	US 11,807,674 B2
	Hepcidin analogues and uses thereof
Mark Leslie Smythe, Bardon (AU); Gregory Thomas Bourne, Brisbane (AU); Simone Vink, Taringa (AU); Brian Troy Frederick, Ben Lomand, CA (US); Praveen Madala, Brisbane (AU); Anne Pernille Tofteng Shelton, Valby (DK); and Jacob Ulrik Fog, Bagsvaerd (DK)
Assigned to Protagonist Therapeutics, Inc., Newark, CA (US)
Filed by Protagonist Therapeutics, Inc., Newark, CA (US)
Filed on Nov. 16, 2020, as Appl. No. 17/099,308.
Application 17/099,308 is a continuation of application No. 16/839,368, filed on Apr. 3, 2020, abandoned.
Application 16/839,368 is a continuation of application No. 16/553,486, filed on Aug. 28, 2019, abandoned.
Application 16/553,486 is a continuation of application No. 16/289,451, filed on Feb. 28, 2019, granted, now 10,501,515, issued on Dec. 10, 2019.
Application 16/289,451 is a continuation of application No. 16/037,982, filed on Jul. 17, 2018, granted, now 10,442,846, issued on Oct. 15, 2019.
Application 16/037,982 is a continuation of application No. 15/828,214, filed on Nov. 30, 2017, granted, now 10,030,061, issued on Jul. 24, 2018.
Application 15/828,214 is a continuation of application No. 15/720,333, filed on Sep. 29, 2017, abandoned.
Application 15/720,333 is a continuation of application No. 14/775,469, granted, now 9,822,157, issued on Nov. 21, 2017, previously published as PCT/US2014/030352, filed on Mar. 17, 2014.
Claims priority of provisional application 61/800,284, filed on Mar. 15, 2013.
Claims priority of provisional application 61/800,048, filed on Mar. 15, 2013.
Prior Publication US 2022/0348626 A1, Nov. 3, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 38/10 (2006.01); A61K 38/08 (2019.01); A61K 38/04 (2006.01); C07K 5/00 (2006.01); C07K 7/00 (2006.01); C07K 16/00 (2006.01); C07K 17/00 (2006.01); C07K 14/575 (2006.01); A61K 38/00 (2006.01)

CPC C07K 14/575 (2013.01) [A61K 38/00 (2013.01)]

4 Claims

1. A method of treating a disease of iron metabolism in a subject, comprising administering to the subject in need thereof an effective amount of at least one peptide according to formula I′:

R1′—X′—Y′—R2′ (I′)(SEQ ID NO:21)

or a pharmaceutically acceptable salt thereof, wherein

R1′ is hydrogen, a C1-C6 alkyl, a C6-C12 aryl, a C1-C20 alkanoyl or pGlu;

R2′ is —NH₂or —OH;

X′ is a peptide sequence having the formula Ia′

X1-X2-X3-X4-X5-X6-X7-X8-X9-X10 (Ia′)(SEQ ID NO:13)

wherein

X1 is Asp, Ida, pGlu, bhAsp, or absent;

X2 is Thr;

X3 is His;

X4 is Phe or Dpa;

X5 is Pro or bhPro;

X6 is Ile, Cys, or Arg;

X7 is Cys, Ile, Leu, Val, Phe, D-Ile or D-Cys;

X8 is Ile, Arg, Phe, Gln, Lys, or Glu;

X9 is Phe; and

X10 is Lys or absent;

and

Y′ is a peptide sequence having the formula IIa′

Y1-Y2-Y3-Y4-Y5-Y6-Y7-Y8-Y9-Y10-Y11-Y12-Y13-Y14-Y15 (IIa′)(SEQ ID NO:16)

wherein

Y1 is Gly or Val;

Y2 is Pro, Ala, Cys, Gly, or absent;

Y3 is Arg, Lys, Pro, Gly, Ala, Trp, or absent;

Y4 is Ser, Arg, Gly, Trp, Ala, His, Tyr, or absent;

Y5 is Lys, Met, Arg, Ala, or absent;

Y6 is Gly, Ser, Lys, Ile, Ala, or absent;

Y7 is Trp, Lys, Gly, Ala, Ile, or absent;

Y8 is Val, Thr, Ala, Glu, Lys, or absent;

Y9 is Cys, Tyr, or absent;

Y10 is Met, Lys, Tyr, or absent;

Y11 is Arg, Met, Cys, Lys, or absent;

Y12 is Arg, Ala, or absent;

Y13 is Cys, Val, or absent;

Y14 is Arg, Cys, Thr, or absent; and

Y15 is Thr, Arg, or absent;

wherein the peptide of formula I′ comprises two cysteine residues linked via a disulfide bond, wherein the peptide is optionally PEGylated on R1′, X′, or Y′;

wherein a side chain of an amino acid of the peptide is optionally conjugated to a lipophilic substituent or a polymeric moiety; and

wherein the disease of iron metabolism is selected from the group consisting of hereditary hemochromatosis, iron hemochromatosis, human factors engineering (HFE) mutation hemochromatosis, ferroportin mutation hemochromatosis, transferrin receptor 2 mutation hemochromatosis, hemojuvelin mutation hemochromatosis, hepcidin mutation hemochromatosis, juvenile hemochromatosis, neonatal hemochromatosis, hepcidin deficiency, transfusional iron overload, and thalassemia.