BPCIA在2010年三月生效後，生物相似藥廠商開始可以利用簡化的文件向美國食品和藥物管理局（FDA）申請藥品許可證，這個新醫療法賦予FDA決定如何落實法案的權力。基於不同生物製劑之間缺乏比較性這個已知的事實，加上公眾安全的考量，在還沒有累積大量經驗可以歸納出哪些是比較分析必要的資訊之前，FDA會保守的要求生物相似藥廠商以BPCIA提出申請時，必須提供臨床試驗資料來證明與參照藥品之間沒有臨床上有意義的差異。 雖然BPCIA給出了解決專利糾紛的框架，俗稱專利舞蹈(patent dance)，依照目前聯邦巡迴上訴法院對BPCIA的解釋，認為BPCIA法案不強制生物相似藥申請者遵循其規定之專利糾紛解決程序，雖然就目前的最新發展來看，迴避專利舞蹈可以避免一些程序上的麻煩，但真正參照藥品廠商和生物相似藥公司的輸贏仍是在訴訟戰場上見真章。 美國FDA在2015年3月6日核准了的一個生物相似藥-Zarxio( filgrastim-sndz)，目前尚不清楚均等論這種不確定性在生物相似藥上影響的程度，但藉由簡化新藥申請上市的小分子藥物所涉入的侵權訴訟做有限度的推論可以發現，小分子藥物的均等謬論案件是牽涉到外圍專利，當專利不再提供足夠的誘因去激勵專利權人時，學名藥廠商就會贏得均等論謬論案件。因為生物製劑是一種製程決定的產物，因此其專利通常是集中在製程。以BPCIA和專利法為框架來分析過去的相關侵權訴訟，可以預測生物相似藥廠商在轉化前步驟、轉化步驟、調劑、或包裝做改變，其成功的機會較大，而在細胞培養會純化步驟做改變，成功的機會最小。然而，最終還是要看法院將來如何解決生物相似藥的侵權問題，各方都要意識到科學與法律議題的複雜性，及妥適解決侵權訴訟的重要性。 台灣廠商要進入生物相似藥的領域，是困難重重的。生物相似藥的開發及法規成本，不如想像中低，鑒於蛋白質藥『產能』一直被看作是市場發展受阻的主要原因，藥廠委外合作(CRO、CMO或NRDO) 的模式能快速與國際藥廠接軌，逐步奠定台灣在藥物開發的供應鏈合作利基並提昇國際知名度。 / The Biologics Price Competition and Innovation of 2009 was activated on March in 2010. Now the US Food and Drug Administration (FDA) can approve biosimilars and was empowered to how to practice. Given the known issues with lack of comparability between different biologics preparations, and the Agency’s strong interest in protecting public safety, it is probable that, until it has developed a body of experience with regards to the amount and kind of data needed to make comparability evaluations, the FDA will adopt a conservative approach and require at least some clinical studies before approving biologics under BPCIA. Though BPCIA provide the frame for resolving patent issues, that is so-called patent dance, Federal Circuit said that parties were not compelled to dance. Thus the law uncertainty was shifted to patent infringement. FDA approved the first biosimilar, Zarxio (filgrastim-sndz), on 6, March, 2015. It is unclear how biosimilar will be treated in court based on doctrine of equivalence. Based on the experience from generics, courts tends to adjust the scope of equivalents to improve the correspondence between patent scope and desired patent incentives. In contrast, biologics is path depended. That is to say process decided what biologics would be. Both the BPCIA and patent law guide the shape of infringement suits. Follow-on biologics companies will be most successful when they make a change in the pretransformation process, the transformation process, the formulation, or the packaging. They will be least successful when they make a change in the cell culture conditions or the purification process. It remains to be seen how courts will address issues of infringement for follow-on biologics, but all parties should be aware of the complexity of the scientific and legal issues and the importance of addressing them properly. The cost for development and the complexity of regulation in biosimilars were tremendously high. Thus it is difficult for biopharmaceutical industries in Taiwan to enter this field. In the light of unmet production capacity in protein drug, pharmaceutical industries in Taiwan could apply the mode of CRO, CMO or NRDO to integrate into global biopharmaceutical community.

The dissertation employs laboratory experimental methodology to study decision-making when people face trade-offs between ethical and economic values. More explicitly, the three chapters investigate 1) consumer behaviour when a substantially equivalent version of a product is more expensive because it was produced without child labour, 2) the interaction between an expert advisor and an ignorant decision-maker, when the former may gain from lying and the latter has to decide whether or not to trust in the advice, and 3) fairness in divisions of an economic gain between two people who were both involved in creating the gain, but only one of them provided real effort. Here, a focus is on the impact of power structure, i.e. who decides, on divisions and fairness judgments. All studies discuss implications of experimental behaviour for market and business domains. In addition, the thesis emphasizes ethical theories as complementary to normative benchmark from economic and psychological theory. / La tesis utiliza una metodología experimental para investigar las decisiones de los individuos cuando hay un conflicto entre valores éticos y económicos. Mas específicamente, los tres capítulos investigan sobre 1) el comportamiento del consumidor cuando se enfrenta a dos versiones de un mismo producto, siendo una de ellas más cara por ser producida sin trabajo infantil, 2) la interacción entre un agente experto y un agente desinformado que debe tomar una decisión confiando o no en el consejo del experto, el cuál puede mentir para ganar más dinero, y 3) el reparto justo de una ganancia económica entre dos personas de las cuales sólo una ha contribuido trabajando en un ejercicio. Este último estudio se centra en el impacto de la estructura de poder, es decir quién decide, en el reparto y en los juicios de que es lo justo. Los estudios analizan las implicaciones del comportamiento experimental sobre los mercados y las empresas. Además, la tesis propone teorías éticas para complementar las teorías económicas y psicológicas.

隨著醫療科技的進展，人類對於疾病的成因、機轉、病程、及治療，在不斷地研究突破下，有著持續的進步而對人類的健康有著不可或缺的貢獻。其中藥品，正是人類對抗疾病最關鍵、也最普遍的方式之一，對公共衛生的重要性自不待言。 其中，由於生命科學的本質使然，開發新的藥品對於研究發展的倚賴，遠勝於其他產業，因此，創新研發藥廠對於開發一項新藥的平均投資，已達十三億美元之譜；此外，由於藥物對人體的生理功能、體內恆定能造成極大的影響，因此世界各國的醫藥衛生主管機關無不對於藥品的上市加以嚴格的管制，使得現今開發一項藥品平均約耗時十至十五年。藥品開發的巨大投入與耗時極長的開發期間，使得製藥產業亟需經由智慧財產權的制度來提供其投入研發創新之誘因。然而，因為智慧財產之保護，也使得新藥往往售價高昂而造成公眾近用之阻礙。而學名藥正是解決這樣的問題的關鍵之一，亦為世界各國所大力推動。在推動學名藥產業上，實驗實施免責為制度上極為重要的考量之一。本文及希望藉由對製藥產業特質之探究，美國普通法上以及成文法上實驗實施免責的探討，我國實驗實施免責之規定與判決之研究，來找出我國當下實驗實施免責的規定於製藥產業中適用時所可能發生的問題，以及相對應的可能改進方案。 本文第二章本章先行探討製藥產業之特質；第三章討論美國普通法上實驗實施免責之概念，並歸結出美國普通法上實驗實施免責的三項適用要件；第四章探討美國成文法上實驗實施免責之立法背景、相關判決以及對生物科技領域各層面的影響；第五章則先行探討世界貿易組織於「與貿易相關智慧財產權協定」中對於專利權之限制基礎。其後探討我國專利法中之一般實驗實施免責以及藥事法中針對製藥產業之實驗實施免責之相關規定，並由學者論述以及相關判決中，探討我國實驗實施免責之相關規定於製藥產業實務上所可能面臨之問題，並提出可能之解決方案。 / With the progress of medical technology, humans have been furthering the understanding of the etiologies, mechanisms, courses, and treatments of diseases. Such continued progresses have contributed significantly to improving human health. Among all the treatments, the pharmaceutical is one of the key and common ways with which humanity fight diseases. Its importance to public health is beyond doubt. Due to the nature of the life sciences, the pharmaceutical industry depends more on research and development than other industries do. Therefore, on average, it costs innovative pharmaceutical companies 1.3 billion U.S. dollars to develop a new drug. Furthermore, countries around the world pose strict regulations on new drugs’ entering the market since drugs cause huge impacts on the physiological functions and internal balances of the human body. Hence, it generally takes ten to fifteen years for a new drug to be fully developed. The enormous investment and lengthy developing period makes the pharmaceutical companies extremely dependant on the intellectual property system to provide them with the incentive for research and development. However, it is also because of the intellectual property protection that makes new drugs expensive and difficult for the public to access. The Generic drug, however, is one of the key solutions to solve this problem and is intensively promoted by countries all over the world. Regarding the promotion of the generic drug industry, the experimental use exemption is one of the vital systemic considerations. There are discussions on the characters of the pharmaceutical industry, on the common law and statutory experimental use exemptions of the United States, and on the related regulations and precedents of the experimental use exemption in Taiwan. Through the above discussions, the thesis is aimed at identifying the possible problems the regulations on experimental use exemption might cause when applied to the practice of the pharmaceutical industry and at proposing possible solutions to such problems. The characters of the pharmaceutical industry are discussed in Chapter two. The concepts and the criteria of the common law experimental use exemptions are discussed in Chapter three. The legislation background, related precedents, and impacts on the field of biotechnology of the statutory experimental use exemptions in the United States are illustrated in Chapter four. Lastly, in chapter five, the restrictions on patent right in the Agreement on Trade-Related Aspects of Intellectual Property Rights of the World Trade Organization is first discussed. The related regulations on experimental use exemptions in Taiwan are later discussed. Lastly, through the scholars’ opinions and related precedents, the possible problems of application of the experimental use exemption in Taiwan are illustrated and the probable solutions are proposed.

生物藥品是很多先前具致命性和難以治療的疾病領域，像是癌症、自體免疫疾病及神經系統疾病內最被看好的現行新穎療法。近年來，隨著探索出突破性小分子藥物愈趨困難，加上生物藥品在新藥研發過程中有較低的折損率與較高的成功產出率，使得越來越多藥廠紛紛轉向開發利潤豐厚的大分子生物產品。此外許多暢銷生物藥品專利期即將屆至，從而帶來對相對價廉、通常被稱為原廠生物藥品仿製版本之「生物相似性藥品」的龐大治療需求。然而，由於生物藥品和小分子藥物在分子大小及結構複雜程度方面存在截然不同的特性與本質差異，因此建立一套專屬於生物相似性藥品的上市許可規範勢在必行。 作為於2010年3月23日正式簽署公告之「患者保護及可負擔照護法案」中的一部分，美國國會通過了「生物藥品價格競爭與創新法」(BPCIA)。BPCIA的生效被視為製藥產業最重要的變革之一，旨在藉由競爭達到維護公眾健康、促進生物技術創新和控制醫療支出之目的，同時取得適當之三方利益平衡。BPCIA即以Hatch-Waxman法案下的化學學名藥核准途徑為模版，創建生物藥品簡易上市申請程序。 本論文的結構主要區分為兩大部分進行研究，其一提供了製藥產業概觀與全球生物藥品市場的發展趨勢，其二則聚焦在BPCIA新建立的核准前專利爭端解決程序下，生物相似性藥品面臨「專利舞蹈」時的法律評估及智慧財產權管理。 論文的第一部分係根據從各種市場研究報告收集、整理而成的統計數據，以系統性的方式深入介紹全球製藥產業，並分析生物相似性藥品的市場機會和潛在隱憂。另外此部分亦詳細說明了生物相似性藥品的生理活性、知識斷層與製程依賴性之間的關係、分析技術對生物產品做完整定性的不足以及生物相似性藥品的開發流程。 論文的第二部分則以討論BPCIA的重要條文規定為主，包括專利舞蹈制度和上市審查要求，諸如生物相似性之證明、可互換性之認定與適應症外推。其他相關議題，包含參考藥品的法定專屬權保護期長度、生物相似性藥品自動替換之立法化、專利資訊交換機制的可能濫用及原廠與生物相似藥廠達成反競爭協議之風險皆會予以進一步探討。除此之外，本部分也介紹了歐盟和台灣生物相似性藥品上市法規的沿革與現況。 本文試圖透過對生物相似性藥品的全方位綜合研究成果，提出可行的市場進入方案及善用專利和營業祕密優勢之智慧財產權保護佈局策略。 / Biologics represent many of the most promising novel therapies for previously deadly and intractable disease areas like cancer, autoimmune disease and neurological disorders. As discovery of breakthrough small-molecule drugs becomes more difficult, together with lower attrition rate and higher productivity of biologics in the new drug research and development (R＆D) process, pharmaceutical companies are increasingly turning to develop lucrative large-molecule biological products in recent years. In addition, the patents on numerous blockbuster biologics treatments will soon expire, bringing soaring demand for relatively inexpensive generic versions of originator biologics, generally known as “biosimilars.” However, due to contrasting characteristics and natural differences in terms of size and structural complexity between biologics and small-molecule drugs, it is necessary to create a regulatory pathway solely for biosimilars. As part of the Patient Protection and Affordable Care Act which was officially signed into law on March 23, 2010, the U.S. Congress passed the Biologics Price Competition and Innovation Act (BPCIA). The BPCIA is considered one of the more significant overhauls to the pharmaceutical industry, aiming to strike a proper balance among securing public interests, stimulating biotechnology innovation and controlling healthcare expenditure through competition. It established an abbreviated approval pathway for biosimilars modeled closely after the Hatch-Waxman Act’s approval process for generic chemical drugs. The structure of this thesis is divided into two major parts, of which the first part provides an overview of pharmaceutical industry and trends in the global biologics market, whereas the second part focuses on the legal assessment and intellectual property management of biosimilars under BPCIA’s new pre-approval patent dispute resolution process, the “patent dance”. The first part starts from the in-depth systematic introduction of global pharmaceutical industry based on statistics collected from various market research reports, then analyzes the market opportunities and potential concerns for biosimilars. Moreover, this part illustrates the physiological properties, the relationship between “knowledge gap”and manufacturing path-dependence, the insufficieny of analytical techniques in fully characterizing biological products, and the development process of biosimilars in details. The second part discusses key provisions of the BPCIA, including the patent dance procedures and regulatory requirements, such as demonstrating biosimilarity, interchangeability and extrapolation. Other relevant issues include the length of statutory exclusivities granted to reference products, legislations on biosimilar automatic substitution, potential abuses of patent information exchange mechanism and risks of reaching anti-competitive agreements between pioneers and biosimilar manufacturers will be further discussed. Besides, this part describes the timeline and status quo of EU and Taiwan’s biosimilar approval regulations. With comprehensive study on multiple aspects of biosimilars, this article tries to propose feasible market access plans and robust intellectual property protection strategies capitalizing upon patents and trade secrets.

面對未來全球人口成長、可耕地減少等現象，生物技術在農業上的應用日益增加。其中，基因改造技術等基因層次相關的平臺應用技術更是提升農作物價值的關鍵—透過跨物種功能應用，大幅提升育種效率。自1996年基改作物商業化種植開始至今，美國都是全球最大種植國家，也是基改作物研發先驅國家。生技農業政策以及和基因改造作物有關法規之制訂使基改作物在美國蓬勃發展，尤其是專利保護對於種子產業之影響尤為深遠。專利權所提供的完善保護使大量資本進入種子產業，投入資源將農業生物技術應用於種子培育上，此舉也促成Monsanto等跨國農業生技公司之興起，主導全球基因改造作物之市場。 Monsanto將研發重心放在基改種子之研發，其在生技種子相關營業比重遠高於同業，同時，其投入特殊性狀之基改種子研發之回收遠高於其他公司之相同營業項目之投資報酬率。Monsanto積極藉由併購取得基因、基因轉殖技術以及種子種源。掌握關鍵基因、基因轉殖技術以及大量且優良種源使含有Monsanto轉殖基因作物在市場上佔有極大的比例。在美國，超過一半以上之主要作物種植面積為基因改造作物，尤其是基因改造大豆，佔大豆總種植面積之比例高達94%。市面上絕大多數基改大豆係Monsanto的抗嘉磷塞（RounupReady，RR1Y）基改大豆種子。藉由智慧財產保護策略，Monsanto並進一步限制RR1Y及其他基改作物之使用方式。 惟RR1Y專利將在2014年到期，農民可在2014年時留種種植基改大豆種子而不用每年購買種子，或購買學名（generic）抗嘉磷塞轉基因大豆種子。在美國所種植之大豆約有四成會外銷，而外銷國家基改作物規範法規是出口與否之關鍵。若未取得歐盟、中國等主要外銷國家基改作物主管機關之批准，呈交包括基因之轉殖植物對環境衝擊之風險評估、包含該基因之轉殖植物所製成食品之安全性評估等基改作物資訊，則抗嘉磷塞基因大豆無法進入該國糧食市場。然而，在目前美國農業生技基改作物相關規範下，學名基改種子廠必須在專利種子專利到期後，才能進行實驗及田間試驗，呈交相關資料以符合基改作物主管機關之要求。透過建立學名基改作物快速獲得核准查驗登記之程序，允許學名廠依賴專利基改作物原廠之實驗及田間試驗資料以建立其學名基改作物之安全性與性狀表現有效性，同時，允許學名基改作物在原基改作物開發廠專利期滿前即可開始進行試驗，可以使學名抗嘉磷塞大豆種子以及其他學名基改種子能在原專利基改作物種子專利到期後順利進入市場，促使基改作物種子價格競爭，並對於專利基改作物研發公司進行適度之補償，以促進產業發展。 / The development of new technologies in plant breeding has led to improvements in the efficiency scientists produce improved plant varieties. Genetic modification is among the developments that support plant breeding. The introduction of genetically modified crops has revolutionized the agriculture industry. With patent protection available on GM traits, varieties and other aspects of seed production, private R&D investments in the seed industry have increased tremendously. Monsanto has been the leading company in investing agricultural biotechnology and has obtained a dominant position in the GM traits found in soybeans, cotton, corn and other commercialized crops. Currently, over 90 percent of soybeans planted in the United States were herbicide-resistant, with Monsanto’s Roundup Ready being the dominant soybeans planted. In 2014, however, the agriculture industry will be facing the expiration of a patent for Roundup Ready soybeans. Despiate the fact that the patent expiration date is approaching, the agricultural biotech industry has no guideline in place to tell its players exactly how to transition seamlessly from patent monopolies to generic competition. The transition problem is espectially significant for soybeans exported to oversea markets as more than 40 percent of the soybeans grown in the U.S. are exported. In order for those soybeans to be accepted in the grain channel, regulatory approvals are required in countries that import soybeans. Obtaining data, which includes scitific data on the trait being developed, for regulatory approvals can take years to complete. If a generic trait is to reach market immediately after the original trait go off patent, the data generation process should begin before patent expiration. A Hatch-Waxman type patent infringement defense for activities necessary to obtain regulatory approvals for biotech traits can ensure that seed companies have sufficient time to obtain registrations for a generic Roundup Ready trait or other generic traits. Current legislation should be modified to adequately oversee the transition to the generic use of genetically modified crops and, in the mean time, ensure the availability of generic modified crops.

Cette thèse est un recueil de trois articles sur la théorie microéconomique. Les deux premiers traitent de la question de la course vers le bas lorsque les gouvernements se livrent à la concurrence pour certains facteurs mobiles. Le troisième article propose une extension du problème d'appariement plusieurs-à-un en y introduisant des agents de tailles différentes. Dans le premier article, nous montrons comment le résultat standard de course vers le bas (race-to-the-bottom) peut être évité en introduisant du bien public dans un modèle de compétition fiscale. Notre économie comporte deux juridictions peuplées par de la main-d’œuvre parfaitement mobile répartie en deux catégories : qualifiée et non-qualifiée. Les gouvernements, en poursuivant un objectif Rawlsien (max-min), annoncent simultanément leur projet d'investissement en bien public avant d'adopter une politique de taxation non-linéaire du revenu. Les travailleurs, après avoir observé la politique de taxation des différents gouvernements et leurs promesses d'investissement en bien publique, choisissent chacun un lieu de résidence et une offre de travail. Ainsi, les gouvernements atteignent leurs objectifs de redistribution en cherchant à attirer de la main-d’œuvre productive à travers la fourniture de bien public en plus d'une politique de taxation favorable. Nous montrons qu'il existe des équilibres où les travailleurs qualifiés paient une taxe strictement positive. En outre, lorsque l'information sur le type des travailleurs est privée, il existe, pour certaines valeurs des paramètres, des équilibres où la main-d’œuvre non-qualifiée bénéficie d'un transfert net (ou subvention) de la part du gouvernement. Dans le second article, nous étudions comment le modèle standard de compétition des prix à la Bertrand avec des produits différenciés pourrait fournir des informations utiles pour les programmes de citoyenneté par investissement dans les Caraïbes. Nous montrons que lorsque les pays peuvent être classés en deux types en fonction de la taille de leur demande, l'imposition d'un prix minimum uniforme et d'un quota maximum appropriés amène les pays à un résultat efficace qui Pareto domine l'équilibre de Nash non coopératif. Enfin, le troisième article explore une extension du problème standard d'appariement plusieurs-à-un en y incorporant des agents de tailles différentes (familles de réfugiés) d'un côté, à assigner à des foyers de capacités différentes de l'autre. La taille d'une famille de réfugiés représente le nombre de membres qui la compose. Une caractéristique spécifique à ce modèle est qu'il n'autorise pas de répartir les membres d'une même famille entre différents foyers. Il est bien connu que, dans ces conditions, bon nombre de propriétés désirables des règles d'appariement s'effondrent. Nous faisons donc l'hypothèse des priorités croissantes avec la taille pour chaque foyer, c'est-à-dire qu'une famille d'accueil préférerait toujours un plus grand nombre de réfugiés tant que la capacité de son foyer le permet. Nous montrons qu'un appariement stable par paire existe toujours sous cette hypothèse et nous proposons un mécanisme pour le trouver. Nous montrons que notre mécanisme est non-manipulable du point de vue des réfugiés : aucun groupe de réfugiés ne pourrait tirer profit d'une déclaration truquée de leurs préférences. Notre mécanisme est également optimal pour les réfugiés en ce sens qu'il n'existe aucun autre mécanisme stable par paire qui serait plus profitable à tous les réfugiés. / This thesis is a collection of three articles on microeconomic theory. The first two articles are concerned with the issue of race-to-the-bottom when governments engage in competition for some mobile factor. The third article proposes an extension for the many-to-one matching problem by introducing different-size agents. In the first article, we show how the standard race-to-the-bottom result can be avoided by introducing public good into a tax competition model. Our economy has two jurisdictions populated by perfectly mobile workers divided into two categories: skilled and unskilled. Governments, in pursuit of a Rawlsian objective (max-min), simultaneously announce their plans for investing in public good before deploying a nonlinear income tax schedule. After observing the tax schedules of the governments and their promises to invest in public good, each worker chooses a place of residence and a supply of labour. Thus, governments achieve their redistribution objectives by seeking to attract productive labour through the provision of public goods in addition to favorable taxation policy. We show that there exist equilibria where skilled workers pay a strictly positive tax. In addition, when information on the type of workers is private, there are equilibria for certain parameter values in which unqualified workers receive a net transfer (or subsidy) from the government. In the second article, we investigate how the Bertrand standard price competition with differentiated products could provide useful insight for Citizenship By Investment programs in the Caribbean. We show that when countries can be classified into two types according to the size of their demand, imposing appropriate uniform minimum price and maximum quota brings countries to an efficient outcome that Pareto dominates the Non-Cooperative Nash Equilibrium. Finally. in the third article, we explore an extension of the standard many-to-one matching problem by incorporating different-size agents (refugee families) on the many side of the market, to be assigned to entities (homes) with different capacities on the other side. A specific feature of this model is that it does not allow refugee families to be split between several homes. It is well known that many of the desirable properties of matching rules are unachievable in this framework. We introduce size-monotonic priority ranking over refugee families for each home, that is, a host family (home) would always prefer a greater number of members of refugee families until its capacity constraint binds. We show that a pairwise stable matching always exists under this assumption and we propose a mechanism to find it. We show that our mechanism is strategy-proof for refugees: no refugee family could benefit from misrepresenting his preferences. Our mechanism is also refugees optimal pairwise stable in the sense that there is no other pairwise stable mechanism that would be more profitable to all refugees.