Abstract: The present invention comprises growth hormone releasing peptides/peptidomimetics (GHRP) capable of causing release of growth hormone from the pituitary. Compositions containing the GHRP's of this invention are used to promote growth in mammals either alone or in combination with other growth promoting compounds, especially IGF-1. In a method of this invention GHRP's in combination with IGF-1 are used to treat Type II diabetes. An exemplary compound of this invention is provided below.

Abstract: Human growth hormone variants are disclosed having enhanced affinity for the growth hormone receptor. Also disclosed are human growth hormone variants conjugated to one or more chemical groups, such as poly(ethylene glycol), which is believed to prolong the in vivo half-life of the variants.

Abstract: Human growth hormone variants, DNA encoding the variants, vectors, host cells, pegylated forms of the variants, as well as methods of making the variants are disclosed.

Abstract: The present invention comprises growth hormone releasing peptides/peptidomimetics (GHRP) capable of causing release of growth hormone from the pituitary. Compositions containing the GHRP's of this invention are used to promote growth in mammals either alone or in combination with other growth promoting compounds, especially IGF-1. In a method of this invention GHRP's in combination with IGF-1 are used to treat Type II diabetes. An exemplary compound of this invention is provided below.

Abstract: Formulations containing NPH insulin are useful for treating hyperglycemic disorders, such as diabetes, in a mammal in need of treatment. One such formulation, which is preferably administered parenterally, more preferably by injection, comprises IGF-I and NPH insulin, in amounts of from or about 1 to 10 mg IGF-I and from or about 0.2 to 2 mg NPH insulin in a pharmaceutically acceptable carrier. Another such formulation comprises IGF-I and NPH insulin in an acetic acid salt buffer. Still another formulation comprises IGF-I and NPH insulin in a weight ratio of NPH insulin to IGF-I of from or about 10:1 to 1:50 (w/w), from or about 0.05 to 0.3M of an osmolyte, from or about 0.1 to 10 mg/mL of a stabilizer, and from or about 5 to 100 mM of a buffer at from or about pH 5 to 7. A still further composition comprises NPH insulin in an acetic acid salt buffer.

Abstract: A method is disclosed that comprises administering insulin-like growth factor-I (IGF-I) to a mammal so as to sustain its biological activity in the mammal comprising administering a therapeutically effective amount of IGF-I to the mammal to provide an exposure to IGF-I for a period of time that stimulates the maximum biological response in the mammal, then discontinuing said administration for a period of time equal to or less than the time period used for administration, and repeating this pattern of administration and discontinuance of administration for a period as long as necessary to achieve or maintain the desired biological response in the mammal.

Abstract: A formulation for IGF-I is disclosed that is useful in treating hyperglycemic disorders and, in combination with growth hormone, in enhancing growth of a mammal. Also disclosed is a process for preparing a formulation of growth hormone and IGF-I from the IGF-I formulation. The IGF-I formulation comprises about 2-20 mg/ml of IGF-I, about 2-50 mg/ml of an osmolyte, about 1-15 mg/ml of a stabilizer, and a buffered solution at about pH 5-5.5, optionally with a surfactant.

Abstract: Methods of enhancing myocardial contractility and cardiac performance in a mammal with congestive heart failure are disclosed. In a first method a mammal with congestive heart failure is treated by administering to the mammal an effective amount of a combination of growth hormone (GH) and insulin-like growth factor (IGF-I). A second method comprises administering to the mammal an effective amount of a combination of GH and IGF-I in the presence of an ACE inhibitor. This method results in enhancement of myocardial contractility and cardiac performance above the level achieved with ACE inhibition alone. Preferably the mammal is a human.

Abstract: The present document discloses the formation of imine adducts, preferably between a primary amine of a biologically active polypeptide and a reactive aldehyde group of a physiologically acceptable carrier. The imine adduct of human growth hormone and dextran is specifically described. These adducts serve to release the biologically active polypeptide via the reversible reaction in the formation of the imine adduct bond. These adducts have a surprising degree of stability that permits the use of the complex as a sustained release preparation. A key advantage of this technology is that after hydrolysis the complex releases the unmodified pharmaceutical. Thus, these adducts can be used as pharmaceutical compositions useful for the sustained release of the biologically active polypeptide over a predetermined, desired period of time.

Abstract: Methods of enhancing myocardial contractility and cardiac performance in a mammal with congestive heart failure are disclosed. In a first method a mammal with congestive heart failure is treated by administering to the mammal an effective amount of a combination of growth hormone (GH) and insulin-like growth factor (IGF-I). A second method comprises administering to the mammal an effective amount of a combination of GH and IGF-I in the presence of an ACE inhibitor. This method results in enhancement of myocardial contractility and cardiac performance above the level achieved with ACE inhibition alone. Preferably the mammal is a human.

Abstract: A method is disclosed for treating obese mammals or preventing obesity from occurring in mammals. This method involves administering to the mammal an effective amount of growth hormone in combination with an effective amount of IGF-I. Preferably, the growth hormone is given so as to have a maintained, continual therapeutically effective presence in the blood, such as by continuous infusion or frequent injections, or by use of a long-acting formulation.

Abstract: A formulation for IGF-I is disclosed that is useful in treating hyperglycemic disorders and, in combination with growth hormone, in enhancing growth of a mammal. Also disclosed is a process for preparing a formulation of growth hormone and IGF-I from the IGF-I formulation. The IGF-I formulation comprises about 2-20 mg/ml of IGF-I, about 2-50 mg/ml of an osmolyte, about 1-15 mg/ml of a stabilizer, and a buffered solution at about pH 5-5.5, optionally with a surfactant.

Abstract: A ligand-mediated immunofunctional assay (LIFA) method for detecting the presence and the concentration of polypeptide hormone binding proteins which comprises capturing the binding protein with a solid phase bound first antibody, saturating the bound hormone binding protein with the ligand polypeptide hormone, and detecting the bound ligand polypeptide hormone with a detectably labeled second antibody specific for the ligand polypeptide hormone. In the absence of added saturating polypeptide hormone, the LIFA measures the amount of hormone binding protein bound to the endogenous ligand polypeptide hormone. A growth hormone binding protein assay illustrates the method of the present invention. LIFA assay results indicate that increased binding protein substantially increases growth hormone activity. Methods of use and formulations of growth hormone binding protein, growth hormone, insulin-like growth factor-I and insulin-like growth factor binding protein are disclosed.

Abstract: A method is disclosed for stimulating a mammal's or avian's immune response, particularly immune-compromised mammals, by administration of IGF-I, alone or in combination with growth hormone. Preferably, the IGF-I is native-sequence, mature human IGF-I.

Abstract: A method is disclosed that comprises administering insulin-like growth factor-I (IGF-I) to a mammal so as to sustain its biological activity in the mammal comprising administering a therapeutically effective amount of IGF-I to the mammal to provide an exposure to IGF-I for a period of time that stimulates the maximum biological response in the mammal, then discontinuing said administration for a period of time equal to or less than the time period used for administration, and repeating this pattern of administration and discontinuance of administration for a period as long as necessary to achieve or maintain the desired biological response in the mammal.

Abstract: A combined formulation for IGF-I and growth hormone (GH) is useful for enhancing growth of a mammal. This formulation, which may be administered by infusion or injection to enhance growth, comprises IGF-I and GH, each in amounts of 0.1 to 100 mg/ml, in a pharmaceutically acceptable carrier at a pH of about 5-6 containing a surfactant, wherein the amounts of IGF-I and GH in the composition are effective to promote growth of a mammal more than an equivalent dose of IGF-I or GH alone, and wherein the weight ratio of IGF-I to GH in the composition ranges from 0.002:1 to 240:1.

Abstract: A method is disclosed for the prophylactic treatment of mammals at risk for acute renal failure, whether due to renal ischemia or nephrotoxic damage. This method involves administering to the mammal, before or at the time that the acute renal failure is expected to occur or is occurring, an effective amount of IGF-I. Preferably, the IGF-I is native-sequence, mature human IGF-I.

Abstract: A ligand-mediated immunofunctional assay (LIFA) method for detecting the presence and the concentration of polypeptide hormone binding proteins which comprises capturing the binding protein with a solid phase bound first antibody, saturating the bound hormone binding protein with the ligand polypeptide hormone, and detecting the bound ligand polypeptide hormone with a detectably labeled second antibody specific for the ligand polypeptide hormone. In the absence of added saturating polypeptide hormone, the LIFA measures the amount of hormone binding protein bound to the endogenous ligand polypeptide hormone. A growth hormone binding protein assay illustrates the method of the present invention.

Abstract: A method is disclosed for stimulating a mammal's or avian's immune response, particularly immune-compromised mammals, by administration of IGF-I, alone or in combination with growth hormone. Preferably, the IGF-I is native-sequence, mature human IGF-I.

Abstract: A method is disclosed for producing an anabolic state in a mammal by co-administration by subcutaneous injection of a combination of effective amounts of IGF-I and an IGF binding protein in a defined molar ratio in the absence of growth hormone so as to produce a greater anabolic response in the mammal than that achieved using IGF-I alone in an amount equal to that used for IGF-I in the combination. Preferably, the IGF-I is native-sequence, mature human IGF-I, the binding protein is IGFBP-3, and the mammal is human or a non-human animal of economic importance such as a cow or pig.