HRP20211448T1 - Alfa4beta7 integrin tioeter peptidni antagonisti - Google Patents

Alfa4beta7 integrin tioeter peptidni antagonisti Download PDF

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HRP20211448T1
HRP20211448T1 HRP20211448TT HRP20211448T HRP20211448T1 HR P20211448 T1 HRP20211448 T1 HR P20211448T1 HR P20211448T T HRP20211448T T HR P20211448TT HR P20211448 T HRP20211448 T HR P20211448T HR P20211448 T1 HRP20211448 T1 HR P20211448T1
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methylbenzoyl
pen
peptide
pharmaceutically acceptable
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HRP20211448TT
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Ashok Bhandari
Dinesh V. Patel
Genet Zemede
Brian Troy FREDERICK
Larry C. Mattheakis
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Protagonist Therapeutics, Inc.
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Publication of HRP20211448T1 publication Critical patent/HRP20211448T1/hr

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    • C07K7/50—Cyclic peptides containing at least one abnormal peptide link
    • C07K7/54—Cyclic peptides containing at least one abnormal peptide link with at least one abnormal peptide link in the ring
    • C07K7/56—Cyclic peptides containing at least one abnormal peptide link with at least one abnormal peptide link in the ring the cyclisation not occurring through 2,4-diamino-butanoic acid
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    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70546—Integrin superfamily
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    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
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Claims (15)

1. Molekula peptida ili njegova farmaceutski prihvatljiva sol, naznačena time što sadrži slijed odabran između sljedećih: (2-metilbenzoil)-(N-Me-Arg)-Ser-Asp-Thr-Leu-Pen-Trp-(β-homoGlu)-(D-Lys) (SEQ ID NO: 61); (2-metilbenzoil)-(N-Me-Arg)-Ser-Asp-Thr-Leu-Pen-Trp-Glu-(N-Me-Lys) (SEQ ID NO: 62); (2-metilbenzoil)-(N-Me-Arg)-Ser-Asp-Thr-Leu-Pen-2-Nal-(β-homoGlu)-(D-Lys) (SEQ ID NO: 70); (2-metilbenzoil)-(N-Me-Arg)-Ser-Asp-Thr-Leu-Pen-Phe (4-tBu)-(β-homoGlu)-(D-Lys) (SEQ ID NO: 270); (2-metilbenzoil)-(N-Me-Arg)-Ser-Asp-Thr-Leu-Pen-Phe (4-tBu)-(β-homoGlu)-(N-Me-Lys) (SEQ ID NO: 287); ili (2-metilbenzoil)-(N-Me-Arg)-Ser-Asp-Thr-Leu-Pen-Phe (4-tBu)-(β-homoGlu) (SEQ ID NO: 134), pri čemu molekula peptida sadrži tioetersku vezu između 2-metilbenzoila i Pena.
2. Molekula peptida ili njegova farmaceutski prihvatljiva sol prema zahtjevu 1, naznačena time što dalje sadrži terminalnu modifikacijsku skupinu odabranu iz skupine koju čine: DIG, PEG4, PEG13, PEG25, PEG1K, PEG2K, PEG4K, PEG5K, polietilen glikol molekulske mase od 400Da do 40.000Da, IDA, Ac-IDA, ADA, glutarinska kiselina, izoftalna kiselina, 1,3-fenilendioctena kiselina, 1,4-fenilendioctena kiselina, 1,2-fenilendioctena kiselina, AADA, prikladne alifatske kiseline, prikladne aromatske kiseline i heteroaromatske kiseline.
3. Molekula peptida ili njegova farmaceutski prihvatljiva sol, naznačena time, da je molekula peptida dimer koji sadrži dva peptidna monomera, pri čemu molekula peptida sadrži slijed ili strukturu odabranu od sljedećeg: ((2-metilbenzoil)-(N-Me-Arg)-Ser-Asp-Thr-Leu-Pen-Trp-(β-homoGlu)-(D-Lys) -NH2)2 (SEQ ID NO: 151); ((2-metilbenzoil)-(N-Me-Arg)-Ser-Asp-Thr-Leu-Pen-(2-Nal)-(β-homoGlu)-(D-Lys) -NH2)2 (SEQ ID NO : 161); ((2-metilbenzoil)-(N-Me-Arg)-Ser-Asp-Thr-Leu-Pen-Phe(4-tBu)-(β-homoGlu)-(D-Lys) -NH2)2(SEQ ID NO: 222); ((2-metilbenzoil)-(N-Me-Arg)-Ser-Asp-Thr-Leu-Pen-Phe(4-tBu)-(β-homoGlu)-(D-Lys) -OH)2 (SEQ ID NO: 223); ili ((2-metilbenzoil)-(N-Me-Arg)-Ser-Asp-Thr-Leu-Pen-Trp-Glu-(N-Me-D-Lys)-NH2)2 (SEQ ID NO: 152), pri čemu su dva peptidna monomera povezana DIG-om i svaki peptidni monomer sadrži tioetersku vezu između 2-metilbenzoila i Pena.
4. Molekula peptida ili njegova farmaceutski prihvatljiva sol prema zahtjevu 3, naznačena time da sadrži sljedeći slijed ili strukturu: ((2-metilbenzoil)-(N-Me-Arg)-Ser-Asp-Thr-Leu-Pen-Phe (4-tBu)-(β-homoGlu)-(D-Lys) -NH2)2 (SEQ ID NE: 222).
5. Molekula peptida ili njegova farmaceutski prihvatljiva sol prema zahtjevu 3, naznačena time što sadrži sljedeći slijed ili strukturu: ((2-metilbenzoil)-(N-Me-Arg)-Ser-Asp-Thr-Leu-Pen-Phe (4-tBu)-(β-homoGlu)-(D-Lys) -OH)2 (SEQ ID NE: 223).
6. Farmaceutski pripravak, naznačen time, da sadrži molekulu peptida ili njegovu farmaceutski prihvatljivu sol prema bilo kojem od zahtjeva 1-5, i farmaceutski prihvatljiv nosač, razrjeđivač ili pomoćnu tvar.
7. Farmaceutski pripravak prema zahtjevu 6, naznačen time što je molekula peptida ili njegova farmaceutski prihvatljiva sol dimer koji sadrži dva peptidna monomera, i gdje molekula peptida sadrži sljedeći slijed ili strukturu: ((2-metilbenzoil)-(N-Me-Arg)-Ser-Asp-Thr-Leu-Pen-Phe (4-tBu)-(β-homoGlu)-(D-Lys) -NH2)2 (SEQ ID NO: 222), gdje su dva peptidna monomera povezana DIG-om i svaki peptidni monomer sadrži tioetersku vezu između 2-metilbenzoila i Pena.
8. Farmaceutski pripravak prema zahtjevu 6, naznačen time što je molekula peptida ili njegova farmaceutski prihvatljiva sol dimer koji sadrži dva peptidna monomera, i gdje molekula peptida sadrži sljedeći slijed ili strukturu: ((2-metilbenzoil)-(N-Me-Arg)-Ser-Asp-Thr-Leu-Pen-Phe (4-tBu)-(β-homoGlu)-(D-Lys)-OH)2 (SEQ ID NO: 223), gdje su dva peptidna monomera povezana DIG-om i svaki peptidni monomer sadrži tioetersku vezu između 2-metilbenzoila i Pena.
9. Molekula peptida ili njegova farmaceutski prihvatljiva sol prema bilo kojem od zahtjeva 1-5 ili farmaceutski pripravak prema bilo kojem zahtjevu 6-8 za uporabu u liječenju ili sprječavanju bolesti ili stanja povezanih s biološkom funkcijom integrina α4β7 , pri čemu je bolest ili stanje odabrano iz skupine koju čine upalna bolest crijeva (IBD), IBD odraslih, IBD djece, IBD adolescenata, ulcerozni kolitis, Crohnova bolest, celijakija (nontropical Sprue), enteropatija povezana sa seronegativnim artropatijama, mikroskopski kolitis , kolagenski kolitis, eozinofilni gastroenteritis, radioterapija, kemoterapija, pouchitis nastao nakon proktokolektomije i ileoanalne anastomoze, rak probavnog sustava, pankreatitis, dijabetes melitus ovisan o inzulinu, mastitis, kolecistitis, holangitis, periholangitis, kronični bronhitis, kronični sinusitis, astma, primarna skleroza, infekcija virusom humane imunodeficijencije (HIV) u gastrointestinalnom traktu, eozinofilična astma, eozinofilni ezofagitis, gastritis, kolitis, mikroskopski kolitis i bolest transplantata protiv domaćina (GVDH).
10. Molekula peptida ili njegova farmaceutski prihvatljiva sol ili farmaceutski pripravak za uporabu prema zahtjevu 9, gdje molekula peptida ili njezina farmaceutski prihvatljiva sol dimer koji sadrži dva peptidna monomera, i gdje molekula peptida sadrži jednu od sljedećih sekvenci ili struktura: ((2-metilbenzoil)-(N-Me-Arg)-Ser-Asp-Thr-Leu-Pen-Phe (4-tBu)-(β-homoGlu)-(D-Lys) -NH2)2 (SEQ ID NO: 222); ili ((2-metilbenzoil)-(N-Me-Arg)-Ser-Asp-Thr-Leu-Pen-Phe (4-tBu)-(β-homoGlu)-(D-Lys) -OH)2 (SEQ ID NE: 223), pri čemu su dva peptidna monomera povezana DIG-om i svaki peptidni monomer sadrži tioetersku vezu između 2-metilbenzoila i Pena.
11. Molekula peptida ili njegova farmaceutski prihvatljiva sol ili farmaceutski pripravak za uporabu u skladu s bilo kojim od patentnih zahtjeva 9-10, gdje je bolest ili stanje upalna bolest crijeva.
12. Molekula peptida ili njegova farmaceutski prihvatljiva sol ili farmaceutski pripravak za uporabu prema zahtjevu 11, naznačena time što upalna bolest crijeva je Crohnova bolest ili ulcerozni kolitis.
13. Molekula peptida ili njegova farmaceutski prihvatljiva sol ili farmaceutski pripravak za uporabu prema zahtjevu 12, gdje je molekula peptida ili njegova farmaceutski prihvatljiva sol dimer koji sadrži dva peptidna monomera, i gdje molekula peptida sadrži jednu od sljedećih sekvenci ili struktura : ((2-metilbenzoil)-(N-Me-Arg)-Ser-Asp-Thr-Leu-Pen-Phe (4-tBu)-(β-homoGlu)-(D-Lys) -NH2)2 (SEQ ID NO: 222); ili ((2-metilbenzoil)-(N-Me-Arg)-Ser-Asp-Thr-Leu-Pen-Phe (4-tBu)-(β-homoGlu)-(D-Lys) -OH)2 (SEQ ID NE: 223), pri čemu su dva peptidna monomera povezana DIG-om i svaki peptidni monomer sadrži tioetersku vezu između 2-metilbenzoila i Pena.
14. Molekula peptida ili njegova farmaceutski prihvatljiva sol ili farmaceutski pripravak za uporabu u skladu s bilo kojim od patentnih zahtjeva 9-13, gdje se molekula peptida ili njegova farmaceutski prihvatljiva sol ili farmaceutski pripravak primjenjuju oralno, parenteralno ili lokalno.
15. Molekula peptida ili farmaceutski prihvatljiva sol za uporabu prema zahtjevu 14, naznačena time što se molekula peptida ili njegova farmaceutski prihvatljiva sol ili farmaceutski pripravak primjenjuju oralno.
HRP20211448TT 2014-05-16 2015-05-15 Alfa4beta7 integrin tioeter peptidni antagonisti HRP20211448T1 (hr)

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