Merck & Co., Inc. (USA) In November 2004, Ono in-licensed from Merck & Co., Inc., Whitehouse Station N.J. USA (“Merck”), a new class of type II diabetes oral drug ONO-5435/MK-0431 and a drug for chemotherapy-induced nausea and vomiting ONO-7436/MK-0869. ONO-5435/MK-0431 is a selective dipeptidyl-peptidase (DPP) 4 inhibitor, a drug enhancing a natural body system called the incretin system, to help regulate blood sugar, and that is a totally novel mechanism of action. In Japan, it has been co-developed with Banyu Pharmaceutical Co., Ltd., Merck's Japanese subsidiary under the License Agreement between Ono and Merck and was launched in December 2009 by Ono as “GALCTIV® Tablet” and by Banyu as “JANUVIA® Tablet”. The drug has been commercialized by Merck as “JANUVIA® Tablet” in Europe and the US. ONO-7436/MK-0869 is a selective neurokinin (NK) 1 antagonist that is expected to treat chemotherapy induced nausea and vomiting not only in acute phase but in delayed phase as well. It has been developed solely by Ono in Japan and was launched as “EMEND® Capsule” in December 2009. It has been commercialized in Europe and the US by Merck & Co., Inc. as “EMEND®”. Novartis AG (Switzerland) In December 2005, Ono signed an agreement with Novartis AG on the co-development and commercialization in Japan of ONO-2540/ENA713D for the treatment of Alzheimer's disease. The drug is the first transdermal patch developed using rivastigmine (oral drug), which is currently in use in over 70 countries outside Japan for the treatment of Alzheimer's disease. ONO-2540/ENA713D has been commercialized in the US. Co-development is underway with Novartis Pharma K.K., the Japanese subsidiary of Novartis AG. GlaxoSmithKline plc. (UK) ONO-4128/873140 is an AIDS treatment drug with a novel mechanism (a cellular chemokine receptor (CCR5) antagonist) discovered by Ono and out-licensed to GlaxoSmithKline (GSK) of the UK, which had been undertaking worldwide development. However, clinical trials conducted in Europe and North America by GSK detected an undeniable causal relationship between the drug and abnormal changes in liver function values. Development has therefore been halted. Nonetheless, ONO-4128/873140 still remains a significant resource since clinical outcome obtained to date has shown a remarkable decrease in HIV virus in treated patients and the use of a CCR5 receptor antagonist as an AIDS treatment drug is not expected to induce the emergence of drug resistance in HIV virus.  Utilizing information obtained to date, Ono and GSK are engaged in drug discovery efforts for a new compound that is safe and strongly pharmaco-active, as an alternative to ONO-4128/873140. Schering-Plough Corporation (USA) In November 2000, Ono signed a licensing agreement with Schering-Plough of the USA. Under the agreement, Schering-Plough was granted rights to develop and commercialize in Latin America the leukotriene receptor antagonist (for the treatment of bronchial asthma and allergic rhinitis), Ono® Capsule and the bronchial asthma drug Ono® Dry Syrup. Currently, Schering-Plough sells the two products (Latin American trademark: Azlaire) in 12 countries including Mexico, Peru, Panama and the Dominican Republic. Medarex Inc. (USA) In May 2005, Ono entered into a collaborative research agreement with Medarex Inc. of the USA to research and develop a fully human anti-PD-1 antibody drug with a novel mechanism of action with promising potential for the treatment of cancer.  Already, a fully human anti-PD-1 antibody ONO-4538/MDX-1106 has been created and Medarex is undertaking clinical trials in the US on malignant tumors. In Japan, Ono is undertaking clinical trials in line with the progress of development overseas. In March 2006, a new co-development agreement was signed on the development of a fully-human antibody drug to work as antibodies against the SDF-1 protein, which is thought to be involved in inflammation and in the proliferation and metastasis of cancer cells. Array BioPharma Inc. (USA) In November 2005, Ono signed a research collaboration agreement with Array BioPharma Inc., on drug discovery involving kinases. Under the agreement terms, Array is currently undertaking the creation of small molecule drug candidates targeting a multiple number of kinases selected by Ono. Array has already succeeded in logically and efficiently identifying several lead compounds with powerful kinase inhibiting properties by using the company's technological expertise in the X-ray crystallography of proteins. These compounds are being evaluated for efficacy and safety using animal experiments. The development and commercialization of compounds created through this collaboration are to be conducted by Ono. Locus Pharmaceuticals, Inc. (USA) In July 2006, Ono signed a research collaboration agreement with Locus Pharmaceuticals, Inc. of the USA on drug discovery involving kinases. Under the agreement terms, Locus is currently using computer aided drug design technology to undertake the creation of small molecule drug candidates targeting a multiple number of kinases selected by Ono. In November 2007, a second research collaboration agreement on new kinase drug discovery was signed. The development and commercialization of compounds created through this collaboration are to be conducted by Ono. Helsinn (Switzerland) In October 2006, Ono signed a licensing agreement with Sapphire Therapeutics, Inc. of the USA (now Helsinn Therapeutics (U.S.), Inc., a subsidiary of Helsinn of Switzerland) on the novel cancer anorexia/cachexia drug ONO-7643 (RC-1291) under development by Helsinn. Under the agreement, Ono acquired the exclusive development and marketing rights of the drug in Japan, South Korea and Taiwan. Clinical trials are now underway by Helsinn in the USA and by Ono in Japan. Paion AG (Germany) Ono entered into a license agreement with CeNeS Limited of UK (currently Paion AG) regarding a new short-acting general anesthetic, CNS-7056 in August 2007, and obtained the exclusive rights in Japan to develop and commercialize it. CNS-7056 rapidly induces deep sedation and its duration of action is short. Therefore it is anticipated that the compound is developed as a sedative agent for the induction and maintenance of anaesthesia as well as for mechanical ventilation in the intensive care unit (ICU) with excellent potential in controllability and safety. Nissan Chemical Industries, Ltd. (Japan) In December 2007, Ono entered into a license agreement for a new therapeutic agent for thrombocytopenia discovered by Nissan Chemical Industries, Ltd. (Nissan). Under this agreement, Ono was granted the worldwide exclusive rights to develop and commercialize the compound.  This is a low molecule compound orally active and capable of increasing platelet counts. Ono and Nissan are jointly developing the compound, with Ono now undertaking pre-clinical studies for the compound and Nissan being responsible for the development and manufacture of the drug substance. Caption：Chemical Research Laboratories, Nissan Chemical Industries, Ltd. (Japan) Evotec AG (Germany) In March 2008, Ono signed a collaboration agreement with Evotec AG of Germany on fragment-based drug discovery involving proteases. The collaboration applies Evotec's proprietary fragment-based drug discovery platform, EVOlution (TM) to identify novel, small molecular weight compounds active against a protease target chosen by Ono. Ono has worldwide exclusive rights to develop and commercialize compounds thus created by Evotec. Progenics Pharmaceuticals, Inc. (USA) In October 2008, Ono entered into an agreement with Progenics Pharmaceuticals, Inc. of USA to develop and commercialize in Japan the subcutaneous injection drug methylnaltrexone bromide. This is a drug administered for the treatment of intractable constipation induced by opioid pain medication. It is already an approved drug in Europe and the US and is being marketed by Progenics in the US and by its European and American partner Wyeth. In Japan, Ono is engaged in development activities under its sole rights. Xention Limited (UK) Ono signed a drug discovery agreement targeting ion channels with Xention Limited of UK in March 2009. Xention will apply its proprietary ion channel drug discovery platform to design small molecule drug candidates having activity against ion channels selected by Ono - ion channels of key pathophysiological importance. Ono will perform clinical development and commercialization of compounds in the world. Tioga Pharmaceuticals, Inc. (USA) In September 2009, Ono entered into a license agreement with Tioga Pharmaceuticals, Inc. of the USA with respect to an IBS drug, and obtained the rights to exclusively develop and commercialize asimadoline (INN) in Japan, Korea and Taiwan. Tioga plans to initiate Phase III studies in the U.S. during the 1st quarter of 2010, and Ono plans to start Phase I studies in Japan during the 2st quarter of 2010.