US 2006/0040312 A1Published application

Uses of kappa-conotoxin PVIIA

AssigneeCognetix, Inc.

InventorsAnn Cornell-Bell, Karen Pemberton, Davis Temple, Richard Layer, R. McCabe, Robert Jones

Life of this patent

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Abstract

The invention relates to uses of kappa-conotoxin PVIIA (κ-PVIIA), analogs and derivatives for activating ATP-sensitive K+ channels. The activation of ATP-sensitive K+ channels is useful for opening KATP channels which can be used to treat a wide range of disease and injury states, including cerebral and cardiac ischemia and asthma.

Claims21

Dependent claims

A method for treating disorders associated with radical depolarization of excitable membranes by activating a KATP channel which comprises administering to an individual in need thereof an effective amount of an active agent selected from the group consisting of:

(a) a compound of the following formula
Cys-Xaa1-Ile-Xaa2-Asn-Gln-Xaa3-Cys-Xaa4-Gln-Xaa5-Leu-Asp-Asp-Cys-Cys-Ser-Xaa1-Xaa3-Cys-Asn-Xaa1-Xaa4-Asn-Xaa3-Cys-Val (SEQ ID NO:1), wherein Xaa1 and Xaa3 are independently Arg, homoarginine, ornithine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys, any synthetic basic amino acid, His or halo-His;
Xaa2 is Pro or hydroxy-Pro (Hyp);
Xaa4 is Phe, Tyr, meta-Tyr, ortho-Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr, Trp (D or L), neo-Trp, halo-Trp (D or L) or any synthetic aromatic amino acid;
and Xaa5 is His or halo-His,
(b) an analog of the compound of (a), said analog selected from the group consisting of:
(SEQ ID NO:2)
κ-PVIIA[R18A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Ala-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:3)
κ-PVIIA[R22A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Ala-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:4)
κ-PVIIA[I3A]:
Cys-Arg-Ala-Hyp-Asn-Gln-Lys-Cys-Phe-GIn-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:5)
κ-PVIIA[κ19A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Ala-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:6)
κ-PVIIA[R2A]:
Cys-Ala-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:7)
κ-PVIIA[F9A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Ala-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:8)
κ-PVIIA[κ25A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Ala-Cys-Val;
(SEQ ID NO:9)
κ-PVIIA[R2κ]:
Cys-Lys-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:10)
κ-PVIIA[κ7A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Ala-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:11)
κ-PVIIA[F9M]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Met-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:12)
κ-PVIIA[F9Y]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Tyr-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:13)
κ-PVIIA[R2Q]:
Cys-Gln-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:14)
κ-PVIIA[H11A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-Ala-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:15)
κ-PVIIA[D14A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Ala-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:16)
κ-PVIIA[Q6A]:
Cys-Arg-Ile-Hyp-Asn-Ala-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:17)
κ-PVIIA[N21A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Ala-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:18)
κ-PVIIA[S17A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ala-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:19)
κ-PVIIA[N24A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Ala-Lys-Cys-Val;
(SEQ ID NO:20)
κ-PVIIA[L12A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Ala-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:21)
κ-PVIIA[D1A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Ala-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:22)
κ-PVIIA[Q10A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Ala-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:23)
κ-PVIIA[V27A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Ala;
(SEQ ID NO:24)
κ-PVIIA[O4A]:
Cys-Arg-Ile-Ala-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
and
(SEQ ID NO:25)
κ-PVIIA[N5A]:
Cys-Arg-Ile-Hyp-Ala-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(c) a derivative of (a) or (b);
and
(d) a physiologically acceptable salt thereof.

103 more elements

A method for treating cardiac ischemia which comprises administering to an individual in need thereof an effective amount of an active agent selected from the group consisting of:

(a) a compound of the following formula
Cys-Xaa1-Ile-Xaa2-Asn-Gln-Xaa3-Cys-Xaa4-Gln-Xaa5-Leu-Asp-Asp-Cys-Cys-Ser-Xaa1-Xaa3-Cys-Asn-Xaa1-Xaa4-Asn-Xaa3-Cys-Val (SEQ ID NO:1), wherein Xaa1 and Xaa3 are independently Arg, homoarginine, ornithine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys, any synthetic basic amino acid, His or halo-His;
Xaa2 is Pro or hydroxy-Pro (Hyp);
Xaa4 is Phe, Tyr, meta-Tyr, ortho-Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr, Trp (D or L), neo-Trp, halo-Trp (D or L) or any synthetic aromatic amino acid;
and Xaa5 is His or halo-His,
(b) an analog of the compound of (a), said analog selected from the group consisting of:
(SEQ ID NO:2)
κ-PVIIA[R18A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Ala-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:3)
κ-PVIIA[R22A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Ala-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:4)
κ-PVIIA[I3A]:
Cys-Arg-Ala-Hyp-Asn-Gln-Lys-Cys-Phe-GIn-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:5)
κ-PVIIA[κ19A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Ala-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:6)
κ-PVIIA[R2A]:
Cys-Ala-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:7)
κ-PVIIA[F9A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Ala-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:8)
κ-PVIIA[κ25A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Ala-Cys-Val;
(SEQ ID NO:9)
κ-PVIIA[R2κ]:
Cys-Lys-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:10)
κ-PVIIA[κ7A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Ala-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:11)
κ-PVIIA[F9M]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Met-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:12)
κ-PVIIA[F9Y]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Tyr-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:13)
κ-PVIIA[R2Q]:
Cys-Gln-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:14)
κ-PVIIA[H11A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-Ala-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:15)
κ-PVIIA[D14A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Ala-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:16)
κ-PVIIA[Q6A]:
Cys-Arg-Ile-Hyp-Asn-Ala-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:17)
κ-PVIIA[N21A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Ala-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:18)
κ-PVIIA[S17A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ala-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:19)
κ-PVIIA[N24A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Ala-Lys-Cys-Val;
(SEQ ID NO:20)
κ-PVIIA[L12A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Ala-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:21)
κ-PVIIA[D1A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Ala-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:22)
κ-PVIIA[Q10A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Ala-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:23)
κ-PVIIA[V27A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Ala;
(SEQ ID NO:24)
κ-PVIIA[O4A]:
Cys-Arg-Ile-Ala-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
and
(SEQ ID NO:25)
κ-PVIIA[N5A]:
Cys-Arg-Ile-Hyp-Ala-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(c) a derivative of (a) or (b);
and
(d) a physiologically acceptable salt thereof.

103 more elements

Dependencies are inferred from the claim text.

Facts

Application: 11/259,039Filed 27 Oct 2005
Priority: 22 Sep 1999
Published: 23 Feb 2006
Term ends: Not estimatedThe source records don’t support an estimate.

Classification9 codes

A61K 38/17
Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof: from animals; from humans
A61P 9/10
Drugs for disorders of the cardiovascular system: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary…
A61P 11/06
Drugs for disorders of the respiratory system: antiasthmatics
A61P 27/02
Drugs for disorders of the senses: ophthalmic agents

Family

Application60/155,135Us provisional application · filed 22 Sep 1999
Application60/219,438Us provisional application · filed 20 Jul 2000
Application09/666,837Continuation · filed 21 Sep 2000
Application10/627,685Continuation · filed 28 Jul 2003
Application11/259,039Continuation · filed 27 Oct 2005
US 2004/0092447 A1Published application
US 2006/0040312 A1This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

(a) a compound of the following formula
Cys-Xaa1-Ile-Xaa2-Asn-Gln-Xaa3-Cys-Xaa4-Gln-Xaa5-Leu-Asp-Asp-Cys-Cys-Ser-Xaa1-Xaa3-Cys-Asn-Xaa1-Xaa4-Asn-Xaa3-Cys-Val (SEQ ID NO:1), wherein Xaa1 and Xaa3 are independently Arg, homoarginine, ornithine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys, any synthetic basic amino acid, His or halo-His;
Xaa2 is Pro or hydroxy-Pro (Hyp);
Xaa4 is Phe, Tyr, meta-Tyr, ortho-Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr, Trp (D or L), neo-Trp, halo-Trp (D or L) or any synthetic aromatic amino acid;
and Xaa5 is His or halo-His,
(b) an analog of the compound of (a), said analog selected from the group consisting of:
(SEQ ID NO:2)
κ-PVIIA[R18A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Ala-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:3)
κ-PVIIA[R22A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Ala-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:4)
κ-PVIIA[I3A]:
Cys-Arg-Ala-Hyp-Asn-Gln-Lys-Cys-Phe-GIn-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:5)
κ-PVIIA[κ19A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Ala-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:6)
κ-PVIIA[R2A]:
Cys-Ala-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:7)
κ-PVIIA[F9A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Ala-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:8)
κ-PVIIA[κ25A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Ala-Cys-Val;
(SEQ ID NO:9)
κ-PVIIA[R2κ]:
Cys-Lys-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:10)
κ-PVIIA[κ7A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Ala-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:11)
κ-PVIIA[F9M]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Met-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:12)
κ-PVIIA[F9Y]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Tyr-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:13)
κ-PVIIA[R2Q]:
Cys-Gln-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:14)
κ-PVIIA[H11A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-Ala-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:15)
κ-PVIIA[D14A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Ala-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:16)
κ-PVIIA[Q6A]:
Cys-Arg-Ile-Hyp-Asn-Ala-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:17)
κ-PVIIA[N21A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Ala-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:18)
κ-PVIIA[S17A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ala-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:19)
κ-PVIIA[N24A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Ala-Lys-Cys-Val;
(SEQ ID NO:20)
κ-PVIIA[L12A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Ala-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:21)
κ-PVIIA[D1A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Ala-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:22)
κ-PVIIA[Q10A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Ala-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(SEQ ID NO:23)
κ-PVIIA[V27A]:
Cys-Arg-Ile-Hyp-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Ala;
(SEQ ID NO:24)
κ-PVIIA[O4A]:
Cys-Arg-Ile-Ala-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
and
(SEQ ID NO:25)
κ-PVIIA[N5A]:
Cys-Arg-Ile-Hyp-Ala-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-
Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val;
(c) a derivative of (a) or (b);
and
(d) a physiologically acceptable salt thereof.

103 more elements

Facts

Application

11/259,039Filed 27 Oct 2005

Priority

22 Sep 1999

Published

23 Feb 2006

Term ends

Not estimatedThe source records don’t support an estimate.

Classification9 codes

A61K 38/17
Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof: from animals; from humans
A61P 9/10
Drugs for disorders of the cardiovascular system: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary…
A61P 11/06
Drugs for disorders of the respiratory system: antiasthmatics
A61P 27/02
Drugs for disorders of the senses: ophthalmic agents

Family

Application60/155,135Us provisional application · filed 22 Sep 1999

Application60/219,438Us provisional application · filed 20 Jul 2000

Application09/666,837Continuation · filed 21 Sep 2000

Application10/627,685Continuation · filed 28 Jul 2003

Application11/259,039Continuation · filed 27 Oct 2005

US 2004/0092447 A1Published application

US 2006/0040312 A1This patent

From the US filing history. Foreign family members aren’t listed.