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Title:  Peptide specificity of anti-myelin basic protein and the administration of myelin basic protein peptides to multiple sclerosis patients

United States Patent:  6,252,040

Inventors:  Warren; Kenneth G. (Alberta, CA); Catz; Ingrid (Alberta, CA)

Assignee:  The Governors of the University of Alberta (CA)

Appl. No.:  055263

Filed:  April 6, 1998

Foreign Application Priority Data:  Oct 22, 1991[CA] (2053799-0)


Abstract

Human myelin basic protein (h-MBP) has a molecular weight of 18.5 KD and contains 170 amino acid residues. Synthetic peptides ranging in length from about 8 to 25 residues and covering the entire length of the protein have been produced. Antibodies to h-MBP (anti-MBP) were found to be neutralized by the synthetic peptides, in vitro, which span the h-MBP from about amino acid residue 61 to about amino acid residue 106. The peptides, which cover both the amino (about residues 1 to 63) and carboxy (about residues 117 to 162) terminals of h-MBP did not neutralize purified anti-MBP. Intrathecal administratin of peptide MBP(75-95), MBP(86-95), or MBP(82-98) produced complete binding-neutralization of free (F) anti-MBP with no change in bound (B) levels. A control peptide MBP35-58 had no effect on F or B anti-MBP levels. Intravenous administration of MBP(75-95), MBP(86-95), or MBP(82-98) resulted in significant decline of F and B CSF anti-MBP levels. Administration of MBP synthetic peptides to MS patients either intrathecally or intravenously did not have any adverse neurological effects and systemic complications did not occur. The MBP epitope for MS anti-MBP has been localized to an area between amino acid 86 and amino acid 95.

SUMMARY OF INVENTION

According to the present invention there is provided, peptides which are substantially homologous in sequence to a part of the amino acid sequence of a human myelin basic protein. These peptides are capable of neutralizing or modulating the production of anti-MBP.

According to the present invention the peptides are of the formula:

R1 -Val-His-Phe-Phe-Lys-Asn-Ile-R2

and salts thereof, wherein R1 and R2 are independently selected from the group consisting of hydrogen, hydroxy, the residue of an amino acid and the residue of a polypeptide; provided that R1 and R2 are not both hydrogen or hydroxyl at the same time. The peptide can contain substitutions, deletions or additions thereof, provided that the peptide maintains its function of neutralizing or modulating the production of anti-MBP.

Examples of said peptides are selected from:

MBP75-95

Lys Ser His Gly Arg Thr Gln Asp Glu Asn Pro Val Val His Phe Phe Lys Asn Ile Val Thr

MBP64-78

Ala Arg Thr Ala His Tyr Gly Ser Leu Pro Gln Lys Ser His Gly

MBP61-75

His His Pro Ala Arg Thr Ala His Tyr Gly Ser Leu Pro Gln Lys

MBP69-83

Tyr Gly Ser Leu Pro Gln Lys Ser His Gly Arg Thr Gln Asp Glu

MBP80-97

Thr Gln Asp Glu Asn Pro Val Val His Phe Phe Lys Asn Ile Val Thr Pro Arg

MBP91-106

Lys Asn Ile Val Thr Pro Arg Thr Pro Pro Pro Ser Gln Gly Lys Gly

MBP84-93

Asn Pro Val Val His Phe Phe Lys Asn Ile

MBP85-94

Pro Val Val His Phe Phe Lys Asn Ile Val

MBP86-95

Val Val His Phe Phe Lys Asn Ile Val Thr

MBP87-96

Val His Phe Phe Lys Asn Ile Val Thr Pro

MBP82-98

Asp Glu Asn Pro Val Val His Phe Phe Lys Asn Ile Val Thr Pro Arg Thr

Further according to the present invention there is provided pharmaceutical compositions, which comprises as an active ingredient a peptide as described above, either alone or in combination, in admixture with a pharmaceutical acceptable carrier.

Further according to the present invention, there is provided a method of treating multiple sclerosis comprising administering an effective amount of a peptide as, described above, either alone or in combination to effectively neutralize or modulate the production of anti-human myelin basic protein.

Claim 1 of 13 Claims

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

1. A method of treating multiple sclerosis in a patient in need thereof by administering to said patient an effective amount of a peptide of the sequence: Asp Glu Asn Pro Val Val His Phe Phe Lys Asn Ile Val Thr Pro Arg Thr in admixture with a pharmaceutical acceptable carrier.

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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.

 

 

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