Methods for treatment of insulin-like growth factor-1 (IGF-1) deficiency

• US 7,258,864 B2
• Filed: 09/09/2004
• Issued: 08/21/2007
• Est. Priority Date: 09/12/2003
• Status: Active Grant

• Current Assignee: Ipsen Biopharmaceuticals, Inc. (Ipsen Sa)
• Original Assignee: Tercica Incorporated (Ipsen Sa)
• Inventors: Clark, Ross G.
• Primary Examiner(s): Bunner; Bridget
• Assistant Examiner(s): Dang; Ian
• Application Number:
  US10/939,111
• Publication Number:
  US 20050059598A1
• Time in Patent Office: 1,076 Days
• Field of Search: None
• US Class Current: 424/198.1
• CPC Class Codes: A61K 38/30 Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2 insulin-like growth factor binding protein A61K38/1754
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/48 of the pancreatic hormones
• CPC Class Codes: G01N 2333/65 Insulin-like growth factors (Somatomedins), e.g. IGF-1, IGF-2
• CPC Class Codes: G01N 2800/04 Endocrine or metabolic disorders

Abstract

The present invention provides methods and compositions for increasing the growth rates, alleviating the symptoms, or improving the metabolism of human patients having insulin-like growth factor-1 deficiency (IGFD). The invention relates to methods comprising administering insulin-like growth factor-I to a patient having a height which, at the time of treatment or prior to initial treatment with IGF-1, is at least about 2 standard deviations below normal for a subject of the same age and gender, a blood level of insulin-like growth factor-I that, and at the time of treatment or prior to initial treatment with IGF-1, is below normal mean levels, usually at least about 1 standard deviations below normal mean levels, for age and gender.

Claims

1. A method for treating a human pediatric subject having insulin-like growth factor-1 deficiency (IGFD) comprising;

administering to a human pediatric subject an effective amount of insulin like growth factor-1 (IGF-1), wherein the subject is characterized as follows;

at the time of treatment or prior to initial treatment with IGF-1, has or had a height at least about 2 standard deviations (SD) below the normal mean height for a human pediatric subject of the same age and gender,

at the time of treatment or prior to initial treatment with IGF-1, has or had a blood level of IGF-1 at least about −

1 SD below normal mean levels for a human pediatric subject of the same age and gender, and

the human pediatric subject does not have Laron syndrome or partial growth hormone insensitivity syndrome,

wherein said administering is effective to treat IGFD in the human pediatric subject.

2. The method of claim 1, wherein the subject is further characterized as having a blood level of growth hormone binding protein (GHBP) which is at least normal for a subject of the same age and gender.

3. The method of claim 1, wherein the subject is further characterized as having a blood level of growth hormone (GH) which is at least normal.

4. The method of claim 1, wherein said administering alleviates at least one symptom of IGFD.

5. The method of claim 1, wherein said administering provides for an increase in growth rate or height.

6. The method of claim 1, wherein the subject has a blood level of IGF-1 that is at least about 2.0 SD below normal mean levels for a subject of the same age and gender.

7. The method of claim 1, wherein IGF-1 is administered in a dose of about 20 to 240 μ

g/kg/day.

8. The method of claim 7, wherein said IGF-1 is administered subcutaneously.

9. A method for treating a human adult subject having insulin-like growth factor-1 deficiency (IGFD) comprising;

administering to a human adult subject an effective amount of insulin like growth factor-1 (IGF-1), wherein the subject is characterized as follows;

at the time of treatment or prior to initial treatment with IGF-1, has or had a height at least about 2 standard deviations (SD) below a normal mean for a human adult subject of the same age and gender,

at the time of treatment or prior to initial treatment with IGF-1, has or had a blood level of IGF-1 at least about −

1 SD below normal mean levels for a human adult subject of the same age and gender, and

the human adult subject does not have Laron syndrome or partial growth hormone insensitivity syndrome,

wherein said administering provides for treatment of IGFD in the human adult subject.

10. The method of claim 9, wherein the subject is further characterized as having a blood level of growth hormone binding protein (GHBP) which is at least normal for a subject of the same age and gender.

11. The method of claim 9, wherein the subject is further characterized as having a blood level of growth hormone (GH) which is at least normal.

12. The method of claim 9, wherein said administering alleviates at least one symptom of IGFD.

13. The method of claim 9, wherein the subject has a blood level of IGF-1 that is at least about 2.0 SD below normal mean levels for a subject of the same age and gender.

14. The method of claim 9, wherein IGF-1 is administered in a dose of about 20 to 240 μ

g/kg/day.

15. The method of claim 14, wherein said IGF-1 is administered subcutaneously.

16. A method for achieving at least normal insulin-like growth factor-1 (IGF-1) levels for age and gender in a human subject having insulin-like growth factor-1 deficiency (IGFD), comprising

administering an effective amount of insulin-like growth factor (IGF-1) to the human subject, wherein the human subject is characterized as follows:

at the time of treatment or prior to initial treatment with IGF-1, has or had a height at least about 2 standard deviations (SD) below a normal mean for a human subject of the same age and gender, and

at the time of treatment or prior to initial treatment with IGF-1, has or had a blood level of IGF-1 at least about −

1 SD below normal mean levels for a human subject of the same age and gender,

wherein the human subject does not have Laron syndrome or partial growth hormone insensitivity syndrome, and wherein said administering achieves normal blood IGF-1 levels for age and gender in the human subject.

17. The method of claim 16, wherein the subject is further characterized as having a blood level of growth hormone binding protein (GHBP) which is at least normal for a subject of the same age and gender.

18. The method of claim 16, wherein the subject is further characterized as having a blood level of growth hormone (GH) which is at least normal.

19. The method of claim 16, wherein the subject has a blood level of IGF-1 that is at least about 2.0 SD below normal mean levels for a subject of the same age and gender.

20. The method of claim 16, wherein IGF-1 is administered in a dose of about 20 to 240 μ

g/kg/day.

21. The method of claim 20, wherein said IGF-1 is administered subcutaneously.

22. A method for treating a human subject having a primary insulin-like growth factor-1 deficiency (IGFD) comprising;

administering to a human subject having primary insulin-like growth factor-1 deficiency (IGFD) an effective amount of insulin like growth factor-1 (IGF-1), wherein the human subject is characterized as follows;

at the time of treatment or prior to initial treatment with IGF-1, has or had a height at least about 2 standard deviations (SD) below a normal mean for a human subject of the same age and gender,

at the time of treatment or prior to initial treatment with IGF-1, has or had a blood level of IGF-1 at least about −

1 SD below normal mean levels for a human subject of the same age and gender, and

has a blood level of growth hormone (GH) which is at least normal,

wherein the human subject does not have Laron syndrome or partial growth hormone insensitivity syndrome, and wherein said administering provides for treatment of IGFD in the human subject.

23. The method of claim 22, wherein the subject is further characterized as having a blood level of growth hormone binding protein (GHBP) which is at least normal for a subject of the same age and gender.

24. The method of claim 22, wherein said administering alleviates at least one symptom of IGFD.

25. The method of claim 22, wherein the subject is a human pediatric subject and said administering provides for an increase in growth rate or height.

26. The method of claim 22, wherein the subject has a blood level of IGF-1 that is at least about 2.0 SD below normal mean levels for a subject of the same age and gender.

27. The method of claim 22, wherein IGF-1 is administered in a dose of about 20 to 240 μ

g/kg/day.

28. The method of claim 27, wherein said IGF-1 is administered subcutaneously.

29. A method for achieving at least normal insulin-like growth factor-1 (IGF-1) levels for age and gender in a human subject having primary insulin-like growth factor-1 deficiency (IGFD), comprising

administering an effective amount of insulin-like growth factor (IGF-1) to a human subject, wherein the human subject is characterized as follows:

at the time of treatment or prior to initial treatment with IGF-1, has or had a height at least about 2 standard deviations (SD) below normal mean for a human subject of the same age and gender,

at the time of treatment or prior to initial treatment with IGF-1, has or had a blood level of IGF-1 at least about −

1 SD below normal mean levels for a human subject of the same age and gender, and

has a blood level of growth hormone (GH) which is at least normal;

wherein the human subject does not have Laron syndrome or partial growth hormone insensitivity syndrome, wherein said administering achieves normal blood IGF-1 levels for age and gender in the human subject.

30. The method of claim 29, wherein the subject is further characterized as having a blood level of growth hormone binding protein (GHBP) which is at least normal for a subject of the same age and gender.

31. The method of claim 29, wherein the subject has a blood level of IGF-1 that is at least about 2.0 SD below normal mean levels for a subject of the same age and gender.

32. The method of claim 29, wherein IGF-1 is administered in a dose of about 20 to 240 μ

g/kg/day.

33. The method of claim 32, wherein said IGF-1 is administered subcutaneously.