IP Library › Granted Patent US 10,501,515
Granted Patent B2
US 10,501,515 · App. 16/289,451 · Granted Dec 10, 2019

Hepcidin analogues and uses thereof

Inventors: Mark Leslie Smythe (Bardon, AU); Gregory Thomas Bourne (Brisbane, AU); Simone Vink (Taringa, AU); Brian Troy Frederick (Ben Lomand, CA); Praveen Madala (Brisbane, AU); Anne Pernille Tofteng Shelton (Valby, DK); Jacob Ulrik Fog (Bagsvaerd, DK)
Assignee: Protagonist Therapeutics, Inc.
C07K14/575A61K38/00
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Quick Facts
Patent No.
US 10,501,515
App. No.
16/289,451
Granted
Dec 10, 2019
Kind
B2
Abstract

The present invention relates, inter alia, to certain hepcidin peptide analogues, including peptides and dimers thereof, and to the use of the peptides and peptide dimers in the treatment and/or prevention of a variety of diseases, conditions or disorders, including treatment and/or prevention of iron overload diseases, which include hereditary hemochromatosis and iron-loading anemias, and other conditions and disorders described herein.

Claims (344)

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

(I′)

(SEQ ID NO: 21)

R1′-X′-Y′-R2′

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 —NH 2 or —OH;

X′ is a peptide sequence having the formula Ia′

(Ia′)

(SEQ ID NO: 13)

X1-X2-X3-X4-X5-X6-X7-X8-X9-X10

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, IIe, Leu, or Val;

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

X9 is Phe or bhPhe; and

X10 is Lys, Phe or absent;

wherein if Y′ is absent, X7 is Ile; and

Y′ is a peptide sequence having the formula IIa′

(IIa′)

(SEQ ID NO: 16)

Y1-Y2-Y3-Y4-Y5-Y6-Y7-Y8-Y9-Y10-Y11-Y12-Y13-Y14-Y15

wherein

Y1 is Gly, Cys, Ala, Phe, Pro, Glu, Lys, D-Pro, Val, Ser or absent;

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

Y3 is Arg, Lys, Pro, Gly, His, 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, IIe, Ala, Pro, Val or absent;

Y7 is Trp, Lys, Gly, Ala, IIe, Val or absent;

Y8 is Val, Thr, Gly, Cys, Met, Tyr, Ala, Glu, Lys, Asp, Arg or absent;

Y9 is Cys, Tyr or absent;

Y10 is Met, Lys, Arg, Tyr or absent;

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

Y12 is Arg, Lys, Ala or absent;

Y13 is Arg, Cys, Lys, Val or absent;

Y14 is Arg, Lys, Pro, 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 hereditary hemochromatosis, iron hemochromatosis, HFE (human factors engineering) mutation hemochromatosis, hepcidin deficiency, transfusional iron overload, or thalassemia.

2. The method of claim 1 , wherein the peptide of Formula I′ is PEGylated on R1′, X′, or Y′, or wherein a side chain of an amino acid of the peptide of Formula I′ is conjugated to a lipophilic substituent or a polymeric moiety.

3. The method of claim 1 , wherein R1′ is hydrogen, isovaleric acid, isobutyric acid or acetyl.

4. The method of claim 1 , wherein X′ is a peptide sequence having formula Ib′

(Ib′)

(SEQ ID NO: 14)

X1-Thr-His-X4-X5-X6-X7-X8-Phe-X10

wherein

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

X4 is Phe or Dpa;

X5 is Pro or bhPro;

X6 is Ile, Cys or Arg;

X7 is Cys, IIe, Leu or Val;

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

X10 is Lys or absent;

or having formula Ic′

(Ic′)

(SEQ ID NO: 15)

X1-Thr-His-X4-X5-Cys-I1e-X8-Phe-X10

wherein

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

X4 is Phe or Dpa;

X5 is Pro or bhPro;

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

X10 is Lys or absent.

5. The method of claim 1 , wherein X1 is Asp, X4 is Phe, and X5 is Pro.

6. The method of claim 1 , wherein the peptide of Formula I′ comprises one of the following sequences:

(SEQ ID NO: 29)

DTHFPICIFGPRSKGWVC;

(SEQ ID NO: 38)

DTHFPCIIFGPRSKGWVCK;

(SEQ ID NO: 128)

DTHFPCIIFEPRSKGWVCK;

(SEQ ID NO: 164)

DTHFPCIIFGPRSKGWACK;

(SEQ ID NO: 168)

DTHFPCIIFGPRSKGWVCKK;

(SEQ ID NO: 57

DTHFPCIIFVCHRPKGCYRRVCR;

(SEQ ID NO: 125)

DTHFPCIKFGPRSKGWVCK;

(SEQ ID NO: 173)

DTHFPCIKFKPRSKGWVCK;

(SEQ ID NO: 106)

DTHFPCIIFGPRSRGWVCK;

(SEQ ID NO: 135)

DTHFPCIKFGPKSKGWVCK;

(SEQ ID NO: 207)

DTHFPCIKFEPRSKGCK;

(SEQ ID NO: 265)

DTHFPCIKFEPKSKGWECK;

(SEQ ID NO: 245)

DTHFPCIKFEPRSKKCK;

(SEQ ID NO: 247)

DTHFPCIKFEPRSKGCKK;

(SEQ ID NO: 249)

DTHFPCIKFKPRSKGCK;

or

(SEQ ID NO: 250)

DTHFPCIKFEPKSKGCK,

or a pharmaceutically acceptable salt thereof.

7. The method of claim 1 , wherein the peptide of Formula I′ comprises one of the following sequences:

(SEQ ID NO: 29)

Isovaleric acid-DTHFPICIFGPRSKGWVC-NH 2 ;

(SEQ ID NO: 38)

Isovaleric acid-DTHFPCIIFGPRSKGWVCK-NH 2 ;

(SEQ ID NO: 128)

Isovaleric acid-DTHFPCIIFEPRSKGWVCK-NH 2 ;

(SEQ ID NO: 164)

Isovaleric acid-DTHFPCIIFGPRSKGWACK-NH 2 ;

(SEQ ID NO: 168)

Isovaleric acid-DTHFPCIIFGPRSKGWVCKK-NH 2 ;

(SEQ ID NO: 57)

Isovaleric acid-DTHFPCIIFVCHRPKGCYRRVCR-NH 2 ;

(SEQ ID NO: 172)

Isovaleric acid-DTHFPCI(K(PEG8))FGPRSKGWVCK-NH 2 ;

(SEQ ID NO: 173)

Isovaleric acid-DTHFPCIKF(K(PEG8))PRSKGWVCK-NH 2 ;

(SEQ ID NO: 199)

Isovaleric acid-DTHFPICIFGPRS(K(PEG8))GWVCNH 2 ;

(SEQ ID NO: 200)

Isovaleric acid-DTHFPICIFGPRS(K(PEG4))GWVCNH 2 ;

(SEQ ID NO: 201)

Isovaleric acid-DTHFPCIIFGPRSRGWVC(K(PEG8))-NH 2 ;

(SEQ ID NO: 202)

Isovaleric acid-DTHFPCIIFGPRSRGWVC(K(PEG4))-NH 2 ;

(SEQ ID NO: 203)

Isovaleric acid-DTHFPCIIFGPRSRGWVC(K(PEG2))-NH 2 ;

(SEQ ID NO: 183)

Isovaleric acid-DTHFPCI(K(Palm))FGPRSKGWVCK-NH 2 ;

(SEQ ID NO: 217)

Isovaleric acid-DTHFPCIKF)K(Palm))PRSKGWVCK-NH 2 ;

(SEQ ID NO: 219)

Isovaleric acid-DTHFPCIKFGP(K(Palm))SKGWVCK-NH 2 ;

(SEQ ID NO: 220)

Isovaleric acid-DTHFPCIKFGPRS(K(Palm))GWVCK-NH2;

(SEQ ID NO: 221)

Isovaleric acid-DTHFPCIKFGPRSKGWVC(K(Palm))-NH 2 ;

(SEQ ID NO: 222)

Isovaleric acid-DTHFPCI(K(PEG3-Palm))FGPRSKGWVCK-

NH 2 ;

(SEQ ID NO: 223)

Isovaleric acid-DTHFPCIKF(K(PEG3-Palm))PRSKGWVCK-

NH 2 ;

(SEQ ID NO: 224)

Isovaleric acid-DTHFPCIKFGP(K(PEG3-Palm))SKGWVCK-

NH 2 ;

(SEQ ID NO: 225)

Isovaleric acid-DTHFPCIKFGPRS(K(PEG3-Palm))GWVCK-

NH 2 ;

(SEQ ID NO: 226)

Isovaleric acid-DTHFPCIKFGPRSKGWVC(K(PEG3-Palm))-

NH 2 ;

(SEQ ID NO: 176)

Isovaleric acid-DTHFPCIKFGPRSKGWVC(K(PEG8))-NH 2 ;

(SEQ ID NO: 241)

Isovaleric acid-DTHFPCI(K(isoGlu-Palm))FEPRSKGCK-

NH 2 ;

(SEQ ID NO: 242)

Isovaleric acid-DTHFPCIKF-K(isoGlu-Palm)-PRSKGCK-

NH 2 ;

(SEQ ID NO: 243)

Isovaleric acid-DTHFPCIKFEP(K(isoGlu-Palm))SKGCK-

NH 2 ;

(SEQ ID NO: 265)

Isovaleric acid-DTHFPCIKFEP(K(isoGlu-Palm))SKGWECK-

NH 2 ;

(SEQ ID NO: 244)

Isovaleric acid-DTHFPCIKFEPRS(K(isoGlu-Palm))GCK-

NH 2 ;

(SEQ ID NO: 245)

Isovaleric acid-DTHFPCIKFEPRSK(K(isoGlu-Palm))CK-

NH 2 ;

(SEQ ID NO: 246)

Isovaleric acid-DTHFPCIKFEPRSKGCK(K(isoGlu-Palm))-

NH 2 ;

(SEQ ID NO: 248)

Isovaleric acid-DTHFPCI-K(Dapa-Palm)-FEPRSKGCK-NH 2 ;

(SEQ ID NO: 249)

Isovaleric acid-DTHFPCIK(F(Dapa-Palm))PRSKGCK-NH 2 ;

(SEQ ID NO: 250)

Isovaleric acid-DTHFPCIKFEP(K(Dapa-Palm))SKGCK-NH 2 ;

(SEQ ID NO: 251)

Isovaleric acid-DTHFPCIKFEPRS(K(Dapa-Palm))GCK-NH 2 ;

(SEQ ID NO: 252)

Isovaleric acid-DTHFPCIKFEPRSK(K(Dapa-Palm))CK-NH 2 ;

(SEQ ID NO: 253)

Isovaleric acid-DTIFPCIKFEPRSKGC(K(Dapa-Palm))K-

NH 2 ;

or

(SEQ ID NO: 254)

Isovaleric acid-DTHFPCIKFEPRSKGC(K(Dapa-Palm))-NH 2 ,

or a pharmaceutically acceptable salt thereof, wherein the peptide of Formula I′ comprises two cysteine residues linked via a disulphide bond.

8. The method of claim 1 , wherein the peptide of formula I′ comprises one of the following sequences:

(SEQ ID NO: 29)

DTHFPICIFGPRSKGWVC;

(SEQ ID NO: 38)

DTHFPCIIFGPRSKGWVCK;

(SEQ ID NO: 128)

DTHFPCIIFEPRSKGWVCK;

(SEQ ID NO: 164)

DTHFPCIIFGPRSKGWACK;

(SEQ ID NO: 168)

DTHFPCIIFGPRSKGWVCKK;

(SEQ ID NO: 57

DTHFPCIIFVCHRPKGCYRRVCR;

(SEQ ID NO: 125)

DTHFPCIKFGPRSKGWVCK;

(SEQ ID NO: 173)

DTHFPCIKFKPRSKGWVCK;

(SEQ ID NO: 106)

DTHFPCIIFGPRSRGWVCK;

(SEQ ID NO: 135)

DTHFPCIKFGPKSKGWVCK;

(SEQ ID NO: 207)

DTHFPCIKFEPRSKGCK;

(SEQ ID NO: 265)

DTHFPCIKFEPKSKGWECK;

(SEQ ID NO: 245)

DTHFPCIKFEPRSKKCK;

(SEQ ID NO: 247)

DTHFPCIKFEPRSKGCKK;

(SEQ ID NO: 249)

DTHFPCIKFKPRSKGCK;

or

(SEQ ID NO: 250)

DTHFPCIKFEPKSKGCK.

9. The method of claim 1 , wherein the peptide comprises one of the following sequences:

(SEQ ID NO: 29)

Isovaleric acid-DTHFPICIFGPRSKGWVC-NH 2 ;

(SEQ ID NO: 38)

Isovaleric acid-DTHFPCIIFGPRSKGWVCK-NH 2 ;

(SEQ ID NO: 128)

Isovaleric acid-DTHFPCIIFEPRSKGWVCK-NH 2 ;

(SEQ ID NO: 164)

Isovaleric acid-DTHFPCIIFGPRSKGWACK-NH 2 ;

(SEQ ID NO: 168)

Isovaleric acid-DTHFPCIIFGPRSKGWVCKK-NH 2 ;

(SEQ ID NO: 57)

Isovaleric acid-DTHFPCIIFVCHRPKGCYRRVCR-NH 2 ;

(SEQ ID NO: 172)

Isovaleric acid-DTHFPCI(K(PEG8))FGPRSKGWVCK-NH 2 ;

(SEQ ID NO: 173)

Isovaleric acid-DTHFPCIKF(K(PEG8))PRSKGWVCK-NH 2 ;

(SEQ ID NO: 199)

Isovaleric acid-DTHFPICIFGPRS(K(PEG8))GWVCNH 2 ;

(SEQ ID NO: 200)

Isovaleric acid-DTHFPICIFGPRS(K(PEG4))GWVCNH 2 ;

(SEQ ID NO: 201)

Isovaleric acid-DTHFPCIIFGPRSRGWVC(K(PEG8))-NH 2 ;

(SEQ ID NO: 202)

Isovaleric acid-DTHFPCIIFGPRSRGWVC(K(PEG4))-NH 2 ;

(SEQ ID NO: 203)

Isovaleric acid-DTHFPCIIFGPRSRGWVC(K(PEG2))-NH 2 ;

(SEQ ID NO: 183)

Isovaleric acid-DTHFPCI(K(Palm))FGPRSKGWVCK-NH 2 ;

(SEQ ID NO: 217)

Isovaleric acid-DTHFPCIKF)K(Palm))PRSKGWVCK-NH 2 ;

(SEQ ID NO: 219)

Isovaleric acid-DTHFPCIKFGP(K(Palm))SKGWVCK-NH 2 ;

(SEQ ID NO: 220)

Isovaleric acid-DTHFPCIKFGPRS(K(Palm))GWVCK-NH2;

(SEQ ID NO: 221)

Isovaleric acid-DTHFPCIKFGPRSKGWVC(K(Palm))-NH 2 ;

(SEQ ID NO: 222)

Isovaleric acid-DTHFPCI(K(PEG3-Palm))FGPRSKGWVCK-

NH 2 ;

(SEQ ID NO: 223)

Isovaleric acid-DTHFPCIKF(K(PEG3-Palm))PRSKGWVCK-

NH 2 ;

(SEQ ID NO: 224)

Isovaleric acid-DTHFPCIKFGP(K(PEG3-Palm))SKGWVCK-

NH 2 ;

(SEQ ID NO: 225)

Isovaleric acid-DTHFPCIKFGPRS(K(PEG3-Palm))GWVCK-

NH 2 ;

(SEQ ID NO: 226)

Isovaleric acid-DTHFPCIKFGPRSKGWVC(K(PEG3-Palm))-

NH 2 ;

(SEQ ID NO: 176)

Isovaleric acid-DTHFPCIKFGPRSKGWVC(K(PEG8))-NH 2 ;

(SEQ ID NO: 241)

Isovaleric acid-DTHFPCI(K(isoGlu-Palm))FEPRSKGCK-

NH 2 ;

(SEQ ID NO: 242)

Isovaleric acid-DTHFPCIKF-K(isoGlu-Palm)-PRSKGCK-

NH 2 ;

(SEQ ID NO: 243)

Isovaleric acid-DTHFPCIKFEP(K(isoGlu-Palm))SKGCK-

NH 2 ;

(SEQ ID NO: 265)

Isovaleric acid-DTHFPCIKFEP(K(isoGlu-Palm))SKGWECK-

NH 2 ;

(SEQ ID NO: 244)

Isovaleric acid-DTHFPCIKFEPRS(K(isoGlu-Palm))GCK-

NH 2 ;

(SEQ ID NO: 245)

Isovaleric acid-DTHFPCIKFEPRSK(K(isoGlu-Palm))CK-

NH 2 ;

(SEQ ID NO: 246)

Isovaleric acid-DTHFPCIKFEPRSKGCK(K(isoGlu-Palm))-

NH 2 ;

(SEQ ID NO: 248)

Isovaleric acid-DTHFPCI-K(Dapa-Palm)-FEPRSKGCK-NH 2 ;

(SEQ ID NO: 249)

Isovaleric acid-DTHFPCIK(F(Dapa-Palm))PRSKGCK-NH 2 ;

(SEQ ID NO: 250)

Isovaleric acid-DTHFPCIKFEP(K(Dapa-Palm))SKGCK-NH 2 ;

(SEQ ID NO: 251)

Isovaleric acid-DTHFPCIKFEPRS(K(Dapa-Palm))GCK-NH 2 ;

(SEQ ID NO: 252)

Isovaleric acid-DTHFPCIKFEPRSK(K(Dapa-Palm))CK-NH 2 ;

(SEQ ID NO: 253)

Isovaleric acid-DTIFPCIKFEPRSKGC(K(Dapa-Palm))K-

NH 2 ;

or

(SEQ ID NO: 254)

Isovaleric acid-DTHFPCIKFEPRSKGC(K(Dapa-Palm))-NH 2 ,

10. The method of claim 1 , wherein the disease of iron metabolism is hereditary hemochromatosis, iron hemochromatosis, HFE (human factors engineering) mutation hemochromatosis, hepcidin deficiency, transfusional iron overload, or thalassemia.

11. The method of claim 1 , wherein the disease of iron metabolism is hereditary hemochromatosis (HH).

12. The method of claim 1 , wherein the disease of iron metabolism is a thalassemia, optionally thalassemia intermedia, alpha thalassemia, or β-thalassemia.

13. The method of claim 12 , wherein the disease of iron metabolism is β-thalassemia.

14. The method of claim 1 , wherein the peptide of formula I′ is: Isovaleric acid-DTHFPCIIFGPRSKGWVCK-NH 2 (SEQ ID NO:38) or Isovaleric acid-DTHFPCIIFEPRSKGWVCK-NH 2 (SEQ ID NO:128).

15. The method of claim 1 , wherein the peptide of formula I′ is: Isovaleric acid-DTHFPCI(K(PEG8))FGPRSKGWVCK-NH 2 (SEQ ID NO:172) or Isovaleric acid-DTHFPCIKF(K(PEG8))PRSKGWVCK-NH 2 (SEQ ID NO:173).

16. The method of claim 1 , wherein the peptide of formula I′ is: Isovaleric acid-DTHFPCIIFGPRSRGWVC(K(PEG8))—NH 2 (SEQ ID NO:201).

17. The method of claim 1 , wherein the peptide of formula I′ is: Isovaleric acid-DTHFPCI(K(Palm))FGPRSKGWVCK-NH 2 (SEQ ID NO:183).

18. The method of claim 1 , wherein the peptide of formula I′ is: Isovaleric acid-DTHFPCIKF(K(Palm))PRSKGWVCK-NH 2 (SEQ ID NO:217).

19. The method of claim 1 , wherein the peptide of formula I′ is: Isovaleric acid-DTHFPCIKFGP(K(Palm))SKGWVCK-NH 2 (SEQ ID NO:219) or Isovaleric acid-DTHFPCIKFGPRSKGWVC(K(Palm))—NH 2 (SEQ ID NO:221).

20. The method of claim 1 , wherein the peptide of formula I′ is: Isovaleric acid-DTHFPCI(K(PEG3-Palm))FGPRSKGWVCK-NH 2 (SEQ ID NO:222).

21. The method of claim 1 , wherein the peptide of formula I′ is: Isovaleric acid-DTHFPCIKF(K(PEG3-Palm))PRSKGWVCK-NH 2 (SEQ ID NO:223).

22. The method of claim 1 , wherein the peptide of formula I′ is: Isovaleric acid-DTHFPCIKFGP(K(PEG3-Palm))SKGWVCK-NH 2 (SEQ ID NO:224).

23. The method of claim 1 , wherein the peptide of formula I′ is: Isovaleric acid-DTHFPCIKFGPRS(K(PEG3-Palm))GWVCK-NH 2 (SEQ ID NO:225) or Isovaleric acid-DTHFPCIKFGPRSKGWVC(K(PEG3-Palm))—NH 2 (SEQ ID NO:226).

24. The method of claim 1 , wherein the peptide of formula I′ is: Isovaleric acid-DTHFPCIKFGPRSKGWVC(K(PEG8))—NH 2 (SEQ ID NO:176).

25. The method of claim 1 , wherein the peptide of formula I′ is: Isovaleric acid-DTHFPCI(K(isoGlu-Palm))FEPRSKGCK-NH 2 (SEQ ID NO:241).

26. The method of claim 1 , wherein the peptide of formula I′ is: Isovaleric acid-DTHFPCIKF(K(isoGlu-Palm))PRSKGCK-NH 2 (SEQ ID NO:242).

27. The method of claim 1 , wherein the peptide of formula I′ is: Isovaleric acid-DTHFPCIKFEP(K(isoGlu-Palm))SKGCK-NH 2 (SEQ ID NO:243).

28. The method of claim 1 , wherein the peptide of formula I′ is: Isovaleric acid-DTHFPCIKFEPRS(K(isoGlu-Palm))GCK-NH 2 (SEQ ID NO:244).

29. The method of claim 1 , wherein the peptide of formula I′ is: Isovaleric acid-DTHFPCI(K(Dapa-Palm))FEPRSKGCK-NH 2 (SEQ ID NO:248).

30. The method of claim 1 , wherein the peptide of formula I′ is: Isovaleric acid-DTHFPCIKFEP(K(Dapa-Palm))SKGCK-NH 2 (SEQ ID NO:250).

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 3, 2019
From: TOFTENG SHELTON, ANNE PERNILLE; FOG, JACOB ULRIK
To: ZEALAND PHARMA A/S
Reel/Frame 049344/0108 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 3, 2019
From: SMYTHE, MARK LESLIE; BOURNE, GREGORY THOMAS; VINK, SIMONE; FREDERICK, BRIAN T.; MADALA, PRAVEEN
To: PROTAGONIST THERAPEUTICS, INC.
Reel/Frame 049344/0142 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 3, 2019
From: ZEALAND PHARMA A/S
To: PROTAGONIST THERAPEUTICS, INC.
Reel/Frame 049344/0167 →
Continuity (5)
Continuation 15720333 · Sep 29, 2017
Continuation 14775469
Provisional Application 61800048 · Mar 15, 2013
Provisional Application 61800284 · Mar 15, 2013
Related Publication 20190185536A1 · Jun 20, 2019
Cited By (6)
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