Human growth hormone conjugated with biocompatible polymer
OwnerJohn Jacobs, Shiliang Qin +3inventors
InventorsJohn Jacobs, Shiliang Qin, Mingyu Zhang, Huaina Li, Myung-Ok Park
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Abstract
The present invention relates to conjugates of biocompatible polymers and hGH, particularly PEG-hGH, where the activated biocompatible polymer is conjugated to a carboxyl group of hGH at a molar ratio of 2:1 or less, preferably 1:1, methods of preparation, and related pharmaceutical compositions. The PEG-hGH conjugates have up to 20% of the activity of the native hGH while the in vivo half life is increased 10 fold. The PEG-hGH conjugates may be used therapeutically to treat growth retardation or growth failure, especially short stature in children, and conditions related to aging.
Claims28
A conjugate of biocompatible polymer-human Growth Hormone (hGH), wherein the biocompatible polymer is conjugated to a carboxyl group of hGH at a molar ratio of 2:1 or less.
A method of preparing a conjugate of biocompatible polymer-hGH comprising:
- (a) providing a purified hGH protein;
- (b) activating a biocompatible polymer with the stepwise addition of a coupling reagent;
- and
- (c) conjugating the activated biocompatible polymer to a carboxyl group of the hGH at a molar ratio of 2:1 or less,
- wherein the molar ratio of the hGH to the activated biocompatible polymer is 1:1 to 1:20, the ratio of the hGH to the coupling reagent is 1:1 to 1:50, and pH is in the range of 2 to 5.
A method of treating short stature in children by administering an effective amount of a composition comprising PEG-hGH to a patient in need thereof at a frequency of no more than twice/week, wherein the PEG is conjugated to a C-terminus carboxyl group of hGH at a molar ratio of 1:1 and the PEG-hGH has 10-20% of the activity of unconjugated hGH.
A method of treating adverse effects associated with aging selected from the group consisting of decrease in lean muscle, increase in blood pressure, increase in cholesterol, increase in body fat, loss of skin tone, and decrease in bone density by administering an effective amount of a composition comprising PEG-hGH to a patient in need thereof, wherein the PEG is conjugated to a carboxyl group of hGH at a molar ratio of 1:1.
Dependencies are inferred from the claim text.