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Commentary: Isolated Stem CellsPatentable as Cultural Artifacts? [復制鏈接]

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發表于 2009-3-5 00:53 |只看該作者 |倒序瀏覽 |打印
作者:Mats G. Hanssona, Gert Helgessona, Richard Wessmanb, Rudolf Jaenischc作者單位:aCentre for Bioethics at Karolinska Institutet and Uppsala University, Department of Public Health and Caring Sciences, Uppsala Science Park, Uppsala, Sweden;bDepartment of Law, Uppsala University, Uppsala, Sweden;cWhitehead Institute for Biomedical Research and Department of Biology, Massachusetts  
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          【摘要】# q; U5 ^# A  u  i. C/ F9 V
      This article argues that an isolated embryonic stem cell basically represents a cultural artifact that has no equivalent to cells of the embryo, and that it is likely that the isolation of adult stem cells has a similar consequence. An isolated stem cell could thus be distinguished as something other than the stem cell existing as part of a human body. Since isolation of stem cells implies modification, product patents should, where the results carry enough novelty, inventive step, and potential for industrial application, as a matter of principle be a viable option for patent authorities. Questions of morality, which may affect the patentability, should also be viewed in light of the distinction between isolated result and body part. At the same time, it is essential that patent authorities do not accept broad patent claims that will be detrimental to research.
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  U0 |4 Z! `. h' |: k% @Disclosure of potential conflicts of interest is found at the end of this article.
0 H/ e& _; R3 c$ L0 G! A2 t. v          【關鍵詞】 Stem cells Patent Ethics
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Recently, the European Patent Office (EPO) rejected an application from the Wisconsin Alumni Research Foundation (WARF) for a patent on five stem cell lines. Previously, in the "Edinburgh case," regarding a patent involving genetic markers used to identify stem cells, the EPO review panel came to the conclusion that any claims involving human embryonic stem cells (hESC) violated the European Patent Convention. Both cases are pending appeal . Cases such as these touch upon several difficult questions, not least the morality of stem cell research in general and stem cell patents in particular. In order to further the discussion in these matters, it is important to have a clear understanding of the underlying biological facts.( E8 _  I* f( w1 q2 r* |

: H% f2 c1 }7 B& O! CBiological facts are rarely transferable to moral arguments. However, ethical opinions and policy-making in relevant areas should be consistent with such facts. According to paragraph 7 of Directive 98/44/EC on the legal protection of biotechnical inventions, the European Group on Ethics in Science and New Technologies to the European Commission (EGE) evaluates ethical aspects of biotechnology. The EGE has evaluated the ethical aspects of patenting inventions involving human stem cells . This article argues that, since isolation of stem cells implies modification, product patents may in some cases be a viable option for patent authorities. Furthermore, the modification in question should be taken into consideration in the assessment of applications to patent a particular method or use involving stem cells or stem cell technology.( o2 B2 X/ W# Q$ i$ [; E$ O' ]& W

" L8 I( m+ y( b( OTHE EPIGENETIC STATE OF THE GENOME AND ADAPTATION TO GROWTH IN TISSUE CULTURE$ e* z% W; V) v4 E4 ^+ F5 ?
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EGE claims that one should distinguish among: (a) "stem cells freshly derived from an organ or tissue which have not yet been subjected to any modification and which are capable of being propagated as stem cell lines," (b) "unmodified stem cell lines which refer to cultured lines of cells which have been propagated originally from freshly derived stem cells and which have not been modified in any other way...," and (c) "modified stem cell lines which refer to cultured lines of cells, propagated from stem cells or stem cell lines, which have been modified either by genetic manipulation, or by treatment that causes the cells to differentiate in a particular way" . Only the last kind of cells may be patented as products, according to EGE.
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However, the only "unmodified" human stem cells are those still present in the human body or embryo. Embryonic stem (ES) cells are isolated from in vitro fertilized (IVF) embryos that have been cultured in vitro up to the blastocyst stage. If used for infertility treatment, such embryos are transplanted into the uterus of a woman. If used for the derivation of an ES cell line, the blastocysts are explanted into a special culture medium and cultured in vitro for an extended period of time, generating a novel cell type that is not part of the blastocyst. Already, the act of placing a cell into a culture medium implies modification, hence even a "freshly derived" stem cell has been subjected to modification. The main reason is that isolation of ES cells selects for in vitro survival and proliferation of cells under adverse culture conditions .
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) K0 D3 F, _2 e2 A/ LThe brief in vitro culture of explanted mouse embryos has been shown to lead to LOI of sensitive genes such as Igf2 in the blastocyst . Although ES cells can contribute to normal development when introduced into a host embryo, they do not have the potential to generate an organism in contrast to the blastocyst from which they were derived. Thus, the derivation of ES cells is a process that leads to a novel cell type with novel characteristics that neither exist in the embryo nor in the fetus.
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An isolated stem cell should then be distinguished as something other than the stem cell still existing as part of a human body. This opens a possibility for legal consideration of patenting the method for manipulating the growth conditions but also for patenting an isolated stem cell as a unique result of modifying the cell by placing it in an appropriate medium.
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IN LINE WITH EUROPEAN UNION DIRECTIVE 98/44/ K4 B( E. }3 A" x5 \$ f
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Paragraph 2 of Directive 98/44/EC on the legal protection of biotechnical inventions states that "an element isolated from the human body ... may constitute a patentable invention" .6 E4 a9 C- E( d4 ]1 I
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COMPATIBLE WITH STRONG VIEWS ON POTENTIALITY, x* W! D9 s; S" ~% U% }' d  y

: q  F, S+ ?3 r" p6 u& bThere is today no international consensus on the moral status of human embryonic stem cells, and there are different policies for patenting among national patent offices that reflect a wide diversity of moral cultures .
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The legal argumentation for different national patent policies is complex. However, there seems to be one moral consideration that is common to the policies excluding patentability of hESC. Patentability implies, according to this view, research on embryos or variants thereof that carry the potential of developing into a mature human being, and is therefore wrong. An associated argument is that the research involves destruction of embryos carrying such a potentiality, but we will not go into this aspect here, acknowledging for the sake of the argument that there are embryos that really are "spare" in the sense that they are extra numerous embryos created through IVF and would be destroyed anyway .
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The potentiality of an entity and its moral implications has been an issue regarding the ethics of embryo research for some time . According to a weak view of potentiality, possibility and probability are seen as necessary conditions for potentiality. The embryo must, according to this view, have a real physical possibility of developing into a mature human being (e.g., through implantation and favorable development conditions), and this development must be probable. If these necessary conditions are not fulfilled, the embryo does not carry more potentiality and, therefore, not more moral weight than a sperm and an egg taken together but kept apart in two different Petri dishes. The underlying moral considerations of the referred patent policies seem, however, to be based on another view, where the potentiality of an entity refers to its intrinsic qualities. We call this the strong view of potentiality. The potentiality of the embryo denotes, according to this view, the inherent capacity or potency to develop into a mature human being. As such, it is worthy of moral consideration or protection, even if external conditions are lacking in order to make this development probable or even possible.% D" h( M) N' X6 f

$ K- `, M3 q3 Y7 E  E1 ^As argued above, the derivation of ES cells is a process that leads to a novel cell type with novel intrinsic qualities that do not exist in the embryo. The derivation process is, furthermore, not reversible. The ES cells do not carry any potentiality, not even in the strong sense, and should therefore be, in principle, patentable. Based on the weak view on potentiality, patentability of hESC should not be controversial. Taking the diversity of moral cultures into consideration, it may be seen as an advantage of our proposal that ES cells may be patentable and policy makers can still honor strong views on the potentiality of a human embryo.
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0 N6 D* [! l. P* w7 ~NOT NECESSARILY LEADING TO BROAD PATENTS
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, x5 L: q6 f! B- I: A" h% ]" CEGE argues that a right to patent "unmodified" stem cells implies too broad patents, since several technological applications may be derived from one original achievement. This is an important concern that was also expressed when genes were proposed as patentable. That this concern should not be taken lightly is evident when we look at how the WARF patents were handled by USPTO. As described by Loring and Campbell, USPTO issued a broad patent on December 1, 1998, claiming primate (including human) ES cells and on March 13, 2001, a second patent focusing on hESC , and they are charging both academic and commercially based researchers large fees for a license.! \6 t8 _) w# Q) |+ P& `
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The fundamental principle of a patent is to protect reasonable commercial claims and inventive achievements as a means to promote technological development and application of research into different sectors of society. The two WARF patents seem to have violated this principle by granting claims with an unreasonable scope leading to a situation that, in fact, may be detrimental to stem cell research. In analogy to the development in gene patenting, whether the result in terms of an isolated stem cell in a specific culture medium or a propagated stem cell line carries enough novelty, inventive step, and potential for industrial application has to be proven by the researcher. We suggest that the patent authorities may consider them as objects both for product and method patents that fulfill, in principle, the legal requirements for such patents, but that the scope of the patents must be reasonable and well informed by the scientific development and the foreseen effects of a patent on research and other commercial interests. In order not to frustrate research that could advance knowledge regarding the many detailed steps involved, we suggest as a preliminary guideline that patent authorities should take a conservative view regarding the scope of patents with a limitation to the intrinsic qualities of both the patented ES cells and the patented methodologies (i.e., on its potentiality in the strong sense described above).
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Product and method patents of ES cells and related technologies may be broadly categorized as related to: (a) isolation of ES cells, (b) derivations of ES cells (through genetic modification or otherwise), (c) methods of culturing ES cells, and (d) methods of using ES cells (differentiation/transplantation). A conservative policy would, for example, imply that claims may be restricted to ES cells deriving from a particular species, and that the scope of potential differentiation should be restricted to derivates of one specified tissue only. The patent should only cover a particular cell line and only specific uses (i.e., differentiation into one specific kind of tissue or a specific kind of transplantation). If the next step in a process (e.g., derivation) is an obvious next step without any need for further invention, this step does not provide the necessary prerequisite for a patent. It should be observed that these are only examples of what a conservative view may imply. It should also be noted that there are two possibilities of limiting patents, on the one hand through restrictions on the area of patentability and on the other through determining the extent of protection for the patent. Due account shall be taken of any element that is equivalent to an element specified in the claims. The closer determination of scope of protection and equivalent elements is, however, a question that must be decided in future infringement trials.
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COMMERCIALIZATION AND CONSENT6 W  @- p* M( f0 p. H/ @4 O1 M
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EGE has also put forward two ethical arguments against product patenting of human stem cells. They argue that isolated stem cells "are so close to the human body, to the fetus or to the embryo they have been isolated from, that their patenting may be considered as a form of commercialization of the human body" (. The ethical discussion about commercialization of human body parts is far from settled, but the point in this context is that what is commercialized is not something "close to a human body" but a product being a result of an advanced biotechnical process, a technique which human nature is "incapable of accomplishing by itself." Similarity with human body parts has never been a matter of consideration regarding patenting of biotechnical products. Rather, trying to develop something that is close to nature has been a drive in many technological developments.
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Secondly, EGE argues in accord with Article 3 of the Charter of Fundamental Rights and with Recital 26 of the 1998 European Union (EU) Patent Directive, which states that "... the person from whose body the material is taken must have had an opportunity of expressing free and informed consent thereto ..." . However, this right does not apply regarding the results of a research study, and since stem cells placed in a culture medium and being viable are results in this sense, the donor has no right to withdraw consent at that point, requiring that the cells should either be destroyed or made unidentifiable.9 Z0 h( T; V! S5 e( A0 {  {  A
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CONCLUSION. |9 u& g$ j$ k
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An isolated embryonic stem cell represents a cultural artifact that has no equivalent to cells of the embryo. Isolation of adult stem cells likely implies the same kind of modification. An implication of this is that isolated stem cells constitute research results that, in principle, fulfill the legal requirements of both product and method patents. In order for patents not to be detrimental to research and industrial application, it is vital that patent authorities assume a conservative approach in order to set a reasonable balance between different interests and limit the scope of the patents.+ J% A; [2 I+ f( \3 J: t
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DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
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3 i8 y) B3 n' TThe authors indicate no potential conflicts of interest.' O/ Y/ @; E' W3 Y( ~

  D+ S! F- c  M/ A: fACKNOWLEDGMENTS
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We are grateful to Paul Berg, Cahill Professor of Biochemistry, Emeritus at Stanford University School of Medicine, for helpful comments in the preparation of this article. M.G.H. acknowledges economic support for multidisciplinary research in the area from the Knut and Alice Wallenberg's Foundation (the national Biobank Program within Wallenberg Consortium North and Swegene), the Swedish Foundation for Strategic Research (the Ethical, Legal and Social Aspects of Genome and Gene Technology Research  Programme), and the EU Sixth Framework Programme Cancer Control and Prevention using Registries and Biobanks. This publication reflects only the authors' views. Neither the European Community nor the other funders are liable for any use that may be made of the information herein. None of the authors or their institutions have intellectual property applications pending that would be influenced by widespread adoption of the patent position advanced in this work.
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好帖子,要頂!

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越辦越好~~~~~~~~~`  

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干細胞之家微信公眾號
爺爺都是從孫子走過來的。  

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是樓主原創嗎  

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長時間沒來看了 ~~  

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呵呵 哪天得看看 `~~~~  

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太棒了!  

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你加油吧  

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