2007 the Thailand government announced two additional government use compulsory licenses on patents for the AIDS drug Kaletra (LPV+RTV)[42] and the heart disease drug Plavix (clopidogrel bisulfate),[43] also with a proposed royalty of 0.5 percent.

On January 29, 2007, the Minister of Public Health’s Department of Disease Control, issued a decree regarding the exploitation of patents on drugs & medical supplies by the government on the combination drug lopinavir & ritonavir, which is marketed under the trade name of Kaletra by Abbott.

The Thailand government has repeated said that the patent owners my negotiate for higher royalties, but so far have show no interest in doing so, while waging an intense lobbying and public relations campaign against the Thailand government. Thailand’s actions have been widely supported in treatment and public health circles, and attacked by the pharmaceutical industry.

V. LATIN AMERICA

A. Argentina

On October 18, 2005, Health Minister Gines Gonzalez Garcia announced the government would issue compulsory licenses on the patents for Tamiflu. However, it was later determined that patents on Tamiflu had not been not granted in Argentina.

B. Dominican Republic

There have been requests for compulsory licenses on the patents for Plavix, a heart disease drug. On May 14, 2002, the French embassy in Dominican Republic wrote to Sr. Hugo Guiliani Cury, Secretary of State of the Dominican Republic, expressing opposition to the compulsory license[44].

C. Chile

In December 2004, Essential Inventions requested a compulsory license to supply Glivec to Chile[45].

D. Ecuador

In 2003, Acromax, a local manufacturer, petitioned the patent office to grant a compulsory license for the fix-dose combination of Lamivudine (3TC) and AZT (sold under the trade-name Combivir by Glaxo). The request was rejected and Glaxo granted Ecuador preferential prices on all their HIV-AIDS medicines. ACROMAX appealed and the request was rejected again.[46]

E. Brazil

On January 8, 2001, 12 days before President Clinton left office, USTR filed a complaint over the Brazil compulsory licensing law in the WTO Dispute Settlement Body. USTR officials called this the “Merck” case. At issue was Article 68 of Brazil’s patent law, which allows compulsory licenses to be issued in situations where the patent holder does not locally manufacture the patented product (known as a “local working” provision). The US received a large amount of negative publicity, and on June 25, 2001, the Bush administration withdrew the complaint. However, under the agreement between the two countries, Brazil agreed to provide the US with advance notice if a license is issued under Article 68 of the Brazil patent act, and disputes would be discussed through a bilateral “Consultative Mechanism.” The agreement was not made public.

In early 2001, Brazil announced it was considering compulsory licenses for patents on nelfinavir and efavirenz.

In March 2001, the Brazil government reached a settlement with Merck, for price discounts on efavirenz, in return for not issuing a compulsory license.

On August 22, 2001, Brazilian Health Minister Jose Serra announced the Brazilian government would issue a compulsory license for the manufacture of the antiretroviral drug nelfinavir (sold under the brand name Viracept by Roche) to the Brazilian pharmaceutical producer Far Manguinhos. On August 28, the two parties resumed talks, and on August 31, they reached an agreement; Roche will sell the drug in Brazil at an additional 40% discount, and Brazil will not issue the compulsory license.

On September 5, 2003, the Brazilian government issued a decree that would allow it to produce or import generic anti-AIDS drugs without the consent of companies holding the patent on those medications. The health minister made it clear that the decree was meant to apply to antiretroviral drugs – specifically lopinavir, efavirenz and nelfinavir. The ministry said in a statement it had negotiated with the name-brand companies in August seeking a reduction of more than 40%, but was offered a maximum discount of 6.7%. Brazil and Merck reached an agreement in November.

In 2005, Health Minister Humberto Costa signed a decree declaring the patent of Kaletra in the public interest and appropriate for compulsory licensing. A subsequent settlement with Abbott reduced the price of by 46 percent.

In 2005, the government of Brazil declared that they were considering issuing compulsory licenses to permit the manufacture of Viread. “As a result of discussions with the Brazilian government Gilead reached agreement with the Brazilian Health Ministry in May 2006 to reduce the price of Viread in Brazil by approximately 50%.”[47]

Brazil also used the threat of compulsory licenses on the patents for Gleevic to obtain a price discount of more than 65 percent.

On April 25, 2007, the Brazilian The Minister of Health, José Gomes Temporão, signed Decree 866, published in the Federal Official Gazette Government, declaring the AIDS drug efavirenz to be of public interest. This started a process that culminated in the compulsory licensing of the patent of the antiretroviral drug Efavirenz on May 4, 2007, in a dramatic televised ceremony attended by the Health Minister José Gomes Temporão and President Luiz Inácio Lula Da Silva. The Brazil action on Efavirenz followed a similar decision by Thailand. Because of the Thailand compulsory license authorized competition from generic suppliers, Merck was forced to offer Efavirenz at a much lower price in Thailand. The Brazil government was unable to obtain similar price concessions from Merck, and issued the compulsory licenses.

In Spring 2007, 75,000 (about 38 percent of those receiving treatment) of Brazilian AIDS patients were taking Efavirenz, in combination with other products. Efavirenz is sold by Bristol Myers Squibb in the United States for $15.67 per day.[48] Before the compulsory license, Merck had been charging $1.59 per day in Brazil, a deep discount from the U.S. price, but still difficult for the Brazil government, given the differences in average incomes and the large number of persons receiving treatment in Brazil. Merck had offered to sell Efavirenz for $.65 per day in Thailand. The current generic prices were about $.45 per day, and falling as demand for the generic versions grow. Generic competition may drive prices for Efavirenz below $.25 per day.


VI. AFRICA

Compulsory licensing in Africa is now fairly common, but often not widely publicized. A typical compulsory license may be based upon model authorizations prepared by organizations who are engaged in providing treatment for AIDS, in order to satisfy donor requirements that purchases of generic medicines are consistent with trade rules.

A. Cameroon

On January 2005, the nonprofit corporation Essential Inventions requested the Minister of Public Health to grant ex officio licenses for the patents relevant for importation, manufacture or sale of generic versions of the following medicines used in the treatment of HIV/AIDS: Nevirapine/Viramune®, Lamivudine/3TC®, and Fixed dose combinations of Lamivudine and Zidovudine/Combivir®. The request is still pending[49].

B. Ghana

In October 2005, the Minister of Health issued a government use compulsory licenses for importation into Ghana of Indian generic HIV-AIDS medicines[50].

C. Guinee

On April 18, 2005, the Ministry of Health issued compulsory licenses for importation on patents on drugs to treat HIV-AIDS.

D. Eritre

On June 5 2005, the Minister of Health issued compulsory licenses for importation into Eritrea of generic HIV-AIDS medicines[51].

E. Mozambique

On April 5, 2004, Mozambique’s Deputy Minister of Industry and Commerce issued Compulsory License no. 01/MIC/04 for patent rights to lamivudine, stavudine and nevirapine. The license was granted to Pharco Moçambique Lda, a local producer that plans on manufacturing the antiretrovirals as a fixed-dose combination. Royalties are not to exceed 2% of sales[52].

F. South Africa

On March 7, 2001, Indian pharmaceutical manufacturer CIPLA formally requested the South African Department of Trade and Industry issue compulsory licenses to patents on the following HIV drugs: nevirapine, lamivudine, zidovudine, stavudine, didanosine, efavirenz, indinavir and abacavir.

On September 19, 2002, Hazel Tau, working with the Treatment Action Campaign (TAC), filed a complaint with South Africa’s Competition Commission against GlaxoSmithKline (GSK) and Boehringer Ingelheim (GI). Twelve parties would join the complaint, which charged GSK and BI with excessive pricing in respect of ritonavir, lamivudine, ritonavir+lamivudine and nevirapine.

On October 16, 2003, after an extended investigation, the South Africa Competition Commission issued a statement, saying:

pharmaceutical firms GlaxoSmithKline South Africa (Pty) Ltd (GSK) and Boehringer Ingelheim (BI) have contravened the Competition Act of 1998. The firms have been found to have abused their dominant positions in their respective anti-retroviral (ARV) markets.

In particular the Commission has found the firms have engaged in the following restrictive practices:

1. Denied a competitor access to an essential facility

2. Excessive pricing

3. Engaged in an exclusionary act

On December 10, the competition commission announced it had reached a settlement with GSK. The settlement required GSK to:

1) extend a voluntary licence granted to Aspen Pharmacare in October 2001 in respect of the public sector to include the private sector;

2) grant up to three more voluntary licences on terms no less favourable than those granted to Aspen Pharmacare;

3) permit the licensees to export the ARVs to sub-Saharan African countries;

4) permit the importation of the drugs for distribution in South Africa if the licensee does not have manufacturing capability in South Africa;

5) permit licensees to combine the relevant ARV with other antiretroviral medicines; and

6) charge royalties of no more than 5% of the net sales of the relevant ARVs.

Shortly thereafter, a similar settlement was reached with BI.

G. Swaziland

On April 20, 2004, the Ministry of Health and Social Welfare in Swaziland noted the existence of an emergency relating to AIDS, and authorized procurement of medicines for HIV/AIDS “in the best cost/effective way possible on the international market irrespective of the existence of any patent or other Intellectual Property protection applicable in Swaziland until such time as it will no longer be considered essential to address the current Public Health crisis related to HIV/AIDS.”

H. Zambia

On September 21, 2004 the Zambian Minister of Domestic Trade and Consumer Affairs issued a compulsory license for lamivudine, stavudine and nevirapine. The license was granted to Pharco Ltd., a local producer, which will produce a triple fixed-dose combination. A maximum royalty rate of 2.5% applies[53].

I. Zimbabwe

In May 2002, Zimbabwe’s Minister of Justice, Legal and Parliamentary Affairs declared a Period of Emergency in order to override antiretroviral drug patents for a period of 6 months[54]. The declaration included a government use compulsory license to make, use or import generic HIV/AIDS medicines. In 2003, the period of emergency was extended by five years (until 31 December 2008). With assistance from India, Zimbabwe has begun local production of antiretrovirals though the generic company Varichem Pharmaceuticals (Private) Limited.

VII. MIDDLE EAST

A. Israel

“In January 1992, BTG-Israel filed an application in the Israeli Patent Office for a compulsory license to manufacture BTG’s Bio-Hep-B under Biogen’s Israeli patent which license, upon approval, would enable BTG to produce the vaccine in Israel and likely to export the vaccine to countries in which neither Biogen nor others have been granted a blocking patent. In September 1995 the Registrar ruled in an interlocutory decision that BTG-Israel is entitled to a compulsory license to the Biogen patent. Biogen’s appeal of the interlocutory decision was rejected.”[55]

“Biogen appealed the Registrar’s decision to the District Court of Tel Aviv, Israel, and moved for a stay of the license, which was granted ex parte pending hearings with both parties. Following hearings which took place in December 1996, the motion was denied in January 1997; however, the ex parte stay was left in force pending Biogen’s appeal to the Supreme Court and maintained by the Supreme Court pending the decision by the District Court on the merits of Biogen’s appeal. The District Court heard the appeal in early March 1997, and in June 1997 the District Court denied Biogen’s appeal and subsequent motion for a stay pending Biogen’s appeal of the District Court decision to the Supreme Court on the merits. In March 1998 the Supreme Court granted Biogen the right to appeal the District Court’s decision. A date has not yet been set for the hearing. In the absence of any action by the Supreme Court, the compulsory license is now effective and allows BTG-Israel to produce the vaccine in Israel upon receipt of regulatory approval and to export the vaccine to countries in which neither Biogen nor others have been granted a blocking patent.”[56]

The Biogen Israeli patent expired in December 1999, before the Supreme Court ruled on the compulsory license.

[1] This work is licensed under the Creative Commons Attribution-Noncommercial 3.0 License.
[2] 104TH Congress, Report, Senate, 2d Session, 104-394, Pharmaceutical Industry Special Equity Act Of 1996, Report Together With Minority Views [To accompany S. 1277]. For more information: http://thomas.loc.gov/cgi-bin/cpquery/?&item=&&sid=cp104pqlQi&&refer=&r_n=sr394.104&&dbname=cp104&&sid=cp104pqlQi&&sel=TOC_0&
[3] For more information: http://www.cptech.org/ip/health/cl/cipro/
[4] The United States’ Statement Of Interest, November 2005., NTP, INC., Plaintiffs, V. RESEARCH IN MOTION, LTD., Defendant., Civil Action No. 3:01CV767.
[5] See video excerpts from November 8, 2005 Hearings of the Subcommittee on Health of the House Committee on Energy and Commerce, http://www.cptech.org/ip/health/tamiflu/hearingexcerpts11082005.html
[6] Petition available at: http://www.scotusblog.com/movabletype/archives/Zoltek.pdf
[7] September 5, 2001, “National Institutes of Health and WiCell Research Institute, Inc., Sign Stem Cell Research Agreement,” http://www.nih.gov/news/pr/sep2001/od-05.htm. Memorandum of Understanding between WiCell Research Institute, Inc. and Public Health Service: http://stemcells.nih.gov/staticresources/research/registry/MTAs/Wicell_MOU.pdf
[8] For more information: http://www.essentialinventions.org/drug/ritonavir.html
[9] For more information: http://www.essentialinventions.org/drug/latanoprost.html
[10] For more information: http://www.essentialinventions.org/eii2omb-5jan07.pdf
[11] See U.S. Code tit. 35. §§ 202(c)(4) and 209(d)(I).
[12] For more information: http://www.ftc.gov/opa/2002/07/amgen.htm
[13] For more information: http://www.ftc.gov/opa/2006/04/bostonscigui.htm
[14] United States Of America, Plaintiff V. Microsoft Corporation, Defendant. Civil Action No. 98-1232 (CKK), Final Judgment, (November 12, 2002), available at: http://www.usdoj.gov/atr/cases/f200400/200457.htm. For a detailed account of work to implement the order, see: Interim Joint Status Report On Microsoft’s Compliance With The Final Judgments, available at: http://www.usdoj.gov/atr/cases/f201300/201386.htm.
[15] For more information: http://www.ftc.gov/os/adjpro/d9302/070205opinion.pdf and
http://www.ftc.gov/os/adjpro/d9302/070205finalorder.pdf
[16] eBay Inc. v. MercExchange, L.L.C., 126 S. Ct. 1837, 1839-1841 (U.S. 2006), available at: http://www.supremecourtus.gov/opinions/05pdf/05-130.pdf
[17] “Patently Obvious,” Wall Street Journal, May 3, 2007; Page A16, http://online.wsj.com/article/SB117815853947390467.html.
[18] Finisar Corp. v. DirecTV Group, Inc, available at: http://www.fr.com/news/Finisar-Judgement.pdf
[19] Paice LLC v. Toyota Motor Corp., 2006 WL 2385139(E.D.Tex. Aug 16, 2006) (NO. 2:04CV211DF).
[20] Voda v. Cordis Corp., No. CIV-03-1512, 2006 WL 2570614 (W.D. Okla. Sept. 5, 2006)
[21] Sundance, Inc. v. DeMonte Fabricating Ltd., 2007 WL 37742. (E.D. Mich. Jan. 4, 2007).
[22] Innogenetics, N.V v. Abbott Laboratories, Fed. Cir. App. 2007-1145, 2007 U.S. Dist. LEXIS 3148 (W.D.Wis. 2007)(Crabb, J.).
[23] Innogenetics, N.V v. Abbott Laboratories, 12 January 2007. W.D.Wis. 2007.
[24] Harold Wegner, Innogenetics v. Abbott, April 24, 2007, IPFrontline.com http://www.ipfrontline.com/depts/article.asp?id=14866&deptid=7
[25] Official publication: http://canadagazette.gc.ca/partI/2006/20060701/html/regle11-e.html
[26] AstraZeneca Annual Report and Form 20-F Information 2005
[27] Torpham v. Commissioner of Patents and Canada (AG), May 7, 2004 FCTD (MacKay J.) Abuse of Exclusive Rights/Section 65 of the Patent Act/Compulsory Licence /Request to Supply Bulk Lisinopril for Production of Tablets in Canada for Export to the U.S.
[28] Merck v. Brantford Chemicals and Commissioner of Patents and Canada (Attorney General), February 2, 2005 FCA (Rothstein, Evans, Malone JJ.A.) Compulsory Licence/Patent Act/Res Judicata/Functus Officio/Final Decisions.
[29] http://decisions.fct-cf.gc.ca/en/2006/2006fc1341/2006fc1341.html. Citation: 2006 FC 1341, Vancouver, British Columbia, November 7, 2006, Brantford Chemicals Inc. (sub. nom. Apotex Pharmachem Inc.)Appellant, and The Commissioner Of Patents, Attorney General Of Canada And Merck & Co., Inc. Respondents. Reasons For Judgment And Judgment.
[30] ARTICLE 5 – OTHER ACTIONS
5.1 Patent Validity; Enforceability. Immediately upon the Effective Date, or as soon as possible thereafter, ROCHE shall discontinue any opposition, challenge,
compulsory license application or the like with respect to the CHIRON Licensed Patents.
5.2 Compulsory Licensing. ROCHE covenants and agrees on behalf of itself and its Affiliates to not support any third party in seeking compulsory licensing of the
CHIRON Licensed Patents in any jurisdiction. As used in this Section, “support” shall have the same meanings as in Section 7.2(b).
[31] VAN OVERWALLE, G. & VAN ZIMMEREN, E., ‘Reshaping Belgian Patent Law: The Revision of the Research Exemption and the Introduction of a Compulsory License for Public Health’, IIP Forum (Japanese journal) 2006;64:42-4.
[32] AGCM. 21 February 2006. PRESS RELEASE: Pharmaceuticals: Antitrust says Glaxo has made amends and abuse of dominant position discontinued Granting of licence opens way for manufacture of generic migraine drugs. PROCEEDING reference n. A363, case GLAXO-PRINCIPI ATTIVI.
[33] 26 March 2007. Press Release, A364 – Merck – Active Ingredients (Conclusion Of Investigation): Antitrust Authority Rules Merck Must Grant Free Licences For The Active Ingredient Finasteride. The Authority accepts and renders obligatory a commitment presented by the companies Merck & Co. Inc. and Merck Sharp & Dohme (Italia) in order to conclude the investigation launched in February 2005 into possible abuse of a dominant position. Expected price reductions for the drug to benefit consumers and the National Health System. http://www.agcm.it/agcm_eng/COSTAMPA/E_PRESS.NSF/
92e82eb9012a8bc6c125652a00287fbd/28653b373e56772ac12572ab003a4d68
[34] The Indian Patents (Amendments) Act 2005, available at: http://www.ipindia.nic.in/ipr/patent/patent_2005.pdf
[35] Translated text of the actual license is available at: http://lists.essential.org/pipermail/ip-health/2004-December/007233.html
[36] Translated text of the actual license is available at: http://www.cptech.org/ip/health/c/malaysia/arv-license.html. For more information: Chee Yoke Ling, Malaysia’s Experience in Increasing Access to Antiretroviral Drugs: Exercising the “Government Use” Option (Third World Network, IPR Series No 9, 2006), available at: http://www.twnside.org.sg/title2/IPR/IPRS09.pdf
[37] For more information: http://www.cptech.org/ip/health/cl/recent-examples.html#Korea
[38] Kim Cheong-won, “Health Regulator Seeks to Produce Bird Flu Drug,” the Korea Times.
[39] Kathrin Hille, “Taiwan employs compulsory licensing for Tamiflu,” FT, November 25 2005.
[40] Taiwan issues compulsory license for making Tamiflu, Nov 25, 2005.
[41] Translated text of the actual license is available at: http://www.cptech.org/ip/health/c/thailand/thaicl4efavirenz.html
[42] Translated text of the actual license is available at: http://www.cptech.org/ip/health/c/thailand/thai-cl-kaletra_en.pdf
[43] Translated text of the actual license is available at: http://www.cptech.org/ip/health/c/thailand/thai-cl-clopidogrel_en.pdf
[44] The letter (in Spanish) is available at: http://www.cptech.org/ip/health/c/dr/
[45] For more information: http://www.essentialinventions.org/drug/imatinibmesylate/index.html
[46] Lucia Gallardo, El negocio del VIH/SIDA Patentes farmaceuticas ¿para que y para quien? (2006, Universidad Andina Simon Bolivar).
[47] SEC Form 10-Q — Quarterly report [Sections 13 or 15(d)], Period of Report: 2006-09-30.
[48] Price at Drugstore.com, 5 May 2007.
[49] For more information, http://www.essentialinventions.org/docs/cameroon/
[50] Text of the actual license is available at: http://www.cptech.org/ip/health/cl/Ghana.png
[51] Text of the actual license is available at: http://www.cptech.org/ip/health/cl/Eritrea.png
[52] Translated text of the actual license is available at: http://www.cptech.org/ip/health/c/mozambique/moz-cl-en.pdf
[53] Text of the actual license is available at: http://www.cptech.org/ip/health/c/zambia/zcl.html
[54] Text of the actual license is available at: http://www.cptech.org/ip/health/c/zimbabwe/zim05242002.html
[55] Bio-Technology General Corp., 10-K Report, April 1, 1996.
[56] Savient Pharmaceuticals Inc, Form:10-K Filing Date: 3/26/1998.