@@@̺(11800*830=9794õ) :14337271<210705>
--ڿ ߾ http://kr.abionbio.com/ko/ſCEO. 2
ٹȭ ġ-ڱ ξ ġ--Ҿ ġ - = 70 ̻ġ
-- ΰ CRO, 濵- ڽ ȹ
**۷ι Ÿ, ̿ž ߴɷ --ٽηµ 10̻ ܹ/-ܹ ȣۿо ڵ(ΰ )
**Ѱη + ӻ-㰡 Ͽ , L/O
**, CRO 濵 Ȯ --м Ʈũ +ִм ߱BGI Joint Lab -- ûذ3, 6-7
[[ӿ Ȳ]]
==濵Ѱ ſǥ̻ - б ǰ ڻ (‘00.02) - б д (‘04.03~) - б п ο (’13.10~) - ̷âк ܻ (‘13.11~) - ̺¢ ǥ̻ (’10.07~)
==Ѱ λ - б 濵 (’89.02) - Ĺ̼ ̻ (’09.10~’13.12) - ̺¢ λ (’14.01~) - MIT ڻ (’96.05) - ߸ũ (‘01.01~05.01)
==μ CTOڻȣ - ̼ ̻ (’05~’15.01) - ̺¢ CTO (’15.02~)
==Ѱ ̻迵 - հб д ڻ (’09.02) - ̺¢ ̻ (’09.08~)
==CRO ̻ - б а ڻ( ’00.02) - ߱ ̻ (’01.06~’12.10)- ̺ ̻ (’13.10~)
[[Ȳ]] ֽļ7,717,014->8544361<>()4,983,300+427347()+40(bw)=5410647,()2,733,714/500<ں3,855鸸->4269鸸-(켱ں)> ָ-
ſ ǥ̻ Ư ()2,709,400 --35.11% (1 ݵ)()357,000--4.63% Ÿ ()1,919,600--24.87% [7/29,3ڹ-()427347 ߰] Ϻũݵ 1ȣ (IBijŻ)()491,803--6.37% LBũνݵII (LBκƮƮ)() 400,000--5.18% KoFC-IMM R&D-Biz Creation 2013-2ȣ (IMMκƮƮ)() 400,000--5.18% ( 6 ݵ )()1,439,211--18.65%
[[繫]]繫() 2014 2013
2,483,938,149 1,991,385,431
-4,725,768,584 -3,491,408,778
-5,327,719,371 -3,530,827,160
[[Ұ]]
̺ ġ ȯ ġḦ ̿ ž ̿ ý ϴ --- 2007 б г ó ̷ б ηµ ߽ ټ Ͽ ٹȭ ܹġ, ڱðξ ٻġ, Ҿ üġ, C-MET inhibitors(, ) ϰ ִ.
â̳ Ȯϰ ǥ ‘Perpetual Pharmaceutical Pearl Provider’ ΰǿ 巯 Ӿ ٽ ž ĺ ߱Ͽ ǰȭ, â ٽ (Intellectual Property) ߾ ߰ Ư Ʈ ϰ , ̸ ġ, Ư ƿ츣 IP ϰ ִ. ̿ ž ý ð Ը ڰ ҿǴ High Risk ̸, Ư ڳ žళ , սô뿡 ߸߾ ̺ ѱ, ѱȭп ؿ ̿ Ȯ .
[[]]
**2015>>01. ֿ LMO
**2014>>12. ѱ ġ(15)-- SBIκƮƮ ġ(20)-- ijŻ ġ(20) 11. ģȭ -- --ָκƮƮ ġ(20) 07. KONEX 06. ()۷̿ ̺() ȣ
**2013>>12. LBκƮƮ ġ (30), IMMκƮƮ ġ (30) 09. ұû 04. λ 02. IBijŻ ġ (15) 01. ѱƮʽ ġ (20)
**2012>>12. () պ 03. ()̿ պ
**2011>>09. Ŀܱ License-out
**2010>>09. ISO9001 08. INNO-BIZ
**2009>>12. ó 03. μ
**2007>>04. ȸ
[[ο < 8,082,900(õ)>]]
-==߱Ⱓ ::(ȣ)-
1. üǾǰ Ȯ --- 90,000 ==2010.01.18 ~ 2010.11.30 : ǰǾǰó(10172÷334)-- -Ϸ
2. ǥ ڸ Ȱ Cancer Molecular Diagnostics --471,000 ==2010.06.01~ 2012.05.31 :: ߱û( S1072705)---Ϸ
3. 2 in 1 siRNA ̿ ̷ ġ ȭа --588,000 ==2010.10.01~ 2012.09.30 :: ߱û( S1069951)--- -Ϸ
4. Ҿ ȯ ܹ Ÿ ü ž ---2,720,000 ==2010.04.01~ 2015.11.30 :: ڿ(10035329-2010-01)---5/5
5. ܹ Ÿ̵ ̸ Ȱ ü --- 360,000 == 2012.03.01 ~ 2014.02.28 :: ߱û( S2042960)--- Ϸ
6. Liquid Biopsy Device ̿ CDx contents ---620,000 ==2013.11.20~ 2016.09.19
:: ̷âк(2013M3C8A1078455) -- - 2/3
7. RUO, IUO IVD ŰƮ ̿ ӻ(Ź) ---485,600 ==2013.11.20~ 2016.09.19
::̷âк(2013M3C8A1079319)--- 2/3
8. ѱ ŰƮ ǿȭ --- 300,000 == 2014.02.01~ 2015.11.30 :: ǰǾǰó(14182534)--- 1/2 9. Capillary Assembled Microchip(CAs-chip) Ȱ PCR POCT(point of care testing) ̸ ̿ ȣ ȯ --22,100 ==2014.09.01 ~2014.12.31 :: ߱û(S2205018)----Ϸ
10. 鿪ȯ м ȭ -- 300,000 ==2014.11.01~ 2017.10.30 :: ̷âк(2014M3C1B3064733)---1/3
11. ص ---1,592,000 ==2014.11.21~ 2017.10.15 ::п( UC1400131D)---1/3
12. ġḦ c-Met ž ĺ --400,000 ==2014.12.01~2017.11.30 :: ̷âк(2014073811)--- 1/3
13. ̿Ǿǰ ǰ(QbD) --- 134,200 ==2015.04.21~ 2015.12.10 :: ǰǾǰó(00158076700)--- 1/1
[[R&D]]##žళ R&D Principles
**۷ι Ÿ ** L/O & ** ֵ **Ÿ Ưȭ ̿žళ **(** κ Ƿ, <ܰ˻- κ > κ ȯ赵 /-/ġ Ǵܿ : Ʈʽ ACDx, ETRI ecH GEI/IOBIO + CRO services : AbClon ChemOn ν, BGI) ** **Ư㿡
##ȭ A
==2013 : : ٹȭ ġ кŸ ̿
==2014 : : HPV õ ġ
**1>> -- ټ ܹġ, ٻġ, üġ ̿ Ǿǰ ߿ ϰ , Ư ٹȭ ġ -Ÿ Ͽ ڱðξ, Ҿ ġ ϷϿ ӻ ӻ غϰ ִ.
==߿ ߿ 1>CNS-(ABN101=MSġ) 2>ڱðξġ 3>üġ (Ҿġ) 4>c-Met(, )
<> λ : ġ--ĺ == --
1.CNSо
-----ABN101 == ܹ(ī) : R&D(13.01~15.12) ӻ(16.01~17.06) ӻ(17.07~18.12)
2.
-----ABN201 =ü : R&D(13.01~15.03) ӻ(15.03~16.02) ӻ(16.03~18.12)
-----ABN202 =ü+ ü(ADC) : R&D(14.06~16.04) ӻ(16.05~17.09)ӻ(17.10~18.12)
-----ABN203 =ü : R&D(14.07~16.04) ӻ(16.05~17.09) ӻ(17.10~18.12)
-----ABN301/ABN302 =siRNA(ڱðξ) : R&D(13.01~16.01) ӻ(16.02~17.05)ӻ(17.06~18.12)
-----ABN401 =ȭ : R&D(14.12~17.04)ӻ(17.05~18.12)
**2>>ƯȲ -- Interferon-Ÿ ġ , HPV õ ġ , ڱðξ ġ , CD24 ǥ ϴ , θ ƿȭ ̸ ̸ ̿ ŰƮ, ǥع ڸ ߱ϱ ó, м , Ư Ȳ(÷ )
##Patents
=*=Human Interferon-beta Mutein : PCT KR <0781666 2004.11.02> US< 8101716 2005.11.02 > JP <4637913 2005.11.02 > CN BR EP <1809661 2005.11.02 >
=*=Modified Interferon-beta Conjugated with Polyethylene Glycol : PCT< PCT-KR2014-006743 2014.07.24> KR< 10-2014-0093983 2014.07.24 >
=*=Stabilized Formulations of Interferon beta Mutant : KR <10-2015-0049200 2015.04.07>
=*=Composition for Treatment of Cervix Cancer : PCT KR <0962301 2006.11.03 > US< 8377899 2009.05.01>
=*=Composition for Treatment of HPV-related Cancers : KR <1197627 2010.01.18 > KR <1520383 2012.08.02 > PCT PCT MX< MX/a/2015/001428 2015.01.30> BR JP <2015-525365 2015.01.30> US <14/419,234 2015.02.02> CA <2880777 2015.02.02> UA EP<13825116 2015.02.27> IN<1660/DELNP/2015 2015.02.27>AU<2013297196 2015.02.27> RU< 2015106855 2015.03.02>
=*=TP53's Dynamics and Regulation in Response to Single and Combination Therapy : US <62/148,403 2015.04.16>
=*=Sensitizing Composition for Cancer Comprising an Agent Inhibiting Expression of Oncogenes of HPV Virus : KR <10-2015-0066218 2015.05.12 >
=*-Data Processing, Analysis Method of Gene Expression Data to Identify Endogenous Reference Genes : KR <1007926 2007.12.27> PCT EP <11166073.4 2011.05.13> JP <2012-140384 2012.06.22> US <13/631,279 2012.09.28>
=*=Antigen Derived from Extracellular Domain of Multi-transmembrane Protein and Uses Thereof : KR <1334207 2011.11.17> KR <10-2013-0081099 2013.07.10> US <13/803,090 2013.03.14>
=*=Primers for Detecting Methylations of Promoter and a Kit for Diagnosing a Cancer Using the Same : KR <10-2011-0072438 2011.07.21>
=*=Method to Inhibit Cancer Targeting CD24 : US <8425906 2008.12.30 >
=*=Monoclonal Antibodies Specific to Claudin 3 and 4, and The Use Thereof : KR <10-2015-0026568 2015.02.25 >
=*=Dendron Conjugated Antibody and Use Thereof : KR <10-2015-0059264 2015.04.27>
=*=Immunocytokine Conjugated with Human Interferon Beta-mutein and Method for Preparing Thereof : KR <10-2015-0030037 2015.03.03>
===ܹ ġ<ٹȭ>: Ÿ (ī) =ABN101(Carbiferon) Enhaced IFN-beta for Multiple Sclerosis
*MS ַ 20~40 ȣ(<-2), 4õȯ, ̱ 1õ1ߺ. οԼ ϰ .. ڰ ϴ (ȯ ݽ ߺ) θ ǰ ...ô ýŰ ֿħ..CNS Ű Myelin shath ϴ ڰ鿪 Ű濰ջ/ȭ --(, , ȭŸ ) ̻, ýŰ濰( ϴ ÷/þ帲) (ݽŸ, Ǵ 财-躯- ϴ Ϲݽ/, ȸ鸶--İ̻//̸,/ϰ ) 3, - ,..з RRMS(-ȭ : Ϲ), BMS(缺, 10%- ġ=CIS), SPMS() PPMS()
* ***SCδ FDA rhIFN-beta 1b[ƺؽ-qW.IM][ż-qD.SC][Ÿ-EOD.SC] rhIFN-beta 1a[-TiW.SC], ***ֻ : []1ȸ [Ƽ긮] 1Ⱓ1ֱ(5) [Ʈ] ***汸 : [], [] < MS-[Ƕ]> Ϻ , -2012 126 Ը, 150 ( Ȯ )
* ī IFN-Ÿ1a , ȯǼ<1ȸ ȸ >--< >ۿ /ȿ --RRMSܿ پ MS Ȯ --ܵ ǰ ÿ ȿ/ۿ -- (1/10) <ݰ > žĺ. ---> ^^MS 䱸[ -------ۿ밨-- 䱸] : RRMS, SPMS, CIS --3ȸ 1ȸ SCȽ --Ծ ȿ--ֻ ۿ 氨--(hostCellκ 꼺10) డ1/10
=== Ÿ ٹȭ First-Line Treatment Ǵ ġ, ī ٹȭ ġ Ƿ 信 Ͽ ȯ Ǽ డ μ ߿ ִ ž ĺ .
* ܹġ 2012 788 , 2017 1,134 7.5% ǰ ִ. ٹȭ ʳ ؼ 250 ȯڰ ٹȭΰ ִ , ̱ 30 ̻ α 1000 1 ٹȭ ȯ. 2,300 ȯڰ ִ ǰ . ž ̾ ӿ ֿ 7 ٹ ȭ ġ а Ȯ븦 ̶ . ̱ , , , Ż, Ϻ 7 89 Ը ߴ ٹ ȭ ġ 2015 ̸ 115 Ȯ . ġ ̱ Ż Ͽ ‧Ƿ о þü ҽý䰡 27 ‘ٹ ȭ’ ̴.
^^^ī̶
**25° ƹ̳ ȭŰ rhIFN-beta1a 27°ġ Ⱑ Arg Thr ̵ ̿.
ΰ Ÿ ƹ̳ ȭ, ߰ȭ(80° Ͽ 25° ƹ̳ ȭ) Ÿ Biobetter version --- ̱ 21 IP Ȯ
< ī > : ** <ȿ > site-directed mutagenesis ϳ <߰ ȭadditional glycosylation> Agreegation, 꼺, Ư ==>*鿪ۿ*꼺 *ü ݰ Ȱ : ü .
< ߴܰ>: (2016 1б ӻ )
<> : ȭ ٹȭ(RRMS) Clinically Isolated Syndrome(CIS)
<ǥ > :ٹȭ ġ Ÿ ӻ Ǿǰû(EMA) Phase1ӻ CTA(Clinical Trial Application)
## õ IFN-ß (Betaseron, Rebif, Avonex)
**ص (ȿ 1/10 Ƿ 300mcg ٷ ȿ ) --Ÿ, ** ʿ(44mcg 3ȸ)+ۿ빮 : , Ÿ **鿪(Ư ̿ )--Ÿ **ʹ డ (-- 15000 ҿ) : ƺؽ,
==>##ī Ư : ݰ . ణ /ٸ ེ ߰, ȿ , 鿪 ۿ ,
## Ÿ: First line Tx -- RRMS(Relapsing-Remitting MS) & Clinically isolated syndrome(CIS)
## Ȯ尡 : SPMS(secondary ProgressiveMS), RNA viral disease(HCV, SARS, West Nile Virus), Chemotherapy adjuvant, Demyelinating Disease, Myelitis, Neuritis, Optic Neuritis
## Variable types of MS, Open Up possibilities --MS а Ȯ : 켱 RRMS, ״ PPMS(༺), SPMS(༺)
==ϰ 밡 --ġ ȿ Ͽ ȿ (ܹ )
##IP Portfolio of ABN101-Carbiferon
***Human IFN-beta mutein ==Granted : (ѱ-901127) PCT(060511) US(120124) JP(101203) Braz(081021) China(121107) EP(110518-----밡-̷-ɶ--¸--, Ʈ-ũ, 110817-, 110830- Ű)==Applied : (India-070518)
**Modified IFN-beta Conjugated with Polyethylene Glycol ==Applied : (ѱ-140724) (PCT-140724)
**Immunocytokine conjugated with human IFN beta-mutein and method for preparing thereof ==Applied : (ѱ-150303)
**Stabilized Formulation of IFN beta mutant ==Applied :(ѱ-150407)
^^ IP(Intelectual property-) Portfolio(ڷ) ^^EP(Ư) ^^PCT-ؿƯûڰݿ켱(ٱƯ켱, ̿ Ư-Ưû , Ư㼭 , Ư ¿ ؿ ϴ Ư PCT ûϸ ־, PCT û 30̳ Ư Ͽ PCTû ڷ ұؼ Ư㸦 ... , PCT ġ ʰ Ư ϰ û 1Ⱓ 켱 ȣǸ 1⳻ ׳ ۼ ) ^^EP(Ư, EUROPEAN PATENT)
===ٻġ<ڱðξ>: Anti-E6/E7(2-in-1) siRNA = Sensitizer in HPV-related Cancers(Cervix cancer)
*ڱðξ 2, 3<ߵ1>, ڱðξġ ̿Ǿǰ , ǰ First in Class, 2010 Ը 18--2018 24 Ը : Ư Chemo-RT ȵ ڱðξȯڰ Ÿ
* 2-in01 siRNAٻġ ʷ Ը ⼭ chemical modulationμ <ٽ > 鼭 ڱðξϰ ΰξ , ܵġῡ 쿡 ȿ , ӵ鿡 RNAiġ ۷ι R&Dο ؼ Ȯ
==WHO Ϳ õ ڷῡ ϸ ڱðξ 迡 2и 1 . ̺ ٻġ ڱðξ ϴ HPV ΰ ÿ ν ġϸ, ȭ ġ 缱 ġ ó ġȿ شȭ ž.
^^^ Anti-E6/E7(2-in-1) siRNA ڱðξ ֿ HPV(Human Papilloma Virus) HPV 16 18 ߾ E6/E7 Ÿٻ ڵ ϴ, ڸ <>ü , ġ Ͽ< ϴ ȹ ȭ + ۿ > ϴ μ ̷ (anti-viral)siRNAġ -- ӻ --ұû
***ȿ : 4-5 nude mice HPV18 type-(+)HeLa cells SCѴ, 6, 8, 10, 12, 14, 16, 18, 20° siRNA 2mg/Kg IV óġϸ鼭, ÿ 7, 9, 11, 13, 15, 17, 19, 21° 1>0.5mg/Kg low-dose Cisplat Tx(IP) :ڱðξ 뷮(20-40mg/m^2) 2>2mg/Kg High-dose Cisplat. Tx(IP):ڱðξ 뷮(70-90mg/m^2) óؼ ==> siRNA+highCDDP 籫 <, , , ȿ Ȯε>
<>ڱðξ, HPV ̷ ߵǴ ı dz
<߾ Ư> : ڱðξ ġῡ chemotherapy and/or 缱 ġ .....Ϲ缱 (Concurrent Chemoradiation Therapy/CCRT) ġȿ شȭ ִ ż Sensitizer
HPV 100 ̻ --缺 warts , ִ ξ, , κΰξ, , , ϵ : Ư HPV 16/18 ξϿ 70%̻ , E6 E7 ΰ ߾ڴ p53 pRb ıϿ , Anti-E6/E7 (2-in-1) siRNA (21mer Double Strand RNA) ̷ Capsid protein ȣǾ E6 and E7 mRNA ÿ ݹް ϰ ȴ.
##ڱðξϿ ذ ʿ伺 = ABN301/302 (Anti-E6/E7 siRNA) 帧
*1>Concurrent Chemoradiation Therapy(: CCRT)
--Cisplatin Low Dose(40mg/m^2) RadioTherapy (EOD for 1 wk) : 6ȸ ݺ CCRT Failure (Stage IB: Residual Tumor Mass / Stage IB2~IVA: Distant /Local relapse) -->
*2> High Dose Combined Chemo. ::: Cisplatin High Dose(70~90mg/m^2 )+Paclitaxel // Cisplatin High Dose(70~90mg/m^2)+Irinotecan ==>Therapy Failure(No improvement in overall survival / Higher adverse effects ) ==>
*3>New Medicines to Fulfill Medical Unmet Needs :: ABN301/302 ġ شȭ (**During High Dose Chemo. : • Improvement in relapse-free survival or overall survival • Reduced dose of chemo.(reduced adverse effects by high dose chemo.) **During CCRT : • Maximizing the effectiveness of CCRT (reduced metastasis and relapse)
##ABN301/302 for Cervical Cancer ---ABN301/302 (Anti-E6/E7 siRNA) ߱
@1>Lead discovery-->LIBRARY-->LEAD==>Modification(@2> or@3>)-->Candidate>
@1-1>Lead Discovery(ι ߱)
**siRNA library Screening **Cytotoxic effects at low concentration **Verification of target-related protein/mRNA level change (TP53, E7, E6, p21) **Senescence at low concentration **Synergism analysis in combination therapy
==>@1-2>Lead Validation(ι ġ) ::: **Combination with chemotherapy in vivo ** Combination with radiation therapy in vivo
@2>Lead Optimization(ι ȭ) **Cytotoxic effects at low concentration **Verification of target-related protein/mRNA level change (TP53, E7, E6, p21) ** Senescence at low concentration ** Serum stability test **Combination therapy
@3>Derivatives Production( ) by Chemical modifications: 2′-OMe-modified nucleotides 2′-F-modified nucleotides
##Originality of ABN301/302 = ABN301/302 (Anti-E6/E7 siRNA)
**1>2-in-1 siRNA
•`2 in 1 siRNA system`: E6 and E7 oncogene þ
•ȭ/缱 ó ġȿ • Sensitizer<> ۿ
• HPV-related cancer research (Anal cancer, Head and Neck cancer, Oral cancer, Penile cancer, Lung cancer, etc.)
**2> , ȿ
•2'-OMe ٻ ȭ ȭ: ġŸ ջ ּȭ
•siRNA POOL technology •Polymer based nanoparticle( ó) ---Ÿ ɷ
**3> شȭ
•2'-OMe ȭ ȭ: û
•Formulation optimization - Polymer based delivery system
**4> ̼ •siRNAs are regulated as drugs : Under FDA’s Center for Drug Evaluation and Research [CDER]
•siRNAs are synthetic molecules (cGMP) Polymer based nanoparticle (non-viral vector) : (Easy to commercialize)
^^^IP Portfolio
---------Patent I : HIT ==Anti E6/E7(2-in-1)siRNA----------
-----------------------Patent II-----------------------<>---------------Patent III------------------
Screening Lead Derivative Candidate siRNA Pool(SP)
HPV 18type, 10 Library *T116-426/T16-450 7/4 No.5/No.4 HPV type18SP
HPV 16type, 10 Library *T16-366/T16-448/T16-497 7/4/4 No.2/No.2/No.2 HPV type16SP
Patent 1 : Composition for tratment of cervix cancer =Granted : (ѱ-10-0962301, US 8377899) (PCT 2008/054184)
Patent II : Composition for tratment of HPV related cancers =Granted(ѱ 10-1197627)( PCT/KR2011/000365) Patent III : composition for tratment of HPV related cancers =Pending(ѱ 10-2012-0072132)(PCT/KR/2013/003202)
<>ξٻġ
---簡 ٻġ siRNA ̿ ġμ ڱðξ, ΰξ ϰ . siRNA ̿ ġ 忡 õ Ȳ, ȸ siRNA ̿ ̿Ͽ ̷ ̳ Ư ܹ ȯ ̷ ٽġ , ̿ Ը ȮǾ . ӻ ߿ ־ ڰ RNAi . 2011 Jain PharmaBiotech RNAi ġ , RNAi Ǿǰ 2020 12 Ը ..
--- siRNA ٻġ, ΰ ̷ õ ϵ üδ ڱðξϿ HPV ߾ E6 E7 ÿ ν ġϴ â 2-in-1 ý Ư¡ ϰ . Ư HPV õ ġḦ ȭп Ǵ 缱 Ͽ ġϴ , siRNA (sensitizer) Ͽ ġ ȿ ̹Ƿ, ڱðξ 2A 豺 Ȥ 2B ̻ ȯڿ Ǵ ȭй缱 ġ (concurrent chemoradiation therapy; CCRT) ȿ شȭ Ű, Ǵ 缱 뷮 ν ȭо ۿ ҽų .
--- siRNA ٻġ ġ 缱 ġᰡ ȿ ڱðξ ȯڸ Ÿ ϰ , â ۿ Ŀ ڱðξ Ư ġᰡ ϴٴ , ڱðξ ġḦ siRNA Ǿǰ first-in-class ġ ȿ Ǵ.
[] --簡 siRNA ٻġ .
<>ù°, â 2-in-1 siRNA ý ġ siRNA ⼭ chemical modification ǥ ٸ ⼭. ȭ Ų ġ siRNA Pool ӻ siRNA ġ .
<>°, ܵġ Ѱ ذ ִ ο ġ. ڱðξϿ HPV E6/E7 Ÿ ϴ κ siRNA intratumoral injection ܵġḦ Ͽ, ̴ ӻ Ұ. , ġ ֻ縦 Ͽ ġ ϰ ӻ 밡ɼ ν ܵġ Ѱ غϿ.
<>°, siRNA ⸦ ȭ Ű off-target effect ҽ ÿ, siRNA Pool technology Ͽ ȿ شȭ ״. , ൿ Ư ִ ڸ ü ν ȿ , ̼ ȮϿ. <> : ڱðξ ġḦ siRNA ġ ӻ ӻܰ biosimilar Ǵ generic ߵǰų ǵǰ ʴ. HPV ȯ ﹰ Ȳ Ͽ, siRNA ġ ñ Ͽ RNAi ġ ۷ι R&D pipeline ӵ ȹ .
===üġ<Ҿ>: Anti-Claudin 3/4 - B12 Antibody
*Ҿ 50-70뿡 ȣ, ų1500 , 10... ߺ - 22%̻ : 밳 -ȭпġᰡ ǥġ, ġ ϻȰҰ , ۷ιԸ 2,1, 300 Ը, Ҿüġ üǾǰ ۿ ҽŰ ȿ Ű , ҾϿ ƯȭŲ ǥüġ.. Ư Claudin3&4 ҾϿܿ پ Ͽ ..
==Ҿ 3 ̻ ¿ ܵǴ 찡 60% , ǥġ 缱ġ ϰ Ǵµ, üġ ġ ȿ, ۿ ǥġ ž.
^^^Anti-Claudin 3/4 - B12 Antibody
ü Tight junction protein Claudin ܹ Claudin 3/4 Pan-carcinoma marker ... â ۱ ̿ ü ũ ...1 Ÿ Ҿ ϰ Claudin 3/4 ÿ Targeting ϴ ü ġ ...
-----Claudin tight juntion ʼܹ --ҾϿ Claudin3/4 ...ܱ ڵ ĺü . Olaparib Avastin Ҿġ ̳ Olaparib PARPμ DNAջ ִ ҾϿ ְ, Avastin VEGFμ ̸ Ű Ҿ Ư ġ . Ҿpredictor ˷ Claudin3/4 Ÿٻ Ҿ Ư̼ /ġ ü B12 , Ҿ inViVo 30% ũⰡ پ Ȯ, ̾ B12 Conjugate material X(Ǵ anti-cancer payLoad) ó , ȿ ߰, Ȯ...< +ü-payload=ִȿ> ^^Claudin-3/4 ߾˷ pan-carcinoma markeṟ Ҿġ ٸ Ͽ -- Ȯ
< > : Ҿ, ĵ, , , ,
<߾ Ư>
Ҿ ġῡ Chemotherapy ġ (ǥüġ--ȿ up, ۿdown)... in vivo efficacy test
== ϴ 10 ϰ ġ...Ҿ Ͼ ߿ ұϰ, ȯ ũ ϰ , ҾϿ ˻簡 , κ ȯڿ Ư Ÿ 60% ̻ ȯڰ 3 ̻ · ܵDZ .. Ҿ ȣ 40~60 ü ȯ 40밡 24%, 50밡 22.5%, 60밡 17.5% ϰ ִ.
*** ü ġ
ġ ü 40% ̻ ʰ ü ߿ ְ ϸ, 2015 Ŀ 7.4 Ѵ . 20 ü ġ κ (49%) AIID (ڰ鿪ȯ; 35%) Ư ȯ õǾ ִ. üǾǰ ֿ 鿪ȯ κ ϰ ְ, α о ȯ ǰ ־ Ը Ȯ . üǾǰ õǴ 忡 Ǹŵǰ , Ǿǰ ϵǾ ǷẸ ϴ 찡 ݴ Ǹŵǰ ִ ̾ 强 ſ Ŭ ϰ ִ. üǾǰ 2016 3,000 Ը ̹Ƿ ű üǾǰ ǰȭ ȭ Ը ȸ ɼ ſ .
===c-Met : c-Met TyrosineKinase ü -c-Met TK ATP Ͽ ϼ л/ħ, κ ϼ ȣ (, , Ҽ, CNS ), ATPۿ ġ Ÿ, Ÿc-Met TK inhibitors carbozantinib foretinib ӻ..
[[CRO]]
**1>м(Molecular Genetic Analysis)
---PDx(Patient- derived Tumor Graft) Tumor Models Ư Ը <>PDx model Ĵ ̵
---siRNA <>Hit-Lead-Candidate /Hit to Lead, <>Lead to Candidate/siRNA PK(Pharmacokinetic)/TK(Toxicokinetic)/PD(Pharmacodynamic) Analysis
---м <>м <>Microarray/Cell Line Authentication <>ٻ&и
---ü-CDx(.Companion Dx) <>IVD-CDx ü
**2>м <> <>鿪ȭ(IHC) <>H&E <>special stain <>̵
**3>鿪м
---鿪м <>ELISA <>Other Assays/Customized services
---ü <>Phage display Library Screening <>IgG ȯ&ý
**4>ºм --м : ɼִ , а, , ǥ Ÿ , ó&
>>2015.08.12 <ڳ>ѱ ǰ Ϻ ‘Ȱ’ --Ϻ ̾ ѱ ‘(UP)’
- Zڵ ǰ ¾ü 33 Ϻ ֻ ǰ ü ǰϰ ִ.
1965 ȭ , ѱ Ϻ ڸ ް ״. ϼ 50 忡 ־ (win-win) ĪѴ. ѱ ĵǰų ߴ ν װ âߴ. Ϻ ()ڸ ̰ Ű.
....==ѱ ұ Ϻ 1
ֱ Ϻ а ġ ϰ ִ ִ. ̿ž (Companion diagnostics) ý ϴ ̺ , , , а üϰ ֱ 3Ⱓ 150 ġ Ҵ. ̺ û Ұ, ռ, ȱ к ˻Ʃ , 鿪 ߴ. 11(2012)̴ 2 25(2014) ߴ. ѱó 繫 “̺ Ϻ Ⱑ ù ؿ 35 ڸ Ұ, ߰ 3 鼭 ġ ϰ ִ. ɼ Ǵ ”̶ ߴ.
....ѱ ġ Ƿ Ϻ 1 ǰ ϴ ̷ ʵ ִ. ٰ ü ü ̿Ƽ̴ 2012 Ϻ ġ 1 ü Ÿ (NDA·Non-Disclosure Agreement) ξ. Ÿ ̿Ƽ ٰ ü ̸鼭, 䱸 ̴. ̿Ƽ̿ Ÿ ģ 1 Ǹ 븮 üߴ. “Ϻ Ʈ Ǹ ۷ ŷ ʴ Ϲε, 赵 3̾ ѱ ̷ 幮 ”̶ ߴ.
“ Ȱ δ” “ѱ Ϻ ° ǰ Ȱ س ȣȣ ӵ ”̶ ߴ.
[ ΰ Ȱ 嵵 ]
ѱܿ , װк ȣ ī 츶ڽ ν бȮ ȯ 2011 2013 ‘뽺ٽ ̿ Ŭ(LIPOzyme vesicle) Ĩ(Lab on a chip) ’ ƴ. ü(vesicle) ΰ ġ, Ⱦ ü ϴ ȿ ϴ ü ʿϴ. ü δ 뷮 Ұ, ̼ü Ĩ(chip) ̿ ü ۿ ߰, ȿ . üμ ΰ(liposome) ȭ Ȱ ɼ ̴. Ư ϰ ߰ ϰ ִ.
>>2015.08.10 IMMκƮƮ, ̺ ڿ ȸ---2⸸ 40 …ڽ ŵ
IMMκƮƮ( IMM) 2 ߴ ڳؽ ̺ ȸߴ. ߰ ڱȸ(Ʈ) žళ߰ ڽ мȴ.
5 ڰýýۿ IMM 'KoFC-IMM R&D-Biz Creation 2013-2ȣ ' ؿ ̺ ֽ 30 ָ ܿ Űߴ. Ű ȸ ݾ 28 800 ִ Ű ܰ 9360̴.
IMM 2013 12 ̺ ȯȯ켱(RCPS) 40 ָ μߴ. ִ డ 3750 μ 15 ̴. μǺλä(BW) 40 ָ μ Ը 30 ÷ȴ.
IMM ̹ ܸŰ κ ȸߴ. ̹ 12 ָκƮƮ( ָ) μǥ(Ʈ) 20 ָ Űߴ ϸ 2 ȵ 35 ȸ ̴.
IMM ̺ ֽļ 30 ( 3.69%). 3 ̺ ִ 1 2250 ϸ ġ 36 7500 ȴ.
迡 IMM ȸ Ȳ ġ ߰ Ű ġ ִ. ֱ TSκƮƮ ū Ҹ DSڹ ǥ ڰ յ ̺ ž ̴.
IMM ڴ "Ϻ ڱ ȸ ŵ "̶ "̺ ġ Ȳ̾ ڽ ñ ϰ 忡 ʴ Ű "̶ .
2007 б дг гó ̺ ġ ġ ĺ ϴ ̿ 7 ڳؽ 忡 ߴ.
ٹ߰ȭ ܹġ ڱðξϿ ٻġ(siRNA), ҾϿ üġ ӻ ̸ ؿܽ ֿ Ʈʿ Ϸ ӻ ̼ ƿ ڽ ɼ ٴ ް ִ. óijŻ IMM ָ ѱƮʽ IBijŻ, LBƮƮ ֿ ڷ ڸϰ ִ.
>>2015-08-06 <>'ū' , ̿ü ̺ -- 15, ...ܹġ ž
ھ ū Ҹ DSڹ ǥ ̿ü '̺' ֽ 鿴. DSڹ ڱ ƴ ߿ ʼ ϸ鼭 谡 ָϰ ִ.
4 óijŻ迡 ǥ ̺ 15 ġ ߴ. ִ 1 1700 12 8200 ľǵƴ. ڵ ǥ " ڱ ڿ 幮 ̽" Ҵ.
ǥ ̺¿ ž Ǯ̵ȴ. ̺ ڿ "ٹ߰ȭ ܹġ â ž ϰ ڱ ڴٴ ū յ κ"̶ ߴ.
̺ ٹ߰ȭ ܹġ ī ϴ ַϰ ִ. ο ܰ ġ 10 1 Ұ е ϰ ִ. ص ȿ ݰǴ ִ. ݰⰡ ª ݺ ( 1~3ȸ) ؾ ϴ ڵ. ī ȿ ݰ( 1ȸ) ȴ.
̺ ڴ " 250 ȯڰ ٹȭ ΰ ִ ȴ" " ġε ϰ ִ" ߴ. ̾ "ī ϷǸ "̶ ߴ.
ڱðξϿ ٻġ(siRNA) ߵ ̴. siRNA 缱 ġᰡ ȿ ڱðξ · ȯڸ Ÿ Ѵ. ڱðξ 4° ϴ ̴. Ǽ ڱðξ ٸ ġ ο ġ ʿϴ. siRNA ϷǸ ȿ ȴ.
ǥ DSڹ ֱ '' ڹ . ü , 2013 ڹ 1 ͷ 1(39.22%·ݵ ) ߴ. ڷ 4 ͷ 50% Ȯ ̾ MHź÷ Ұ 5 ͷ 75% Ͷ߸ ߴ. ̺ ֱ TSκƮƮ ټ óijŻκ ڸ ġߴ. ѱƮʽ IBijŻ, LBκƮƮ, IMMκƮƮ Ͽ콺 95 ľǵȴ.
>>2015-08-06 <>TSκƮ, žళ߾ü ̺ --ݵ 4 3000 μ…žళ CRO ַ¾ü
TSκƮƮ žళ߿ Ը ΰ ִ ̿ü ̺¿ 5 ߴ. 3 óijŻ迡 TSκƮ ̺ 4 3000 μߴ. డ ִ 1 1700, 5 ġ Ÿ. TSκƮ 'TS 2012-5 ' ڸ ߴ. 300 Ը ݵ, 迵ȣ λ ǥݵŴ ð ִ. ݵ ó ű ֽĿ ϴ ƴ϶ óijŻ ̹ ߴ ֽ ٽ ø ̴.
̺ 2007 б дг г ó 7 ڳؽ 忡 ߴ. ž ӻŹ(CRO) ַ ϴ ü. ָκƮƮ 20 ϸ鼭 (SI) .
ٹ߰ȭ ܹġ ڱðξϿ ٻġ(siRNA), ҾϿ üġ ϴ ߰ ִ. ٹ߰ȭ ġ ص ſ ȿ ݰǴ ־. ݰⰡ ª ݺ ( 1~3ȸ) ؾ ϴ ڵ. ̺ ī ȿ ݰ( 1ȸ) ȴ. siRNA 缱 ġᰡ ȿ ڱðξ · ȯڸ Ÿ Ѵ. ϷǸ ȿ ִٴ ȸ ̴. ̺ ſ ǥ ִ( 29.82%) ڸ öִ. óijŻ ڸ ġؿԴ. ѱƮʽ IBijŻ, LBκƮƮ, IMMκƮƮ Ͽ콺 95 ľǵȴ.
>>2015. 07. 29 ̺, 60 Ը 3ڹ
[ ⿵ ] ̺ 29 ڱ 60 Ը ָ 3ڹ ϱ ߴٰ ߴ. ֹడ 11700̸ ֽļ 427347ִ.
>>2015.07.24. ڳؽ, ŷ·ŷ
[̵ϸ Ӽ ] ڳؽ ŷ ŷ ŷϺ þ..
24 ѱŷҿ ̳ ڳؽ ŷ 359000 ϴ 73000 þ. ŷ 217000ַ ŷ 4700 ߴ.
ŷ Ȱ 105910 ġ ŷư, ̿ý(51190) ̺(46140) ڸ ̾.
ðѾ ü Ż(5290), ͻ(42305000), ̹̿(24833000) ̴. ̳ ŷ 359000 90 þ.
>>2015-03-03 ̺, ž --‘BIO-Europe 2015’ R&D ȫ
žళ ̿ óο̺() (ǥ̻ ſ) R&D ȫ 3 9Ϻ 11ϱ ĸ ֵǴ ‘BIO-EUROPE 2015’ Ѵٰ 2 .
̺ ̹ 縦 žళ ٹȭ ġ ܹ ġ ڱðξϿ siRNA ġ ȸ簡 ϰ ִ ž Ұϰ ۷ι ü ̴.
‘BIO-Europe’ ִ ̿ ȸ ؿ 42 1,200 , 2õ ڰ ̼ 1:1 Ʈʸ ֽ ǰ, ̴ .
7 ڳؽ ̺ ٹ߰ȭ ܹġ ڱðξϿ ٻġ(siRNA), ҾϿ üġ ϰ , ӻ ӻ (CRO) м ϰ ִ.
>>2014-11-20 <>ָ, ڳؽ ̺ 20 --·Ʈ μ… ó
ָκƮƮ( ָ) ڳؽ ̺¿ 20 ߴ. ӻ յ ž ġ ڴ.
18 óijŻ迡 ָ 'IBKC-ָ ̷âݵ ̿' ̺ ֽ 35 7000(5.15%) μߴ.
ָ 2 ̴ 12 7000ָ 15 7000ִ 峻 żߴ. 20 ִ IMMκƮƮ ̴ Ʈ μ ϸ ߴ. ܰ ִ 7800, 3750 20 Ը.
ָ ڴ "̺ ߰ ִ" "ڿ Բ ġ ִٴ Ǵܿ ڿ " ߴ.
ָ (̿ص) Ǿ ̿ ġ ó â ϴٴ Ǵ ڸ ̲ ̴.
ġ ġ ĺ ϴ ̿ó ̺ 2007 б дг г ó 7 ڳؽ 忡 ߴ. ӻ ܰ迡 ִ ٹ߰ȭ ܹġ ڱðξϿ ٻġ(siRNA), ҾϿ üġ ̸ ӻ ӻ ӻ(CRO) м ϰ ִ.
ִִ ſ ̺ ǥ̻ Ư 40.56% ̴. óijŻ ȯȯ켱ָ μ ѱƮʽ(9.75%), IBijŻ(7.31%), LBκƮƮ(5.95%), IMMκƮƮ(5.95%) 95 ϰ ִ.
ָ ڴ " ڽ غϱ⺸ ġ ̴µ ַ "̶ " ڽ "̶ ٺô.
迡 ̺ ڽ ƴ ɼ ġ ִ. ڴ "̺ Ȯϰ ְ ӻ ܰ迡 ܹġ ٻ ġ δ" " ƴ Ưʻ 嵵 "̶ ߴ.
>>2014.08.18 <̳ټȴ>ڳؽ & CEO] ̺ ſ ǥ “۷ι ִ ž ߿ ”
"常 ƴ ۷ι 忡 θ Ǹŵ ִ ž ̴ϴ."
ǻ ſ ̺ ǥ() 18 "۷ι ǥ ž ϰ ִ" "' ʴ о' ְ Ǵ ǥ" ̰ . ̺ 21 ڳؽ ߴ.
2007 б г ó ̺ ٹȭ ܹ ġ ڱðξϿ ٻġ, ҾϿ üġ ̴. ̵ ȯ ġ .
ǥ 'ð ' Ѵ.
״ "츮 κ ̿ žళߺ , Ǹű Ѵ" "츮 츮 ϴ о žళ߿ ϱ žళ߸ ϰ .Ǹſ پ ٱ 翡 (̼ ƿ) "̶ ߴ.
ٹȭ ܹ ġ ڱðξϿ ٻ ġ, ҾϿ ü ġ ٱ Ǹ ϰ ִ.
ǥ " ٱ 翡 ʰ ۷ι 忡 Ǹŵ ʴ " "츮 Ѵٸ '' Ǵ "̶ ߴ.
״ " ۷ι 1% ʴ´" "츮 ϴ ó ۷ι ǥ ϰ ֱ ΰġ Ϲ ϱ "̶ ߴ.
̿Ǿǰ Ϲ ռǾǰ ũⰡ ũ ü ̿ ľ ϹǷ ȭ ΰϰ Ư ̳ Ҽ ؾ Ѵ. ŭ ȿ پ 庮 ΰġ â ִ.
ǥ "̿Ǿǰ ۿ Ȯ ġ̳ ȯ پ ȿ ִ" " , ÷ܱ ʿ 庮 Ư ȣ Ⱓ 忡 Ȯ ִ ִ" ߴ.
̿Ǿǰ ܰ迡 ־ ̺ ϰ ִ κ ӻŹ(CRO) . м , м , 鿪м ϰ ִ.
̿ó ؿ ϱ. ǥ ں Ư ִ ʿϴٰ ߴ. ̸ ؼ Ư㸦 ڻ ȭų ִ ý ʿϴٴ ̴. ״ "ں پ ϱ ؼ Ư㸦 ȸ ݿ ڻȭ ִ ý Ѵ" "Ư ο ϴ â ؼ Ư ǿ ʿϴ" ߴ.
**^^^ٹȭ ߺ
>>ߺ :ٹ ȭ(multiple sclerosis, MS) ߺ <ε> 鿪ü谡 ȰȭǸ鼭 ĵ B T 庮(blood-brain barrier, BBB) ߽Ű Եʿ , Żȭ(demyelination), Ű(neurodegeneration) Ű ǰ ִ.
>>,% : (̻=/)63.5--48.9--÷48--Ƿ.40>>-- న25---23--19--ٰ17-ﰨ14.7--13.4-- 汤11>
>>ܿ MS ġ ۿ <Ű濰 Ű (lymphocyte) ǥ > fingolimod<淹Ͼ> (lymph node) ϰ, teriflunomide ʿ ν ߽Ű ԵǴ . Alemtuzumab<Ʈ> T B θ ״ٰ ϰ, Rituximab(CD20 Ŭüǥ, ı ) Ofatumumab(CLLġ-Ƹ) Ocrelizumab(RAġ - RA .. MS ) B ıϸ, natalizumab<Ƽ긮> ߽Ű ԵǴ BBB ϵ .
>> MS ǥ ġ : ؿ -ȭ ٹȭ(relapsing-remitting multiple sclerosis, RRMS) 1 ġδ 汸 teriflunomide<> ڰֻ interferon-beta, glatiramer acetate<ż> ְ, 2 MS(secondary-progressive multiple sclerosis. SPMS) ȭ RRMS ϴ mitoxantrone ִ.., ȭ 2 ġ ľó alemtuzumab<Ʈ>, natalizumab<Ƽ긮>, fingolimod<淹Ͼ> ִ.
>>>2015-09-08 [ֵ]14 ī ΰ
̿ ȭ ̺(203400, ǥ̻ ſ) ڻ簡 ٹȭ ܹġ `ī`(Carbiferon) óֱžళ Ǿ 7 ()óžళ( ֻ, ) `ٹȭ ġḦ Ÿ, ī ӻ ` üߴٰ 8 . д籸 ȸǽǿ ֵ Ŀ ֻ ڵ ̺ ڻȣ , å ۰ ڻ ߴ.
̺ ݹ κ ް Ǹ, ̸ ٹȭ ܹġ ĺ ī ӻ ܰ ߿ ϰ ȴ. ٹȭ̶, ô, ýŰ ߽Ű迡 ϴ Ű鿪 ȯ̴. ֿ δ ̳ , ýŰ ݵǴ ȯ ġ Ȱ ȯ ϳ̴.
̹ å ۰ ڻ дп ī ڻ , ̺¿ 10 ̻ ī ؿ شо ְ ̴.
۰ ڻ " 14 Ը ϰ ִ ٹȭ ġ ַ ǰ ִ Ÿ Ͽ ī ̻ ȿ 꼺 ȮεǾ ݹ óžళ ī ȮǾ ӻ迡 ϰ ̴. 꼺 ٹȭ ̿ܿ ̷μ Ȯ밡 ȴ" .
, ̺ ӻ ӻ ī ݿ CRO 帲̿ ǷϿ ī ߿ ϰ ִ. ٳⰣ 翡 ǰ ȭ ִ 帲̿ ̿ "۷ι žμ ī ɼ , ؿ ȸ鵵 ָϰ ־ ؿ ̼ ൵ ⼺ Ѵ" ߴ. ܹ óžళ 2020 ۷ι ž 10 ̻ ǥ ̷âк, ڿ, Ǻΰ R&Dμ ó R&D 踦 ʿ 2020 9Ⱓ 1 600( 5,300, ΰ 5,300) ڵǴ ʴ ۷ι žళ Ʈ̴.
=======
>>210720 ̺, 8<> ڽ …2600 ''//Ѿ 4 PER ġ
2021 07 14 15:00 ǥ Դϴ.
Ͻž ̺ ɻ縦 ߴ. 7Ⱓ ϰ ڽ ھ ٰԴ. ðѾ ִ 2600 ߴ.
ް 14500~17000
̺ 12 ǽŰ ߴ. 2 ѱŷ ڽڽ庻ηκ (IPO) ι 길̴. 8 5~6 俹 ϰ 11~12 û ´. ǥ ְ ̷, ȭ̴. 俹 û ϸ 8 ڽڿ ֱ ŷ ̴.
̺ 2014 7 ڳؽ 忡 ߴ. Ϲݱ⸦ ǥ Ưʸ ϰ ߴ. 5 ڷγ19 ġ öȸ ִ.
ִ 228ִ. 100% ַθ ߴ. 14500~17000 ߴ. 331~388̴. ̺ ü ֽļ 15259371ִ.
̺ 4 ְͺ(PER) 带 ߴ. Ǿ(peer group) Ѿ, ٴ, , ѵ ߷ȴ. 4 ȸ.
Ǿ 4 1б 4б ջ Ͱ ְ PER 28.6. Ѿ 46.3, ٴ 17.2, 38.1, ѵ 12.9 PER ߴ.
PER ̺ 2022 ߴ. ̺ ֿ ABN-401( ϴ ǥ) ȭǴ Ϳ PER ߴ.
̺ ִ 25200̴. 2022 ݱ Ǿ ȯϱ 40% ߴ. ̷ ݱ⸻ 簡ġ 1782100̴.
̺ ִ 42.5%~32.5% 14500~17000 ߴ. ðѾ ִ 2600̴.
ڽ
̺ 𰡴 ټ 븦 δ. ̺ ū ߴ. 40% 2019 ڽڿ 簡ġ 23.3% 16.7%p . Ǿ 4 ֱ 3 ں(WACC) ġ 11.0% ص 29.0%p ߴ.
𰡿 2019 ڽڿ ϴ 3.3%p, 5.8%p 42.5%~32.5% ߴ.
2007 ̺ ǥ ABN401̴. ABN401 ֿ ڼü(c-MET) ǥϴ ̴. ٸ δ ABN101(ٹȭ ̷ ġ) ִ.
ABN101 ߽Űȯ(CNS), ڷγ19 ȣ̷ ȯ, B ̷ ȯ پ ġ ǰ ִ -Ÿ(IFN-β1a) ȿ, , 꼺 ȹ ̴̿. ܿ 7 ߰ ϰ ִ.
̺ ̹ üڱ, ڱ, ӻڱ, ڱ ħ̴.
ABN401 ȣֿ ѱ ϰ ִ ۷ι ӻ1·2 뷮 ƴ. ̱ ӻ 2 ̴. ABN101 Z̿ 뷮 ϰ ӻ 1 ȹ̴.
ü ÷ ̴. 谡 ̴.
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