Pharmaceutical compositions comprising unacylated ghrelin...

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai

Reexamination Certificate

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C530S300000, C530S306000

Reexamination Certificate

active

07666833

ABSTRACT:
The present invention relates to compositions containing unacylated ghrelin and derivatives thereof and their uses in the control of glycemia in ageing patients, GH deficient patients, diabetic patients and obese patients.

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Toshinai, et al., Upregulation of Ghrelin Expression in the Stomach upon Fasting, Insulin-Induced Hypoglycemia, and Leptin Administration, Biochemical and Biophysical Research Communications, vol. 281, pp. 1220-1225, 2001.
Granata, et al., Acylated and Unacylated Ghrelin Promote Proliferaion and Inhibit Apoptosis of Pancreatic beta Cells and Human Islets: Involvement of 3′, 5′-Cyclic Adenosine Monophosphate/Protein Kinase A, Extracellular Signal-Regulated kinase 1/2, and Phosphatidyl Inositol 3-Kinase/Akt Signaling, Endocrinology, vol. 148, No. 2, pp. 512-529, 2007.
Granata, et al., Acylated and unacylate ghrelin promote proliferation and inhibit serum stravation- and cytokine-induced apoptosis of pancreatic beta cells through cAMP/PKA, ERK 1/2 and P13K/Akt, Abstract and poster presented at Meeting of the Endocrine Society, Boston, from Jun. 24, 2006; and.
Prodam, et al., Unacylated Ghrelin (UAG) Enhances the Early Insulin Response to Meal, Improves Glucose Metabolism and Decrease Free Faty Acids Levels in Health Volumteers, Abstract and poster presented at European Congress of Endocrinology, Budapest, from Apr. 28, 2007 to May 2, 2007.
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Marzullo, et al., “The Relationship between Active Ghrelin Levels and Human Obesity Involves Alterations in Resting Energy Expenditure,” J. Clin. Endocr. Metab. 89: 936-939, 2004.
Broglio, et al., Non-Acylated Ghrelin Counteracts the Metabolic but not the Neuroendocrine Response to Acylated Ghrelin in Humans, The Journal of Clinical Endocrinology & Metabolish, vol. 89, No. 6, pp. 3062-3065, Jun. 2004.
Pöykkö, et al., Low Plasma Ghrelin is Associated With Insulin Resistance, Hypertension, and the Prevalence of Type 2 Diabetes, Diabetes, vol. 52, pp. 2546-2553, Oct. 2003.
Cassoni, Paola et al., “Identification, Characterization, and Biological Activity of Specific Receptors for Natural Ghrelin) and Synthetic Growth Hormone Secretagogues and Analogs in Human Breast Carcinomas and Cell Lines,”The Journal of Clinical Endocrinology&Metabolism86(4): 1738-1744 (2001).
Toshinai, Koji et al., “Upregulation of Ghrefin Expression in the Stomach upon Fasting, Insulin-induced Hypoglycemia, and Leptin Administration,”Biochemical and Biophysical Research Communications281: 1220-1225 (2001).

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