DK2601210T3 - Forbedret rekombinant humanfollikelstimulerende hormon - Google Patents
Forbedret rekombinant humanfollikelstimulerende hormon Download PDFInfo
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- DK2601210T3 DK2601210T3 DK11757190.1T DK11757190T DK2601210T3 DK 2601210 T3 DK2601210 T3 DK 2601210T3 DK 11757190 T DK11757190 T DK 11757190T DK 2601210 T3 DK2601210 T3 DK 2601210T3
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- A61K38/00—Medicinal preparations containing peptides
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- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/24—Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g. HCG; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH]
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- C07K14/59—Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g.hCG [human chorionic gonadotropin]; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH]
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- A—HUMAN NECESSITIES
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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Claims (15)
1. Rekombinant FSH-præparat, hvor det rekombinante FSH i præparatet har et glycolyseringsmønster, der omfatter følgende egenskaber: (i) en relativ mængde af glycaner, der bærer N-acetylglucosamin af bisecting-typen (bisGlcNAc) på mindst 20 % af den samlede mængde af glycaner, der er forbundet med FSH i præparatet; og (ii) en relativ mængde af 2,6-koblet sialsyre på mindst 40 % af den samlede mængde af sialsyrer.
2. Rekombinant FSH-præparat ifølge krav 1, hvor glycolyseringsmønsteret endvidere (iii) omfatter en relativ mængde af glycaner, der bærer fucose på mindst 30 % af den samlede mængde af glycaner, der er forbundet med FSH i præparatet; og/eller (iv) er et varieret glycolyseringsmønster, hvor FSH’et i præparatet omfatter mindst 35 forskellige glycanstrukturer, hvor hver af disse forskellige glycanstrukturer har en relativ mængde på mindst 0,1 % af den samlede mængde af FSH’ets glycanstrukturer i præparatet.
3. Rekombinant FSH-præparat ifølge krav 1 eller 2, hvilket præparat er opnået ved fremstilling i den humane cellelinje GT-5s eller en cellelinje, der er afledt deraf, eller en cellelinje, der er homolog dertil.
4. Rekombinant FSH-præparat ifølge et hvilket som helst af kravene 1 til 3, hvor det rekombinante FSH i præparatet har et glycolyseringsmønster, der omfatter følgende egenskaber: (i) en relativ mængde af glycaner, der bærer N-acetylglucosamin af bisecting-typen (bisGlcNAc) på mindst 25 %, fortrinsvis mindst 30 %, af den samlede mængde af glycaner, der er forbundet med FSH i præparatet; og (ii) en relativ mængde af 2,6-koblet sialsyre på mindst 50 %, fortrinsvis mindst 53 %, af den samlede mængde af sialsyrer.
5. Rekombinant FSH-præparat ifølge et hvilket som helst af kravene 1 til 4, der omfatter ét eller flere af følgende karakteristika (a) glycolyseringsmønsteret omfatter en relativ mængde af glycaner, der bærer én eller flere sialsyrerester på mindst 85 %; (b) glycolyseringsmønsteret omfatter en relativ mængde af mindst tetraantennære glycaner på mindst 18 %; (c) et Z-antal på mindst 200; (d) det er et humant rekombinant FSH; (e) det er fremstillet af en human cellelinje eller humane celler; og/eller (f) FSH’et i præparatet omfatter en alphaunderenhed, der har aminosyresekvensen ifølge SEQ ID NO: 1 og en betaunderenhed, der har aminosyresekvensen ifølge SEQ ID NO: 2.
6. Rekombinant FSH-præparat ifølge et hvilket som helst af kravene 1 til 5, hvor glycolyseringsmønsteret omfatter ét eller flere af følgende karakteristika: (i) en relativ mængde af glycaner, der bærer N-acetylglucosamin af bisecting-typen (bisGlcNAc) i intervallet fra ca. 25 % til ca. 50 %; (ii) en relativ mængde af mindst tetraantennære glycaner på mindst 16 %; (iii) en relativ mængde af glycaner, der bærer fucose på mindst 35 %; (iv) en relativ mængde af 2,6-koblet sialsyre på mindst 53 %; (v) en relativ mængde af glycaner, der bærer én eller flere sialsyrerester på mindst 88 %; (vi) et Z-antal på mindst 220; (vii) en relativ mængde af glycaner, der bærer galactose på mindst 95 %; (viii) en relativ mængde af glycanforgreninger, der bærer en terminal galactoseenhed eventuelt modificeret af en sialsyrerest på mindst 60 %; (ix) en relativ mængde af glycaner, der bærer en sulfatgruppe på mindst 3 %; (x) det omfatter mindst 45 forskellige glycanstrukturer, hvor hver af de forskellige glycanstrukturer har en relativ mængde på mindst 0,05 % af den samlede mængde af FSH’ets glycanstrukturer i præparatet; (xi) det omfatter mindst 35 forskellige glycanstrukturer, hvor hver af de forskellige glycanstrukturer har en relativ mængde på mindst 0,1 % af den samlede mængde af FSH’ets glycanstrukturer i præparatet; (xiii) det omfatter mindst 20 forskellige glycanstrukturer, hvor hver af de forskellige glycanstrukturer har en relativ mængde på mindst 0,5 % af den samlede mængde af FSH’ets glycanstrukturer i præparatet; og/eller (xiv) det omfatter mindst 40 % flere forskellige glycanstrukturer end FSH opnået fra CHO-celler i et tilsvarende præparat, hvor hver af de forskellige glycanstrukturer har en relativ mængde på mindst 0,05 % af den samlede mængde af FSH’ets glycanstrukturer i det respektive præparat.
7. Rekombinant FSH-præparat ifølge et hvilket som helst af kravene 1 til 6, hvor glycolyseringsmønsteret omfatter følgende karakteristika: (i) en relativ mængde af glycaner, der bærer N-acetylglucosamin af bisecting-typen (bisGlcNAc) i intervallet fra ca. 25 % til ca. 50 %; (ii) en relativ mængde af mindst tetraantennære glycaner på mindst 16 %; (iii) en relativ mængde af glycaner, der bærer fucose på mindst 35 %; (iv) en relativ mængde af 2,6-koblet sialsyre i intervallet fra ca. 53 % til ca. 99 %; og (v) en relativ mængde af glycaner, der bærer én eller flere sialsyrerester på mindst 88 %.
8. Rekombinant FSH-præparat ifølge et hvilket som helst af kravene 1 til 7, hvor FSH’et (i) er i stand til at stimulere frigivelsen af progesteron i granulosaceller (a) ved koncentrationer, hvor der ikke kan detekteres frigivelse af cAMP over cAMP-frigivelsen i fravær af FSH; og/eller (b) ved at inducere en signaltransduktionsvej, der er uafhængig af cAMP-signalering; og/eller (ii) er i stand til at stimulere eller co-stimulere kimcellemodning ved en biologisk fremgangsmåde, der er uafhængig af cAMP-signalering; og/eller (iii) har ét eller flere af følgende karakteristika, som kan bestemmes i et granulosecelleassay (a) det er i stand til at stimulere frigivelsen af progesteron i granuloseceller i koncentrationer, der er under den minimale koncentration, der er nødvendig for induktion af cAMP-frigivelse via granulosecellerne; (b) det er i stand til at stimulere frigivelsen af mindst 200 ng/ml progesteron i ca. 5xl04 til ca. lxlO5 granulosaceller/ml i FSH-koncentrationer, der ikke inducerer en cAMP-frigivelse, eller som inducerer en cAMP-frigivelse på mindre end 10 pmol/ml; (c) det er i stand til at stimulere frigivelsen af mindst 100 ng/ml progesteron i ca. 5xl04 til ca. lxlO5 granulosaceller/ml ved en koncentration, der er lavere end koncentrationen, der er krævet af humant urinært FSH eller rekombinant FSH fremstillet i CHO-celler (Gonal F); og/eller (d) det er i stand til at stimulere frigivelsen af mindst 100 ng/ml progesteron i ca. 5xl04 til ca. lxlO5 granulosaceller/ml ved en koncentration, hvor humant urinært FSH eller rekombinant FSH, der er fremstillet i CHO-celler (Gonal F), ikke resulterer i en tilsvarende frigivelse af progesteron; og/eller (iv) det er i stand til at frembringe follikelvækst hos en kvinde efter administration af en enkelt dosis, hvor dosen fortrinsvis omfatter 25 til 500 IU FSH og fortrinsvis er egnet til parenteral administration, navnlig ved subkutan injektion.
9. Farmaceutisk sammensætning, der omfatter rekombinant FSH-præparat ifølge et hvilket som helst af kravene 1 til 8.
10. Farmaceutisk sammensætning ifølge krav 9, hvilken sammensætning er i form af en enkelt enhedsdosis, der omfatter ca. 50 IFF til ca. 400 IFF FSH, navnlig ca. 100 IU til ca. 300 IU FSH.
11. Rekombinant FSH-præparat ifølge et hvilket som helst af kravene 1 til 8 eller farmaceutisk sammensætning ifølge krav 9 eller 10 til anvendelse til fertilitetsbehandling.
12. Rekombinant FSH-præparat eller farmaceutisk sammensætning til anvendelse ifølge krav 11, hvor dosen, der skal administreres til patienten, resulterer i en FSH-koncentration i kredsløbet hos patienten, der ligger i området på ca. 0,05 til ca. 2 IU/L, fortrinsvis ca. 0,1 til ca. 1 IU/L.
13. Rekombinant FSH-præparat ifølge et hvilket som helst af kravene 1 til 8 eller farmaceutisk sammensætning ifølge krav 9 eller 10 til anvendelse i medicin, hvor den medicinske anvendelse omfatter (i) induktion og/eller stimulering af sekretion af kønssteroider ligeledes uafhængig af cAMP; eller (ii) stimulering eller co-stimulering af kimcellemodning ved hjælp af en biologisk fremgangsmåde, der er uafhængig af cAMP-signalering; og (iii) induktion og/eller stimulering af sekretionen af kønssteroider ved FSH- koncentrationer, hvor der ikke induceres detekterbar frigivelse af cAMP over cAMP-frigivelsen i fravær af FSH.
14. Rekombinant FSFFpræparat eller farmaceutisk sammensætning ifølge et hvilket som helst af kravene 11 til 13 til anvendelse til fertilitetsbehandling, hvor fertilitetsbehandlingen indbefatter assisterede reproduktive teknologier, induktion af ægløsning, in-vitro befrugtning, for eksempel in-vitro befrugtning med intracytoplasmatisk sperminjektion, gamete intrafallopian transfer, intrauterin insemination, behandling af anovulatorisk funktionsforstyrrelse hos kvinder, behandling af svær hormonmangelforstyrrelse for ægmodning hos kvinder, behandling af manglende spermproduktion hos mænd og/eller muliggørelse eller forbedring af kimcellemodning, såsom follikulogenese og spermatogenese, navnlig follikelmodning hos kvinder, for eksempel i løbet af in-vitro fertiliseringsstimuleringsprotokoller og/eller til behandling af anovulatorisk forstyrrelse.
15. Rekombinant FSH-præparat eller farmaceutisk sammensætning til anvendelse ifølge et hvilket som helst af kravene 11 til 14, hvor det rekombinante FSH-præparat eller den farmaceutiske sammensætning har ét eller flere af følgende karakteristika: (i) det/den er i stand til at inducere follikelvækst og/eller modning af æg efter administration af blot en enkelt dosis; og/eller (ii) det/den har en lavere halveringstid i kredsløb hos et eller flere mennesker, cynomolgus-aber, rotter og/eller mus end FSH-præparater opnået fra menneskelig urin og/eller udtrykt i CHO-celler; og/eller (iii) det/den har en lavere biotilgængelighed hos ét eller flere mennesker, cynomolgus-aber, rotter og/eller mus end FSH-præparater opnået fra human urin og/eller udtrykt i CHO-celler; og/eller (iv) det/den har en terapeutisk effekt hos ét eller flere mennesker, cynomolgus-aber, rotter og/eller mus, der er lig med eller højere end FSH-præparatets opnået fra human urin og/eller udtrykt i CHO-celler.
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| PCT/EP2010/004769 WO2012016576A1 (en) | 2010-08-04 | 2010-08-04 | Improved recombinant human follicle-stimulating hormone |
| PCT/EP2011/063492 WO2012017058A1 (en) | 2010-08-04 | 2011-08-04 | Improved recombinant human follicle-stimulating hormone |
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| WO2012016576A1 (en) | 2010-08-04 | 2012-02-09 | Glycotope Gmbh | Improved recombinant human follicle-stimulating hormone |
| EP2717904A1 (en) | 2011-06-06 | 2014-04-16 | Ferring BV | Pharmaceutical preparation comprising recombinant fsh |
| JO3092B1 (ar) | 2011-08-08 | 2017-03-15 | Ferring Bv | مركب لتحفيز مسيطر عليه للمبيض |
| RS58881B1 (sr) * | 2012-07-30 | 2019-08-30 | Trophogen Inc | Dugodelujući superagonisti glikoproteinskih hormona |
| CN104543416B (zh) * | 2013-10-09 | 2018-06-19 | 中国科学院大连化学物理研究所 | 一种调节雌性动物繁殖性能的功能性单糖饲料及其应用 |
| CN103740754B (zh) * | 2013-10-25 | 2015-06-24 | 中国食品药品检定研究院 | 含有鼠神经生长因子的表达载体及细胞 |
| BR112016023668A2 (pt) | 2014-04-18 | 2017-10-17 | Glycotope Gmbh | hiperestimulação ovariana controlada com hormônio de estimulação de folículo humano recombinante aperfeiçoado |
| EP3091033A1 (en) * | 2015-05-06 | 2016-11-09 | Gamamabs Pharma | Anti-human-her3 antibodies and uses thereof |
| WO2017025566A1 (en) * | 2015-08-10 | 2017-02-16 | Glycotope Gmbh | Improved recombinant factor vii |
| EA201890163A1 (ru) * | 2015-09-17 | 2018-10-31 | Гликотоп Гмбх | Композиция фолликулостимулирующего гормона млекопитающего с повышенной стабильностью |
| CN106053861A (zh) * | 2016-07-28 | 2016-10-26 | 高常青 | 一种卵泡刺激素生物活性强度检测方法 |
| EP4055038A4 (en) * | 2019-11-06 | 2023-11-15 | The Regents of the University of Colorado, a body corporate | MODIFIED FOLLICLE-STIMULATING HORMONE AND METHOD OF USE THEREOF |
| CN115433276B (zh) * | 2021-09-07 | 2024-04-02 | 苏州晟济药业有限公司 | 一种vhh抗体或其抗原片段的突变体及其应用 |
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| WO2024100549A1 (en) * | 2022-11-08 | 2024-05-16 | Oncogreen Therapeutics S.A. | Compounds for use in macrophage reprogramming |
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| RS32804A (en) * | 2001-10-22 | 2007-02-05 | Applied Research Systems Ars Holding N.V., | Gonadotrophins for folliculogenesis |
| JP4913604B2 (ja) * | 2004-02-13 | 2012-04-11 | グリコトープ ゲーエムベーハー | 高活性糖タンパク質−製造条件、及びその効率的製造方法 |
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| GB2459641B (en) * | 2008-04-16 | 2012-06-27 | Ubiquisys Ltd | Basestation power control |
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| WO2012016576A1 (en) | 2010-08-04 | 2012-02-09 | Glycotope Gmbh | Improved recombinant human follicle-stimulating hormone |
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- 2011-08-04 EA EA201390194A patent/EA029955B1/ru not_active IP Right Cessation
- 2011-08-04 EP EP11757190.1A patent/EP2601210B1/en not_active Revoked
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- 2011-08-04 JP JP2013522259A patent/JP6001534B2/ja not_active Expired - Fee Related
- 2011-08-04 SG SG2012093191A patent/SG186755A1/en unknown
- 2011-08-04 WO PCT/EP2011/063492 patent/WO2012017058A1/en active Application Filing
- 2011-08-04 SI SI201130854A patent/SI2601210T1/sl unknown
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- 2011-08-04 ES ES11757190.1T patent/ES2576868T3/es active Active
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- 2011-08-04 CN CN201180037096.3A patent/CN103068839B/zh active Active
- 2011-08-04 PL PL11757190.1T patent/PL2601210T3/pl unknown
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- 2011-08-04 KR KR1020137005553A patent/KR20130136448A/ko not_active Application Discontinuation
- 2011-08-04 DK DK11757190.1T patent/DK2601210T3/da active
- 2011-08-04 US US13/814,059 patent/US9527899B2/en active Active
- 2011-08-04 EP EP16168841.1A patent/EP3075744B1/en not_active Revoked
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2012
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2013
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2016
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- 2016-06-24 JP JP2016125181A patent/JP2016168055A/ja not_active Withdrawn
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