Biomaterials Research (2007) 11(1) : 1-11 <Review> Biomaterials Research 7 The Korean Society for Biomaterials w The Market Analysis of Pharmaceutical Proteins 1 Á 2Á 2, *Á 3, * Byung-Ok Jung 1, Jong-Ku Son 2, Joon Woo Lee 2, *, and Young Seon Choi 3, * 1 d Š ˆ Š, 2 Š Š h e TCI h, 3 Š f ŒŠ 1 Dept. of Food Science & Technology, Seoul National University of Technology, #172 Gongneung 2-dong, Nowon-gu, Seoul 139-743, Korea 2 Dept. of Industrial Information Analysis, TCI Division, Korea Institute of Science & Technology Information(KISTI), #206-9, Cheongnyangni-dong, Dongdaemun-gu, Seoul 130-741, Korea 3 Nano-Bio Chemistry Group, Institut Pasteur Korea, 39-1, Hawolgok-dong, Seongbuk-gu, Seoul 136-791, Korea (Received January 8, 2007/Accepted February 12, 2007) Recent advance in genetic engineering and production of the monoclonal antibody(mab) allows one to generate therapeutic proteins in large amounts. Therapeutic proteins we overview here include interferon, insulin, EPO, colony stimulating factor (CSF), blood factor, therapeutic enzymes, therapeutic hormones, and cytokines (growth factors, interleukins etc.). We focused on the recent progress in research and development of MAb-based therapeutics and analyzed the recent market trend related to the therapeutic proteins. Key words: Therapeutic proteins, Monoclonal antibody (MAb), Market analysis, ˆ,, Œ, l Šf fd d Šl g l Šf fdf g Œ Š f l f f. f f l f ef, l x f Š f rlš f. ƒ f u f f g f f zj f l x h f s vvf ŒŠh Š eh Š f fdš l f ˆ(protein therapeutics)f f v f. t f f igš lf hhš dš f f x d lf e i gš f ˆf Š f d., eh Šf f} Št f fš f Š f d lf Š f f. f d l Št f hh Š 1970 1980 t t f Š s e f j f. f s f f Šf f Š f ~f Š f f, f f iš f *Equally contributed. sf hf: jwlee@kisti.re.kr, yschoi@pasteur.or.kr Š. f f ˆ Š if Œ h f d l l f f f f Š f Š f g f ll., l x h f g g f rw l fš Œ h Š f Š Œ fš. hf h (Genentech) f f (Eli Lily)f f. h Š giš f f f f f f Š Humulin f ˆ f fš, f h ˆf l l hf l x h jf Š f. f d lf f ˆf, l f ˆ f f ˆf, ehf giš f f Š x d lf Œ f Š. f f gœ f 1 f f ˆf j f ehf iff Š eš x d lf Š f ehf giš f ~f f, u j f f f} Št f ˆ f Š l f Š f fšf Š ~hf f dš Št Š f Šf f ~f Š f 1 f ˆ Š lf f f ˆf Š f. f d lf j ft l ŠŠ l l Š ƒfhf fdš 1
2 h Á i ÁfjdÁu, h hf f ŒŠh Š f ˆ Š fdf h h f f ghf l f. ƒ l f ˆf eif } (Crohn's disease), Œl~ i (non-hodgkin lymphoma) Œ f hf l f x } f Š. t f f d lf f f Œf f Š l hf } f. f DNA if,, f l hh t f d, de h f Š } x l f. jd f d l f, f f ŠŠ, EPO, z f ff(csf), Œ hh (blood factor), x h(enzymes), Œ hh(hormonal therapies), gff(growth factors), f ~(interleukins)f ŠŠ f xf(cytokines) f f. u f} Štf f d lf f Œ Š, f ˆ f v f f.» w j w (Monoclonal Antibody) 1980 t FDA ff Š f f Š ft gœ, f, z f ff f f } Št f hˆœ i l f x d f. eh Š t f ~f lf f j fdš Š l, l Š f Š f f Œ z f ft fdf hf l f ˆf Š f. f Š d f j hf f Štf. gœ f f f l f f lœ hf Š f g ehf l i f l f f ~f Š }f d. Šl Štf d l f f Št f t f igš f. l, l i gš f Še fš ff }f Št f t h f, f Š Šef t xfš d Še g g ŠŠ f Št ~ xœ h(affinity maturation)f t xœ l. f Š f ~f Št f xœ hf hhš g fdš ft l Št l f Š Št fehf f. Š Š t Š Š Še ƒfhf ŠŠ ƒ f l f Table 1. e f f} Št x h hˆ Št i ~ hdl ( ) Orthoclone Muromomab T lymphocyte surface Ortho Biotech Prevention of acute kidney trasplant 1 (1986) OKT3 CD3 antigen CD3 rejection ReoPro Abciximab Platelet surfact receptor Centocor Prevention of blood clots (1994) GPIIb/IIIa Rituxan Rituximab B lymphocyte surface Genentech/IDEC Non-Hodgkin's lymphoma (1997) MabThera antigen CD20 pharmaceuticals e 2 (1998) Zenpax Dalizumab alpha-antigen of the IL-2 Hoffman-La Roche Prevention of acute kidney trasplant (1997) receptor rejection e(1999) Simulect Basiliximab alpha-antigen of the IL-2 Norvatis Prevention of acute organ rejection in,e (1998) receptor allogenic renal transplantation Synagis Palivizumab repiratory syncytial virus MdeImmune/Abbott Prophylaxis of lower respiratory tract (1998) Lab. disease e(1999) Remicade Infiximab TNF-alpha Centocor Treatment of Crohn's disease & rheumatoid (1997) arthritis e(1999) Herceptin Trastuzumab Human epidermal growth Genentech/Roche Treatment of metastatic breast cancer if (1998) factor receptor 2 tumor overexpresses HERs protein e(2000) Mylotarg Gemtuzumab CD33 antigen of leukemic Wyeth Ayerst Acute byeloid leukaemia (2000) zogamicin blast cells Campath Alemtuzumab CD52 Milennium/ILEX B cell chronic lymphocytic leukemia (B-CLL),e (2001) Zevalin Ibritumonab CD20 antigen on surface IDEC Non-Hodgkin's lymphoma (2002) Tiuxetan of B lymphocytes e(2004) Humira Adalimumab TNF-alpha Abbot Lab. rhumatoid arthritis (2002) e(2003) Xolair Omalizumab IgE Genentech Persistent asthma (2003) BEXXAR Tositumomab-I131 B lymphocyte surface antigen CD20 Corixa Non-Hodgkin's lymphoma (2003) Raptiva Efalizumab human CD11a Genentech chronic plaque psoriasis (2003) Erbitux Cetuximab EGFR Imclone Systems Colerectal cancer (2004) Avastin Bevacizumab VEGF Genentech First-line metastatic cancer of colon or rectum (2004) Biomaterials Research 2007
hd lf g 3 f l Š hhf i l f ƒh Še Š xœ f Šef Š dfš ghf l f. Š t x d l f j hf fe f lf t f df h hf. k f f Šef ~ f k Št l fš f Œ ~ hf f f Š Š d f f Œ f. u ŒlhŒ k fdš f Št hiš f Štf d f f f f. Š Št f ˆf t fdf wš f Œf f ft igš f ft xœhf ˆf h h f ˆ Š de f fe Š f. f} Št Š Še ŠŠ f ƒhhf Š. Š Št f ƒh h Š x h d Š Š f f f lœ x d. Št f ˆf f f h ( fd ) f (f ) 1~3 f l. t k Štf f Štf ~ Št(chimeric antibody) hiš HAMA (human anti-mouse antibody) ff ~ Št h išf, d lf jf ff ff~ ff, f Š fdf jf eš Šef flš ŠŠ Š dš ef CDR (complementarity determination region)f hdš e f e Š Štf f Œ Št(humanized antibody) Š. Š u l f (phage display), f f Št f l f Št(fully human antibody) hiš f l f. me (Cytokines) f xff t igšl, l ih f df Š jdš l ƒh igš dt ŠŠ Œh hf t ~f ff ŒŠh h h f(chemical messenger)f Šf Š. f f xff Œ l, ff Œf f hš f f h f jdš Šf Š f. f ~(interleukins), z f ff(granulocyte-colony stimulating factor, G-CSF), f (inteferon), i ff(tumor necrosis Table 2. e f f xf hˆ hˆ f j hdl ( ) Intron A recomb. IFN-α-2b E. coli Schering Plough Cancer, genital warts, hepatitis 1 (1986) e 2 (2000) Referon A recomb. IFN-α-2a E. coli Hoffman-La Roche Hairy cell leukemia (1986) Actimune recomb. IFN-Å-1b E. coli Genentech Chronic granulomatous (1990) Proleukin recomb. IL-2 E. coli Chiron Renal cell carcinoma (1992) Betasteron recomb. IFN-β-1b E. coli Berlex Lab./Chiron Relapsing, remitting multiple sclerosis (1993) Betaferon recomb. IFN-β-1b E. coli Schering Plough Multiple sclerosis (1995) Avonex recomb. IFN-β-1b CHO Biogen Relapsing multiple sclerosis (1996) e(1997) (1997) Neumega recomb. IL-11 E. coli Genetics Institute Prevention of chmotherapy-induced thrombocytopenia Infergen recomb. IFN-α E. coli Amgen/Yamanouchi Europe Chronic hepatitis C (1997) e(1999) Rebit recomb. IFN-β-1a CHO Ares-Serono Relapsing, remitting multiple sclerosis e(1998) (2002) Rebetron recomb. IFN-α-2b E. coli Schering Plough Chronic hepatitis C (1999) Beromun recomb. IFN-α-1a E. coli Boehringer Ingelheim Soft tissue sarcoma of the limbs to e(1997) prevent or delay amputation PegIntron A PEGlated recomb. IFN-α-2b E. coli Schering Plough Chronic hepatitis C e(2000) (2001) Viraferon recomb. IFN-α-2b E. coli Schering Plough Chronic hepatitis B and C e(2000) VirageronPeg PEGlated recomb. IFN-α-2b E. coli Schering Plough Chronic hepatitis C e(2000) Alfatronol recomb. IFN-α-2b E. coli Schering Plough hepatitis B, C and various cancers e(2000) Vitron recomb. IFN-α-2b E. coli Schering Plough hepatitis B and C e(2000) Kineret Anakinra, recomb. IL-1 receptor antagonist E. coli Amgen Rhumatoid arthritis (2001) e(2002) Pegasys PEGlated recomb. IFN-α-2a E. coli Hoffman-La Roche hepatitis C,e(2002) Vol. 11, No. 1
4 h Á i ÁfjdÁu factors, TNFs) f Š, f f xff Š i f f l, Š i f f f x, ih ff d. f x ff f f l l ihfffl, l ihff f xff l. (Growth Factors) gff -z f ff(g-csf), - z f ff(granulocyte-macrophage colony stimulating factor, GM-CSF), f (erythropoietin, EPO), f (thrombopoietin, TPO), f -e gff(insulin-like growth factor, IGF), gff (epidermal growth factor, EGF), Œ e gff (platelet-derived growth factor, PDGF), e fff (fibroblast growth factor, FGF), hf gff(transforming growth factor, TGF) f Š. y (Hormones) giš Œ lf } f gœ hˆf f. f f giš DNA f f dš l utf f d l 1982 f f fš hˆœ 20 f f u f f ˆ jf Š f. 1990 f } f jf fš f Œ Š. g Œ f 1985 h fš ƒ Šf f f ˆŒ f l, fš f. f f h fš f Œ x Œ l f. z (Enzymes) g Š i f ŒhdŠh, Šf h, Š h l d d f. ŒhdŠh eš d f ƒ ~ h ƒf hf ŠŠf Œh dšfdf Š f h f. 1993 h fš el x df ˆ fff giš DNase el Œff x Š f fd fš f DNA Š Table 3. e f gff hˆ hˆ f j hdl ( ) Epogen recomb. human EPO Mammalian cell Amgem Anemia 1 (1989) Procrit recomb. human EPO Mammalian cell Ortho Biotech Anemia (1990) Leukine recomb. GM-CSF S. cerevisiae Immunex Autologous bone marrow (1991) transplation Neupogen Filgrastim, recomb. G-CSF E. coli Amgem Chemotherapy-induced (1991) neuropenia Noerecormon recomb. human EPO CHO Boehringer-Mannheim Anemia (1991) Aranesp Darbepoetin-α, long-acting CHO Amgem Anemia e 2 (1997) EPO analog Nespo Darbepoetin-α, long-acting CHO Dompre Biotec Anemia,e(2001) EPO analog Neulasta PEGfilgrastim, recomb. E. coli Amgem Neutropenia,e(2002) PEGylated filgrastim Table 4. e f f hˆ hˆ f j hdl ( ) Humilin recomb. human insulin E. coli Eli Lilly Diabetes melitus 1 (1982) Novolin recomb. human insulin S. cerevisiae Novo Nordisk Diabetes melitus (1991) Humalog Insulin Lispro, insulin analog E. coli Eli Lilly Diabetes melitus,e 2 (1996) Insuman recomb. human insulin E. coli Hoechst AG Diabetes melitus e(1997) Lipro Bio Lysprol, short-acting insulin analog E. coli Eli Lilly Diabetes melitus NovoRapid Insulin Aspart, short-acting recomb. S. cerevisiae Novo Nordisk Diabetes melitus e(1997) e(1999) human insulin analog Lantus Insulin glagine, long-acting recomb. E. coli Aventis Pharmaceuticals Diabetes melitus,e(2000) human insulin analog Optisulin Insulin glagine, long-acting recomb. E. coli Aventis Pharmaceuticals Diabetes melitus e(2000) human insulin analog Novolog Insulin Aspart, short-acting recomb. S. cerevisiae Novo Nordisk Diabetes melitus (2001) human insulin analog Biomaterials Research 2007
~f Œ g ~ Šf Š. x (Blood Factors) g e f Œ hh 7i f giš Factor VIII hˆf jif f f. g h FDAf ff Š hˆf fš hd lf g 5 Table 5. e f x h hˆ f hdl ( ) Activase Alteplase, rh-tpa Genentech Acute myocardial infarction 1 (1987) Pulmozyme Domase-alpha, rdnase Genentech cystic fibrosis (1993) Cerezyme Recomb. beta-glucocerebrosidase Genzyme Gaucher's disease (1994) e 2 (1997) Ecokinase Galenus Mannheim Acute myocardial infarction e(1996) Reteplase, rtpa (3 f ff h Œ~) Retavase Reteplase, rtpa (3 f ff Beohringer-Mannheim Acute myocardial infarction (1996) h Œ~) /Centcor Rapilysin Reteplase, rtpa (3 f ff Beohringer-Mannheim Acute myocardial infarction e(1996) h Œ~) TNKase Tenecteplase ( Œ Œ~f rpa) Genentech Myocardial infarction (2000) Fabrazyme Recomb. alpha-glucocerebrosidase Genzyme Babry's disease (alphagalactosidase e(2001) A deficiency) Replagal Recomb. alpha-glucocerebrosidase TKT Europe Babry's disease (alphagalactosidase e(2001) A deficiency) Fasturtec (Elitex) rasburicase, rurate oxidase Sanofi- Synthelabo Hyperuricaemia e(2001) (2002) Tenecteplase TNK-tPA ( Œ Œ~f rpa) Beohringer-Mannheim Myocardial infarction e(2001) Aldurazyme Laronidase BioMarin Pharmaceutical /Genzyme Hurler and Hurler-Scheie forms of mucopolysaccharidosis (2003) Hemophilia A x df giš l 1992 ff. f 1 f 1993 f f } fƒ f f zl fƒ f l f x df ff Š. f }, h f ƒƒ f fš giš Œ Œ~f Factor VIII e r f Table 6. e f hˆ f hdl ( ) Recombivax rhbsag Merck Hepatitis B prevention 1 (1986) Comvax Combination vaccine containing rhbsag, Merck vaccination of infants agains Hemophilus (1993) Hemophilus b conjugate MPO and influenza type B and hepatitis B recombinant hepatitis B vaccine Twinrix Combination vaccine containing rhbsag SmithKlineBeacham, immunization against hepatitis A and B e 2 (1996) Glaxo SmithKline (2001) Tritanrix-HP Combination vaccine containing rhbsag SmithKlineBeacham hepatitis B, diphtheria, tetanus and e(1996) pertussis Lymerix rospa SmithKlineBeacham Lyme disease vaccine (1998) Primavax Combination vaccine containing rhbsag Pasteur merieux MSD hepatitis B, diphtheria, tetanus and e(1998) pertussis Procomvax Combination vaccine containing rhbsag merieux H. influenza type B and hepatitis B e(1999) Triacelluvax Combination vaccine containing Chiron SpA diphtheria, tetanus and pertussis e(1999) r(modified) pertussis toxin Hexavac Combination vaccine containing rhbsag Aventis Pasteur hepatitis B, diphtheria, tetanus, polio, e(2000) pertussis and H. influenza type B Infanrix-Hexa Combination vaccine containing rhbsag SmithKlineBeacham hepatitis B, diphtheria, tetanus, polio, e(2000) pertussis and H. influenza type B Hepacare rs, pre-s and pre-s2 hepatitis B surface Medeva Pharma hepatitis B e(2000) antigen Infanrix-Penta Combination vaccine containing rhbsag SmithKlineBeacham hepatitis B, diphtheria, tetanus, polio Pediarix and pertussis e(2000) (2002) HBVAXPRO rhbsag Aventis Pharma children and adolescents hepatitis B e(2001) Amirix Combination vaccine containing rhbsag GlaxoSmithKline hepatitis A and B e(2002) Vol. 11, No. 1
6 h Á i ÁfjdÁu (Vaccines) ut d f 1986 } BŒ df Š hepatitis B Šef y fl, g f f f u 10 f f. 2005 9e g e f d f 20i f f f, } f, MSD fš j f. f fif S. cerevisiae fdš f ff, f Še i f Šef ŒŠŠ Š hg j f f.» xy frf f d l f gg g f f Š l 20 h Š f f l f. u ehtš f fdš f d lf Š f Š f f l ff, f eš fdš f v Š f fdš Š f. g Œ u Œ f ~ ~f x h hˆ ŒŠ lš f. g Œ, Œ x, Œh dš Œ l x ~f f f hf d f. f Š l f } f t. Š l 30 l f f f l ~f e ŒŠŠ f h i Š f. f f fdš d, ilf s Š l hhf Š ff, df Š Š ~ e t Š Š f Š. m giš DNA f f, f f hš f f } f i f l Š ƒ f f lf f f. f Š giš DNA f f Šf d gf, f Š f g f ~f f ˆ f f h fdf eš f. ƒhš l j x f g ed Š g ef f f ~f dš ~f hh l ht dš Š h fdf hf hi eš iff dfš h Œf Š jf f gh ~f gf hf 20% f l Š f v f. u lœf eff l ft t f Œf Š Š eš h hf t ~ ~ Œ ~ l ff fdš Š e Š x fš f g f l ~ f ftf ff ihš f ~f x h lh ff, e d Œ f. f d lf f e f lf f f, u e f f d l Š f l Š f. f f l x hf Š e f f d l j Œ hš hˆ f Table 7. t Œ u d f f f ˆf j f f f DNA RNA f ˆ f ehf f ˆf. f ehf Š fš lh d Œ Š f f l ehf x (antisense) f ˆf f Š. Table 7. e f f d l Product Class Indication Company/Organization Crop Status Various single chain Fv antibody fragments Antibody Non-Hodgkin's lymphoma Large Scale Biology Corp Viral vectors in tobacco Phase I CaroRX Antibody Dental caries Planet Biotechnology Inc. Transgenic tobacco Phase II E. colt heat labile toxin Vaccine Diarrhoea Prodigene Inc. Transgenic maize Phase I Arntzen group (Tacket et al. 1998) Transgenic potato Phase I Gastric lipase Therapeutic enzyme Cystic fibrosis, pancreatitis Meristem Therapeutics Transgenic maize Phase II Hepatitis B virus surface Vaccine Hepatitis B Arntzen group (Tacket et al. 1998) Transgenic potato Phase I antigen Thomas Jefferson University/Polish Academy of Sciency Transgenic lettuce Phase I Human intrinsic factor Dietary Vitamin B12 deficiency Cobento Biotech AS Transgenic Arabidopsis Phase II Lactoferrin Dietary Gastrointestinal infections Meristem Therapeutics Transgenic maize Phase I Norwalk virus capsid Vaccine Norwalk virus infection Arntzen group (Tacket et al. 1998) Transgenic potato Phase I protein Rabies glycoprotein Vaccine Rabies Yusibov et al(2002) Viral vectors in Phase I spinach f : EMBO reports1) Biomaterials Research 2007
약제용 단백질의 시장동향 분석 또한 이미 출시된 제품을 바탕으로 하여 적응증을 확대하거 나 제형을 개선한 제품들 또한 지속적으로 의약용 단백질 관 련 기술의 진보에 기여할 것으로 보인다. 실제로 인터페론 베 타, 성장호르몬, EPO 등에 대한 서방형(서서히 분비되는 제품 으로 투약의 편리성을 지님) 개발이 활발히 이루어지고 있다. 애초에 소수의 환자군을 목표로 했던 의약품들이 점차 그 적 응증을 넓혀 더 큰 상업적 성공을 이루어 내고 있기도 하다. 그 예로 현재까지 가장 성공적인 단백질 치료제로 평가받고 있 는 암젠사의 Epogen은 처음에 만성 신부전증 환자의 빈혈 치 료제로 승인 받았으나, 점점 적응증을 넓혀 현재는 암 치료와 화학요법에 따른 빈혈치료제로도 사용되고 있다. 7 치 특징을 감안하여 고부가가치 창출을 위해 기술 개발 및 산 업화에 집중적으로 투자하고 있는 상황이다. 의약용 단백질의 구성비는 생물산업 전체의 40% 내외로 생 물의약품의 구성비율은 생물산업 전체규모의 50%정도이며, 의 약용 단백질은 생물의약품의 80% 정도를 차지하고 있다. 산업 용 단백질의 구성비는 생물산업 전체의 20% 내외로, 생물화학 /바이오식품/바이오에너지 및 자원의 구성비는 생물산업 전체규 모의 40%이고, 이중에서 산업용 단백질 제품은 약 50% 정도 를 차지하고 있는 상황이다. 시장동향 시장 특성 단백질 제품 이란 바이오기술에 의해 생산된 펩타이드 (peptides) 중에서 고부가가치의 기능성 단백질 및 효소류를 일 컫는 것으로, 일반적인 영양원 구성성분의 단백질이나, 기술차 원에서의 단백질 공학과는 구별되는 제품차원의 정의이다. 단 백질 제품이란 생물산업제품 중에서 생물의약품/생물화학/바이 오식품 등에 활용되는 핵심 제품군을 뜻하는 것이며, 바이오(생 자료 : (주)인트론 물공학)기술에 의해 개발되는 제품이다. 단백질 제품은 크게 질 단백질 제품의 위치. 병의 치료 및 예방 등에 사용되는 의약용 단백질 과 효소반 응 및 진단 목적의 산업용 단백질 로 대별될 수 있다. 생물 산업 전체규모의 60% 내외 정도를 차지하고 있는 단백질제품 단백질 치료제 분야는 화학합성 의약품 부문과 달리 제네릭 은 생물산업 발전의 지속적인 핵심 또는 견인차 역할을 할 것 (generic) 약제를 생산하는 업계의 위협을 거의 찾아볼 수 없는 으로 전망되고 있다. 만큼 시장에서 넘볼 수 없는 승자로 확고히 자리매김 하고 있 다. 이 시장은 고도의 전문적 제조기술의 확보, 난치성 질환들 을 겨냥하고 있다는 특성, 엄격한 생산공정 통제, 획기적인 혁 신성 등을 담보하고 있는 분야이기 때문에 시장진입장벽이 매 우 높다. 시장동향 국내시장 오늘날 생물산업을 미래 전략산업으로 육성하기 위한 국가간 의 경쟁이 날로 치열해지고 있다. 특히 생물산업을 선점하고 단백질 제품의 정의. 있는 미국과 유럽 일부 국가들은 포스트 게놈(post-genome) 연구에 투자를 본격화하여 불치병으로 여겨지던 질환의 치료제 생물산업 시장규모에서 단백질 제품의 정확한 시장규모 예측 나 건강 보조제 등의 단백질 의약품 개발에 총력을 다하고 있 은 어려운 실정이나 생물산업제품 전체시장의 핵심을 이루고 다. 2006년 전 세계 단백질 의약품 시장규모는 437억 달러에 있으며, 전체 생물산업 시장의 60% 내외를 차지하고 있는 상 달하고, 5년 후인 2011년에는 그 두배인 885억 달러에 이를 황이다. 단백질 제품은 생물산업제품의 시장확대와 산업발전을 것으로 추정된다. 우리나라의 단백질 의약품 시장규모는 올해 선도하는 중추적 역할을 수행하고 있으며, 많은 성공사례를 창 14억 달러로 전 세계의 3.2% 수준에 불과하나, 연평균 30% 출하고 있다. 예로 단백질제품을 개발하고 있는 미국의 암젠사 이상의 고성장이 지속되어, 2011년에는 2006년 대비 4.5배 는 3개 의약용 단백질을 판매하여 '00년 $32억 매출 (순이익 증가한 64억 달러의 시장규모를 형성할 것으로 예상된다. $11억)이라는 경이적인 성과를 기록함으로써 대형 생물산업 전 문기업으로 성장 중에 있다. 생물산업분야에 참여하고 있는 세 해외시장 계의 대기업 및 생물산업 전문기업들은 단백질제품의 고부가가 미국 뉴욕에 본사를 두고 있는 시장조사기관 칼로라마 인포 Figure 2. Figure 1. Vol. 11, No. 1
8 h Á i ÁfjdÁu f : l f ˆ, ƒ t f (2006. 11. 24)2) Figure 3. l f ˆ g h. f (Kalorama) u Š ' l x h g ', l x h(protein therapeutics) f g 2010 f 870 gš f h Š f. f, f, f, l hh, hh, Š lh f vf Š Š jf g l Š f } g Š f. h l x h gf l 2001 250 Œ Š f 2005 510 2 f Œ f } Œi f f., f l x h gf gl f z Š dff g gf 80% f f heš f e d vf Œ f f. d hf hˆ f v, f f erv l Š. h hf ŒŠŠ f ˆ Š hf h fš fe ghf r g g f h Š j f. l 1990 f d f f ~ f h x h f l x h gf g Œ fš u f} Št hˆ f Šf f. f} Št f f h, g f, l, eh lœ l f : l f ˆ, ƒ t f (2006. 11. 24)2) Figure 4. l f ˆ g h. hf f f d vi ~l Š f x ff f. Š ƒ t f, 2006 h l f ˆ g 437 Š, 5 f 2011 f 885 f f vh. Š, f gi f Datamonotorf fš x d l g 2002 303 2010 591 l Š f ~. f Š g f ˆ f g f f, 2001~2002 f CAGR( h g )f 9% Š f. f : 2005 Š jd f f, Šhs (2005/12)3) Figure 5. l f ˆ g h (2001~2010). x d l gf f, f, f} Št hˆ f Š f g wš f. Datamonotor f f Š x d l if gf j Š ˆ d f ˆ 2010 l f g f f f h Š. ƒ x d f CAGR 45.3% ~ f g f Š f f. f f CAGR 13%, f Š g Œ Pegylated interferons, Schering-Plough's Peg-Intron(pegylated interferon alpha), Roche's Pegasys(pegylated interferon alpha 2a)f j Š f Š. Š, h1 l f ˆf ƒ hf Š l f ˆ h gf } Œ Œ f, hˆf Œ Š f f. h (generic)f l hˆf ƒ f Š hiš hˆf Š, f h hf h f Š f ˆ Š h gf h Š f. l f ˆf d l (utf l f ˆf v 1982 ), h Š t Š f., u f, gœ, f, Biomaterials Research 2007
Table 8. x d l hˆ g h (2004~2010) hd lf g 9 ( e: ) 2004 2006 2008 2010 CAGR(%) Erythropoietin 9,478 10,212 11,581 12,908 7.4 Insulin 5,207 6,436 7,360 8,050 8.0 Monoconal antibody(cancer) 3,706 5,092 6,501 7,818 18.1 Interferon alpha 2,714 3,715 4,573 5,518 13.0 Blood clothing factor 3,406 3,813 4,133 4,323 5.9 Colony stimulating factor 2,739 3,205 3,486 3,877 6.6 Interferon beta 3,052 3,567 3,656 3,721 6.6 Monoclonal antibody(other) 2,029 2,763 3,504 4,321 15.8 Growth hormone 1,902 2,043 2,110 2,122 2.5 Therapeutic vaccine 186 527 944 1,442 45.3 Plasminogen activator 678 701 696 684 0.7 Growth factor 243 349 428 502 17.8 Interleukin 242 256 251 245 3.2 Other 2,510 3,163 3,380 3,539 6.5 f : 2005 Š jd f f, Šhs (2005/12)3) Table 9. h1 l f ˆ ƒ Œ l f ˆ( ˆ ) f d ƒ f (Humulin) Eli Lilly 2002 f (Novolin) Novo Nordisk 2002 f gœ (Nutropin) gœ Š Genentech 2002 f gœ (Humatrope) gœ Š Eli Lilly 2002 f (Intron-A) Œ Schering-Plough 2002 ƒ f (Epogen) Œ Amgen 2004 ƒ f (Procrit) Œ Johnson & Johnson 2004 tpa(activase) h Genentech 2005 f gœ (Protropin) gœ Š Genentech 2005 G-CSF(Neupogen) Š x Amgen 2006 f : LG j h, 20064) f f l f ˆ f 20 f lƒ f i, f fš h hˆf f ~ f f. w t SKh f j LG Šf h f f s h f ˆf d f h Œ Œ ff hf l f ˆ ƒ u hf f f f l f f} Št f ˆ f f l l f e f l Š f h f hf. LGŒŠ( f, z f ff, f g Œ, f ), f(f gœ, f ), hf ˆ(z f ff), hfh ( f ), dh (f ), h (f gœ, f, f, z f ff), ~ (z f ff) f l f ˆf Š ff ƒ h hˆf Œf d f h h f Š f Œ~ f., f j LG Šf lhf f f ˆ f Š lhš f f gš f l f f f. FDA ff Š Š f f GSK f lšš h f Šd Œ Š, f gœ f e ƒ Šf v Š h f hˆ ˆl f f Š g f Œ Š. Š LG Š f g h f lœ x Š f Œ Št ljš f. Š dh f d i x h fl Š g Š f. l 1991 r Š 10 80 e f f fš 2001 f ˆŒ Š. fl i fd Œ, dr, Œ Š d df f 2004 12e d f ˆ w Š f },,, h f j w f Šhf 2006 l j h l w f f f. Vol. 11, No. 1
10 h Á i ÁfjdÁu Œx h g CJf xf jdh f z ( hˆ)f x Š gf f f. 1998 g gf h h heš f CJf xf f g hiš hˆf hf fdš xf 4 hf 1994 jdh f z de f. Šl g jdh hˆ ƒ gf lšjf u h f 2 EPOf hf f Š g g r Š f l hf gde f Š f hf. f f ŒŠf Š f, Š e r sf f h x d Štf f Œ Š lš f. f ŒŠf d Š Š 2000 Št j f lšš 2001 f f ef h ~hf f Š u f (ISU ABXIS) xf Štf l f ŒŠ f. g jf x d Št Œ f GPIIb/IIIa fdš Œ flf Œh l Štf ISU301, g,, e x f EGF dt fdš f e Š ISU101 f f. s j Š e r sf f h x d Št Š f. f hf BŒ x d f Œ Št g x d Št Šf, g f Š eš j jf. f f f s hf l x h ƒ f} Š t x h f fš l l l l Š t f g jdš f v hf } hf lh f. Šd t frf l f ˆ f gg g f f Š l 20 h Š f f l f. 1980 t f f f Š ft gœ, f, z f ff f f} Št f f hˆœ d f. 1980 le 3 f i Š s f fš f h Œ x hf f h, Š ihf h, CŒ x hf f h l f ˆ h f vlš 2001 40 Š f 11 fff Š 20 le 1 3s Š Œ f gš f hf rvš. g f 100 e Š f j 20% f f g fš hf j f Š f. 5 f 1985 Larry Souza f fš z f fff ehf } Š ƒ veš 4 f 1989 hf ˆ f ƒ. 2 f 1991 FDAf ff ff hf h Š l x hf Š f g. f Š t f f f 1992 u v f 10 t Š 4 f 1996 20 t Š t gf l Š f. 1999 f f h x h FDA f ff Š 2000 ~,, ~ f l x h FDAf jš g f f. ƒ 2002 f, 2004 f Š Šf hf f f f f fl l. t g l ehf Š f f Š l x hf jhhf xjš f u f h f lf Š f. ƒ g l h fš f ˆf ~ f l h ˆ l fhf f l f } ƒlf. Š Šf Š ehtš, h Š u f fdš fthf j d ~ f r Š Š f Š f Œ Š f. 2005 9e l h jf l x h, l, Œ Š, Š, 5 l 20 l. f j f g f lh hƒ Paliferminf g e ff f. f h, f h f, xf, hff lf f ˆ 2000 Š Š 8 16 f f rvš, l hf 10 Ž Š l j f. h f h 2f Š f h 1976 t x ~ ƒf Robert Swanson ŒŠff Dr. Herbert Boyer fš f f l f ˆf Š g 30 f f l f ˆf j f. h 1990 2000 t x f ~f 2006 f 2010 l u Š 5 f f Š Œf g jf f hflf l ~ d f. Š u Š 5 f Š f hflf f f f Š Š, FDAf ff Š e f. 1981 3 f fš xf l x h, Œ ƒ ~ƒ l jš f. f ˆ ƒ x h j Š f hf f ˆf 1990 t FDAf ff f ~ ~ f f. xf f j j Š f Œ ƒ f hf hˆf Procleix f 1999 ˆŒ Š f jš v l f f. e f Š f f ˆ j ƒ f} Št Š hf f Š Biomaterials Research 2007
hd lf g 11 Št f ˆ gf g Š f. ŒlhŒ k f dš x d f Št Š h f d 1998 g f h, xf, h Š Š i f f Št Š f. ~ k e Št Œf Š Œf f Œ Œ ~f f x Š f dš f g f Št Š f f Š f. f ff Štf f Œ Š ƒ l 10 f Št f Š f. 1988 f f l x h j Š g 1500 f lef f hš f h ˆf f hˆ j Š f. Š 2002 1e x f Š Š f Š f f f ƒ Š f. l x h ut f} Št f l f i lš f g 5 f h ˆf j ff 11 f hˆf f f u f Š hf Š f. f g hf f l x h f eš f f f h f f f. š x 1. Julian, K.-C. et al., Molecular farming for new drugs and vaccines, EMBO Reports, 6, 593-599 (2005). 2. l f ˆ, ƒ t f, 2006. 11. 24. 3. 2005 Š jd f f, Šhs, 2005. 12. 4. LG j h, 2006. 5. sœ, l f ˆ f,, 2005. 6. g, ~f, Š fš. 7. fl, d g Š f f ˆ g, LG j h, 2002. 8. e i, ehfgiš l f ˆf Œ, Biosafety, 23, Š Š e, 2005. 9. http://www.yeskisti.net/yeskisti/index.jsp. 10. http://www.bch.or.kr. 11. http://www.yakup.com. Vol. 11, No. 1