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GDF-9/BMP-15 modulators for the treatment of bone disorders

一种BMP-15、GDF-9的技术，应用在骨骼疾病、性疾病、疾病诊断等方向，能够解决刺激等问题

Inactive Publication Date: 2009-04-15
WYETH LLC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although experiments have shown that these compounds consistently increase bone mineral density in patients with osteoporosis, there are still serious problems with the use of bisphosphonates for the treatment of osteoporosis, including irritation of the esophagus and upper gastrointestinal tract.

Method used

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Examples

Experimental program
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Effect test

Embodiment 1

[0219] Example 1: Bone Mineral Density in GDF-9 Knockout Mice

[0220] The effect of GDF-9 null mutations on bone mineral density was analyzed in female mice. GDF-9 knockout mice have been described previously (Dong et al., Nature 383:531-535 (1996)). Total, trabecular and cortical volumetric bone mineral density (vBMD) was determined in 16-week-old (Table 1) and 10-month-old (Table 2) female mice as follows. Volumetric bone mineral density (vBMD, mg / cm2) of the left femur was assessed using XCT Research peripheral quantitative computed tomography densitometer (pQCT; StratecMedizinetechnik, Pforzheim, Germany). 3 ). A 0.5 mm thick pQCT slice was obtained from the proximal 2.5 mm of the distal femur and was used to calculate total and trabecular BMD of the distal femoral metaphysis. Density of the cortex was assessed using a second slice obtained 6 mm proximal to the femur. Tomographic slices have an in-plane pixel size of 0.07 mm. After acquiring the images, display the i...

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PUM

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Abstract

The invention provides methods for treating or preventing bone degenerative disorders. The disorders treated or prevented include, for example, osteopenia, osteomalacia, osteoporosis, osteomyeloma, osteodystrophy, Paget's disease, osteogenesis imperfecta, and bone degenerative disorders associated with chronic renal disease, hyperparathyroidism, and long-term use of corticosteroids. The disclosed therapeutic methods include administering to a mammal an inhibitor of GDF-9 or BMP-15 in an amount effective to: (1 ) treat or prevent a bone degenerative disorder; (2) slow bone deterioration; (3) restore lost bone; (4) stimulate new bone formation; and / or (5) maintain bone mass and / or bone quality. The invention also provides methods for administering a GDF-9 agonist or a BMP-15 agonist to treat a bone disorder characterized by increased bone density or mass.

Description

[0001] This application claims priority to US Provisional Application No. 60 / 787,246, filed March 28, 2006, the entire contents of which are incorporated herein by reference. technical field [0002] The technical field of the invention relates to the use of modulators of GDF-9 and BMP-15 in the treatment of bone diseases, such as osteoporosis, osteopenia, osteomalacia, osteodystrophy and fractures. Background technique [0003] Members of the transforming growth factor-beta (TGF-beta) superfamily possess physiologically important growth regulatory and morphogenetic properties (Kingsley et al., Genes Dev. 8:133-146 (1994); Hoodless et al., Curr. Topics Microbiol. Immunol. 228:235-272 (1998)). In recent years, much attention has been focused on the roles of two TGF-β superfamily members in ovarian function and fertility: growth and differentiation factor-9 (GDF-9) and bone morphogenetic protein-15 (BMP-15, also Known as GDF-9b; McNatty et al., Reprod. 128:379-386 (2004); Jue...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/17A61K38/18A61K39/395A61P19/08A61P19/10A61P15/18A61K45/00
CPCA61K31/675A61K33/00C07K14/51G01N2333/51C07K14/4753A01K2227/105C12Q2600/158A61K38/179A61K45/06G01N33/74A01K2217/075C07K16/22C12Q1/6883A01K67/0276G01N2800/10A61K31/663A61K38/00G01N33/50G01N2800/108G01N2333/475A61P1/04A61P15/18A61P19/00A61P19/08A61P19/10A61P35/00A61P5/18A61K2300/00A61K38/18A61K39/395
Inventor E·S·舍恩F·J·贝克斯三世Y·P·卡罗迪V·M·谢纳苏库基M·V·钱加瓦拉A·巴帕特P·E·史蒂维斯G·S·科普夫
Owner WYETH LLC
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