SorCS1-Like Agent for Use in the Treatment of Insulin Resistance and Diseases Related Thereto

Patent metadata

Field	Value
Publication number	US-2016015778-A1
Application number	US-201514753665-A
Country	US
Kind code	A1
Filing date	Jun 29, 2015
Priority date	Jun 10, 2009
Publication date	Jan 21, 2016
Grant date	—

Abstract

The present invention relates to Sor CS1-like agents, including Sor CS1, nucleic acid molecule encoding expression of Sor CS1 and fragments thereof, as well as vectors containing said nucleic acid and to cells expressing Sor CS1 and said fragments, for use in the treatment of insulin resistance.

First claim

1 - 71 . (canceled)

72 . A method of treatment of insulin resistance, or a disease and/or a disease associated with insulin resistance selected from the group consisting of insulin resistance syndrome, Type 2 diabetes mellitus, impaired glucose tolerance, the metabolic syndrome, hyperglycemia, hyperinsulinemia, arteriosclerosis, hypercholesterolemia, hypertriglyceridemia, hyperlipidemia, dyslipidemia, obesity, polycystic ovarian syndrome, hypercoagulability, hypertension, microalbuminuria, and any combination thereof, said method comprising administering to an individual in need thereof a therapeutically effective amount of a composition comprising an agent selected from the group consisting of:
(a) polypeptide selected from the group consisting of:
(i) an amino acid sequence comprising of SEQ ID NOs: 5, 10, 15, 21, 27, 33, 37, 39, 43, 47 and 51;
(ii) a biologically active homolog of the amino acid sequence of (a) wherein said homolog has at least 90% sequence identity to said SEQ ID NO: 5, 10, 15, 21, 27, 33, 37, 39, 43, 47 and 51, and
wherein said homolog competes for binding with the polypeptide of (a) to a SorCS1 binding site of an insulin receptor; and

(iii) a biologically active fragment of any of (a) or (b) wherein said fragment comprises at least 15 contiguous amino acids of any of (a) or (b), and
wherein said homolog competes for binding with the polypeptide of (a) to a SorCS1 binding site of an insulin receptor;

(b) a nucleic acid sequence encoding a polypeptide as defined in (a); (c) a vector comprising the nucleic acid molecule as defined in (b), and (d) an isolated host cell transformed or transduced with the nucleic acid of (b) or the vector of (c).

73 . The method according to claim 72 , wherein said polypeptide consists of an amino acid sequence selected from the group consisting of: SEQ ID NOs: 5, 10, 15, 21, 27, 33, 37, 39, 43, 47 and 51.

74 . The method according to claim 72 , wherein said polypeptide consists of the amino acid sequence of SEQ ID NO: 5.

75 . The method according to claim 72 , wherein said polypeptide consists of the amino acid sequence of SEQ ID NO: 10.

76 . The method according to claim 72 , wherein said polypeptide consists of the amino acid sequence of SEQ ID NO: 15.

77 . The method according to claim 72 , wherein said polypeptide is a variant polypeptide described therein, wherein any amino acid specified in the selected sequence is altered to provide a conservative substitution.

78 . The method according to claim 72 , wherein said polypeptide has at least 98% sequence identity to sequence selected from the group consisting of SEQ ID NOs: 5, 10, 15, 21, 27, 33, 37, 39, 43, 47 and 51.

79 . The method according to claim 72 , wherein said polypeptide has at least 99% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 5, 10, 15, 21, 27, 33, 37, 39, 43, 47 and 51.

80 . The method according to claim 72 wherein the polypeptide is glycosylated.

81 . The method according to claim 72 , wherein the polypeptide is glycosylated in any one of amino acid residue corresponding to positions 184, 352, 433, 765, 776, 816, 847, 908 and 929 of SEQ ID NO: 1.

82 . The method according to claim 72 , wherein the polypeptide consists one of a polypeptide selected from the group consisting of:
SEQ ID NO: 88; SEQ ID NO: 89; SEQ ID NO: 90; SEQ ID NO: 91; SEQ ID NO: 92; SEQ ID NO: 93; SEQ ID NO: 94; and SEQ ID NO: 95.

83 . The method according to claim 72 , wherein the polypeptide is capable of forming at least one intramolecular cystin bridge.

84 . The method according to claim 72 , comprising a dimer of said polypeptide linked through at least one intermolecular cystin bridge.

85 . The method according to claim 72 , wherein said polypeptide further comprises an affinity tag, such as a polyhis tag, a GST tag, a HA tag, a Flag tag, a C-myc tag, a HSV tag, a V5 tag, a maltose binding protein tag, a cellulose binding domain tag.

86 . The method according to claim 72 , wherein the disease associated with insulin resistance is insulin resistance syndrome.

87 . The method according to claim 72 , wherein the disease associated with insulin resistance is Type 2 diabetes mellitus.

88 . The method according to claim 72 , wherein the disease associated with insulin resistance is impaired glucose tolerance.

89 . The method according to claim 72 , wherein the disease associated with insulin resistance is the metabolic syndrome.

90 . The method according to claim 72 , wherein the disease associated with insulin resistance is hyperglycemia.

91 . The method according to claim 72 , wherein the disease associated with insulin resistance is hyperinsulinemia.

92 . The method according to claim 72 , wherein the disease associated with insulin resistance is arteriosclerosis.

93 . The method according to claim 72 , wherein the disease associated with hypercholesterolemia.

94 . The method according to claim 72 , wherein the disease associated with insulin resistance is hypertriglyceridemia.

95 . The method according to claim 72 , wherein the disease associated with insulin resistance is hyperlipidemia.

96 . The method according to claim 72 , wherein the disease associated with insulin resistance is dyslipidemia.

97 . The method according to claim 72 , wherein the disease associated with insulin resistance is obesity.

98 . The method according to claim 72 , wherein the disease associated with insulin resistance is polycystic ovarian syndrome.

99 . The method according to claim 72 , wherein the disease associated with insulin resistance is hypercoagulability.

100 . The method according to claim 72 , wherein the disease associated with insulin resistance is hypertension.

101 . The method according to claim 72 , wherein the disease associated with insulin resistance is microalbuminuria.

Assignees

• Univ Aarhus

Inventors

• Pedersen Karen-Marie
• Nykjaer Anders

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P9/12

  Antihypertensives · CPC title

• A61P3/06

  Antihyperlipidemics · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P3/04

  Anorexiants; Antiobesity agents · CPC title