US2007060519A1PendingUtilityA1
Hsp therapy in conjunction with a low antigenicity diet
Est. expiryJan 28, 2024(expired)· nominal 20-yr term from priority
A61K 38/018A61K 38/164A61K 38/1709A61P 3/10
50
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Claims
Abstract
The present invention fragments and analogs of heat shock proteins in combination with a low antigenicity diet for suppression, prevention and treatment of diabetes. The invention is exemplified using DiaPep277™, an analog of residues 437-460 of human Hsp60 in combination with a hydrolyzed casein diet. The invention further relates to orally active pharmaceutical compositions comprising Hsp60 fragments and analogs, such as DiaPep277, useful for suppression, prevention or treatment of diabetes and to a regimen for delaying the onset of type 1 diabetes and for inhibition of insulitis.
Claims
exact text as granted — not AI-modified1 . A method for suppression, prevention or treatment of diabetes, comprising administering to an individual in need thereof a fragment of Hsp60 or analog thereof in conjunction with a low antigenicity diet.
2 . The method according to claim 1 wherein a diabetogenic protein is omitted from the diet or replaced with hydrolyzed or denatured form.
3 . The method according to claim 2 wherein the diabetogenic protein is selected from the group consisting of: casein, lactoglobulin, albumin, (pro)insulin, wheat gluten, soy bean proteins, and heat shock proteins.
4 . The method according to claim 1 wherein the diet comprises hydrolyzed or denatured protein.
5 . The method according to claim 4 wherein the hydrolyzed protein is selected from the group consisting of: casein hydrolysate, whey hydrolysate, soy hydrolysate, or a mixture thereof.
6 . The method according to claim 4 wherein the hydrolyzed protein is hydrolyzed casein.
7 . The method according to claim 1 wherein the protein source of the diet is replaced with free amino acids, short-chain peptides, or mixtures thereof.
8 . The method according to claim 1 wherein the diabetes is type 1 diabetes.
9 . The method according to claim 1 wherein the diabetes is latent autoimmune diabetes in adults (LADA).
10 . The method of claim 1 wherein the hsp60 fragment comprises residues 437-460 having the sequence Val-Leu-Gly-Gly-Gly-Cys-Ala-Leu-Leu-Arg-Cys-Ile-Pro-Ala-Leu-Asp-Ser-Leu-Thr-Pro-Ala-Asn-Glu-Asp (SEQ ID NO:1), or a salt or functional derivative thereof.
11 . The method of claim 1 wherein the analog of hsp60 comprises DiaPep277 having the sequence: Val-Leu-Gly-Gly-Gly-Val-Ala-Leu-Leu-Arg-Val-Ile-Pro-Ala-Leu-Asp-Ser-Leu-Thr-Pro-Ala-Asn-Glu-Asp (SEQ ID NO:2), or a salt or functional derivative thereof.
12 . The method of claim 1 wherein the hsp60 fragment or analog comprises a sequence selected from the group consisting of:
residues 31-50 of human Hsp60: Lys-Phe-Gly-Ala-Asp-Ala-Arg-Ala-Leu-Met-Leu-Gln-Gly-Val-Asp-Leu-Leu-Ala-Asp-Ala (SEQ ID NO:3);
residues 136-155 of human Hsp60: Asn-Pro-Val-Glu-Ile-Arg-Arg-Gly-Val-Met-Leu-Ala-Val-Asp-Ala-Val-Ile-Ala-Glu-Leu (SEQ ID NO:4);
residues 151-170 of human Hsp60: Val-Ile-Ala-Glu-Leu-Lys-Lys-Gln-Ser-Lys-Pro-Val-Thr-Thr-Pro-Glu-Glu-Ile-Ala-Gln (SEQ ID NO:5);
residues 166-185 of human Hsp60: Glu-Glu-Ile-Ala-Gln-Val-Ala-Thr-Ile-Ser-Ala-Asn-Gly-Asp-Lys-Glu-Ile-Gly-Asn-Ile (SEQ ID NO:6);
residues 195-214 of human Hsp60: Arg-Lys-Gly-Val-Ile-Thr-Val-Lys-Asp-Gly-Lys-Thr-Leu-Asn-Asp-Glu-Leu-Glu-Ile-Ile (SEQ ID NO:7);
residues 255-274 of human Hsp60: Gln-Ser-Ile-Val-Pro-Ala-Leu-Glu-Ile-Ala-Asn-Ala-His-Arg-Lys-Pro-Leu-Val-Ile-Ile (SEQ ID NO:8);
residues 286-305 of human Hsp60: Leu-Val-Leu-Asn-Arg-Leu-Lys-Val-Gly-Leu-Gln-Val-Val-Ala-Val-Lys-Ala-Pro-Gly-Phe (SEQ ID NO:9);
residues 346-365 of human Hsp60: Gly-Glu-Val-Ile-Val-Thr-Lys-Asp-Asp-Ala-Met-Leu-Leu-Lys-Gly-Lys-Gly-Asp-Lys-Ala (SEQ ID NO:10);
residues 421-440 of human Hsp60: Val-Thr-Asp-Ala-Leu-Asn-Ala-Thr-Arg-Ala-Ala-Val-Glu-Glu-Gly-Ile-Val-Leu-Gly-Gly (SEQ ID NO:11);
residues 436-455 of human Hsp60: Ile-Val-Leu-Gly-Gly-Gly-Cys-Ala-Leu-Leu-Arg-Cys-Ile-Pro-Ala-Leu-Asp-Ser-Leu-Thr (SEQ ID NO:12);
residues 466-485 of human Hsp60: Glu-Ile-Ile-Lys-Arg-Thr-Leu-Lys-Ile-Pro-Ala-Met-Thr-Ile-Ala-Lys-Asn-Ala-Gly-Val (SEQ ID NO:13);
residues 511-530 of human Hsp60: Val-Asn-Met-Val-Glu-Lys-Gly-Ile-Ile-Asp-Pro-Thr-Lys-Val-Val-Arg-Thr-Ala-Leu-Leu (SEQ ID NO:14);
residues 343-366 of human Hsp60: Gly-Lys-Val-Gly-Glu-Val-Ile-Val-Thr-Lys-Asp-Asp-Ala-Met (SEQ ID NO:15);
or a salt or functional derivative thereof.
13 . The method of claim 1 wherein the Hsp60 fragment or analog is administered by a route of administration selected from oral, nasal, bronchial, topical, transdermal and systemic administration.
14 . The method of claim 1 wherein the Hsp60 fragment or analog is administered orally.
15 . The method according to claim 14 wherein the Hsp60 fragment or analog is administered in a dosage ranging from about 0.02 mg/kg to about 10 mg/kg.
16 . The use according to claim 15 wherein the Hsp60 fragment or analog is administered in a dosage ranging from about 0.05 mg/kg to about 2 mg/kg.
17 . The method of claim 1 wherein the Hsp60 fragment or analog is formulated for oral administration.
18 . A method for delaying the onset of type 1 diabetes and for inhibition of insulitis, comprising:
i. administering a fragment of Hsp60 or analog thereof; and ii. maintaining a hydrolyzed casein diet.
19 . The method of claim 18 wherein the Hsp60 fragment or analog comprises residues 437-460 having the sequence Val-Leu-Gly-Gly-Gly-Cys-Ala-Leu-Leu-Arg-Cys-Ile-Pro-Ala-Leu-Asp-Ser-Leu-Thr-Pro-Ala-Asn-Glu-Asp (SEQ ID NO:1).
20 . The method of claim 18 wherein the Hsp60 fragment or analog comprises DiaPep277 having the sequence: Val-Leu-Gly-Gly-Gly-Val-Ala-Leu-Leu-Arg-Val-Ile-Pro-Ala-Leu-Asp-Ser-Leu-Thr-Pro-Ala-Asn-Glu-Asp (SEQ ID NO:2).
21 . The method of claim 18 wherein the Hsp60 fragment or analog comprises a sequence selected from the group consisting of:
residues 31-50 of human Hsp60:
Lys-Phe-Gly-Ala-Asp-Ala-Arg-Ala-Leu-
(SEQ ID NO:3)
Met-Leu-Gln-Gly-Val-Asp-Leu-Leu-Ala-
Asp-Ala;
residues 136-155 of human Hsp60:
Asn-Pro-Val-Glu-Ile-Arg-Arg-Gly-Val-
(SEQ ID NO:4)
Met-Leu-Ala-Val-Asp-Ala-Val-Ile-Ala-
Glu-Leu;
residues 151-170 of human Hsp60:
Val-Ile-Ala-Glu-Leu-Lys-Lys-Gln-Ser-
(SEQ ID NO:5)
Lys-Pro-Val-Thr-Thr-Pro-Glu-Glu-Ile-
Ala-Gln;
residues 166-185 of human Hsp60:
Glu-Glu-Ile-Ala-Gln-Val-Ala-Thr-Ile-
(SEQ ID NO:6)
Ser-Ala-Asn-Gly-Asp-Lys-Glu-Ile-Gly-
Asn-Ile;
residues 195-214 of human Hsp60:
Arg-Lys-Gly-Val-Ile-Thr-Val-Lys-Asp-
(SEQ ID NO:7)
Gly-Lys-Thr-Leu-Asn-Asp-Glu-Leu-Glu-
Ile-Ile;
residues 255-274 of human Hsp60:
Gln-Ser-Ile-Val-Pro-Ala-Leu-Glu-Ile-
(SEQ ID NO:8)
Ala-Asn-Ala-His-Arg-Lys-Pro-Leu-Val-
Ile-Ile;
residues 286-305 of human Hsp60:
Leu-Val-Leu-Asn-Arg-Leu-Lys-Val-Gly-
(SEQ ID NO:9)
Leu-Gln-Val-Val-Ala-Val-Lys-Ala-Pro-
Gly-Phe;
residues 346-365 of human Hsp60:
Gly-Glu-Val-Ile-Val-Thr-Lys-Asp-Asp-
(SEQ ID NO:10)
Ala-Met-Leu-Leu-Lys-Gly-Lys-Gly-Asp-
Lys-Ala;
residues 421-440 of human Hsp60:
Val-Thr-Asp-Ala-Leu-Asn-Ala-Thr-Arg-
(SEQ ID NO:11)
Ala-Ala-Val-Glu-Glu-Gly-Ile-Val-Leu-
Gly-Gly;
residues 436-455 of human Hsp60:
Ile-Val-Leu-Gly-Gly-Gly-Cys-Ala-Leu-
(SEQ ID NO:12)
Leu-Arg-Cys-Ile-Pro-Ala-Leu-Asp-Ser-
Leu-Thr;
residues 466-485 of human Hsp60:
Glu-Ile-Ile-Lys-Arg-Thr-Leu-Lys-Ile-
(SEQ ID NO:13)
Pro-Ala-Met-Thr-Ile-Ala-Lys-Asn-Ala-
Gly-Val;
residues 511-530 of human Hsp60:
Val-Asn-Met-Val-Glu-Lys-Gly-Ile-Ile-
(SEQ ID NO:14)
Asp-Pro-Thr-Lys-Val-Val-Arg-Thr-Ala-
Leu-Leu;
residues 343-366 of human Hsp60:
Gly-Lys-Val-Gly-Glu-Val-Ile-Val-Thr-
(SEQ ID NO:15)
Lys-Asp-Asp-Ala-Met;
or a salt or functional derivative thereof.
22 . The method of claim 18 wherein the Hsp60 fragment or analog is administered orally.
23 . The method of claim 22 wherein the Hsp60 fragment or analog is administered in a dosage ranging from about 0.02 mg/kg to about 10 mg/kg.
24 . The method of claim 18 wherein the Hsp60 fragment or analog is administered in a dosage ranging from about 0.05 mg/kg to about 2 mg/kg.
25 . A pharmaceutical composition for oral administration comprising an Hsp60 fragment or analog.
26 . The pharmaceutical composition of claim 25 wherein said Hsp60 fragment or analog comprises residues 437-460 having the sequence Val-Leu-Gly-Gly-Gly-Cys-Ala-Leu-Leu-Arg-Cys-Ile-Pro-Ala-Leu-Asp-Ser-Leu-Thr-Pro-Ala-Asn-Glu-Asp (SEQ ID NO:1).
27 . The pharmaceutical composition of claim 25 wherein said Hsp60 fragment or analog comprises DiaPep277 having the sequence: Val-Leu-Gly-Gly-Gly-Val-Ala-Leu-Leu-Arg-Val-Ile-Pro-Ala-Leu-Asp-Ser-Leu-Thr-Pro-Ala-Asn-Glu-Asp (SEQ ID NO:2).
28 . The pharmaceutical composition of claim 25 wherein said Hsp60 fragment is selected from a sequence consisting of:
residues 31-50 of human Hsp60:
Lys-Phe-Gly-Ala-Asp-Ala-Arg-Ala-Leu-
(SEQ ID NO:3)
Met-Leu-Gln-Gly-Val-Asp-Leu-Leu-Ala-
Asp-Ala;
residues 136-155 of human Hsp60:
Asn-Pro-Val-Glu-Ile-Arg-Arg-Gly-Val-
(SEQ ID NO:4)
Met-Leu-Ala-Val-Asp-Ala-Val-Ile-Ala-
Glu-Leu;
residues 151-170 of human Hsp60:
Val-Ile-Ala-Glu-Leu-Lys-Lys-Gln-Ser-
(SEQ ID NO:5)
Lys-Pro-Val-Thr-Thr-Pro-Glu-Glu-Ile-
Ala-Gln;
residues 166-185 of human Hsp60:
Glu-Glu-Ile-Ala-Gln-Val-Ala-Thr-Ile-
(SEQ ID NO:6)
Ser-Ala-Asn-Gly-Asp-Lys-Glu-Ile-Gly-
Asn-Ile;
residues 195-214 of human Hsp60:
Arg-Lys-Gly-Val-Ile-Thr-Val-Lys-Asp-
(SEQ ID NO:7)
Gly-Lys-Thr-Leu-Asn-Asp-Glu-Leu-Glu-
Ile-Ile;
residues 255-274 of human Hsp60:
Gln-Ser-Ile-Val-Pro-Ala-Leu-Glu-Ile-
(SEQ ID NO:8)
Ala-Asn-Ala-His-Arg-Lys-Pro-Leu-Val-
Ile-Ile;
residues 286-305 of human Hsp60:
Leu-Val-Leu-Asn-Arg-Leu-Lys-Val-Gly-
(SEQ ID NO:9)
Leu-Gln-Val-Val-Ala-Val-Lys-Ala-Pro-
Gly-Phe;
residues 346-365 of human Hsp60:
Gly-Glu-Val-Ile-Val-Thr-Lys-Asp-Asp-
(SEQ ID NO:10)
Ala-Met-Leu-Leu-Lys-Gly-Lys-Gly-Asp-
Lys-Ala;
residues 421-440 of human Hsp60:
Val-Thr-Asp-Ala-Leu-Asn-Ala-Thr-Arg-
(SEQ ID NO:11)
Ala-Ala-Val-Glu-Glu-Gly-Ile-Val-Leu-
Gly-Gly;
residues 436-455 of human Hsp60:
Ile-Val-Leu-Gly-Gly-Gly-Cys-Ala-Leu-
(SEQ ID NO:12)
Leu-Arg-Cys-Ile-Pro-Ala-Leu-Asp-Ser-
Leu-Thr;
residues 466-485 of human Hsp60:
Glu-Ile-Ile-Lys-Arg-Thr-Leu-Lys-Ile-
(SEQ ID NO:13)
Pro-Ala-Met-Thr-Ile-Ala-Lys-Asn-Ala-
Gly-Val;
residues 511-530 of human Hsp60:
Val-Asn-Met-Val-Glu-Lys-Gly-Ile-Ile-
(SEQ ID NO:14)
Asp-Pro-Thr-Lys-Val-Val-Arg-Thr-Ala-
Leu-Leu;
residues 343-366 of human Hsp60:
Gly-Lys-Val-Gly-Glu-Val-Ile-Val-Thr-
(SEQ ID NO:15)
Lys-Asp-Asp-Ala-Met;
or a salt or functional derivative thereof.
29 . The pharmaceutical composition according to claim 25 wherein the Hsp60 fragment or analog is administered in a dosage ranging from about 0.02 mg/kg to about 10 mg/kg.
30 . A method of treating an individual in need thereof by administering a pharmaceutical composition comprising a fragment or an analog of a heat shock protein in conjunction with maintenance of a low antigenicity diet.
31 . The method of claim 30 wherein the heat shock protein is Hsp60.
32 . The method of claim 30 wherein the fragment of the heat shock protein comprises residues 437-460 having the sequence Val-Leu-Gly-Gly-Gly-Cys-Ala-Leu-Leu-Arg-Cys-Ile-Pro-Ala-Leu-Asp-Ser-Leu-Thr-Pro-Ala-Asn-Glu-Asp (SEQ ID NO:1).
33 . The method of claim 30 wherein the fragment or the analog of the heat shock protein comprises DiaPep277 having the sequence: Val-Leu-Gly-Gly-Gly-Val-Ala-Leu-Leu-Arg-Val-Ile-Pro-Ala-Leu-Asp-Ser-Leu-Thr-Pro-Ala-Asn-Glu-Asp (SEQ ID NO:2), and the diet comprises a hydrolyzed casein diet.
34 . The method of claim 30 wherein the fragment of the heat shock protein is selected from a sequence consisting of:
residues 31-50 of human Hsp60:
Lys-Phe-Gly-Ala-Asp-Ala-Arg-Ala-Leu-
(SEQ ID NO:3)
Met-Leu-Gln-Gly-Val-Asp-Leu-Leu-Ala-
Asp-Ala;
residues 136-155 of human Hsp60:
Asn-Pro-Val-Glu-Ile-Arg-Arg-Gly-Val-
(SEQ ID NO:4)
Met-Leu-Ala-Val-Asp-Ala-Val-Ile-Ala-
Glu-Leu;
residues 151-170 of human Hsp60:
Val-Ile-Ala-Glu-Leu-Lys-Lys-Gln-Ser-
(SEQ ID NO:5)
Lys-Pro-Val-Thr-Thr-Pro-Glu-Glu-Ile-
Ala-Gln;
residues 166-185 of human Hsp60:
Glu-Glu-Ile-Ala-Gln-Val-Ala-Thr-Ile-
(SEQ ID NO:6)
Ser-Ala-Asn-Gly-Asp-Lys-Glu-Ile-Gly-
Asn-Ile;
residues 195-214 of human Hsp60:
Arg-Lys-Gly-Val-Ile-Thr-Val-Lys-Asp-
(SEQ ID NO:7)
Gly-Lys-Thr-Leu-Asn-Asp-Glu-Leu-Glu-
Ile-Ile;
residues 255-274 of human Hsp60:
Gln-Ser-Ile-Val-Pro-Ala-Leu-Glu-Ile-
(SEQ ID NO:8)
Ala-Asn-Ala-His-Arg-Lys-Pro-Leu-Val-
Ile-Ile;
residues 286-305 of human Hsp60:
Leu-Val-Leu-Asn-Arg-Leu-Lys-Val-Gly-
(SEQ ID NO:9)
Leu-Gln-Val-Val-Ala-Val-Lys-Ala-Pro-
Gly-Phe;
residues 346-365 of human Hsp60:
Gly-Glu-Val-Ile-Val-Thr-Lys-Asp-Asp-
(SEQ ID NO:10)
Ala-Met-Leu-Leu-Lys-Gly-Lys-Gly-Asp-
Lys-Ala;
residues 421-440 of human Hsp60:
Val-Thr-Asp-Ala-Leu-Asn-Ala-Thr-Arg-
(SEQ ID NO:11)
Ala-Ala-Val-Glu-Glu-Gly-Ile-Val-Leu-
Gly-Gly;
residues 436-455 of human Hsp60:
Ile-Val-Leu-Gly-Gly-Gly-Cys-Ala-Leu-
(SEQ ID NO:12)
Leu-Arg-Cys-Ile-Pro-Ala-Leu-Asp-Ser-
Leu-Thr;
residues 466-485 of human Hsp60:
Glu-Ile-Ile-Lys-Arg-Thr-Leu-Lys-Ile-
(SEQ ID NO:13)
Pro-Ala-Met-Thr-Ile-Ala-Lys-Asn-Ala-
Gly-Val;
residues 511-530 of human Hsp60:
Val-Asn-Met-Val-Glu-Lys-Gly-Ile-Ile-
(SEQ ID NO:14)
Asp-Pro-Thr-Lys-Val-Val-Arg-Thr-Ala-
Leu-Leu;
residues 343-366 of human Hsp60:
Gly-Lys-Val-Gly-Glu-Val-Ile-Val-Thr-
(SEQ ID NO:15)
Lys-Asp-Asp-Ala-Met;
or a salt or functional derivative thereof.
35 . The method of claim 30 wherein the Hsp60 fragment or analog is administered orally.
36 . The method according to claim 35 wherein the Hsp60 fragment or analog is administered in a dosage ranging from about 0.02 mg/kg to about 10 mg/kg.
37 . A pharmaceutical composition for improvement of the protective effect of a low antigenicity diet comprising as an active ingredient a fragment of hsp60 or an analog thereof.
38 . The pharmaceutical composition of claim 37 wherein a diabetogenic protein is omitted from the diet or replaced with hydrolyzed or denatured form.
39 . The pharmaceutical composition of claim 38 wherein the diabetogenic protein is selected from the group consisting of: casein, lactoglobulin, albumin, (pro)insulin, wheat gluten, soy bean proteins, and heat shock proteins.
40 . The pharmaceutical composition of claim 37 wherein the diet comprises hydrolyzed or denatured protein.
41 . The pharmaceutical composition of claim 40 wherein the hydrolyzed protein is selected from the group consisting of: casein hydrolysate, whey hydrolysate, soy hydrolysate, or a mixture thereof.
42 . The pharmaceutical composition of claim 40 wherein the hydrolyzed protein is hydrolyzed casein.
43 . The pharmaceutical composition of claim 37 wherein the protein source of the diet is replaced with free amino acids, short-chain peptides, or mixtures thereof.
44 . The pharmaceutical composition of claim 37 wherein the diabetes is type 1 diabetes.
45 . The pharmaceutical composition of claim 37 wherein the diabetes is latent autoimmune diabetes in adults (LADA).
46 . The pharmaceutical composition of claim 37 wherein the Hsp60 fragment or analog comprises residues 437-460 having the sequence Val-Leu-Gly-Gly-Gly-Cys-Ala-Leu-Leu-Arg-Cys-Ile-Pro-Ala-Leu-Asp-Ser-Leu-Thr-Pro-Ala-Asn-Glu-Asp (SEQ ID NO:1).
47 . The pharmaceutical composition of claim 37 wherein the Hsp60 fragment or analog comprises DiaPep277 having the sequence: Val-Leu-Gly-Gly-Gly-Val-Ala-Leu-Leu-Arg-Val-Ile-Pro-Ala-Leu-Asp-Ser-Leu-Thr-Pro-Ala-Asn-Glu-Asp (SEQ ID NO:2).
48 . The pharmaceutical composition of claim 37 wherein the Hsp60 fragment is selected from a sequence consisting of:
residues 31-50 of human Hsp60:
Lys-Phe-Gly-Ala-Asp-Ala-Arg-Ala-Leu-
(SEQ ID NO:3)
Met-Leu-Gln-Gly-Val-Asp-Leu-Leu-Ala-
Asp-Ala;
residues 136-155 of human Hsp60:
Asn-Pro-Val-Glu-Ile-Arg-Arg-Gly-Val-
(SEQ ID NO:4)
Met-Leu-Ala-Val-Asp-Ala-Val-Ile-Ala-
Glu-Leu;
residues 151-170 of human Hsp60:
Val-Ile-Ala-Glu-Leu-Lys-Lys-Gln-Ser-
(SEQ ID NO:5)
Lys-Pro-Val-Thr-Thr-Pro-Glu-Glu-Ile-
Ala-Gln;
residues 166-185 of human Hsp60:
Glu-Glu-Ile-Ala-Gln-Val-Ala-Thr-Ile-
(SEQ ID NO:6)
Ser-Ala-Asn-Gly-Asp-Lys-Glu-Ile-Gly-
Asn-Ile;
residues 195-214 of human Hsp60:
Arg-Lys-Gly-Val-Ile-Thr-Val-Lys-Asp-
(SEQ ID NO:7)
Gly-Lys-Thr-Leu-Asn-Asp-Glu-Leu-Glu-
Ile-Ile;
residues 255-274 of human Hsp60:
Gln-Ser-Ile-Val-Pro-Ala-Leu-Glu-Ile-
(SEQ ID NO:8)
Ala-Asn-Ala-His-Arg-Lys-Pro-Leu-Val-
Ile-Ile;
residues 286-305 of human Hsp60:
Leu-Val-Leu-Asn-Arg-Leu-Lys-Val-Gly-
(SEQ ID NO:9)
Leu-Gln-Val-Val-Ala-Val-Lys-Ala-Pro-
Gly-Phe;
residues 346-365 of human Hsp60:
Gly-Glu-Val-Ile-Val-Thr-Lys-Asp-Asp-
(SEQ ID NO:10)
Ala-Met-Leu-Leu-Lys-Gly-Lys-Gly-Asp-
Lys-Ala;
residues 421-440 of human Hsp60:
Val-Thr-Asp-Ala-Leu-Asn-Ala-Thr-Arg-
(SEQ ID NO:11)
Ala-Ala-Val-Glu-Glu-Gly-Ile-Val-Leu-
Gly-Gly;
residues 436-455 of human Hsp60:
Ile-Val-Leu-Gly-Gly-Gly-Cys-Ala-Leu-
(SEQ ID NO:12)
Leu-Arg-Cys-Ile-Pro-Ala-Leu-Asp-Ser-
Leu-Thr;
residues 466-485 of human Hsp60:
Glu-Ile-Ile-Lys-Arg-Thr-Leu-Lys-Ile-
(SEQ ID NO:13)
Pro-Ala-Met-Thr-Ile-Ala-Lys-Asn-Ala-
Gly-Val;
residues 511-530 of human Hsp60:
Val-Asn-Met-Val-Glu-Lys-Gly-Ile-Ile-
(SEQ ID NO:14)
Asp-Pro-Thr-Lys-Val-Val-Arg-Thr-Ala-
Leu-Leu;
residues 343-366 of human Hsp60:
Gly-Lys-Val-Gly-Glu-Val-Ile-Val-Thr-
(SEQ ID NO:15)
Lys-Asp-Asp-Ala-Met;
or a salt or functional derivative thereof.
49 . The pharmaceutical composition of claim 37 wherein the Hsp60 fragment or analog is administered orally.
50 . The pharmaceutical composition according to claim 49 wherein the Hsp60 fragment or analog is administered in a dosage ranging from about 0.02 mg/kg to about 10 mg/kg.Join the waitlist — get patent alerts
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