CA2485472A1 - Gh secretagogues and uses thereof - Google Patents
Gh secretagogues and uses thereof Download PDFInfo
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- CA2485472A1 CA2485472A1 CA002485472A CA2485472A CA2485472A1 CA 2485472 A1 CA2485472 A1 CA 2485472A1 CA 002485472 A CA002485472 A CA 002485472A CA 2485472 A CA2485472 A CA 2485472A CA 2485472 A1 CA2485472 A1 CA 2485472A1
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- 230000000580 secretagogue effect Effects 0.000 title claims abstract 41
- 239000000203 mixture Substances 0.000 claims abstract 98
- 150000002632 lipids Chemical class 0.000 claims abstract 15
- 230000001925 catabolic effect Effects 0.000 claims abstract 13
- 230000003920 cognitive function Effects 0.000 claims abstract 8
- 230000002503 metabolic effect Effects 0.000 claims abstract 8
- 230000003247 decreasing effect Effects 0.000 claims abstract 5
- 230000002950 deficient Effects 0.000 claims abstract 5
- 230000036737 immune function Effects 0.000 claims abstract 5
- 230000011164 ossification Effects 0.000 claims abstract 5
- 230000015572 biosynthetic process Effects 0.000 claims abstract 4
- 102000018997 Growth Hormone Human genes 0.000 claims 60
- 108010051696 Growth Hormone Proteins 0.000 claims 60
- 239000000122 growth hormone Substances 0.000 claims 60
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 36
- 108090000765 processed proteins & peptides Proteins 0.000 claims 27
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims 24
- 150000001413 amino acids Chemical group 0.000 claims 21
- 206010049287 Lipodystrophy acquired Diseases 0.000 claims 18
- 239000003937 drug carrier Substances 0.000 claims 18
- 208000006132 lipodystrophy Diseases 0.000 claims 18
- 230000004075 alteration Effects 0.000 claims 17
- 239000003795 chemical substances by application Substances 0.000 claims 16
- 235000012000 cholesterol Nutrition 0.000 claims 12
- 230000003187 abdominal effect Effects 0.000 claims 10
- 238000007920 subcutaneous administration Methods 0.000 claims 10
- 229920001184 polypeptide Polymers 0.000 claims 9
- 102000004196 processed proteins & peptides Human genes 0.000 claims 9
- 210000001519 tissue Anatomy 0.000 claims 7
- 208000032928 Dyslipidaemia Diseases 0.000 claims 6
- 208000017170 Lipid metabolism disease Diseases 0.000 claims 6
- 206010062315 Lipohypertrophy Diseases 0.000 claims 6
- 208000008589 Obesity Diseases 0.000 claims 6
- 125000003118 aryl group Chemical group 0.000 claims 6
- 238000012217 deletion Methods 0.000 claims 6
- 230000037430 deletion Effects 0.000 claims 6
- 239000003814 drug Substances 0.000 claims 6
- 230000002209 hydrophobic effect Effects 0.000 claims 6
- 208000006575 hypertriglyceridemia Diseases 0.000 claims 6
- 238000000034 method Methods 0.000 claims 6
- 235000020824 obesity Nutrition 0.000 claims 6
- 208000011580 syndromic disease Diseases 0.000 claims 6
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims 4
- 239000008280 blood Substances 0.000 claims 4
- 210000004369 blood Anatomy 0.000 claims 4
- 239000008103 glucose Substances 0.000 claims 4
- 210000004003 subcutaneous fat Anatomy 0.000 claims 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 3
- 208000030507 AIDS Diseases 0.000 claims 3
- 206010007559 Cardiac failure congestive Diseases 0.000 claims 3
- 208000002705 Glucose Intolerance Diseases 0.000 claims 3
- 206010018429 Glucose tolerance impaired Diseases 0.000 claims 3
- 208000031886 HIV Infections Diseases 0.000 claims 3
- 208000037357 HIV infectious disease Diseases 0.000 claims 3
- 206010019280 Heart failures Diseases 0.000 claims 3
- 206010020100 Hip fracture Diseases 0.000 claims 3
- 206010022489 Insulin Resistance Diseases 0.000 claims 3
- 208000029725 Metabolic bone disease Diseases 0.000 claims 3
- 206010049088 Osteopenia Diseases 0.000 claims 3
- 208000001132 Osteoporosis Diseases 0.000 claims 3
- 230000032683 aging Effects 0.000 claims 3
- 230000000840 anti-viral effect Effects 0.000 claims 3
- 238000002512 chemotherapy Methods 0.000 claims 3
- 208000020832 chronic kidney disease Diseases 0.000 claims 3
- 208000022831 chronic renal failure syndrome Diseases 0.000 claims 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims 3
- 206010012601 diabetes mellitus Diseases 0.000 claims 3
- WAOQOSHNKJFOTO-BMGKTWPMSA-N hex-hgrf Chemical compound C([C@H](NC(=O)C/C=C/CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(N)=O)C1=CC=C(O)C=C1 WAOQOSHNKJFOTO-BMGKTWPMSA-N 0.000 claims 3
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims 3
- 208000014674 injury Diseases 0.000 claims 3
- 210000001596 intra-abdominal fat Anatomy 0.000 claims 3
- 238000007918 intramuscular administration Methods 0.000 claims 3
- 238000001990 intravenous administration Methods 0.000 claims 3
- 230000003387 muscular Effects 0.000 claims 3
- 238000001959 radiotherapy Methods 0.000 claims 3
- 239000003488 releasing hormone Substances 0.000 claims 3
- 229920006395 saturated elastomer Polymers 0.000 claims 3
- 238000001356 surgical procedure Methods 0.000 claims 3
- 238000002560 therapeutic procedure Methods 0.000 claims 3
- 230000000699 topical effect Effects 0.000 claims 3
- 230000008733 trauma Effects 0.000 claims 3
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims 3
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims 3
- 230000009278 visceral effect Effects 0.000 claims 3
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/25—Growth hormone-releasing factor [GH-RF], i.e. somatoliberin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/60—Growth hormone-releasing factor [GH-RF], i.e. somatoliberin
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Endocrinology (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Zoology (AREA)
- Immunology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Gastroenterology & Hepatology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Toxicology (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to use of a GH secretagogue (e.g. GRF or an analog thereof) for (1) altering a lipid parameter in a subject; (2) altering a body composition parameter in a subject, (3) treating a condition characterized by deficient or decreased bone formation in a subject (4) improving daytime vigilance and/or cognitive function in a subject, (5) improving a metabolic condition in a subject, (6) improving anabolism in a catabolic condition in a subject, and/or (7) improving and/or reconstituting immune function in a subject.
Claims (108)
1. Use of an agent selected from the group consisting of:
(a) a growth hormone (GH) secretagogue; and (b) a composition comprising a GH secretagogue and a pharmaceutically acceptable carrier;
for altering a lipid parameter in a subject, wherein said alteration of a lipid parameter results in no or substantially no increase in blood glucose levels in said subject.
(a) a growth hormone (GH) secretagogue; and (b) a composition comprising a GH secretagogue and a pharmaceutically acceptable carrier;
for altering a lipid parameter in a subject, wherein said alteration of a lipid parameter results in no or substantially no increase in blood glucose levels in said subject.
2. Use of a growth hormone (GH) secretagogue for the preparation of a medicament for altering a lipid parameter in a subject, wherein said alteration of a lipid parameter results in no or substantially no increase in blood glucose levels in said subject.
3. The use of claim 1 or 2, wherein said alteration of a lipid parameter is selected from the group consisting of:
(a) a decrease in cholesterol;
(b) a decrease in non-HDL cholesterol;
(c) a decrease in triglyceride;
(d) a decrease in the ratio of total cholesterol:HDL
cholesterol; and (e) any combination of (a) to (d).
(a) a decrease in cholesterol;
(b) a decrease in non-HDL cholesterol;
(c) a decrease in triglyceride;
(d) a decrease in the ratio of total cholesterol:HDL
cholesterol; and (e) any combination of (a) to (d).
4. The use according to any one of claims 1 to 3, wherein said lipid parameter is associated with a condition selected from the group consisting of lipodystrophy, lipohypertrophy, obesity, dyslipidemia, hypertriglyceridemia and syndrome X.
5. The use of claim 4, wherein said lipodystrophy is HIV-related lipodystrophy.
6. Use of an agent selected from the group consisting of:
(a) a growth hormone (GH) secretagogue; and (b) a composition comprising a GH secretagogue and a pharmaceutically acceptable carrier;
for altering a first body composition parameter of a subject, wherein said alteration of a first body composition parameter results in no or substantially no decrease in a second body composition parameter of said subject, wherein said second body composition parameter is selected from the group consisting of:
(i) limb fat;
(ii) subcutaneous fat;
(iii)subcutaneous abdominal tissue (SAT); and (iv) any combination of (i) to (iii).
(a) a growth hormone (GH) secretagogue; and (b) a composition comprising a GH secretagogue and a pharmaceutically acceptable carrier;
for altering a first body composition parameter of a subject, wherein said alteration of a first body composition parameter results in no or substantially no decrease in a second body composition parameter of said subject, wherein said second body composition parameter is selected from the group consisting of:
(i) limb fat;
(ii) subcutaneous fat;
(iii)subcutaneous abdominal tissue (SAT); and (iv) any combination of (i) to (iii).
7. Use of a growth hormone (GH) secretagogue for the preparation of a medicament for altering a first body composition parameter of a subject, wherein said alteration of a first body composition parameter results in no or substantially no decrease in a second body composition parameter of said subject, wherein said second body composition parameter is selected from the group consisting of:
(i) limb fat;
(ii) subcutaneous fat;
(iii)subcutaneous abdominal tissue (SAT); and (iv) any combination of (i) to (iii).
(i) limb fat;
(ii) subcutaneous fat;
(iii)subcutaneous abdominal tissue (SAT); and (iv) any combination of (i) to (iii).
8. The use of claim 6 or 7, wherein said alteration of a first body composition parameter is selected from the group consisting of:
(a) an increase in lean body mass (b) a decrease in trunk fat;
(c) a decrease in visceral fat;
(d) a decrease in abdominal girth;
(e) a decrease in visceral abdominal tissue (VAT);
(f) a decrease in VAT:SAT ratio; and (g) any combination of (a) to (f).
(a) an increase in lean body mass (b) a decrease in trunk fat;
(c) a decrease in visceral fat;
(d) a decrease in abdominal girth;
(e) a decrease in visceral abdominal tissue (VAT);
(f) a decrease in VAT:SAT ratio; and (g) any combination of (a) to (f).
9. The use according to any one of claims 6 to 8, wherein said first body composition parameter is associated with a condition selected from the group consisting of lipodystrophy, lipohypertrophy, obesity, dyslipidemia, hypertriglyceridemia and syndrome X.
10. The use of claim 9, wherein said lipodystrophy is HIV-related lipodystrophy.
11. The use according to any one of claims 6 to 10, wherein said alteration of a first body composition parameter results in an improvement in quality of life of said subject.
12. Use of an agent selected from the group consisting of:
(a) a growth hormone (GH) secretagogue; and (b) a composition comprising a GH secretagogue and a pharmaceutically acceptable carrier;
for treating a condition characterized by deficient or decreased bone formation in a subject.
(a) a growth hormone (GH) secretagogue; and (b) a composition comprising a GH secretagogue and a pharmaceutically acceptable carrier;
for treating a condition characterized by deficient or decreased bone formation in a subject.
13. Use of a growth hormone (GH) secretagogue for the preparation of a medicament for treating a condition characterized by deficient or decreased bone formation in a subject.
14. The use of claim 13 or 14, wherein said condition is selected from the group consisting of osteopenia and osteoporosis.
15. The use according to any one of claims 1 to 14, wherein said subject is HIV positive.
16. The use of claim 15, wherein said subject is receiving antiviral therapy.
17. The use according to any one of claims 1 to 16, wherein said subject suffers from a condition selected from the group consisting of diabetes, glucose intolerance and insulin resistance.
18. Use of an agent selected from the group consisting of:
(a) a growth hormone (GH) secretagogue; and (b) a composition comprising a GH secretagogue and a pharmaceutically acceptable carrier;
for improving (i) daytime vigilance, (ii) cognitive function, or (iii) both (i) and (ii).
(a) a growth hormone (GH) secretagogue; and (b) a composition comprising a GH secretagogue and a pharmaceutically acceptable carrier;
for improving (i) daytime vigilance, (ii) cognitive function, or (iii) both (i) and (ii).
19. Use of a growth hormone (GH) secretagogue for the preparation of a medicament for improving (i) daytime vigilance, (ii) cognitive function, or (iii) both (i) and (ii).
20. The use of claim 18 or 19, wherein said cognitive function is selected from the group consisting of thinking, reasoning, problem solving and memory.
21. Use of an agent selected from the group consisting of:
(a) a growth hormone (GH) secretagogue; and (b) a composition comprising a GH secretagogue and a pharmaceutically acceptable carrier;
for improving a metabolic condition in a subject.
(a) a growth hormone (GH) secretagogue; and (b) a composition comprising a GH secretagogue and a pharmaceutically acceptable carrier;
for improving a metabolic condition in a subject.
22. Use of a growth hormone (GH) secretagogue for the preparation of a medicament for improving a metabolic condition in a subject.
23. The use of claim 21 or 22, wherein said metabolic condition is a catabolic condition, and wherein said method is a method of improving anabolism in said catabolic condition.
24. The use of claim 23, wherein said catabolic condition is muscular wasting.
25. The use of claim 23 or 24, wherein the catabolic condition is related to one selected from the group consisting of chronic renal failure, congestive heart failure, AIDS, hip fracture, trauma or major surgery in a subject.
26. The use according to any one of claims 21 to 25, wherein said subject is an elderly subject.
27. Use of an agent selected from the group consisting of:
(a) a growth hormone (GH) secretagogue; and (b) a composition comprising a GH secretagogue and a pharmaceutically acceptable carrier;
for improving or reconstituting immune function in a subject.
(a) a growth hormone (GH) secretagogue; and (b) a composition comprising a GH secretagogue and a pharmaceutically acceptable carrier;
for improving or reconstituting immune function in a subject.
28. Use of a growth hormone (GH) secretagogue for the preparation of a medicament for improving or reconstituting immune function in a subject.
29. The use of claim 27 or 28, wherein said subject is in an immunodeficient state.
30. The use of claim 29, wherein said immunodeficient state is caused by a condition or treatment selected from the group consisting of aging, HIV infection, chemotherapy treatment and radiotherapy treatment.
31. The use according to any one of claims 1-30, wherein said GH secretagogue is selected from the group consisting of GH-releasing factor (GRF) and a GRF
analog.
analog.
32. The use of claim 31 wherein said GRF analog is a GRF
analog of formula A:
X-GRF Peptide (A) wherein;
the GRF peptide is a peptide of formula B;
A1-A2-Asp-Ala-Ile-Phe-Thr-A8-Ser-Tyr-Arg-Lys-A13-Leu-A15-Gln-Leu-A18-Ala-Arg-Lys-Leu-Leu-A24-A25-Ile-A27-A28-Arg-A30-R0 (B) wherein, A1 is Tyr or His;
A2 is Val or Ala;
A8 is Asn or Ser;
A13 is Val or Ile;
A15 is Ala or Gly;
A18 is Ser or Tyr;
A24 is Gln or His;
A25 is Asp or Glu;
A27 is Met, Ile or Nle;
A28 is Ser or Asn;
A30 is a bond or amino acid sequence of 1 up to 15 residues; and R0 is NH2 or NH-(CH2)n-CONH2, with n=1 to 12; and X is a hydrophobic tail anchored via an amide bond to the N-terminus of the peptide and the hydrophobic tail defining a backbone of 5 to 7 atoms;
wherein the backbone can be substituted by C1-6 alkyl, C3-6 cycloalkyl, or C6-12 aryl and the backbone comprises at least one rigidifying moiety connected to at least two atoms of the backbone;
said moiety selected from the group consisting of double bond, triple bond, saturated or unsaturated C3-9 cycloalkyl, and C6-12 aryl.
analog of formula A:
X-GRF Peptide (A) wherein;
the GRF peptide is a peptide of formula B;
A1-A2-Asp-Ala-Ile-Phe-Thr-A8-Ser-Tyr-Arg-Lys-A13-Leu-A15-Gln-Leu-A18-Ala-Arg-Lys-Leu-Leu-A24-A25-Ile-A27-A28-Arg-A30-R0 (B) wherein, A1 is Tyr or His;
A2 is Val or Ala;
A8 is Asn or Ser;
A13 is Val or Ile;
A15 is Ala or Gly;
A18 is Ser or Tyr;
A24 is Gln or His;
A25 is Asp or Glu;
A27 is Met, Ile or Nle;
A28 is Ser or Asn;
A30 is a bond or amino acid sequence of 1 up to 15 residues; and R0 is NH2 or NH-(CH2)n-CONH2, with n=1 to 12; and X is a hydrophobic tail anchored via an amide bond to the N-terminus of the peptide and the hydrophobic tail defining a backbone of 5 to 7 atoms;
wherein the backbone can be substituted by C1-6 alkyl, C3-6 cycloalkyl, or C6-12 aryl and the backbone comprises at least one rigidifying moiety connected to at least two atoms of the backbone;
said moiety selected from the group consisting of double bond, triple bond, saturated or unsaturated C3-9 cycloalkyl, and C6-12 aryl.
33. The use of claim 32, wherein X is selected from the group consisting of:
1 (R=H or CH3 or CH2CH3) cis or trans 2 (R=H or CH3 or CH2CH3) 3 (R=H or CH3 or CH2CH3) cis or trans, both as racemic mixtures or pure enantiomeric pairs 4 (R=H or CH3 or CH2CH3) cis or trans, both as racemic mixtures or pure enantiomeric pairs (R=H or CH3 or CH2CH3) cis or trans, (when R ~ H) 6 (R=H or CH2 or CH2CH3) cis or trans, both as racemic mixtures or pure enantiomeric pairs 7 (R ~H or CH3 or CH3CH3) cis or trans, (when R ~ H) both as racemic mixtures or pure enantiomeric pairs 8 (R~H or CH3 or CH2CH3) cis or trans, both as racemic mixtures or pure enantiomeric pairs 9 (R~H or CH3 or CH2CH3) cis or trans, (when R ~ H) both as racemic mixtures or pure enantiomeric pairs 10 (R~H or CH3 or CH2CH3) cis or trans, (when R ~ H) 11 (R~H or CH3 or CH2CH3) 12 (R~H or CH3 or CH2CH3) 13 (R~H or CH3 or CH2CH3)
1 (R=H or CH3 or CH2CH3) cis or trans 2 (R=H or CH3 or CH2CH3) 3 (R=H or CH3 or CH2CH3) cis or trans, both as racemic mixtures or pure enantiomeric pairs 4 (R=H or CH3 or CH2CH3) cis or trans, both as racemic mixtures or pure enantiomeric pairs (R=H or CH3 or CH2CH3) cis or trans, (when R ~ H) 6 (R=H or CH2 or CH2CH3) cis or trans, both as racemic mixtures or pure enantiomeric pairs 7 (R ~H or CH3 or CH3CH3) cis or trans, (when R ~ H) both as racemic mixtures or pure enantiomeric pairs 8 (R~H or CH3 or CH2CH3) cis or trans, both as racemic mixtures or pure enantiomeric pairs 9 (R~H or CH3 or CH2CH3) cis or trans, (when R ~ H) both as racemic mixtures or pure enantiomeric pairs 10 (R~H or CH3 or CH2CH3) cis or trans, (when R ~ H) 11 (R~H or CH3 or CH2CH3) 12 (R~H or CH3 or CH2CH3) 13 (R~H or CH3 or CH2CH3)
34. The use of claim 32 or 33, wherein A30 is selected from the group consisting of:
(a) a bond;
(b) an amino acid sequence corresponding to positions 30-44 of a natural GRF peptide, and (c) said amino acid sequence of (b) having a 1-14 amino acid deletion from its C-terminus.
(a) a bond;
(b) an amino acid sequence corresponding to positions 30-44 of a natural GRF peptide, and (c) said amino acid sequence of (b) having a 1-14 amino acid deletion from its C-terminus.
35. The use of claim 32 or 33, wherein said GRF peptide is selected from the group consisting of:
(a) a polypeptide comprising the amino acid sequence of SEQ ID NO: 3;
(b) a polypeptide comprising the amino acid sequence of SEQ ID NO: 5; and (c) the polypeptide of (a) having a 1 to 14 amino acid deletion from its C-terminus.
(a) a polypeptide comprising the amino acid sequence of SEQ ID NO: 3;
(b) a polypeptide comprising the amino acid sequence of SEQ ID NO: 5; and (c) the polypeptide of (a) having a 1 to 14 amino acid deletion from its C-terminus.
36. The use according to any one of claims 31 to 35, wherein said GRF analog is (hexenoyl trans-3)hGRF(1-44) NH2.
37. The use according to any one of claims 31 to 36, wherein said GRF analog is adapted for administration at a dose of about 0.0001 to 2 about mg.
38. The use of claim 37, wherein said GRF analog is adapted for administration at a dose selected from the group consisting of about 1 mg and about 2 mg.
39. The use according to any one of claims 1 to 38, wherein said agent is adapted for administration by a route selected from the group consisting of intravenous, oral, transdermal, subcutaneous, mucosal, intramuscular, intranasal, intrapulmonary, parenteral, intrarectal and topical.
40. The use of claim 39, wherein said agent is adapted for administration by a subcutaneous route.
41. A package comprising an agent selected from the group consisting of:
(a) a growth hormone (GH) secretagogue; and (b) a composition comprising a GH secretagogue and a pharmaceutically acceptable carrier;
together with instructions for altering a lipid parameter in a subject, wherein said alteration of a lipid parameter results in no or substantially no increase in blood glucose levels in said subject.
(a) a growth hormone (GH) secretagogue; and (b) a composition comprising a GH secretagogue and a pharmaceutically acceptable carrier;
together with instructions for altering a lipid parameter in a subject, wherein said alteration of a lipid parameter results in no or substantially no increase in blood glucose levels in said subject.
42. The package of claim 41, wherein said alteration of a lipid parameter is selected from the group consisting of:
(a) a decrease in cholesterol;
(b) a decrease in non-HDL cholesterol;
(c) a decrease in triglyceride;
(d) a decrease in the ratio of total cholesterol:HDL
cholesterol; and (e) any combination of (a) to (d).
(a) a decrease in cholesterol;
(b) a decrease in non-HDL cholesterol;
(c) a decrease in triglyceride;
(d) a decrease in the ratio of total cholesterol:HDL
cholesterol; and (e) any combination of (a) to (d).
43. The package of claim 41 or 42, wherein said lipid parameter is associated with a condition selected from the group consisting of lipodystrophy, lipohypertrophy, obesity, dyslipidemia, hypertriglyceridemia and syndrome X.
44. The package of claim 43, wherein said lipodystrophy is HIV-related lipodystrophy.
45. A package comprising an agent selected from the group consisting of:
(a) a growth hormone (GH) secretagogue; and (b) a composition comprising a GH secretagogue and a pharmaceutically acceptable carrier;
together with instructions for altering a first body composition parameter of a subject, wherein said alteration of a first body composition parameter results in no or substantially no decrease in a second body composition parameter of said subject, wherein said second body composition parameter is selected from the group consisting of:
(i) limb fat;
(ii) subcutaneous fat;
(iii)subcutaneous abdominal tissue (SAT); and (iv) any combination of (i) to (iii).
(a) a growth hormone (GH) secretagogue; and (b) a composition comprising a GH secretagogue and a pharmaceutically acceptable carrier;
together with instructions for altering a first body composition parameter of a subject, wherein said alteration of a first body composition parameter results in no or substantially no decrease in a second body composition parameter of said subject, wherein said second body composition parameter is selected from the group consisting of:
(i) limb fat;
(ii) subcutaneous fat;
(iii)subcutaneous abdominal tissue (SAT); and (iv) any combination of (i) to (iii).
46. The package of claim 45, wherein said alteration of a first body composition parameter is selected from the group consisting of:
(a) an increase in lean body mass (b) a decrease in trunk fat;
(c) a decrease in visceral fat;
(d) a decrease in abdominal girth;
(e) a decrease in visceral abdominal tissue (VAT);
(f) a decrease in VAT:SAT ratio; and (g) any combination of (a) to (f).
(a) an increase in lean body mass (b) a decrease in trunk fat;
(c) a decrease in visceral fat;
(d) a decrease in abdominal girth;
(e) a decrease in visceral abdominal tissue (VAT);
(f) a decrease in VAT:SAT ratio; and (g) any combination of (a) to (f).
47. The package of claim 45 or 46, wherein said first body composition parameter is associated with a condition selected from the group consisting of lipodystrophy, lipohypertrophy, obesity, dyslipidemia, hypertriglyceridemia and syndrome X.
48. The package of claim 47, wherein said lipodystrophy is HIV-related lipodystrophy.
49. The package according to any one of claims 45 to 48, wherein said alteration of a first body composition parameter results in an improvement in quality of life of said subject.
50. A package comprising an agent selected from the group consisting of:
(a) a growth hormone (GH) secretagogue; and (b) a composition comprising a GH secretagogue and a pharmaceutically acceptable carrier;
together with instructions for treating a condition characterized by deficient or decreased bone formation in a subject.
(a) a growth hormone (GH) secretagogue; and (b) a composition comprising a GH secretagogue and a pharmaceutically acceptable carrier;
together with instructions for treating a condition characterized by deficient or decreased bone formation in a subject.
51. The package of claim 50, wherein said condition is selected from the group consisting of osteopenia and osteoporosis.
52. The package according to any one of claims 41 to 51, wherein said subject is HIV positive.
53. The package of claim 52, wherein said subject is receiving antiviral therapy.
54. The package according to any one of claims 41 to 53, wherein said subject suffers from a condition selected from the group consisting of diabetes, glucose intolerance and insulin resistance.
55. A package comprising an agent selected from the group consisting of:
(a) a growth hormone (GH) secretagogue; and (b) a composition comprising a GH secretagogue and a pharmaceutically acceptable carrier;
together with instructions for improving (i) daytime vigilance, (ii) cognitive function, or (iii) both (i) and (ii).
(a) a growth hormone (GH) secretagogue; and (b) a composition comprising a GH secretagogue and a pharmaceutically acceptable carrier;
together with instructions for improving (i) daytime vigilance, (ii) cognitive function, or (iii) both (i) and (ii).
56. The package of claim 55, wherein said cognitive function is selected from the group consisting of thinking, reasoning, problem solving and memory.
57. A package comprising an agent selected from the group consisting of:
(a) a growth hormone (GH) secretagogue; and (b) a composition comprising a GH secretagogue and a pharmaceutically acceptable carrier;
together with instructions for improving a metabolic condition in a subject.
(a) a growth hormone (GH) secretagogue; and (b) a composition comprising a GH secretagogue and a pharmaceutically acceptable carrier;
together with instructions for improving a metabolic condition in a subject.
58. The package of claim 57, wherein said metabolic condition is a catabolic condition, and wherein said method is a method of improving anabolism in said catabolic condition.
59. The package of claim 58, wherein said catabolic condition is muscular wasting.
60. The package of claim 58 or 59, wherein the catabolic condition is related to one selected from the group consisting of chronic renal failure, congestive heart failure, AIDS, hip fracture, trauma or major surgery in a subject.
61. The package according to any one of claims 57 to 60, wherein said subject is an elderly subject.
62. A package comprising an agent selected from the group consisting of:
(a) a growth hormone (GH) secretagogue; and (b) a composition comprising a GH secretagogue and a pharmaceutically acceptable carrier;
together with instructions for improving or reconstituting immune function in a subject.
(a) a growth hormone (GH) secretagogue; and (b) a composition comprising a GH secretagogue and a pharmaceutically acceptable carrier;
together with instructions for improving or reconstituting immune function in a subject.
63. The package of claim 62, wherein said subject is in an immunodeficient state.
64. The package of claim 63, wherein said immunodeficient state is caused by a condition or treatment selected from the group consisting of aging, HIV infection, chemotherapy treatment and radiotherapy treatment.
65. The package according to any one of claims 41 to 64, wherein said GH secretagogue is selected from the group consisting of GH-releasing factor (GRF) and a GRF
analog.
analog.
66. The package of claim 65 wherein said GRF analog is a GRF analog of formula A:
X-GRF Peptide (A) wherein;
the GRF peptide is a peptide of formula B;
A1-A2-Asp-Ala-Ile-Phe-Thr-A8-Ser-Tyr-Arg-Lys-A13-Leu-A15-Gln-Leu-A18-Ala-Arg-Lys-Leu-Leu-A24-A25-Ile-A27-A28-Arg-A30-R0 (B) wherein, A1 is Tyr or His;
A2 is Val or Ala;
A8 is Asn or Ser;
A13 is Val or Ile;
A15 is Ala or Gly;
A18 is Ser or Tyr;
A24 is Gln or His;
A25 is Asp or Glu;
A27 is Met, Ile or Nle;
A28 is Ser or Asn;
A30 is a bond or amino acid sequence of 1 up to 15 residues; and R0 is NH2 or NH- (CH2) n-CONH2, with n=1 to 12; and X is a hydrophobic tail anchored via an amide bond to the N-terminus of the peptide and the hydrophobic tail defining a backbone of 5 to 7 atoms;
wherein the backbone can be substituted by C1-6 alkyl, C3-6 cycloalkyl, or C6-12 aryl and the backbone comprises at least one rigidifying moiety connected to at least two atoms of the backbone;
said moiety selected from the group consisting of double bond, triple bond, saturated or unsaturated C3-9 cycloalkyl, and C6-12 aryl.
X-GRF Peptide (A) wherein;
the GRF peptide is a peptide of formula B;
A1-A2-Asp-Ala-Ile-Phe-Thr-A8-Ser-Tyr-Arg-Lys-A13-Leu-A15-Gln-Leu-A18-Ala-Arg-Lys-Leu-Leu-A24-A25-Ile-A27-A28-Arg-A30-R0 (B) wherein, A1 is Tyr or His;
A2 is Val or Ala;
A8 is Asn or Ser;
A13 is Val or Ile;
A15 is Ala or Gly;
A18 is Ser or Tyr;
A24 is Gln or His;
A25 is Asp or Glu;
A27 is Met, Ile or Nle;
A28 is Ser or Asn;
A30 is a bond or amino acid sequence of 1 up to 15 residues; and R0 is NH2 or NH- (CH2) n-CONH2, with n=1 to 12; and X is a hydrophobic tail anchored via an amide bond to the N-terminus of the peptide and the hydrophobic tail defining a backbone of 5 to 7 atoms;
wherein the backbone can be substituted by C1-6 alkyl, C3-6 cycloalkyl, or C6-12 aryl and the backbone comprises at least one rigidifying moiety connected to at least two atoms of the backbone;
said moiety selected from the group consisting of double bond, triple bond, saturated or unsaturated C3-9 cycloalkyl, and C6-12 aryl.
67. The package of claim 66, wherein X is selected from the group consisting of:
1 (R~H or CH3 or CH3CH3) cis or trans 2 (R~H or CH3 or CH2CH3) 3 (R=H or CH3 or CH2CH3), cis or trans, both as racemic mixtures or pure enantiomeric pairs.
4 (R=H or CH3 or CH2CH3) cis or trans, both as racemic mixtures or pure enantiomeric pairs 5 (R=H or CH3 or CH2CH3) cis or trans, (when R .noteq. H) 6 (R=H or CH3 or CH2CH3) cis or trans, both as racemic mixtures or pure enantiomeric pairs 7 (R=H or CH3 or CH2CH3) cis or trans, (when R .noteq. H) both as racemic mixtures or pure enantiomeric pairs 8 (R=H or CH3 or CH2CH3) cis or trans, both as racemic mixtures or pure enantiomeric pairs 9 (R=H or CH3 or CH2CH3) cis or trans, (when R .noteq. H) both as racemic mixtures or pure enantionmeric pairs (R=H or CH3 or CH2CH3) cis or trans, (when R .noteq. H) 11 (R=H or CH3 or CH2CH3) 12 (R=H or CH3 or CH2CH3) 13 (R=H or CH3 or CH2CH3)
1 (R~H or CH3 or CH3CH3) cis or trans 2 (R~H or CH3 or CH2CH3) 3 (R=H or CH3 or CH2CH3), cis or trans, both as racemic mixtures or pure enantiomeric pairs.
4 (R=H or CH3 or CH2CH3) cis or trans, both as racemic mixtures or pure enantiomeric pairs 5 (R=H or CH3 or CH2CH3) cis or trans, (when R .noteq. H) 6 (R=H or CH3 or CH2CH3) cis or trans, both as racemic mixtures or pure enantiomeric pairs 7 (R=H or CH3 or CH2CH3) cis or trans, (when R .noteq. H) both as racemic mixtures or pure enantiomeric pairs 8 (R=H or CH3 or CH2CH3) cis or trans, both as racemic mixtures or pure enantiomeric pairs 9 (R=H or CH3 or CH2CH3) cis or trans, (when R .noteq. H) both as racemic mixtures or pure enantionmeric pairs (R=H or CH3 or CH2CH3) cis or trans, (when R .noteq. H) 11 (R=H or CH3 or CH2CH3) 12 (R=H or CH3 or CH2CH3) 13 (R=H or CH3 or CH2CH3)
68. The package of claim 66 or 67, wherein A30 is selected from the group consisting of:
(a) a bond;
(b) an amino acid sequence corresponding to positions 30-44 of a natural GRF peptide, and (c) said amino acid sequence of (b) having a 1-14 amino acid deletion from its C-terminus.
(a) a bond;
(b) an amino acid sequence corresponding to positions 30-44 of a natural GRF peptide, and (c) said amino acid sequence of (b) having a 1-14 amino acid deletion from its C-terminus.
69. The package of claim 66 or 67, wherein said GRF peptide is selected from the group consisting of:
(a) a polypeptide comprising the amino acid sequence of SEQ :ID NO: 3;
(b) a polypeptide comprising the amino acid sequence of SEQ ID NO: 5; and (c) the polypeptide of (a) having a 1 to 14 amino acid deletion from its C-terminus.
(a) a polypeptide comprising the amino acid sequence of SEQ :ID NO: 3;
(b) a polypeptide comprising the amino acid sequence of SEQ ID NO: 5; and (c) the polypeptide of (a) having a 1 to 14 amino acid deletion from its C-terminus.
70. The package according to any one of claims 65 to 69, wherein said GRF analog is (hexenoyl trans-3)hGRF(1-44)NH2.
71. The package according to any one of claims 65 to 70, wherein said GRF analog is adapted for administration at a dose of about 0.0001 to 2 mg.
72. The package of claim 71, wherein said GRF analog is adapted for administration at a dose selected from the group consisting of about 1 mg and about 2 mg.
73. The package according to any one of claims 41 to 72, wherein said agent is adapted for administration by a route selected from the group consisting of intravenous, oral, transdermal, subcutaneous, mucosal, intramuscular, intranasal, intrapulmonary, parenteral, intrarectal and topical.
74. The package of claim 73, wherein said agent is adapted for administration by a subcutaneous route.
75. A composition for altering a lipid parameter in a subject, wherein said alteration of a lipid parameter results in no or substantially no increase in blood glucose levels in said subject, said composition comprising a GH secretagogue and a pharmaceutically acceptable carrier.
76. The composition of claim 75, wherein said alteration of a lipid parameter is selected from the group consisting of:
(a) a decrease in cholesterol;
(b) a decrease in non-HDL cholesterol;
(c) a decrease in triglyceride;
(d) a decrease in the ratio of total cholesterol:HDL
cholesterol; and (e) any combination of (a) to (d).
(a) a decrease in cholesterol;
(b) a decrease in non-HDL cholesterol;
(c) a decrease in triglyceride;
(d) a decrease in the ratio of total cholesterol:HDL
cholesterol; and (e) any combination of (a) to (d).
77. The composition of claim 75 or 76, wherein said lipid parameter is associated with a condition selected from the group consisting of lipodystrophy, lipohypertrophy, obesity, dyslipidemia, hypertriglyceridemia and syndrome X.
78. The composition of claim 77, wherein said lipodystrophy is HIV-related lipodystrophy.
79. A composition for altering a first body composition parameter of a subject, wherein said alteration of a first body composition parameter results in no or substantially no decrease in a second body composition parameter of said subject, wherein said second body composition parameter is selected from the group consisting of:
(i) limb fat;
(ii) subcutaneous fat;
(iii)subcutaneous abdominal tissue (SAT); and (iv) any combination of (i) to (iii);
said composition comprising a GH secretagogue and a pharmaceutically acceptable carrier.
(i) limb fat;
(ii) subcutaneous fat;
(iii)subcutaneous abdominal tissue (SAT); and (iv) any combination of (i) to (iii);
said composition comprising a GH secretagogue and a pharmaceutically acceptable carrier.
80. The composition of claim 79, wherein said alteration of a first body composition parameter is selected from the group consisting of:
(a) an increase in lean body mass (b) a decrease in trunk fat;
(c) a decrease in visceral fat;
(d) a decrease in abdominal girth;
(e) a decrease in visceral abdominal tissue (VAT);
(f) a decrease in VAT:SAT ratio; and (g) any combination of (a) to (f).
(a) an increase in lean body mass (b) a decrease in trunk fat;
(c) a decrease in visceral fat;
(d) a decrease in abdominal girth;
(e) a decrease in visceral abdominal tissue (VAT);
(f) a decrease in VAT:SAT ratio; and (g) any combination of (a) to (f).
81. The composition according to claim 79 or 80, wherein said first body composition parameter is associated with a condition selected from the group consisting of lipodystrophy, lipohypertrophy, obesity, dyslipidemia, hypertriglyceridemia and syndrome X.
82. The composition of claim 81, wherein said lipodystrophy is HIV-related lipodystrophy.
83. The composition according to any one of claims 79 to 82, wherein said alteration of a first body composition parameter results in an improvement in quality of life of said subject.
84. A composition for treating a condition characterized by deficient or decreased bone formation in a subject, said composition comprising a GH secretagogue and a pharmaceutically acceptable carrier.
85. The composition of claim 84, wherein said condition is selected from the group consisting of osteopenia and osteoporosis.
86. The composition according to any one of claims 75 to 85, wherein said subject is HIV positive.
87. The composition of claim 86, wherein said subject is receiving antiviral therapy.
88. The composition according to any one of claims 75 to 87, wherein said subject suffers from a condition selected from the group consisting of diabetes, glucose intolerance and insulin resistance.
89. A composition for improving (i) daytime vigilance, (ii) cognitive function, or (iii) both (i) and (ii), said composition comprising a GH secretagogue and a pharmaceutically acceptable carrier.
90. The composition of claim 89, wherein said cognitive function is selected from the group consisting of thinking, reasoning, problem solving and memory.
91. A composition for improving a metabolic condition in a subject, said composition comprising a GH secretagogue and a pharmaceutically acceptable carrier.
92. The composition of claim 91, wherein said metabolic condition is a catabolic condition, and wherein said method is a method of improving anabolism in said catabolic condition.
93. The composition of claim 92, wherein said catabolic condition is muscular wasting.
94. The composition of claim 92 or 93, wherein the catabolic condition is related to one selected from the group consisting of chronic renal failure, congestive heart failure, AIDS, hip fracture, trauma or major surgery in a subject.
95. The composition according to any one of claims 91 to 94, wherein said subject is an elderly subject.
96. A composition for improving or reconstituting immune function in a subject, said composition comprising a GH
secretagogue and a pharmaceutically acceptable carrier.
secretagogue and a pharmaceutically acceptable carrier.
97. The composition of claim 96, wherein said subject is in an immunodeficient state.
98. The composition of claim 97, wherein said immunodeficient state is caused by a condition or treatment selected from the group consisting of aging, HIV infection, chemotherapy treatment and radiotherapy treatment.
99. The composition according to any one of claims 75 to 98, wherein said GH secretagogue is selected from the group consisting of GH-releasing factor (GRF) and a GRF
analog.
analog.
100. The composition of claim 99 wherein said GRF analog is a GRF analog of formula A:
X-GRF Peptide (A) wherein;
the GRF peptide is a peptide of formula B;
A1-A2-Asp-Ala-Ile-Phe-Thr-A8-Ser-Tyr-Arg-Lys-A13-Leu-A15-Gln-Leu-A18-Ala-Arg-Lys-Leu-Leu-A24-A25-Ile-A27-A28-Arg-A30-R0 (B) wherein, A1 is Tyr or His;
A2 is Val or Ala;
A8 is Asn or Ser;
A13 is Val or Ile;
A15 is Ala or Gly;
A18 is Ser or Tyr;
A24 is Gln or His;
A25 is Asp or Glu;
A27 is Met, Ile or Nle;
A28 is Ser or Asn;
A30 is a bond or amino acid sequence of 1 up to 15 residues; and R0 is NH2 or NH-(CH2)n-CONH2, with n=1 to 12; and X is a hydrophobic tail anchored via an amide bond to the N-terminus of the peptide and the hydrophobic tail defining a backbone of 5 to 7 atoms;
wherein the backbone can be substituted by C1-6 alkyl, C3-6 cycloalkyl, or C6-12 aryl and the backbone comprises at least one rigidifying moiety connected to at least two atoms of the backbone;
said moiety selected from the group consisting of double bond, triple bond, saturated or unsaturated C3-9 cycloalkyl, and C6-12 aryl.
X-GRF Peptide (A) wherein;
the GRF peptide is a peptide of formula B;
A1-A2-Asp-Ala-Ile-Phe-Thr-A8-Ser-Tyr-Arg-Lys-A13-Leu-A15-Gln-Leu-A18-Ala-Arg-Lys-Leu-Leu-A24-A25-Ile-A27-A28-Arg-A30-R0 (B) wherein, A1 is Tyr or His;
A2 is Val or Ala;
A8 is Asn or Ser;
A13 is Val or Ile;
A15 is Ala or Gly;
A18 is Ser or Tyr;
A24 is Gln or His;
A25 is Asp or Glu;
A27 is Met, Ile or Nle;
A28 is Ser or Asn;
A30 is a bond or amino acid sequence of 1 up to 15 residues; and R0 is NH2 or NH-(CH2)n-CONH2, with n=1 to 12; and X is a hydrophobic tail anchored via an amide bond to the N-terminus of the peptide and the hydrophobic tail defining a backbone of 5 to 7 atoms;
wherein the backbone can be substituted by C1-6 alkyl, C3-6 cycloalkyl, or C6-12 aryl and the backbone comprises at least one rigidifying moiety connected to at least two atoms of the backbone;
said moiety selected from the group consisting of double bond, triple bond, saturated or unsaturated C3-9 cycloalkyl, and C6-12 aryl.
101. The composition of claim 100, wherein X is selected from the group consisting of:
1 (R=H or CH3 or CH2CH3) cis or trans 2 (R=H or CH3 or CH2CH3) 3 (R=H or CH3 or CH2CH3) cis or trans, both as racemic mixtures or pure enantiomeric pairs 4 (R=H or CH3 or CH2CH3) cis or trans, both as racemic mixtures or pure enantiomeric pairs (R=H or CH3 or CH2CH3) cis or trans, (when R .noteq. H) 6 (R=H or CH3 or CH2CH3) cis or trans, both as racemic mixtures or pure enantiomeric pairs 7 (R=H or CH3 or CH2CH3) cis or trans, (when R .noteq. H) both as racemic mixtures or pure enantiomeric pairs 8 (R=H or CH3 or CH2CH3) cis or trans, both as racemic mixtures or pure enantiomeric pairs 9 (R=H or CH, or CH2CH3) cis or trans, (when R .noteq. H) both as recemic mixtures or pure enantiomeric pairs 10 (R=H or CH3, or CH2CH3) cis or trans, (when R .noteq. H) 11 (R=H or CH, or CH2CH2) 12 (R=H or CH3 or CH2CH3) 13 (R=H or CH3 or CH2CH3)
1 (R=H or CH3 or CH2CH3) cis or trans 2 (R=H or CH3 or CH2CH3) 3 (R=H or CH3 or CH2CH3) cis or trans, both as racemic mixtures or pure enantiomeric pairs 4 (R=H or CH3 or CH2CH3) cis or trans, both as racemic mixtures or pure enantiomeric pairs (R=H or CH3 or CH2CH3) cis or trans, (when R .noteq. H) 6 (R=H or CH3 or CH2CH3) cis or trans, both as racemic mixtures or pure enantiomeric pairs 7 (R=H or CH3 or CH2CH3) cis or trans, (when R .noteq. H) both as racemic mixtures or pure enantiomeric pairs 8 (R=H or CH3 or CH2CH3) cis or trans, both as racemic mixtures or pure enantiomeric pairs 9 (R=H or CH, or CH2CH3) cis or trans, (when R .noteq. H) both as recemic mixtures or pure enantiomeric pairs 10 (R=H or CH3, or CH2CH3) cis or trans, (when R .noteq. H) 11 (R=H or CH, or CH2CH2) 12 (R=H or CH3 or CH2CH3) 13 (R=H or CH3 or CH2CH3)
102. The composition of claim 100 or 101, wherein A30 is selected from the group consisting of:
(a) a bond;
(b) an amino acid sequence corresponding to positions 30-44 of a natural GRF peptide, and (c) said amino acid sequence of (b) having a 1-14 amino acid deletion from its C-terminus.
(a) a bond;
(b) an amino acid sequence corresponding to positions 30-44 of a natural GRF peptide, and (c) said amino acid sequence of (b) having a 1-14 amino acid deletion from its C-terminus.
103. The composition of claim 100 or 101, wherein said GRF
peptide is selected from the group consisting of:
(a) a polypeptide comprising the amino acid sequence of SEQ ID NO: 3;
(b) a polypeptide comprising the amino acid sequence of SEQ ID NO: 5; and (c) the polypeptide of (a) having a 1 to 14 amino acid deletion from its C-terminus.
peptide is selected from the group consisting of:
(a) a polypeptide comprising the amino acid sequence of SEQ ID NO: 3;
(b) a polypeptide comprising the amino acid sequence of SEQ ID NO: 5; and (c) the polypeptide of (a) having a 1 to 14 amino acid deletion from its C-terminus.
104. The composition according to any one of claims 99 to 103, wherein said GRF analog is (hexenoyl trans-3)hGRF(1-44)NH2.
105. The composition according to any one of claims 99 to 104, wherein said GRF analog is adapted for administration at a dose of about 0.0001 to 2 mg.
106. The composition of claim 105, wherein said GRF analog is adapted for administration at a dose selected from the group consisting of about 1 mg and about 2 mg.
107. The composition according to any one of claims 75 to 106, wherein said composition is adapted for administration by a route selected from the group consisting of intravenous, oral, transdermal, subcutaneous, mucosal, intramuscular, intranasal, intrapulmonary, parenteral, intrarectal and topical.
108. The composition of claim 107, wherein said composition is adapted for administration by a subcutaneous route.
Priority Applications (11)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA2485472A CA2485472C (en) | 2004-10-20 | 2004-10-20 | Gh secretagogues and uses thereof |
| AU2005297366A AU2005297366B2 (en) | 2004-10-20 | 2005-10-20 | GH secretagogues and uses thereof |
| PCT/CA2005/001611 WO2006042408A1 (en) | 2004-10-20 | 2005-10-20 | Gh secretagogues and uses thereof |
| KR1020077011178A KR101228229B1 (en) | 2004-10-20 | 2005-10-20 | Gh secretagogues and uses thereof |
| JP2007537087A JP2008516994A (en) | 2004-10-20 | 2005-10-20 | Growth hormone secretagogue and use thereof |
| BRPI0516935-6A BRPI0516935A (en) | 2004-10-20 | 2005-10-20 | gh secretagogues and uses thereof |
| MX2007004682A MX2007004682A (en) | 2004-10-20 | 2005-10-20 | Gh secretagogues and uses thereof. |
| CN200580043640XA CN101084009B (en) | 2003-05-29 | 2005-10-20 | Gh secretagogues and uses thereof |
| EP05797145A EP1812048A4 (en) | 2004-10-20 | 2005-10-20 | Gh secretagogues and uses thereof |
| NO20072136A NO20072136L (en) | 2004-10-20 | 2007-04-24 | Substance that promotes GH secretion and its use |
| HK08106222.9A HK1115803A1 (en) | 2004-10-20 | 2008-06-04 | Gh secretagogues and uses thereof gh |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA2485472A CA2485472C (en) | 2004-10-20 | 2004-10-20 | Gh secretagogues and uses thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2485472A1 true CA2485472A1 (en) | 2006-04-20 |
| CA2485472C CA2485472C (en) | 2011-09-27 |
Family
ID=36242546
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2485472A Active CA2485472C (en) | 2003-05-29 | 2004-10-20 | Gh secretagogues and uses thereof |
Country Status (4)
| Country | Link |
|---|---|
| BR (1) | BRPI0516935A (en) |
| CA (1) | CA2485472C (en) |
| HK (1) | HK1115803A1 (en) |
| MX (1) | MX2007004682A (en) |
-
2004
- 2004-10-20 CA CA2485472A patent/CA2485472C/en active Active
-
2005
- 2005-10-20 BR BRPI0516935-6A patent/BRPI0516935A/en not_active Application Discontinuation
- 2005-10-20 MX MX2007004682A patent/MX2007004682A/en active IP Right Grant
-
2008
- 2008-06-04 HK HK08106222.9A patent/HK1115803A1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| HK1115803A1 (en) | 2008-12-12 |
| MX2007004682A (en) | 2007-07-17 |
| CA2485472C (en) | 2011-09-27 |
| BRPI0516935A (en) | 2008-09-23 |
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