Method of enhancing growth in patients using combination therapy

• US 5,126,324 A
• Filed: 06/07/1990
• Issued: 06/30/1992
• Est. Priority Date: 06/07/1990
• Status: Expired due to Term

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: Clark, Ross G., Cronin, Michael J.
• Primary Examiner(s): NOT, DEFINED
• Application Number:
  US07/535,005
• Time in Patent Office: 754 Days
• Field of Search: 514/4, 514/3, 514/12, 514/21
• US Class Current: 514/6.9
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 38/27 Growth hormone [GH], i.e. somatotropin
• 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: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system

Abstract

A method is disclosed for enhancing growth of a mammal by administration of a combination of effective amounts of IGF-I and GH so as to enhance the growth of the mammal over the enhancement in growth achieved using either IGF-I or GH alone in an amount equal to that used for either IGF-I or GH, respectively, in the combination. Preferably, the mammal is a child, the IGF-I is native-sequence, mature human IGF-I or human brain IGF-I, and the GH is native-sequence, mature human GH with or without a terminal methionine. In another preferred embodiment, the mammal is a non-human animal of economic importance such as a cow or pig.

Claims

1. A method for enhancing growth of a mammal comprising administering systemically and concurrently to the mammal effective amounts of IGF-I and GH, wherein the GH is administered by injections, so as to enhance said growth of the mammal over the enhancement in growth achieved using an equivalent dose of IGF-I or GH alone, without incurring hypoglycemia.

2. The method of claim 1 wherein the mammal is an animal.

3. The method of claim 2 wherein the GH and IGF-I are bovine, ovine, or porcine GH or IGF-I, and the animal is bovine, ovine, or porcine, respectively.

4. The method of claim 1 wherein the mammal is a human.

5. The method of claim 4 wherein the human is a non-adult.

6. The method of claim 4 wherein the IGF-I is human native-sequence, mature IGF-I and the GH is human native-sequence, mature GH.

7. The method of claim 6 wherein the IGF-I has no N-terminal methionine.

8. The method of claim 6 wherein the IGF-I has a specific activity of greater than about 14,000 units/mg by radioreceptor assay using placenta membranes.

9. The method of claim 6 wherein the IGF-I is a human native-sequence IGF-I analog having the glutamic acid at position 3 replaced by another amino acid or deleted.

10. The method of claim 9 wherein the IGF-I is des(1-3)-IGF-I.

11. The method of claim 10 wherein the des(1-3)-IGF-I is in a sterile, isotonic solution containing acetic acid, pH 3.2 to 4.5.

12. The method of claim 6 wherein the IGF-I is in a sterile, isotonic solution containing a citrate buffer, pH 6.

13. The method of claim 6 wherein the GH is recombinant GH.

14. The method of claim 13 wherein the GH is in a sterile, isotonic solution containing mannitol and a phosphate buffer, pH 7.4-7.8.

15. The method of claim 1 wherein the IGF-I is administered by continuous infusion.

16. The method of claim 15 wherein the administration of GH or IGF-I or both is by the subcutaneous or intravenous route.

17. The method of claim 1 wherein the administration of both GH and IGF-I is by the subcutaneous route.

18. The method of claim 15 wherein the GH is injected once daily.

19. The method of claim 1 wherein the effective amount of each of GH and IGF-I is at least 0.1 mg/kg/day.

20. The method of claim 4 wherein the effective amount of each of GH and IGF-I is at least 1 mg/kg/day.

21. The method of claim 1 wherein the IGF-I and GH are administered separately.

22. The method of claim 1 wherein the IGF-I and GH are administered as a single formulation.

23. The method of claim 4 wherein the human to be treated has diabetes.

24. The method of claim 4 wherein the human to be treated experiences hyperinsulinemia or hyperglycemia with GH treatment alone.

25. The method of claim 4 wherein the human to be treated exhibits a reduced anabolic effect when treated with GH alone.

26. The method of claim 25 wherein the human to be treated has reached a maximum growth level and then a decrease in annualized growth rate after having previously been treated with GH alone.

27. The method of claim 25 wherein the human to be treated is at an age that is 2-3 years before his or her growth plate closes.

28. The method of claim 4 wherein the effective amount of GH is less than the dose that gives a maximal growth response using GH alone.

29. The method of claim 4 wherein the effective amount of GH is greater than the dose that gives a maximal growth response using GH alone.