IP Library › Granted Patent US 9,982,016

Granted Patent B2

US 9,982,016 · App. 15/645,680 · Granted May 29, 2018

NPR-B agonists

Inventors: Frank Osterkamp (Berlin, DE); Heiko Hawlisch (Berlin, DE); Gerd Hummel (Berlin, DE); Tobias Knaute (Berlin, DE); Ulf Reimer (Berlin, DE); Ulrich Reineke (Berlin, DE); Bernadett Simon (Bonn, DE); Uwe Richter (Berlin, DE); Edgar Specker (Berlin, DE); Markus Woischnik (Berlin, DE); Mark R. Hellberg (Arlington, TX)

Assignee: Shire Orphan Therapies GmbH

C07K7/06 C07K7/02 C07K7/08

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Quick Facts

Patent No.: US 9,982,016
App. No.: 15/645,680
Granted: May 29, 2018
Kind: B2

External Links

USPTO Patent Center↗ Full Patent PDF↗

Abstract

Disclosed are novel compounds having NPR-B agonistic activity. Preferred compounds are linear peptides containing 8-13 conventional or non-conventional L- or D-amino acid residues connected to one another via peptide bonds.

Claims (757)

1. A compound selected from:

(SEQ ID NO: 21)

Hex-Ser-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-Ser-

Ser-NH 2 ;

(SEQ ID NO: 23)

Hex-Ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-Ser-

Gly-NH 2 ;

(SEQ ID NO: 26)

Hex-Ebe-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-Ser-

NH 2 ;

(SEQ ID NO: 27)

Hex-Ebe-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 28)

Hex-Gab-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-Ser-Ebe-

NH 2 ;

(SEQ ID NO: 29)

Hex-Mam-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-Ser-Ebe-

NH 2 ;

(SEQ ID NO: 30)

Hex-Gly-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 31)

Hex-Ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 32)

Hex-Ser-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 33)

Hex-Pro-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 34)

Hex-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 35)

Hex-Gly-pro-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 36)

Hex-Ser-pro-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 37)

Hex-Mam-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 38)

Hex-Pam-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 39)

Hex-Mpe-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 40)

Hex-Ppe-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 41)

Hex-Inp-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 42)

Hex-Acp-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 43)

Hex-Fir-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 44)

Hex-Nip-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 45)

Hex-Eah-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 46)

Hex-Fio-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 47)

Hex-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Eca-NH 2 ;

(SEQ ID NO: 48)

1339-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 49)

Occ-pro-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 50)

1339-pro-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 51)

1320-pro-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 54)

1340-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 55)

Hex-Tnc-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 56)

Hex-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Chg-NH 2 ;

(SEQ ID NO: 58)

Occ-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 59)

Occ-thz-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 60)

Occ-aze-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 61)

Occ-Az3-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 63)

Occ-Rni-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 64)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-2137;

(SEQ ID NO: 65)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-3816;

(SEQ ID NO: 66)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-3806;

(SEQ ID NO: 69)

Occ-val-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 70)

Occ-tbg-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 71)

Occ-Amcp-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 72)

Occ-Ebc-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 73)

Occ-abu-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 74)

Occ-ser-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 75)

Occ-ala-ala-Phe-Gly-Leu-Lys-leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 76)

Occ-ala-ala-Phe-Gly-Leu-Lys-Ile-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 77)

Occ-ala-ala-Phe-Gly-Leu-Lys-Val-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 78)

Occ-ala-ala-Phe-Gly-Leu-Lys-Chg-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 79)

Occ-ala-ala-Phe-Gly-Leu-Lys-Nle-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 80)

Occ-ala-ala-Phe-Gly-Leu-Lys-Nml-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 83)

933-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 84)

1270-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 85)

4956-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 87)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-504;

(SEQ ID NO: 88)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-559;

(SEQ ID NO: 89)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-3791;

(SEQ ID NO: 91)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-1859;

(SEQ ID NO: 94)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-873;

(SEQ ID NO: 95)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-5116;

(SEQ ID NO: 97)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-5118;

(SEQ ID NO: 98)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-5163;

(SEQ ID NO: 99)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-5164;

(SEQ ID NO: 104)

Occ-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Che;

and

(SEQ ID NO: 105)

Occ-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-5121.

2. The compound of claim 1 , wherein the compound is selected from:

(SEQ ID NO: 47)

Hex-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Eca-NH 2 ;

(SEQ ID NO: 56)

Hex-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Chg-NH 2 ;

(SEQ ID NO: 64)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-2137;

(SEQ ID NO: 65)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-3816;

(SEQ ID NO: 66)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-3806;

(SEQ ID NO: 87)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-504;

(SEQ ID NO: 88)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-559;

(SEQ ID NO: 89)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-3791;

(SEQ ID NO: 91)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-1859;

(SEQ ID NO: 94)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-873;

(SEQ ID NO: 95)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-5116;

(SEQ ID NO: 97)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-5118;

(SEQ ID NO: 98)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-5163;

(SEQ ID NO: 99)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-5164;

(SEQ ID NO: 104)

Occ-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Che;

and

(SEQ ID NO: 105)

Occ-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-5121.

3. The compound of claim 1 , wherein the compound is selected from:

(SEQ ID NO: 21)

Hex-Ser-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-Ser-

Ser-NH 2 ;

(SEQ ID NO: 23)

Hex-Ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-Ser-

Gly-NH 2 ;

(SEQ ID NO: 26)

Hex-Ebe-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-Ser-

NH 2 ;

(SEQ ID NO: 27)

Hex-Ebe-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 28)

Hex-Gab-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-Ser-Ebe-

NH 2 ;

(SEQ ID NO: 29)

Hex-Mam-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-Ser-Ebe-

NH 2 ;

(SEQ ID NO: 30)

Hex-Gly-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 31)

Hex-Ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 32)

Hex-Ser-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 33)

Hex-Pro-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 34)

Hex-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 35)

Hex-Gly-pro-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 36)

Hex-Ser-pro-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 37)

Hex-Mam-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 38)

Hex-Pam-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 39)

Hex-Mpe-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 40)

Hex-Ppe-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 41)

Hex-Inp-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 42)

Hex-Acp-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 43)

Hex-Fir-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 44)

Hex-Nip-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 45)

Hex-Eah-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 46)

Hex-Fio-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 48)

1339-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 49)

Occ-pro-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 50)

1339-pro-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 51)

1320-pro-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 54)

1340-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 55)

Hex-Tnc-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 58)

Occ-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 59)

Occ-thz-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 60)

Occ-aze-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 61)

Occ-Az3-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 63)

Occ-Rni-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 69)

Occ-val-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 70)

Occ-tbg-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 71)

Occ-Amcp-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 72)

Occ-Ebc-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 73)

Occ-abu-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 74)

Occ-ser-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 75)

Occ-ala-ala-Phe-Gly-Leu-Lys-leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 83)

933-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 84)

1270-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

and

(SEQ ID NO: 85)

4956-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 .

4. The compound of claim 1 , wherein the compound is selected from:

(SEQ ID NO: 19)

Hex-Ebe-pro-Phe-Gly-Leu-Pro-Ile-Asp-Arg-Ile-Ser-

Ebe-NH 2 ;

(SEQ ID NO: 20)

Hex-Ebe-pro-Phe-Gly-Leu-Lys-Ile-Asp-Arg-Ile-Ser-

Ebe-NH 2 ;

(SEQ ID NO: 21)

Hex-Ser-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-Ser-

Ser-NH 2 ;

(SEQ ID NO: 23)

Hex-Ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-Ser-

Gly-NH 2 ;

(SEQ ID NO: 26)

Hex-Ebe-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-Ser-

NH 2 ;

(SEQ ID NO: 27)

Hex-Ebe-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 28)

Hex-Gab-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-Ser-Ebe-

NH 2 ;

(SEQ ID NO: 29)

Hex-Mam-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-Ser-Ebe-

NH 2 ;

(SEQ ID NO: 30)

Hex-Gly-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 31)

Hex-Ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 32)

Hex-Ser-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 33)

Hex-Pro-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 34)

Hex-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 35)

Hex-Gly-pro-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 36)

Hex-Ser-pro-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 37)

Hex-Mam-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 38)

Hex-Pam-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 39)

Hex-Mpe-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 40)

Hex-Ppe-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 41)

Hex-Inp-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 42)

Hex-Acp-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 43)

Hex-Fir-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 44)

Hex-Nip-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 45)

Hex-Eah-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 46)

Hex-Fio-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 47)

Hex-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Eca-NH 2 ;

(SEQ ID NO: 48)

1339-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 49)

Occ-pro-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 50)

1339-pro-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 51)

1320-pro-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 54)

1340-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 55)

Hex-Tnc-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 56)

Hex-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Chg-NH 2 ;

(SEQ ID NO: 57)

Hex-ala-ala-Phe-Paa-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 58)

Occ-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 59)

Occ-thz-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 60)

Occ-aze-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 61)

Occ-Az3-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 63)

Occ-Rni-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 64)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-2137;

(SEQ ID NO: 65)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-3816;

(SEQ ID NO: 66)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-3806;

(SEQ ID NO: 69)

Occ-val-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 70)

Occ-tbg-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 71)

Occ-Amcp-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 72)

Occ-Ebc-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 73)

Occ-abu-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 74)

Occ-ser-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 75)

Occ-ala-ala-Phe-Gly-Leu-Lys-leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 76)

Occ-ala-ala-Phe-Gly-Leu-Lys-Ile-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 77)

Occ-ala-ala-Phe-Gly-Leu-Lys-Val-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 78)

Occ-ala-ala-Phe-Gly-Leu-Lys-Chg-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 79)

Occ-ala-ala-Phe-Gly-Leu-Lys-Nle-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 80)

Occ-ala-ala-Phe-Gly-Leu-Lys-Nml-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 82)

Occ-ala-ala-Phe-Gly-Leu-Nmk-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 83)

933-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 84)

1270-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 85)

4956-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 87)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-504;

(SEQ ID NO: 88)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-559;

(SEQ ID NO: 89)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-3791;

(SEQ ID NO: 91)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-1859;

(SEQ ID NO: 94)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-873;

(SEQ ID NO: 95)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-5116;

(SEQ ID NO: 97)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-5118;

(SEQ ID NO: 98)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-5163;

(SEQ ID NO: 99)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-5164;

and

(SEQ ID NO: 100)

Occ-ala-Phe-Gly-Leu-Pro-Leu-Asp-Arg-Ile-NH 2 .

5. The compound of claim 4 , wherein the compound is selected from:

(SEQ ID NO: 21)

Hex-Ser-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-Ser-

Ser-NH 2 ;

(SEQ ID NO: 23)

Hex-Ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-Ser-

Gly-NH 2 ;

(SEQ ID NO: 26)

Hex-Ebe-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-

Ser-NH 2 ;

(SEQ ID NO: 27)

Hex-Ebe-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 28)

Hex-Gab-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-Ser-

Ebe-NH 2 ;

(SEQ ID NO: 29)

Hex-Mam-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-Ser-

Ebe-NH 2 ;

(SEQ ID NO: 30)

Hex-Gly-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 31)

Hex-Ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 32)

Hex-Ser-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 33)

Hex-Pro-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 34)

Hex-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 35)

Hex-Gly-pro-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 36)

Hex-Ser-pro-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 37)

Hex-Mam-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 38)

Hex-Pam-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 39)

Hex-Mpe-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 40)

Hex-Ppe-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 41)

Hex-Inp-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 42)

Hex-Acp-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 43)

Hex-Fir-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 44)

Hex-Nip-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 45)

Hex-Eah-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 46)

Hex-Fio-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 47)

Hex-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Eca-NH 2 ;

(SEQ ID NO: 48)

1339-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 49)

Occ-pro-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 50)

1339-pro-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 51)

1320-pro-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 54)

1340-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 55)

Hex-Tnc-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 56)

Hex-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Chg-NH 2 ;

(SEQ ID NO: 58)

Occ-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 59)

Occ-thz-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 60)

Occ-aze-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 61)

Occ-Az3-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 63)

Occ-Rni-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 64)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-2137;

(SEQ ID NO: 65)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-3816;

(SEQ ID NO: 66)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-3806;

(SEQ ID NO: 69)

Occ-val-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 70)

Occ-tbg-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 71)

Occ-Amcp-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 72)

Occ-Ebc-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 73)

Occ-abu-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 74)

Occ-ser-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 75)

Occ-ala-ala-Phe-Gly-Leu-Lys-leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 76)

Occ-ala-ala-Phe-Gly-Leu-Lys-Ile-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 77)

Occ-ala-ala-Phe-Gly-Leu-Lys-Val-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 78)

Occ-ala-ala-Phe-Gly-Leu-Lys-Chg-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 79)

Occ-ala-ala-Phe-Gly-Leu-Lys-Nle-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 80)

Occ-ala-ala-Phe-Gly-Leu-Lys-Nml-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 83)

933-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 84)

1270-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 85)

4956-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 87)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-504;

(SEQ ID NO: 88)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-559;

(SEQ ID NO: 89)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-3791;

(SEQ ID NO: 91)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-1859;

(SEQ ID NO: 94)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-873;

(SEQ ID NO: 95)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-5116;

(SEQ ID NO: 97)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-5118;

(SEQ ID NO: 98)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-5163;

and

(SEQ ID NO: 99)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-5164.

6. The compound of claim 4 , wherein the compound is selected from:

(SEQ ID NO: 47)

Hex-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Eca-NH 2 ;

(SEQ ID NO: 56)

Hex-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Chg-NH 2 ;

(SEQ ID NO: 64)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-2137;

(SEQ ID NO: 65)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-3816;

(SEQ ID NO: 66)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-3806;

(SEQ ID NO: 87)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-504;

(SEQ ID NO: 88)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-559;

(SEQ ID NO: 89)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-3791;

(SEQ ID NO: 91)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-1859;

(SEQ ID NO: 94)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-873;

(SEQ ID NO: 95)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-5116;

(SEQ ID NO: 97)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-5118;

(SEQ ID NO: 98)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-5163;

and

(SEQ ID NO: 99)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-5164.

7. The compound of claim 4 , wherein the compound is selected from:

(SEQ ID NO: 21)

Hex-Ser-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-Ser-

Ser-NH 2 ;

(SEQ ID NO: 23)

Hex-Ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-Ser-

Gly-NH 2 ;

(SEQ ID NO: 26)

Hex-Ebe-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-

Ser-NH 2 ;

(SEQ ID NO: 27)

Hex-Ebe-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 28)

Hex-Gab-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-Ser-

Ebe-NH 2 ;

(SEQ ID NO: 29)

Hex-Mam-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-Ser-

Ebe-NH 2 ;

(SEQ ID NO: 30)

Hex-Gly-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 31)

Hex-Ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 32)

Hex-Ser-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 33)

Hex-Pro-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 34)

Hex-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 35)

Hex-Gly-pro-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 36)

Hex-Ser-pro-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 37)

Hex-Mam-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 38)

Hex-Pam-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 39)

Hex-Mpe-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 40)

Hex-Ppe-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 41)

Hex-Inp-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 42)

Hex-Acp-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 43)

Hex-Fir-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 44)

Hex-Nip-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 45)

Hex-Eah-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 46)

Hex-Fio-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 48)

1339-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 49)

Occ-pro-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 50)

1339-pro-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 51)

1320-pro-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 54)

1340-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 55)

Hex-Tnc-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 58)

Occ-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 59)

Occ-thz-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 60)

Occ-aze-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 61)

Occ-Az3-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 63)

Occ-Rni-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 69)

Occ-val-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 70)

Occ-tbg-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 71)

Occ-Amcp-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 72)

Occ-Ebc-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 73)

Occ-abu-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 74)

Occ-ser-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 75)

Occ-ala-ala-Phe-Gly-Leu-Lys-leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 83)

933-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 84)

1270-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

and

(SEQ ID NO: 85)

4956-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 .

8. The compound of claim 4 , wherein the compound is selected from:

(SEQ ID NO: 30)

Hex-Gly-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 31)

Hex-Ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 32)

Hex-Ser-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 33)

Hex-Pro-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 34)

Hex-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 35)

Hex-Gly-pro-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 36)

Hex-Ser-pro-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 37)

Hex-Mam-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 38)

Hex-Pam-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 39)

Hex-Mpe-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 40)

Hex-Ppe-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 41)

Hex-Inp-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 42)

Hex-Acp-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 43)

Hex-Fir-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 44)

Hex-Nip-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 45)

Hex-Eah-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

and

(SEQ ID NO: 46)

Hex-Fio-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 .

9. The compound of claim 4 , wherein the compound is selected from:

(SEQ ID NO: 58)

Occ-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 59)

Occ-thz-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 60)

Occ-aze-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 61)

Occ-Az3-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 63)

Occ-Rni-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 64)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-2137;

(SEQ ID NO: 65)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-3816;

(SEQ ID NO: 66)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-3806;

(SEQ ID NO: 69)

Occ-val-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 70)

Occ-tbg-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 71)

Occ-Amcp-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 72)

Occ-Ebc-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

(SEQ ID NO: 73)

Occ-abu-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 ;

and

(SEQ ID NO: 74)

Occ-ser-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-NH 2 .

10. The compound of claim 4 , wherein the compound is selected from:

(SEQ ID NO: 87)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-504;

(SEQ ID NO: 88)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-559;

(SEQ ID NO: 89)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-3791;

(SEQ ID NO: 91)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-1859;

(SEQ ID NO: 94)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-873;

(SEQ ID NO: 95)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-5116;

(SEQ ID NO: 97)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-5118;

(SEQ ID NO: 98)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-5163;

(SEQ ID NO: 99)

Occ-ala-ala-Phe-Gly-Leu-Lys-Leu-Asp-Arg-5164;

and

(SEQ ID NO: 100)

Occ-ala-Phe-Gly-Leu-Pro-Leu-Asp-Arg-Ile-NH 2 .

Assignments (3)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 1, 2021

From: SHIRE ORPHAN THERAPIES GMBH

To: TAKEDA PHARMACEUTICAL COMPANY LIMITED

Reel/Frame 055105/0363 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 25, 2018

From: ALCON RESEARCH, LTD.

To: SHIRE ORPHAN THERAPIES GMBH

Reel/Frame 045630/0834 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 15, 2018

From: OSTERKAMP, FRANK; KNAUTE, TOBIAS; RICHTER, UWE; HAWLISCH, HEIKO; REIMER, ULF; SIMON, BERNADETT; HELLBERG, MARK R.; HUMMEL, GERD; REINEKE, ULRICH; SPECKER, EDGAR; WOISCHNIK, MARKUS

To: ALCON RESEARCH, LTD.

Reel/Frame 045227/0579 →

Continuity (5)

Division 14824353 · Aug 12, 2015

Division 14011855 · Aug 28, 2013

Division 12888556 · Sep 23, 2010

Provisional Application 61245960 · Sep 25, 2009

Related Publication 20170313743A1 · Nov 2, 2017