Harvard College

Yeda Research and Develpment & Co. Ltd

Masha Fridkis-Hareli

Jack L Strominger

Ruth Arnon

Michael Sela

Dvora Teitelbaum

Rina Aharoni

The invention provides heteropolymer compositions and peptide compositions, and methods of making and using therapeutic compositions comprising amino acid heteropolymers for treatment of a subject for an autoimmune or an inflammatory disease, the heteropolymer compositions made by solid state synthesis. The invention also provides kits for assaying binding of a composition to a water-soluble MHC protein.

Synthetic peptides and methods of use for autoimmune disease therapies

Random three- and four-amino acid copolymers having lengths of 14-, 35- and 50-amino acid residues are provided. The random copolymers have amino acids alanine, lysine and one or more of the hydrophobic amino acids valine, phenylalanine, tryptophan and tyrosine. Random three-amino acid copolymer FAK efficiently suppressed EAE induced in SJL/J (H-2S) mice with the encephalitogenic epitope PLP 139-151. Random four-amino acid copolymers VYAK and tryptophan-containing VWAK were efficacious in alleviating severity and duration of symptoms of EAE induced by MBP 85-99 (SEQ ID NO:2), in a humanized mouse model expressing genes for both an HLA-DR-2 linked to multiple sclerosis (MS) in humans and for a T cell receptor from an MS patient.

Copolymers for suppression of autoimmune diseases, and methods of use

Random three- and four-amino acid copolymers having lengths of 14-, 35- and 50-amino acid residues are provided. Fifty-mers of FEAK were effective inhibitors of MBP 85-99- or proteolipid protein (PLP) 40-60-specific HLA-DR-2-restricted T cell clones. These copolymers efficiently suppressed the mouse disease EAE, which was induced in a susceptible SJL/J (H-2) strain of mice with either whole spinal cord homogenate (WSCH) or with the encephalitogenic epitope PLP 139-151 (SEQ ID NO:4). YFAK 50-mer having a molar ratio of about Y 0.8:F 0.2 inhibited binding of biotinylated MBP 85-99 epitope to HLA-DR-2 molecules more efficiently than either unlabeled MBP 85-99 or Copaxone&#xae;. YFAK and FAK copolymers efficiently suppressed EAE induced in SJL/J (H-2) mice with the encephalitogenic epitope PLP 139-151. Copolymers YFAK, VYAK and tryptophan-containing VWAK were efficacious in alleviating severity and duration of symptoms of EAE induced by MBP 85-99 (SEQ ID NO:2), in a humanized mouse model expressing genes for both an HLA-DR-2 linked to multiple sclerosis (MS) in humans and for a T cell receptor from an MS patient.

The invention provides peptide compositions, and methods of making and using therapeutic compositions for treatment of a subject for an autoimmune or an inflammatory disease. The invention also provides kits for assaying binding of a composition to a water-soluble MHC protein.

The invention provides peptide compositions and methods of making and using therapeutic compositions comprising peptides for the treatment of a subject having a demyelinating condition.

Therapeutic peptides for demyelinating conditions

The present invention is directed to polypeptides containing at least three amino acids randomly joined in a linear array; wherein at least one of the three amino acids is an aromatic amino acid, at least one of the three amino acids is a charged amino acid and at least one amino acid is an aliphatic amino acid. In a preferred embodiment the polypeptide contains three or four of the following amino acids: tyrosine, alanine, glutamic acid or lysine. According to the present invention, the present polypeptides bind to antigen presenting cells, purified human lymphocyte antigens (HLA) and/or Copolymer 1-specific T cells. Moreover, according to the present invention, these polypeptides can be formulated into pharmaceutical compositions for treating autoimmune disease. The present invention further contemplates methods of treating an autoimmune disease in a mammal by administering a pharmaceutically effective amount of any one of the present polypeptides to the mammal.

Treatment of autoimmune conditions with Copolymer 1 and related Copolymers

The present invention provides heteropolymer compositions and peptide compositions, and methods of making and using therapeutic compositions comprising amino acid heteropolymers for treatment of a subject for an autoimmune or an inflammatory disease, the heteropolymer compositions made by solid state synthesis. The invention also provides kits for assaying binding of a composition to a water-soluble MHC protein.

Growing community of inventors

Sudbury, MA, United States of America

Masha Fridkis-Hareli