PEGylated hGH improves PK profile Molecule Body weight PEG/hGH Effective size tun (rats) hGH 0.32±0.03 0 496±86 1.35±0.2 hGH(hGHbp)2 0.31±0.01 32±42 8.4±3 PEG-hGH 0.31±0.03 130±7 1.3±0.1 0.32±0.04 70±4 5.8±0.1 0.32±0.04 250 7.5±1 0.32±0.01 300 2.3±0.2 24±7 tes Clark et al. Long-acting Growth Hormones Produced by Conjugation with Polyethylene Glycol, novo nordisk JBC,21969-21877,1996
Molecule Body weight PEG/hGH Effective size CL/W t 1/2 (rats) kg kDa ml/h/kg h hGH 0.32 ± 0.03 0 22 496 ± 86 1.35 ± 0.2 hGH(hGHbp) 2 0.31 ± 0.01 0 80 32 ± 42 8.4 ± 3 PEG-hGH 0.31 ± 0.03 1 35 130 ± 7 1.3 ± 0.1 0.32 ± 0.04 2 51 70 ± 4 5.8 ± 0.1 0.32 ± 0.04 5 250 7.5 ± 1 15 ± 4 0.32 ± 0.01 7 300 2.3 ± 0.2 24 ± 7 PEGylated hGH improves PK profile Clark et al., Long-acting Growth Hormones Produced by Conjugation with Polyethylene Glycol, JBC, 21969-21877, 1996
Presentation outline Novo nordisk Why engineer peptides(and proteins Type 2 diabetes The discovery of the first once daily gLp-1 Further engineering of long acting GLP-1 PLEASE INTERRUPT AND ASK!
• Novo Nordisk • Why engineer peptides (and proteins) • Type 2 diabetes • The discovery of the first once daily GLP-1 • Further engineering of long acting GLP-1 Presentation Outline 17 PLEASE INTERRUPT AND ASK!
Type 2 diabetes
Type 2 diabetes 18
Pancreatic beta cellls and insulin Type 1 Diabetes Lack of insulin production Type 2 Diabetes Insulin resistance and lack of insulin production
Pancreatic beta cells and insulin Type 2 Diabetes Insulin resistance and lack of insulin production Type 1 Diabetes Lack of insulin production
Pato physiology of type 2 diabetes Dia betes diagnosis Insulin resistance o norma Insulin secretion Insulin Decreasing resistance B-cell function Postprandial glucose Fasting glucose Norma 10-5 0 10 15 20 0 Years of diabetes N diabetes Diabetes N= normal Adapted from Bergenstal RM et al. In: Degroot U, Jameson ](eds). Endocrinology 2001; 821-35
20 Diabetes diagnosis Normal Insulin resistance Insulin secretion -cell function Adapted from Bergenstal RM et al. In: Degroot LJ, Jameson J (eds). Endocrinology 2001;821–35. Normal Fasting glucose Plasma glucose N Pre-diabetes N = normal Postprandial glucose Decreasing β-cell function Insulin resistance Years of diabetes -10 -5 0 5 10 15 20 25 30 Prediabetes N Diabetes Patophysiology of type 2 diabetes