Pharm/Biotech
Resources

Outsourcing Guide

Cont. Education

Software/Reports

Training Courses

Web Seminars

Jobs

Buyer's Guide

Home Page

Pharm Patents /
Licensing

Pharm News

Federal Register

Pharm Stocks

FDA Links

FDA Warning Letters

FDA Doc/cGMP

Pharm/Biotech Events

Consultants

Advertiser Info

Newsletter Subscription

Web Links

Suggestions

Site Map
 

 

 

 

Title:  Methods for treatment of multiple sclerosis using peptide analogues of human myelin basic protein

United States Patent:  6,329,499

Inventors:  Ling; Nicholas (San Diego, CA); Gaur; Amitabh (San Diego, CA); Conlon; Paul J. (Solana Beach, CA); Steinman; Lawrence (Palo Alto, CA)

Assignee:  Neurocrine Biosciences, Inc. (San Diego, CA)

Appl. No.:  342408

Filed:  November 18, 1994

Abstract

The present invention is directed toward peptide analogues of human myelin basic protein. The peptide analogue is at least seven amino acids long and derived from residues 86 to 99 of human myelin basic protein. The analogues are altered from the native sequence at least at positions 91, 95, or 97. Additional alterations may be made at other positions. Pharmaceutical compositions containing these peptide analogues are provided. The peptide analogues are useful for treating multiple sclerosis.

SUMMARY OF THE INVENTION

The present invention provides peptide analogues comprising at least 7 amino acids selected from residues 86 to 99 of human myelin basic protein (SEQ. ID No:3) in which either L-lysine at position 91, L-threonine at position 95, or L-arginine at position 97 is altered to another amino acid. In one embodiment, L-lysine at position 91 is altered and one to three additional L-amino acids selected from residues 86, 87, 88, 95, 98 or 99 are altered to another amino acid. In a second embodiment, L-threonine at position 95 is altered and one to three additional amino acids selected from residues 86, 87, 88, 91, 98 and 99 or 86, 87, 88, 97, 98, and 99 are altered to another amino acid. In a third related embodiment, L-arginine at position 97 is altered and one to three additional amino acids selected from residues 86, 87, 88, 95, 98 or 99 are altered to another amino acid. The peptide analogues preferably contain double or triple alterations. In preferred aspects of the invention, the peptide analogues have altered residues 91, 95 or 97 to alanine and the additional amino acids are altered to the corresponding D-form amino acid.

In other embodiments, peptide analogues comprise at least seven amino acids selected from residues 86 to 99 of human myelin basic protein (SEQ. ID No:3) in which either L-lysine at position 91, L-threonine at position 95, or L-arginine at position 97 is altered to another amino acid, and in addition the N-terminal and C-terminal amino acids are altered in order to reduce proteolysis upon administration of the peptide analogue. In a preferred aspect, the N-and C-terminal amino acids are of the D-form.

In other embodiments, the peptide analogues comprise at least seven amino acids selected from residues 86 to 99 of human myelin basic protein (SEQ. ID No:3) in which either L-lysine at position 91, L-threonine at position 95, or L-arginine at position 97 is altered to another amino acid and in addition up to three other amino acid alterations are made. Any residue within 86-99 may be altered except that in a peptide analogue in which residue 91 is altered, residue 97 may not be altered. Likewise, in a peptide analogue in which residue 97 is altered, residue 91 may not be altered.

Other embodiments provide peptide analogues comprising at least seven amino acids selected from residues 86 to 99 of human myelin basic protein (SEQ. ID NO:3) in which either L-lysine at position 91, L-threonine at position 95, or L-arginine at position 97 is altered to another amino acid. In preferred aspects, residue 91, 95 or 97 are altered to either alanine or the corresponding D-amino acid.

Further aspects of the present invention provide a pharmaceutical composition comprising a peptide analogue according to the embodiments set out above in which the peptide analogue is contained in a physiologically acceptable carrier or diluent.

Further aspects of the present invention provide methods of treating multiple sclerosis by administering to a patient a therapeutically effective amount of a pharmaceutical composition comprising a peptide analogue comprising at least seven amino acids selected from residues 86 to 99 of human myelin basic protein (SEQ. ID No:3) in which residues 91, 95 or 97 are altered to another amino acid. Additionally, one to three additional amino acids may be altered or the N-and C-ends are altered to reduce proteolysis upon administration.

Claim 1 of 8 Claims

What is claimed is:

1. A peptide analogue comprising at least seven consecutive amino acids selected from residues 86 to 99 of human myelin basic protein as recited in SEQ ID NO:3, including residue 91, wherein the L-lysine at position 91 is altered to alanine, and proline at position 99 is altered to D-proline.

____________________________________________
If you want to learn more about this patent, please go directly to the U.S. Patent and Trademark Office Web site to access the full patent.

 

 

[ Outsourcing Guide ] [ Cont. Education ] [ Software/Reports ] [ Training Courses ]
[ Web Seminars ] [ Jobs ] [ Consultants ] [ Buyer's Guide ] [ Advertiser Info ]

[ Home ] [ Pharm Patents / Licensing ] [ Pharm News ] [ Federal Register ]
[ Pharm Stocks ] [ FDA Links ] [ FDA Warning Letters ] [ FDA Doc/cGMP ]
[ Pharm/Biotech Events ] [ Newsletter Subscription ] [ Web Links ] [ Suggestions ]
[ Site Map ]