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Title: | 生物科技之評估及策略建議-以GnRH vaccine之專利、經營、學術三構面分析研究為例 |
Authors: | 黃謙銘 |
Contributors: | 劉江彬 黃謙銘 |
Keywords: | 生物 專利 評估 產業 策略 治療性疫苗 性腺刺激素釋放素 技術 科技 Biotechnology patent evaluation industry strategy therapeutic vaccine gonadotropin releasing hormone |
Date: | 2002 |
Issue Date: | 2016-05-10 16:18:10 (UTC+8) |
Abstract: | 生物科技為目前世界各國極力投入之新興產業,此產業無需大量天然資源及低污染的特性,同時又能解決人類的醫療問題並提昇生活水準的未來發展空間,更使得此一新興產業吸引了眾人的眼光。
本論文提出一個評估的模式,讓此產業之技術、產品或專利之價值能夠經系統化的分析後完整呈現,並可基於此分析結果作出策略上之判斷,並以GnRH vaccine技術為例。因為GnRH分子之序列早已發表,經本研究分析得兩種常用的專利保護策略,第一種是將GnRH與不同的載體進行結合,而新生成一個嵌合化合物,並申請此新化合物之專利;第二種是進行GnRH分子結構上之改變以取得新序列的專利保護,取得效果優於自然設計之分子,或藉以增加與免疫載體之結合率。經分析後發現,GnRH疫苗應用理論已經相當成熟,未來幾年應該會有成熟產品通過上市之審核過程;再隨著新科技的進步,可預期將會有更多的新產品會上市,而進一步地有效提昇產品功效並降低製造成本。
本研究最後針對GnRH未來在人用藥品及動物用藥之未來市場加以分析,並對於以重複免疫原在重組型疫苗製備法之開發提出行銷、財務、通路、價格、推廣、臨床實驗之建議,以期能經由策略規劃的角度將生物技術的價值作最大化的管理。 Biotechnology attracts high attentions among many countries recently. New biotechnology will provide a key solution to cure diseases and potentially will be able to increase human life quality without damaging the environment and consuming massy natural resources.
In this thesis, we presented a possible process, which involved in academic, marketing and patent information analysis, to effectively evaluate the feasibility and potential of any novel biological technologies, so as to provide the managerial and strategic suggestions based on the analysis. GnRH repeat immunogens vaccine development was taken as an example to demonstrate if the proposed process can be executed adequately. After discretly cross examining the collected information, we concluded that many independent GnRH vaccine patents are available but will not be effective enough to stop to new competitors to get in this sector because GnRH sequence was disclosed in very early research and nobody held the patent for it and most of GnRH patents were granted to either different GnRH-Carrier chimeras or the GnRH analog sequences. Analysis results show that there is only one company closely approaching the final product approval at this moment. However, any improved technology can easily employed to provide a better product with higher effectiveness and lower cost following the first product`s upcoming marketing clearance and then make the future market very complicated.
Based on those findings, we further analyze the Taiwanese current environment and provide a few managerial suggestions to maximize the value of a novel GnRH vaccine preparation technology. "中文摘要-----1
Abstract-----2
致謝-----3
目錄-----5
表目錄-----6
圖目錄-----7
第一章 緒論
第一節 研究動機-----8
第二節 研究目的與問題-----9
第三節 研究流程-----10
第四節 研究論文架構-----11
第二章 文獻探討
第一節 生技產業之特點分析-----12
第二節 生技產業專利權保護-----17
第三節 分子疫苗產業發展歷程-----21
第四節 荷爾蒙依賴型治療性疫苗-----24
第五節 模版重複聚合酶鏈鎖反應於分子疫苗開發之應用-----31
第六節 本章小結-----39
第三章 研究方法
第一節 研究架構-----40
第二節 研究對象選取-----41
第三節 研究資料蒐集-----42
第四節 研究限制-----44
第四章 個案分析
第一節 概要說明-----45
第二節 Aphton公司計劃個案分析-----52
第三節 Prostherics公司計劃個案分析-----57
第四節 YMB公司計劃個案分析-----59
第五節 UBI公司計劃個案分析-----62
第六節 本章小結-----66
第五章 結論
第一節 研究發現-----68
第二節 策略建議-----72
參考文獻
第一節 中文部份-----81
第二節 英文部份-----82
表目錄
表2-1 治療型疫苗類的合作聯盟策略表-----14
表2-2 1999年世界疫苗產業銷售額-----23
表2-3 2000年全球暢銷用藥-----27
表2-4 2000年全球抗癌用藥銷售比率-----27
表3-1 初步Selected Key Word (SKW) list-----43
表3-2 第二層SKW list-----43
表4-1 各單位對GnRH疫苗所擁有美國專利情形-----46
表4-2 人用GnRH疫苗主要競爭者產品分析-----50
表4-3 動物用GnRH疫苗主要競爭者產品分析-----51
表4-4 UBI與英國的諾丁漢大學合作開發疫苗傳遞系統的研究成果-----65
表5-1 技術優劣點比較表-----75
表5-2 SWOT分析表-----76
表5-3 本產品銷售比例預估表-----79
圖目錄
圖1-1 本研究流程圖-----10
圖2-1 產品生命週期圖-----18
圖2-2 世界過去與未來幾年的市場預估與成長率圖-----23
圖2-3 階梯狀調控的性腺系統-----25
圖2-4 綠膿桿菌外毒素A的三度空間結構圖及功能區-----33
圖2-5 綠膿桿菌外毒素A(PE)的細胞毒化過程-----34
圖2-6 重複模板聚合酶鏈反應-----37
圖3-1 研究架構圖-----40
圖3-2 SKW搜尋流程-----42
圖5-1 本技術產品與其他產品的比較-----70
圖5-2 產業關連圖-----71
圖5-3 潛在市場預估示意圖-----73
圖5-4 全球處方用藥市場銷售分佈圖-----78 |
Reference: | 第一節 中文部份
書:
技術移轉與智慧財產權,中央標準局83年研究發展報告編號八,p8。
期刊:
李連滋、江淑芬,「我國潛在新興產業SWOT分析─以生物技術產業為例」,經濟情勢暨評論季刊第3卷第3期,民國八十六年十一月,頁95-108。
牟敦剛,「推動我國生物技術及相關產業升級之課題探討」,經濟情勢暨評論季刊第2卷第1期,民國八十五年五月,頁76-93。
徐嘉澤,開發毒素受體接合區融合線性重複胜月太片段的抗性腺激素釋素疫苗,國防醫學院生命科學研究所未出版之博士論文,民國90年。
馬莉,「生物技術產業屬最具潛力的高科技產業」,中央綜合月刊第30卷第9期,民國八十六年九月,頁41-44。
高志道、江晃榮,「美日生物技術的競賽-兼談我國發展生技的困境」,科學月刊,民國八十年四月,頁264-271。
張朝龍,生物技術專利權保護程度進入模式的影響性探討,東華大學國際企業研究所未出版之碩士論文,民國89年。
陳怡臻、蕭斯欣,「台灣生物技術產業1997/1998」,台灣生物技術開發中心,1998。
楊旻翰,台灣生技產業前景及各國發展模式分析,中央大學企業管理研究所未出版之碩士論文,民國89年。
羅麗珠,"生物技術的發展與應用─第三篇:生物技術專利保護",86年11月,p41
第二節 英文部份
al-Kafawi AA, Hopwood ML, Pineda MH, Faulkner LC. Immunization of dogs against human chorionic gonadotropin. Am J Vet Res. 1974 Feb;35(2):261-4.
Allured VS, Collier RJ, Carroll SF, McKay DB. Structure of exotoxin A of Pseudomonas aeruginosa at 3.0-Angstrom resolution. Proc Natl Acad Sci U S A. 1986 Mar;83(5):1320-4.
Anderson M, THERAPEUTIC VACCINES: A BOOST TO MARKET SUCCESS? Scrip Reports 2001 January by PJB Publications Ltd.
Bell M, Daley CA, Berry SL, Adams TE. Pregnancy status and feedlot performance of beef heifers actively immunized against gonadotropin-releasing hormone. J Anim Sci. 1997 May;75(5):1185-9.
Bonneau M, Dufour R, Chouvet C, Roulet C, Meadus W, Squires EJ. The effects of immunization against luteinizing hormone-releasing hormone on performance, sexual development, and levels of boar taint-related compounds in intact male pigs. J Anim Sci. 1994 Jan;72(1):14-20.
Broekhuijsen MP, Blom T, van Rijn J, Pouwels PH, Klasen EA, Fasbender MJ, Enger-Valk BE. Synthesis of fusion proteins with multiple copies of an antigenic determinant of foot-and-mouth disease virus. Gene. 1986;49(2):189-97.
Broekhuijsen MP, van Rijn JM, Blom AJ, Pouwels PH, Enger-Valk BE, Brown F, Francis MJ. Fusion proteins with multiple copies of the major antigenic determinant of foot-and-mouth disease virus protect both the natural host and laboratory animals. J Gen Virol. 1987 Dec;68 ( Pt 12):3137-43.
Buschle M, Schmidt W, Zauner W, Mechtler K, Trska B, Kirlappos H, Birnstiel ML. Transloading of tumor antigen-derived peptides into antigen-presenting cells.Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3256-61.
Coffin SE. Future vaccines: recent advances and future prospects. Prim Care. 2001 Dec;28(4):869-87, vii-viii.
DiMarchi R, Brooke G, Gale C, Cracknell V, Doel T, Mowat N. Protection of cattle against foot-and-mouth disease by a synthetic peptide. Science. 1986 May 2;232(4750):639-41.
Disis ML, Gralow JR, Bernhard H, Hand SL, Rubin WD, Cheever MA. Peptide-based, but not whole protein, vaccines elicit immunity to HER-2/neu, oncogenic self-protein. J Immunol. 1996 May 1;156(9):3151-8.
Dunshea FR, Colantoni C, Howard K, McCauley I, Jackson P, Long KA, Lopaticki S, Nugent EA, Simons JA, Walker J, Hennessy DP. Vaccination of boars with a GnRH vaccine (Improvac) eliminates boar taint and increases growth performance. J Anim Sci. 2001 Oct;79(10):2524-35.
Donnelly JJ, Ulmer JB, Hawe LA, Friedman A, Shi XP, Leander KR, Shiver JW, Oliff AI, Martinez D, Montgomery D, et al. Targeted delivery of peptide epitopes to class I major histocompatibility molecules by a modified Pseudomonas exotoxin. Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3530-4.
Dowsett KF, Tshewang U, Knott LM, Jackson AE, Trigg TE. Immunocastration of colts and immunospeying of fillies. Immunol Cell Biol. 1993 Oct;71 ( Pt 5):501-8.
Eidels L, Proia RL, Hart DA. Membrane receptors for bacterial toxins. Microbiol Rev. 1983 Dec;47(4):596-620.
Eidne KA, Flanagan CA, Millar RP. Gonadotropin-releasing hormone binding sites in human breast carcinoma. Science. 1985 Sep 6;229(4717):989-91.
Emons G, Schally AV. The use of luteinizing hormone releasing hormone agonists and antagonists in gynaecological cancers. Hum Reprod. 1994 Jul;9(7):1364-79.
Feldman SR, Rosenberg MR, Ney KA, Michalopoulos G, Pizzo SV. Binding of alpha 2-macroglobulin to hepatocytes: mechanism of in vivo clearance. Biochem Biophys Res Commun. 1985 Apr 30;128(2):795-802.
Fendly BM, Winget M, Hudziak RM, Lipari MT, Napier MA, Ullrich A. Characterization of murine monoclonal antibodies reactive to either the human epidermal growth factor receptor or HER2/neu gene product. Cancer Res. 1990 Mar 1;50(5):1550-8.
Ferro VA, Stimson WH. Investigation into suitable carrier molecules for use in an anti-gonadotrophin releasing hormone vaccine. Vaccine. 1998 Jul;16(11-12):1095-102.
Ferro VA, Stimson WH. Effects of adjuvant, dose and carrier pre-sensitisation on the immunisation efficacy of a GnRH analogue. Drug Des Discov. 1996 Dec;14(3):179-95.
Fraser HM, Baker TG. Changes in the ovaries of rats after immunization against luteinizing hormone releasing hormone. J Endocrinol. 1978 Apr;77(1):85-93.
Fraser HM, Gunn A, Jeffcoate SL, Holland DT. Effect of active immunization to luteinizing hormone releasing hormone on serum and pituitary gonadotrophins, testes and accessory sex organs in the male rat. J Endocrinol. 1974 Nov;63(2):399-406.
Fuerst J, Fiebiger E, Jungwirth A, Mack D, Talwar PG, Frick J, Rovan E. Effect of active immunization against luteinizing hormone-releasing hormone on the androgen-sensitive Dunning R3327-PAP and androgen-independent Dunning R3327-AT2.1 prostate cancer sublines. Prostate. 1997 Jul 1;32(2):77-84.
Furst J, Fiebiger E, Mack D, Frick J, Rovan E. The effect of active immunization against gonadotropin-releasing hormone on the ultrastructure of the rat ventral prostate. Urol Res. 1994;22(2):107-13.
Gendler S, Taylor-Papadimitriou J, Duhig T, Rothbard J, Burchell J. A highly immunogenic region of a human polymorphic epithelial mucin expressed by carcinomas is made up of tandem repeats. J Biol Chem. 1988 Sep 15;263(26):12820-3.
Ghosh S, Jackson DC. Antigenic and immunogenic properties of totally synthetic peptide-based anti-fertility vaccines. Int Immunol. 1999 Jul;11(7):1103-10.
Gonzalez A, Allen AF, Post K, Mapletoft RJ, Murphy BD. Immunological approaches to contraception in dogs. J Reprod Fertil Suppl. 1989;39:189-98.
Goubau S, Silversides DW, Gonzalez A, Laarveld B, Mapletoft RJ, Murphy BD. Immunization of sheep against modified peptides of gonadotropin releasing hormone conjugated to carriers. Domest Anim Endocrinol. 1989 Oct;6(4):339-47.
Gounder C. The progress of the Polio Eradication Initiative: what prospects for eradicating measles? Health Policy Plan. 1998 Sep;13(3):212-33.
Hoskinson RM, Rigby RD, Mattner PE, Huynh VL, D`Occhio M, Neish A, Trigg TE, Moss BA, Lindsey MJ, Coleman GD, et al. Vaxstrate: an anti-reproductive vaccine for cattle. Aust J Biotechnol. 1990 Jul;4(3):166-70, 176.
Hseuh KH, Shang HF, Wang LF, Lo CK, Liao CW, Hwang J (1994) Engineering of Pseudomonas exotoxin A into useful proteins for disease treatment. J. Chinese Biochemical Society. 23, 135-151.
Hsu CT, Ting CY, Ting CJ, Chen TY, Lin CP, Whang-Peng J, Hwang J. Vaccination against gonadotropin-releasing hormone (GnRH) using toxin receptor-binding domain-conjugated GnRH repeats. Cancer Res. 2000 Jul 15;60(14):3701-5.
Hwang J, Chen MS. Structure and function relationship of Pseudomonas exotoxin A. An immunochemical study. J Biol Chem. 1989 Feb 5;264(4):2379-84.
Hwang J, Fitzgerald DJ, Adhya S, Pastan I. Functional domains of Pseudomonas exotoxin identified by deletion analysis of the gene expressed in E. coli. Cell. 1987 Jan 16;48(1):129-36.
Imai A, Ohno T, Iida K, Fuseya T, Furui T, Tamaya T. Gonadotropin-releasing hormone receptor in gynecologic tumors. Frequent expression in adenocarcinoma histologic types. Cancer. 1994 Nov 1;74(9):2555-61.
Irmer G, Burger C, Muller R, Ortmann O, Peter U, Kakar SS, Neill JD, Schulz KD, Emons G. Expression of the messenger RNAs for luteinizing hormone-releasing hormone (LHRH) and its receptor in human ovarian epithelial carcinoma. Cancer Res. 1995 Feb 15;55(4):817-22.
Jacobs E, Watson SA, Michaeli D, Ellis IO, Robertson JF. Anti-gonadotrophin releasing hormone antibodies inhibit the growth of MCF7 human breast cancer xenografts. Br J Cancer. 1999 May;80(3-4):352-9.
Kemp DJ, Coppel RL, Anders RF. Repetitive proteins and genes of malaria. Annu Rev Microbiol. 1987;41:181-208.
Khan CM, Villarreal-Ramos B, Pierce RJ, Demarco de Hormaeche R, McNeill H, Ali T, Chatfield S, Capron A, Dougan G, Hormaeche CE. Construction, expression, and immunogenicity of multiple tandem copies of the Schistosoma mansoni peptide 115-131 of the P28 glutathione S-transferase expressed as C-terminal fusions to tetanus toxin fragment C in a live aro-attenuated vaccine strain of Salmonella. J Immunol. 1994 Dec 15;153(12):5634-42.
Keri G, Horvath A, Nikolics K, Teplan I. In the central role of GnRH in the regulation of reproductive functions: mechanism of action and practical results. J Steroid Biochem. 1985 Nov;23(5B):719-23.
Kounnas MZ, Morris RE, Thompson MR, FitzGerald DJ, Strickland DK, Saelinger CB. The alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein binds and internalizes Pseudomonas exotoxin A. J Biol Chem. 1992 Jun 25;267(18):12420-3.
Ladd A, Tsong YY, Walfield AM, Thau R. Development of an antifertility vaccine for pets based on active immunization against luteinizing hormone-releasing hormone. Biol Reprod. 1994 Dec;51(6):1076-83.
Ladd A, Walfield A, Tsong YY, Thau R. Active immunization against LHRH alone or combined with LHRH-analogue treatment impedes growth of androgen-dependent prostatic carcinoma. Am J Reprod Immunol. 1995 Sep;34(3):200-6.
Levin, MM and Rosanna L, Vaccines and Vaccination in Historical Perspective, New Generation Vaccines. Second Edition, 1997 June by Marcel Deckker, Inc.
Lovejoy DA. Peptide hormone evolution: functional heterogeneity within GnRH and CRF families. Biochem Cell Biol. 1996;74(1):1-7.
Lubran MM. Bacterial toxins. Ann Clin Lab Sci. 1988 Jan-Feb;18(1):58-71.
Millar RP, King JA, Davidson JS, Milton RC. Gonadotrophin-releasing hormone--diversity of functions and clinical applications. S Afr Med J. 1987 Dec 5;72(11):748-55.
Malmgren L, Andresen O, Dalin AM. Effect of GnRH immunisation on hormonal levels, sexual behaviour, semen quality and testicular morphology in mature stallions. Equine Vet J. 2001 Jan;33(1):75-83.
Mast J, Goddeeris BM. Development of immunocompetence of broiler chickens. Vet Immunol Immunopathol. 1999 Sep 20;70(3-4):245-56.
Miller LA, Johns BE, Elias DJ, Crane KA. Comparative efficacy of two immunocontraceptive vaccines. Vaccine. 1997 Dec;15(17-18):1858-62.
Miller LA, Johns BE, Elias DJ, Killian GJ. Oral vaccination of white-tailed deer using a recombinant Bacillus Calmette-Guerin vaccine expressing the Borrelia burgdorferi outer surface protein A: prospects for immunocontraception. Am J Reprod Immunol. 1999 Apr;41(4):279-85.
Miller LA, Johns BE, Killian GJ. Immunocontraception of white-tailed deer with GnRH vaccine. Am J Reprod Immunol. 2000 Nov;44(5):266-74.
Moestrup SK, Gliemann J, Pallesen G. Distribution of the alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein in human tissues. Cell Tissue Res. 1992 Sep;269(3):375-82.
Montecucco C, Papini E, Schiavo G. Bacterial protein toxins penetrate cells via a four-step mechanism. FEBS Lett. 1994 Jun 6;346(1):92-8.
Monzavi-Karbassi B, Kieber-Emmons T. Current concepts in cancer vaccine strategies. Biotechniques. 2001 Jan;30(1):170-2, 174, 176 passim.
Morrison CA, Fishleigh RV, Ward DJ, Robson B. Computer-aided design and physiological testing of a luteinising hormone-releasing hormone analogue for `adjuvant-free` immunocastration. FEBS Lett. 1987 Apr 6;214(1):65-70.
Naglich JG, Metherall JE, Russell DW, Eidels L. Nucleotide, OMIM, ProteinExpression cloning of a diphtheria toxin receptor: identity with a heparin-binding EGF-like growth factor precursor. Cell. 1992 Jun 12;69(6):1051-61.
Oakey RP. Predatory Networking: The Role of Small Firms in the Development of the British Biotechnology Industry. International Small Business Journal. 1993 Vol.11(4), pp.9-22.
O`Hagan DT, MacKichan ML, Singh M. Recent developments in adjuvants for vaccines against infectious diseases. Biomol Eng. 2001 Oct 15;18(3):69-85.
Oonk HB, Turkstra JA, Schaaper WM, Erkens JH, Schuitemaker-de Weerd MH, van Nes A, Verheijden JH, Meloen RH. New GnRH-like peptide construct to optimize efficient immunocastration of male pigs by immunoneutralization of GnRH. Vaccine. 1998 Jul;16(11-12):1074-82.
Pennington JE. Pseudomonas aeruginosa. Vaccines and immunotherapy.Infect Dis Clin North Am. 1990 Jun;4(2):259-70.
Pineda MH, Faulkner LC, Hopwood ML, Lueker DC. Effects of immunizing female rabbits with bovine luteinizing hormone. Proc Soc Exp Biol Med. 1968 Jul;128(3):743-9.
Progress toward global eradication of poliomyelitis, 2001. MMWR Morb Mortal Wkly Rep. 2002 Mar 29;51(12):253-6.
Rankin R, Pontarollo R, Ioannou X, Krieg AM, Hecker R, Babiuk LA, van Drunen Littel-van den Hurk S. CpG motif identification for veterinary and laboratory species demonstrates that sequence recognition is highly conserved. Antisense Nucleic Acid Drug Dev. 2001 Oct;11(5):333-40.
Roberts EB and Mizouchi R. Inter-firm Technological Collaboration: The Case of Japanese Biotechnology. International Journal of Technology Management. 1989 Vol.4(1), pp.43-61.
Schijns VE. Induction and direction of immune responses by vaccine adjuvants. Crit Rev Immunol. 2001;21(1-3):75-85.
Schmidt W, Buschle M, Zauner W, Kirlappos H, Mechtler K, Trska B, Birnstiel ML. Cell-free tumor antigen peptide-based cancer vaccines. Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3262-7.
Seeburg PH, Adelman JP. Characterization of cDNA for precursor of human luteinizing hormone releasing hormone. Nature. 1984 Oct 18-24;311(5987):666-8.
Silversides DW, Allen AF, Misra V, Murphy BD, Mapletoft RJ. A synthetic luteinizing hormone releasing hormone vaccine II. Temporal aspects of titer development and formulation trials in BALB/c mice. J Reprod Immunol. 1988 Oct;14(1):47-58.
Silversides DW, Allen AF, Misra V, Qualtiere L, Mapletoft RJ, Murphy BD.A synthetic luteinizing hormone releasing hormone vaccine. I. Conjugation and specificity trials in BALB/c mice. J Reprod Immunol. 1988 Aug;13(3):249-61.
Singh V. Active immunization of female dogs against luteinizing hormone releasing hormone (LHRH) and its effects on ovarian steroids and estrus suppression. Indian J Exp Biol. 1985 Dec;23(12):667-72.
Singh V. Immunospecificity and affinity studies on anti-luteinizing hormone releasing hormone antibodies developed by azo-LHRH-TT and azo-LHRH-BSA conjugates. Biochem Int. 1992 Aug;27(4):591-9.
Simms MS, Scholfield DP, Jacobs E, Michaeli D, Broome P, Humphreys JE, Bishop MC. Anti-GnRH antibodies can induce castrate levels of testosterone in patients with advanced prostate cancer. Br J Cancer. 2000 Aug;83(4):443-6.
Smyth MJ, Godfrey DI, Trapani JA. A fresh look at tumor immunosurveillance and immunotherapy. Nat Immunol. 2001 Apr;2(4):293-9.
Spalding BJ. How Biotechnology is Faring as an Industry. Chemical Week. Vol.139 Iss.23 Dec 3,1986, pp9-13
Talwar GP. Immunobiology of gonadotropin-releasing hormone. J Steroid Biochem. 1985 Nov;23(5B):795-800.
Talwar GP. Vaccines and passive immunological approaches for the control of fertility and hormone-dependent cancers. Immunol Rev. 1999 Oct;171:173-92.
Tancer RS. Foreign investment in North America and the pharmaceutical industry in Canada. Thunderbird International Business Review. New York. Mar/Apr 1997, pp283-297
Tast A, Love RJ, Clarke IJ, Evans G. Effects of active and passive gonadotrophin-releasing hormone immunization on recognition and establishment of pregnancy in pigs. Reprod Fertil Dev. 2000;12(5-6):277-82.
Turkstra JA, Oonk HB, Schaaper WM, Meloen RH. The role of the individual amino acids of a GnRH-tandem-dimer peptide used as an antigen for immunocastration of male piglets determined with systematic alanine replacements. Vaccine. 2001 Nov 12;20(3-4):406-12.
Ulker H, Kanter M, Gokdal O, De Avila DM, Reeves JJ. The effects of recombinant LHRH fusion proteins on testicular development and histology in ram lambs. Dtsch Tierarztl Wochenschr. 2001 Nov;108(11):459, 462-4.
Vaccine Trends & Developments Worldwide. Theta report 1998 June by PJB Publications Ltd.
Van der Ploeg JR, Drijfhout JW, Feijlbrief M, Bloemhoff W, Welling GW, Welling-Wester S. Immunological properties of multiple repeats of a linear epitope of herpes simplex virus type 1 glycoprotein D. J Immunol Methods. 1989 Nov 30;124(2):211-7.
Van der Zee A, Noordegraaf CV, van den Bosch H, Gielen J, Bergmans H, Hoekstra W, van Die I.P-fimbriae of Escherichia coli as carriers for gonadotropin releasing hormone: development of a recombinant contraceptive vaccine. Vaccine. 1995;13(8):753-8.
Van Leuven F, Cassiman JJ, Van Den Berghe H. Demonstration of an alpha2-macroglobulin receptor in human fibroblasts, absent in tumor-derived cell lines. J Biol Chem. 1979 Jun 25;254(12):5155-60.
Von Mensdorff-Pouilly S, Verstraeten AA, Kenemans P, Snijdewint FG, Kok A, Van Kamp GJ, Paul MA, Van Diest PJ, Meijer S, Hilgers J. Survival in early breast cancer patients is favorably influenced by a natural humoral immune response to polymorphic epithelial mucin. J Clin Oncol. 2000 Feb;18(3):574-83.
Wasowicz K, Kaleczyc J, Sienkiewicz W, Czaja K, Zivcik A, Lakomy M. Influence of active immunization against GnRH on VIP- and NPY-positive innervation of the porcine testis. Folia Histochem Cytobiol. 2001;39(3):269-74.
Wiesmuller KH, Fleckenstein B, Jung G. Peptide vaccines and peptide libraries. Biol Chem. 2001 Apr;382(4):571-9.
Yip YL, Smith G, Koch J, Dubel S, Ward RL. Identification of epitope regions recognized by tumor inhibitory and stimulatory anti-ErbB-2 monoclonal antibodies: implications for vaccine design. J Immunol. 2001 Apr 15;166(8):5271-8.
Zeng XY, Turkstra JA, Meloen RH, Liu XY, Chen FQ, Schaaper WM, (Ria) Oonk HB, Guo DZ, van de Wiel DF. Active immunization against gonadotrophin-releasing hormone in Chinese male pigs: effects of dose on antibody titer, hormone levels and sexual development. Anim Reprod Sci. 2002 Apr 15;70(3-4):223-233.
Zeng W, Ghosh S, Macris M, Pagnon J, Jackson DC. Assembly of synthetic peptide vaccines by chemoselective ligation of epitopes: influence of different chemical linkages and epitope orientations on biological activity. Vaccine. 2001 Jul 16;19(28-29):3843-52.
Zhang Y, Rozell TG, deAvila DM, Bertrand KP, Reeves JJ. Development of recombinant ovalbumin-luteinizing hormone releasing hormone as a potential sterilization vaccine. Vaccine. 1999 Apr 23;17(17):2185-91. |
Description: | 碩士 國立政治大學 經營管理碩士學程(EMBA) |
Source URI: | http://thesis.lib.nccu.edu.tw/record/#A2010000528 |
Data Type: | thesis |
Appears in Collections: | [經營管理碩士學程EMBA] 學位論文
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