SI9620076B - Stabilni reagenti za pripravo radiofarmacevtikov - Google Patents
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- SI9620076B SI9620076B SI9620076A SI9620076A SI9620076B SI 9620076 B SI9620076 B SI 9620076B SI 9620076 A SI9620076 A SI 9620076A SI 9620076 A SI9620076 A SI 9620076A SI 9620076 B SI9620076 B SI 9620076B
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- 0 CC(C)C(C(N(C)[C@@](CCCNC(*)=N)C(NCC(N[C@](C1)([C@]1C(O)=O)C(NCc1cc2cc(NC(CCCCCNC(c3ccc(NN=C4CCCC4)nc3)=O)=O)c1)=O)=O)=O)=O)NC2=O Chemical compound CC(C)C(C(N(C)[C@@](CCCNC(*)=N)C(NCC(N[C@](C1)([C@]1C(O)=O)C(NCc1cc2cc(NC(CCCCCNC(c3ccc(NN=C4CCCC4)nc3)=O)=O)c1)=O)=O)=O)=O)NC2=O 0.000 description 1
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- C—CHEMISTRY; METALLURGY
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- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
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- A61K51/04—Organic compounds
- A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
- A61K51/082—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins the peptide being a RGD-containing peptide
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- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
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- A61K51/04—Organic compounds
- A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
- A61K51/088—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins conjugates with carriers being peptides, polyamino acids or proteins
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- C07B59/008—Peptides; Proteins
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/745—Blood coagulation or fibrinolysis factors
- C07K14/75—Fibrinogen
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2123/00—Preparations for testing in vivo
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Claims (7)
- -1- STABILNI REAGENTI ZA PRIPRAVO RADIOFARMACEVTIKOV PATENTNI ZAHTEVKI 1. Reagent, ki ima formulo: (Q)d'Ln-Hz, in njegove farmacevtsko sprejemljive soli pri čemer, Q je biološko aktivna skupina, izbrana iz skupine: peptidov, polipeptidov in peptidomimetikov; d' je 1-20; Ln je povezovalna skupina s formulo: M1 -[Y1 (CR55R56)f(Z1 pri čemer M1 je •l(CH2)gZ1jg-(CR55R56)g~-; M2 je -(CR55RSVlZ1 (CH2)g]g-; g je neodvisno 0-10; g' je neodvisno 0-1; g" je neodvisno 0-10; f je neodvisno 0-10; -2- f' je neodvisno 0-10; f ‘ je neodvisno 0-1; Y1 in Υ2 sta ob vsakem pojavu neodvisno izbrana iz: c« 56 vezi, O, NR , C=0, 0(=0)0, 0C(=0)0, C(=0)NH-, C=NR , S, SO, S02, S03, NHC(=0), (NH)2C(=0), (NH)2C=S; Z1 je ob vsakem pojavu neodvisno izbran iz C6-C14 nasičenega, delno nasičenega, ali aromatskega karbocikličnega obročnega sistema, 57 substituiranega z 0-4 R ; in heterocikličnega obročnega sistema, 57 substituiranega z 0-4 R ; 55 56 R in R sta ob vsakem pojavu neodvisno izbrana iz: vodika; C^-C^q 57 alkila substituiranega z 0-5 R ; alkarila, pri čemer je aril substituiran z 0-5 R57; 57 58 R je ob vsakem pojavu neodvisno izbran iz skupine: vodika, OH, NHR , C(=0)R58, 0C(=0)R58, 0C(=0)0R58, C(=0)0R58, C(=0)NR58, C=N, SR58, SOR58, S02R58, NHC(=0)R58, NHC(=0)NHR58, 58 NHC(=S)NHR ; ali, alternativno, ko je vezan na dodatno molekulo Q, je 57 58 R ob vsakem pojavu neodvisno izbran iz skupine: O, NR , C=0, 0(=0)0, 00(=0)0, C(=0)N-, C=NR58, S, SO, S02, S03, NHC(=0), (NH)2C(=0), (NH)2C=S; in, 58 R je ob vsakem pojavu neodvisno izbran iz skupine: vodika; C1-C5 alkila; benzila, in fenila; Hz je stabilen hidrazon s formulo: R80 NsC R^-n' R81 V1 -3- pri čemer, 40 R je ob vsakem pojavu neodvisno izbran iz skupine: vezi do Ln, C-j-Cio alkila 52 52 substituiranega z 0-3 R , arila substituiranega z 0-3 R , cikioalkila 52 52 substituiranega z 0-3 R , heterocikla substituiranega z 0-3 R , heterocikloalkila 52 52 substituiranega z 0-3 R , aralkila substituiranega z 0-3 R in alkarila 52 substituiranega z 0-3 R ; 41 52 R je neodvisno izbran iz skupine: vodika, arila substituiranega z 0-3 R , C^-Cio 52 52 alkila substituiranega z 0-3 R , in heterocikla substituiranega z 0-3 R ; 52 R je ob vsakem pojavu neodvisno izbran iz skupine: vezi do Ln, =0, F, Cl, Br, J, -CF3, -CN, -C02R53, -C(=0)R53, -C(=0)N(R53)2i -CHO, -ch2or53, -0C(=0)R53, -0C(=0)0R53a, -OR53, -0C(=0)N(R53)2, -NR53C(=0)R53, -NR54C(=0)0R53a, -NR53C(=0)N(R53)2, -NR54S02N(R53)2, -NR54S02R53a, -S03H, -S02R53a, -SR53, -S(=0)R53a, -S02N(R53)2, -N(R53)2, -NHC(=NH)NHR53, -C(=NH)NHR53, =nor53, no2, co cqa -C(=0)NH0R , -C(=0)NHNRR , -0CH2C02H, 2-(1-morfolino)etoksi; 53 _53a 54 R , R , m R so vsak, ob vsakem pojavu, neodvisno izbrani iz skupine: vodika, 0·|-0β alkila, in vezi do L^; 80 81 85 R in R sta neodvisno izbrana iz skupine: H; 0^-0^q alkila; -CN; -C02R ; oc ec λa -C(=0)R ;-C(=0)N(R )2; C2-Cio 1-alkena substituiranega z 0-3 R ; C2-Ciq 84 84 1 -alkina substituiranega z 0-3 R ; arila substituiranega z 0-3 R ; nenasičenega 84 heterocikla substituiranega z 0-3 R ; in nenasičenega karbocikla 84 80 81 substituiranega z 0-3 R ; pod pogojem, da ko je eden od R in R H ali alkil, potem drugi ni H ali alkil; 80 81 ali, alternativno, R in R sta lahko združena s prikazanim dvovalentnim ogljikovim radikalom, da se tvori: -4-η pri čemer: 02 00 04 R in R sta lahko neodvisno izbrana iz skupine: H; R ; C-j-C-io alkila 84 84 substituiranega z 0-3 R ; C2-C10 alkenila substituiranega z 0-3 R ; C2- C10 alkinila substituiranega z 0-3 R84; arila substituiranega z 0-3 R84; 84 heterocikla substituiranega z 0-3 R ; in karbocikla substituiranega z 0-3 R84; 82 83 ali, alternativno, R , R sta lahko združena, da se tvori združen aromatski ali heterociklični obroč; a in b kažeta položaja opcijskih dvojnih vezi in n je 0 ali 1, 84 R je ob vsakem pojavu neodvisno izbran iz skupine: =0, F, Cl, Br, J, -CF3, -CN, -CO2R85, -C(=0)R85, -C(=0)N(R85)2, -N(R85)3+, -CH2OR85, -0C(=0)R85, -0C(=0)0R85a, -OR85, -0C(=0)N(R85)2, -NR85C(=0)R85, -NR86C(=0)0R85a, -NR85C(=0)N(R85)2, -NR86S02N(R85)2, -NR86S02R85a, -SO3H, -S03Na, -S02R85a, -SR85, -SisOJR853, -S02N(R85)2, -N(R85)2, -NHC(=NH)NHR85, -C(=NH)NHR85, =NOR85, -C(=0)NH0R85, -0CH2C02H, 2-(1-morfolino)etoksi; in R85, R853, in R86 so vsak, ob vsakem pojavu, neodvisno izbrani iz skupine: vodika, C-t-Cg alkila.
- 2. Reagent po zahtevku 1, pri čemer: -5- Q je biološko aktivna molekula, izbrana iz skupine: llb/llla receptorskih antagonistov, llb/llla receptorskih ligandov, peptidov, ki vežejo fibrin, peptidov, ki vežejo levkocite, kemotaktičnih peptidov, somatostatinskih analogov, in peptidov, ki vežejo selektin; d’ je 1 do
- 3; Ln je: pri čemer: 9" je 0-5; f je 0-5; f je 1-5; 1 p 56 Y in y sta ob vsakem pojavu neodvisno izbrana iz: O, NR , C=0, C(=0)0, 56 0C(=0)0, C(=0)NH-, C=NR , S, SO, S02, S03, NHC(=0), (NH)2C(=0), (NH)2C=S; 55 56 R in R sta ob vsakem pojavu neodvisno izbrana iz: vodika, CfC^o alkila, in alkarila; Hz je stabilen hidrazon s formulo: R80 / N=C R40^' R81 R41 -6- pri čemer, 40 R je ob vsakem pojavu neodvisno ozbran iz skupine: arila substituiranega z 0-3 52 52 R , in heterocikla substituiranega z 0-3 R ; 41 52 R je neodvisno izbran iz skupine: vodika, arila substituiranega z 0-1 R , C-1-C3 52 52 alkila substituiranega z 0-1 R , in heterocikla substituiranega z 0-1 R ; 52 53 R je ob vsakem pojavu neodvisno izbran iz skupine: vezi do Ln, -CO2R , -CH2OR53, -S03H, -S02R53a, -N(R53)2, -NHC(=NH)NHR53, in -0CH2C02H; 53 53a R , R sta vsak, ob vsakem pojavu, neodvisno izbrana iz skupine: vodika in C1-C3 alkila; 80 85 R je ob vsakem pojavu neodvisno izbran iz skupine: -C02R ; C2-C5 1-alkena 84 84 substituiranega z 0-3 R ; C2-Cs 1-alkina substituiranega z 0-3 R ; arila 84 84 substituiranega z 0-3 R ; nenasičenega heterocikla substituiranega z 0-3 R ; 81 R je ob vsakem pojavu neodvisno izbran iz skupine: H in C-| -C5 alkila; 80 81 ali, alternativno, R in R , ko sta združena s prikazanim dvovalentnim ogljikovim radikalom tvoritan 82 83 84 pri Čemer sta R in R lahko neodvisno izbrana iz skupine: H in R ; -7- 82 83 ali, alternativno, R , R sta lahko združena, da se tvori združen aromatski ali heterociklični obroč; a in b kažeta položaja opcijskih dvojnih vezi in n je 0 ali 1, 84 85 R je ob vsakem pojavu neodvisno izbran iz skupine: -C02R , ~C(=0)N(R85)2, -CH2OR85, -0C(=0)R85, -OR85, -SO3H, -N(R85)2, -0CH2C02H; ge R je ob vsakem pojavu neodvisno izbran iz skupine: vodika, C1-C3 alkila. 3. Reagent po zahtevku 2, pri čemer: Q predstavlja biološko aktivno molekulo, izbrano iz skupine: llb/llla receptorskih antagonistov in kemotaktičnih peptidov; d’ je 1; L-n je: -(CR55R58)g"-[Y1 (CR55R56)fY2]f'-(CR55R56)g·-, pri čemer: g" je 0-5; f je 0-5; f je 1-5; Y1 in Υ2 sta ob vsakem pojavu neodvisno izbrana iz: O, NR56, C=0, C(=0)0, 0C(=0)0, C(=0)NH-, C=NR56, S, NHC(=0), (NH)2C(=0), (NH)2C=S; -8- „55. „56 . ... R in R sta vodik; Hz je stabilen hidrazon s formulo: R80 N=c R40·»/ R81 R41 pri čemer, 40 R je ob vsakem pojavu neodvisno izbran iz skupine: heterocikla 52 substituiranega z R ; R41 je vodik; 52 R je vez do L*,; 80 85 R je neodvisno izbran iz skupine: -CO2R ; C2-C3 1-alkena substituiranega z 84 84 0-1 R ; arila substituiranega z 0-1 R ; nenasičenega heterocikla 84 substituiranega z 0-1 R ; R81jeH; 84 85 85 R je ob vsakem pojavu neodvisno izbran iz skupine: -CO2R ; -OR ; -SO3H; -N(R85)2; 85 R je ob vsakem pojavu neodvisno izbran iz skupine: H in metila.
- 4. Reagent po zahtevku 3, pri čemer je Q ciklični llb/llla receptorski antagonist. -9-
- 5. Reagenti po zahtevku 4, ki so-10--11-ΝΗ-12--13-ΝΗ-14- ΝΗOCH3
- 6. Komplet za pripravo radiofarmacevtika, ki obsega: (a) vnaprej določeno količino sterilnega, farmacevtsko sprejemljivega reagenta po kateremkoli od zahtevkov 1-3 in 4; (b) vnaprej določeno količino enega ali več sterilnih, farmacevtsko sprejemljivih pomožnih ligandov; (c) vnaprej določeno količino sterilnega, farmacevtsko sprejemljivega reducenta, in (d) opcijsko, vnaprej določeno količino sterilne, farmacevtsko sprejemljive komponente, izbrane iz skupine: prenašalnih ligandov, pufrov, liofilizacijskih sredstev, stabilizacijskih sredstev, sredstev za raztapljanje in bakteriostatikov.
- 7. Komplet za pripravo radiofarmacevtikov, ki obsega: -15- (a) vnaprej določeno količino sterilnega, farmacevtsko sprejemljivega reagenta po kateremkoli od zahtevkov 1 -3 in 4; (b) vnaprej določeno količino dveh sterilnih, farmacevtsko sprejemljivih pomožnih ligandov; (c) vnaprej določeno količino sterilnega, farmacevtsko sprejemljivega reducenta; in (d) opcijsko, vnaprej določeno količino sterilne, farmacevtsko sprejemljive komponente, izbrane iz skupine: prenašalnih ligandov, pufrov, liofilizacijskih sredstev, stabilizacijskih sredstev, sredstev za raztapljanje in bakteriostatikov.
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Application Number | Priority Date | Filing Date | Title |
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US08/476,296 US5750088A (en) | 1993-03-30 | 1995-06-07 | Stable hydrazones linked to a peptide moiety as reagents for the preparation of radiopharmaceuticals |
PCT/US1996/009766 WO1996040637A1 (en) | 1995-06-07 | 1996-06-07 | Stable reagents for the preparation of radiopharmaceuticals |
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SI9620076A SI9620076A (sl) | 1998-08-31 |
SI9620076B true SI9620076B (sl) | 2000-02-29 |
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EP (1) | EP0832068B1 (sl) |
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KR (1) | KR19990022573A (sl) |
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EP0888130B1 (en) * | 1996-03-13 | 2003-07-02 | Bristol-Myers Squibb Pharma Company | New ternary radiopharmaceutical complexes |
US20030124053A1 (en) * | 1996-10-07 | 2003-07-03 | Barrett John Andrew | Radiopharmaceuticals for imaging infection and inflammation |
US6416733B1 (en) * | 1996-10-07 | 2002-07-09 | Bristol-Myers Squibb Pharma Company | Radiopharmaceuticals for imaging infection and inflammation |
HUP0001167A3 (en) * | 1996-10-07 | 2002-03-28 | Du Pont Pharm Co | Radiopharmaceuticals for imaging infection and inflammation |
US6403054B1 (en) | 1997-05-28 | 2002-06-11 | Bristol-Myers Squibb Pharma Company | Ternary ligand complexes useful as radiopharmaceuticals |
US6524553B2 (en) | 1998-03-31 | 2003-02-25 | Bristol-Myers Squibb Pharma Company | Quinolone vitronectin receptor antagonist pharmaceuticals |
US6537520B1 (en) * | 1998-03-31 | 2003-03-25 | Bristol-Myers Squibb Pharma Company | Pharmaceuticals for the imaging of angiogenic disorders |
CA2326978A1 (en) * | 1998-04-03 | 1999-10-14 | Milind Rajopadhye | Radiopharmaceuticals for imaging infection and inflammation and for imaging and treatment of cancer |
HRP990317A2 (en) * | 1998-10-13 | 2000-06-30 | Du Pont Pharm Co | A process for the preparation of a thrombus imaging agent |
US6794518B1 (en) * | 1998-12-18 | 2004-09-21 | Bristol-Myers Squibb Pharma Company | Vitronectin receptor antagonist pharmaceuticals |
CA2349333A1 (en) * | 1998-12-18 | 2000-06-22 | Du Pont Pharmaceuticals Company | Vitronectin receptor antagonist pharmaceuticals |
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1996
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- 1996-06-04 HR HR08/476,296A patent/HRP960250A2/hr not_active Application Discontinuation
- 1996-06-06 MY MYPI96002227A patent/MY133974A/en unknown
- 1996-06-07 CN CN96196141A patent/CN1192733A/zh active Pending
- 1996-06-07 CA CA002222183A patent/CA2222183A1/en not_active Abandoned
- 1996-06-07 CZ CZ973801A patent/CZ380197A3/cs unknown
- 1996-06-07 EP EP96919289A patent/EP0832068B1/en not_active Expired - Lifetime
- 1996-06-07 SK SK1634-97A patent/SK163497A3/sk unknown
- 1996-06-07 EE EE9700313A patent/EE9700313A/xx unknown
- 1996-06-07 NZ NZ310799A patent/NZ310799A/xx unknown
- 1996-06-07 KR KR1019970709054A patent/KR19990022573A/ko not_active Application Discontinuation
- 1996-06-07 PL PL96323995A patent/PL323995A1/xx unknown
- 1996-06-07 MX MX9709126A patent/MX9709126A/es unknown
- 1996-06-07 EA EA199800025A patent/EA000742B1/ru not_active IP Right Cessation
- 1996-06-07 WO PCT/US1996/009766 patent/WO1996040637A1/en not_active Application Discontinuation
- 1996-06-07 JP JP9501990A patent/JPH11507364A/ja not_active Ceased
- 1996-06-07 DE DE69626392T patent/DE69626392T2/de not_active Expired - Fee Related
- 1996-06-07 HU HU9901469A patent/HUP9901469A3/hu unknown
- 1996-06-07 ZA ZA9604854A patent/ZA964854B/xx unknown
- 1996-06-07 BR BR9609003-0A patent/BR9609003A/pt not_active Application Discontinuation
- 1996-06-07 AR ARP960103028A patent/AR003959A1/es not_active Application Discontinuation
- 1996-06-07 SI SI9620076A patent/SI9620076B/sl unknown
- 1996-06-07 ES ES96919289T patent/ES2193245T3/es not_active Expired - Lifetime
- 1996-06-07 AU AU61661/96A patent/AU718683B2/en not_active Ceased
- 1996-06-07 AT AT96919289T patent/ATE233241T1/de not_active IP Right Cessation
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1997
- 1997-10-23 US US08/956,313 patent/US6015904A/en not_active Expired - Fee Related
- 1997-12-05 NO NO975678A patent/NO975678L/no not_active Application Discontinuation
- 1997-12-05 LT LT97-191A patent/LT4380B/lt not_active IP Right Cessation
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