Follow us on Twitter
twitter icon@FreshPatents

Browse patents:
Next
Prev

Myostatin binding agents




Title: Myostatin binding agents.
Abstract: The present invention provides binding agents comprising peptides capable of binding myostatin and inhibiting its activity. In one embodiment the binding agent comprises at least one myostatin-binding peptide attached directly or indirectly to at least one vehicle such as a polymer or an Fc domain. The binding agents of the present invention produced increased lean muscle mass when administered to animals and decreased fat to muscle ratios. Therapeutic compositions containing the binding agents of the present invention are useful for treating muscle-wasting disorders and metabolic disorders including diabetes and obesity. ...


Browse recent Amgen Inc. patents


USPTO Applicaton #: #20120083442
Inventors: Hq Han, Hosung Min, Thomas Charles Boone


The Patent Description & Claims data below is from USPTO Patent Application 20120083442, Myostatin binding agents.

This application is a divisional of U.S. patent application Ser. No. 12/806,880, filed Aug. 23, 2010, which is a divisional of U.S. patent application Ser. No. 12/322,369, filed Jan. 30, 2009, now U.S. Pat. No. 7,803,923, which is a divisional of U.S. patent application Ser. No. 10/742,379, filed Dec. 19, 2003, now U.S. Pat. No. 7,511,012, which hereby claims benefit of U.S. provisional application Ser. No. 60/435,923, filed Dec. 20, 2002, the entire disclosure of each of the above applications is relied upon and incorporated by reference herein.

The present application is being filed along with a Sequence Listing in electronic format. The Sequence Listing is provided as a file entitled A-828-US-DIV3.txt created Oct. 20, 2011, which is 190 KB in size. The information in the electronic format of the Sequence Listing is incorporated herein by reference in its entirety.

Throughout this application various publications are referenced within parentheses or brackets. The disclosures of these publications in their entireties are hereby incorporated by reference in this application in order to more fully describe the state of the art to which this invention pertains.

FIELD OF THE INVENTION

- Top of Page


The invention relates to growth factors and in particular to the growth factor myostatin and agents which bind myostatin and inhibit its activity.

BACKGROUND

- Top of Page


Myostatin, also known as growth/differentiation factor 8 (GDF-8), is a transforming growth factor-β (TGF-β) family member known to be involved in regulation of skeletal muscle mass. Most members of the TGF-β-GDF family are expressed non-specifically in many tissue types and exert a variety of pleitrophic actions. However, myostatin is largely expressed in the cells of developing and adult skeletal muscle tissue and plays an essential role in negatively controlling skeletal muscle growth (McPherron et al. Nature (London) 387, 83-90 (1997)). Recent studies, however, indicate that low levels of myostatin expression can be measured in cardiac, adipose and pre-adipose tissues.

The myostatin protein has been highly conserved evolutionarily (McPherron et al. PNAS USA 94:12457-12461 (1997)). The biologically active C-terminal region of myostatin has 100 percent sequence identity between human, mouse, rat, cow, chicken, and turkey sequences. The function of myostatin also appears to be conserved across species as well. This is evident from the phenotypes of animals having a mutation in the myostatin gene. Two breeds of cattle, the Belgian Blue (Hanset R., Muscle Hypertrophy of Genetic Origin and its Use to Improve Beef Production, eds, King, J. W. G. & Menissier, F. (Nijhoff, The Hague, The Netherlands) pp. 437-449) and the Piedmontese (Masoero, G. & Poujardieu, B, Muscle Hypertrophy of Genetic Origin and its Use to Improve Beef Production., eds, King, J. W. G. & Menissier, F. (Nijhoff, The Hague, The Netherlands) pp. 450-459) are characterized by a “double muscling” phenotype and increase in muscle mass. These breeds were shown to contain mutations in the coding region of the myostatin gene (McPherron et al. (1997) supra). In addition, mice containing a targeted deletion of the gene encoding myostatin (Mstn) demonstrate a dramatic increase in muscle mass without a corresponding increase in fat. Individual muscles of Mstn−/− mice weigh approximately 100 to 200 percent more than those of control animals as a result of muscle fiber hypertrophy and hyperplasia (Zimmers et al. Science 296, 1486 (2002)).

Administration of myostatin to certain strains of mice has been shown to create a condition similar to muscle wasting disorders found associated with cancer, AIDS, and muscular dystrophy, for example. Myostatin administered as myostatin-producing CHO cells to athymic nude mice resulted in a wasting effect with a high degree of weight loss, a decrease of as much as 50% of skeletal muscle mass in addition to fat wasting, and severe hypoglycemia (Zimmers et al. supra).

Loss of myostatin appears to result in the retention of muscle mass and reduction in fat accumulation with aging. It has been shown that age-related increases in adipose tissue mass and decrease in muscle mass were proportional to myostatin levels, as determined by a comparison of fat and muscle mass in Mstn+/+ when compared with Mstn−/− adult knockout mice (McFerron et al. J. Clin. Invest 109, 595 (2002)). Mstn−/− mice showed decreased fat accumulation with age compared with Mstn+/+ mice.

In addition myostatin may play a role in maintaining blood glucose levels and may influence the development of diabetes in certain cases. It is known that, for example, skeletal muscle resistance to insulin-stimulated glucose uptake is the earliest known manifestation of non-insulin-dependent (type 2) diabetes mellitus (Corregan et al. Endocrinology 128:1682 (1991)). It has now been shown that the lack of myostatin partially attenuates the obese and diabetes phenotypes of two mouse models, the agouti lethal yellow (Ay) (Yen et al. FASEB J. 8:479 (1994)), and obese (Lepob/ob). Fat accumulation and total body weight of the Ay/a, Mstn−/− double mutant mouse was dramatically reduced compared with the Ay/a Mstn+/+ mouse (McFerron et al., (2002) supra). In addition, blood glucose levels in the Ay/a, Mstn−/− mice was dramatically lower than in Ay/a Mstn+/+ mice following exogenous glucose load, indicating that the lack of myostatin improved glucose metabolism. Similarly Lepob/ob Mstn−/− mice showed decreased fat accumulation when compared with the Lepob/ob Mstn+/+ phenotype.

Therefore, there is considerable evidence from the phenotypes of over-expressing and knockout animals that myostatin may play a role in contributing to a number of metabolic disorders including disorders resulting in muscle wasting, diabetes, obesity and hyperglycemia.

SUMMARY

- Top of Page


OF THE INVENTION

The present invention is directed to binding agents which bind myostatin and inhibit its activity. The binding agents comprise at least one peptide capable of binding myostatin. The myostatin-binding peptides are preferably between about 5 and about 50 amino acids in length, more preferably between about 10 and 30 amino acids in length, and most preferably between about 10 and 25 amino acids in length. In one embodiment the myostatin-binding peptide comprises the amino acid sequence WMCPP (SEQ ID NO: 633). In another embodiment the myostatin binding peptides comprise the amino acid sequence Ca1a2Wa3WMCPP (SEQ ID NO: 352), wherein a1, a2 and a3 are selected from a neutral hydrophobic, neutral polar, or basic amino acid. In another embodiment the myostatin binding peptide comprises the sequence Cb1b2Wb3WMCPP (SEQ ID NO: 353), wherein b1 is selected from any one of the amino acids T, I, or R; b2 is selected from any one of R, S, Q; b3 is selected from any one of P, R and Q, and wherein the peptide is between 10 and 50 amino acids in length, and physiologically acceptable salts thereof. In another embodiment, the myostatin binding peptide comprises the formula:


c1c2c3c4c5c6Cc7c8Wc9WMCPPc10c11c12c13(SEQ ID NO: 354),

wherein:

c1 is absent or any amino acid;

c2 is absent or a neutral hydrophobic, neutral polar, or acidic amino acid;

c3 is absent or a neutral hydrophobic, neutral polar, or acidic amino acid;

c4 is absent or any amino acid;

c5 is absent or a neutral hydrophobic, neutral polar, or acidic amino acid;

c6 is absent or a neutral hydrophobic, neutral polar, or basic amino acid;

c7 is a neutral hydrophobic, neutral polar, or basic amino acid;

c8 is a neutral hydrophobic, neutral polar, or basic amino acid;

c9 is a neutral hydrophobic, neutral polar or basic amino acid; and

c10 to c13 is any amino acid; and wherein the peptide is between 20 and 50 amino acids in length, and physiologically acceptable salts thereof.

A related embodiment the myostatin binding peptide comprises the formula:


d1d2d3d4d5d6Cd7d8Wd9WMCPPd10d11d12d13(SEQ ID NO: 355),

wherein

d1 is absent or any amino acid;




← Previous       Next →
Advertise on FreshPatents.com - Rates & Info


You can also Monitor Keywords and Search for tracking patents relating to this Myostatin binding agents patent application.

###


Browse recent Amgen Inc. patents

Keyword Monitor How KEYWORD MONITOR works... a FREE service from FreshPatents
1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored.
3. Each week you receive an email with patent applications related to your keywords.  
Start now! - Receive info on patent apps like Myostatin binding agents or other areas of interest.
###


Previous Patent Application:
Pharmaceutical compositions
Next Patent Application:
Control of atp release by red blood cells and therapeutic applications thereof
Industry Class:
Drug, bio-affecting and body treating compositions
Thank you for viewing the Myostatin binding agents patent info.
- - -

Results in 0.37274 seconds


Other interesting Freshpatents.com categories:
Novartis , Apple , Philips , Toyota ,

###

Data source: patent applications published in the public domain by the United States Patent and Trademark Office (USPTO). Information published here is for research/educational purposes only. FreshPatents is not affiliated with the USPTO, assignee companies, inventors, law firms or other assignees. Patent applications, documents and images may contain trademarks of the respective companies/authors. FreshPatents is not responsible for the accuracy, validity or otherwise contents of these public document patent application filings. When possible a complete PDF is provided, however, in some cases the presented document/images is an abstract or sampling of the full patent application for display purposes. FreshPatents.com Terms/Support
-g2-0.4061

66.232.115.224
Browse patents:
Next
Prev

stats Patent Info
Application #
US 20120083442 A1
Publish Date
04/05/2012
Document #
File Date
12/31/1969
USPTO Class
Other USPTO Classes
International Class
/
Drawings
0


Myostatin

Follow us on Twitter
twitter icon@FreshPatents

Amgen Inc.


Browse recent Amgen Inc. patents





Browse patents:
Next
Prev
20120405|20120083442|myostatin binding agents|The present invention provides binding agents comprising peptides capable of binding myostatin and inhibiting its activity. In one embodiment the binding agent comprises at least one myostatin-binding peptide attached directly or indirectly to at least one vehicle such as a polymer or an Fc domain. The binding agents of the |Amgen-Inc
';