公开(公告)号：WO2007112794A1

公开(公告)日：2007-10-11

申请号：PCT/EP2006/070265

申请日：2006-12-29

Applicant: KERYOS SPA ,  VERONESE, Francesco Maria ,  PASUT, Gianfranco ,  TONON, Giancarlo ,  SCHREPFER, RODOLFO

Inventor： VERONESE, Francesco Maria ,  PASUT, Gianfranco ,  TONON, Giancarlo ,  SCHREPFER, RODOLFO

IPC: C08G65/329 ,  A61K47/48

CPC classification number: C08G65/329 ,  A61K47/60 ,  C07K1/1077 ,  C08G65/333

Abstract: There are disclosed chemically active poly(ethylene glycols) and other hydrophilic polymers that are suitable for coupling to pharmaceutically or diagnostically active agents such as peptides, oligonucleotides, proteins or non- peptide molecules. The compounds are represented by the formula Poly-(X-NH-CO-A) n wherein: Poly is a hydrophilic polymer having a molecular weight of from about 300 to 100000 Daltons; A together with -NH-CO- forms a reactive group; X is a spacer moiety or a bond; n is an integer comprised between 1 and 50. The active agents of interest which may be conjugated to the disclosed compounds may be selected from hemoglobin, insulin, urokinase, alpha- interferon, G-CSF, hGH, asparaginase, adenosine deaminase, superoxide dismutase and catalase.

Abstract translation: 公开了化学活性聚（乙二醇）和其它亲水性聚合物，其适于与药学或诊断活性剂如肽，寡核苷酸，蛋白质或非肽分子偶联。 所述化合物由下式表示：Poly-（X-NH-CO-A）n N n其中：Poly是分子量为约300至100000道尔顿的亲水性聚合物; A与-NH-CO-一起形成反应性基团; X是间隔部分或键; 可以与所公开的化合物缀合的感兴趣的活性剂可以选自血红蛋白，胰岛素，尿激酶，α-干扰素，G-CSF，hGH，天冬酰胺酶，腺苷脱氨酶，超氧化物歧化酶 和过氧化氢酶。

公开(公告)号：WO2008017603A1

公开(公告)日：2008-02-14

申请号：PCT/EP2007/057824

申请日：2007-07-30

Applicant: BIO-KER SRL ,  TONON, Giancarlo ,  ORSINI, Gaetano ,  SCHREPFER, Rodolfo ,  TAYLOR, Geoffrey ,  SERGI, Mauro

Inventor： TONON, Giancarlo ,  ORSINI, Gaetano ,  SCHREPFER, Rodolfo ,  TAYLOR, Geoffrey ,  SERGI, Mauro

IPC: C07K14/535 ,  A61K47/48

CPC classification number: C07K14/535 ,  A61K47/60

Abstract: Novel site-specific mono-conjugates of Granulocyte Colony Stimulating Factor (G-CSF) are hereby described, with analogues and derivatives thereof, which stimulate proliferation and differentiation of progenitor cells to mature neutrophiles. These conjugates have been obtained using transglutaminase to covalently and site-specifically bind a hydrophilic, non-immunogenic polymer to a single glutamine residue of the human G-CSF native sequence and analogues thereof. These novel site-specific mono-conjugated derivatives are recommended for therapeutic use since they are stable in solution and exhibit significant biological activity in vitro and a longer bloodstream half-life, as compared to the non-conjugated protein, with a consequent prolonged pharmacological activit y.

Abstract translation: 此处描述了粒细胞集落刺激因子（G-CSF）的新型位点特异性单缀合物，其具有类似物和衍生物，其刺激祖细胞对成熟嗜中性细胞的增殖和分化。 已经使用转谷氨酰胺酶共价并且将亲水的，非免疫原性的聚合物与人G-CSF天然序列的单个谷氨酰胺残基和其类似物结合位点特异性地获得了这些缀合物。 这些新的位点特异性单缀合衍生物被推荐用于治疗用途，因为它们在溶液中稳定并且在体外显示出显着的生物活性，并且与非共轭蛋白相比具有较长的血液半衰期，从而延长药理活性 年。

公开(公告)号：WO2010057774A1

公开(公告)日：2010-05-27

申请号：PCT/EP2009/064599

申请日：2009-11-04

Applicant: BIO-KER SRL ,  TONON, Giancarlo ,  ORSINI, Gaetano ,  SERGI, Mauro ,  SCHREPFER, Rodolfo ,  ESPOSITO, Pierandrea

Inventor： TONON, Giancarlo ,  ORSINI, Gaetano ,  SERGI, Mauro ,  SCHREPFER, Rodolfo ,  ESPOSITO, Pierandrea

IPC: A61K47/48 ,  A61P3/10

CPC classification number: A61K47/60

Abstract: The present invention is related to glucagon-like peptide- 1 (GLP-1) and analogues insulinotropic peptides, monoconjugated to biocompatible polymeric molecules by enzymatic direct and site-specific transglutamination reaction as well as their pharmaceutical formulations and delivery systems for therapeutical application in dismetabolic pathologies such as type 2 diabetes.

Abstract translation: 本发明涉及胰高血糖素样肽-1（GLP-1）和类似物促胰岛素肽，通过酶促直接和位点特异性转谷氨酰胺反应单生物相容性聚合物分子，以及它们的药物制剂和用于治疗代谢异常的递送系统 病态如2型糖尿病。