Yissum Research Development Company of the Hebrew University of Jerusalem Ltd.

Atox Bio Ltd.

Hadasit Medical Research Services and Development Company

Raymond Kaempfer

Gila Arad

Anat Shirvan

Revital Levy

Farhat Osman

Yitzhak Ben-Asouli

Dan Teleman

Amos Shapiro

Nayef Jarrous

Disclosed are peptides comprising amino acid residues of the dimer interface of human B7-1 and B7-2 and compositions and uses thereof.

Isolated peptides derived from the B7 ligand dimer interface and uses thereof

Disclosed are peptides, compositions, combinations, kits and methods for the treatment of viral pathogen infection. Combinations and kits comprise the disclosed peptides together with an additional antiviral therapeutic agent.

Peptides for use in the treatment of viral infections

The present disclosure relates to a method for the treatment of a non-pathogen associated inflammatory disorders in a subject in need thereof, comprising administering to said subject an isolated peptide which specifically binds to an amino acid sequence within the dimer interface of a T cell costimulatory pathway member, particularly the T cell costimulatory pathway members CD28 and CTLA4. The present disclosure also relates to pharmaceutical compositions comprising the isolated peptide and to use of the peptide in treating of a non-pathogen associated inflammatory disorders.

Reduction of inflammatory disease symptoms by short peptides that inhibit signaling through CD28

Disclosed are peptides and methods for the treatment of bacterial infections and associated inflammation. Effective doses and treatment protocols are disclosed.

Synthetic peptides for treatment of bacterial infections

Disclosed are methods and compositions for the inhibition of modulation of T cell costimulatory pathway by a pathogenic agent, particularly, the inhibition of activation of a T cell costimulatory pathway by a pyrogenic exotoxin. The direct interaction of a superantigen with a specific site within the dimer interface of a CD28 family member is inhibited using immunomodulatory peptides. Specific antagonist immunomodulatory peptides comprise amino acid sequences derived from a dimer interface of a T cell co-stimulatory pathway member, or peptides which comprise an amino acid sequence which specifically binds to an amino acid sequence within the dimer interface of a T cell co-stimulatory pathway member. Compositions comprising said peptides and methods for the treatment of immune-related disorders are also disclosed. Such molecules may be used in screening for a test substance which specifically binds to the CD28 molecule and is capable of antagonizing pyrogenic exotoxin-mediated activation of Th1 lymphocytes.

Broad-spectrum in-vivo effective superantigen toxin antagonists based on the interaction between CD28 and the superantigen and uses thereof

Disclosed are methods and compositions for the inhibition of modulation of T cell costimulatory pathway by a pathogenic agent, particularly, the inhibition of activation of a T cell costimulatory pathway, preferably, the CD28/B7 pathway, by a pyrogenic exotoxin. The method of the invention is based on the inhibition of the direct interaction of a superantigen with a specific site within the dimer interface of a CD28 family member, using immunomodulatory peptides. Further disclosed are specific antagonist immunomodulatory peptides comprising an amino acid sequence derived from a dimer interface of a T cell co-stimulatory pathway member, or peptides which comprise an amino acid sequence which specifically binds to an amino acid sequence within the dimer interface of a T cell co-stimulatory pathway member. Compositions comprising said peptides and methods for the treatment of immune-related disorders are also disclosed. Also disclosed is the use of the CD28 molecule or any fragment thereof comprising the sAg binding site in a method of screening for a test substance which specifically binds to the CD28 molecule and is capable of antagonizing pyrogenic exotoxin-mediated activation of Th1 lymphocytes.

The invention relates to peptides having an amino acid sequence substantially homologous to an amino sequence of a domain of a pyrogenic exotoxin, which domain forms a central turn in the exotoxin starting within &#x3b2;-strand 7 and connecting the &#x3b2;-strand 7, via short &#x3b2;-strand 8, to &#x3b1;-helix 4, and ending within &#x3b1;-helix 4, based on the domain numbering ofenterotoxin B. The peptides of the invention are capable of antagonizing toxin-mediated activation of T-lymphocytes, do not have agonist activity, and are capable of eliciting protective immunity against toxic shock induced by a pyrogenic exotoxin or by a mixture of pyrogenic exotoxins. The invention also relates to broad spectrum pharmaceutical compositions for the treatment, protection against or short term prophylaxis of toxin-mediated activation of T cells, comprising as active ingredient at least one peptide according to the invention or a derivative thereof, and to broad spectrum vaccines for conferring long term immunity against toxic shock induced by at least one pyrogenic exotoxin.

Broad spectrum pyrogenic exotoxins antagonists and vaccines

The invention relates to peptides comprising an amino acid sequence homologous to the amino sequence of a fragment of a pyrogenic exotoxin, and functional derivatives of said peptides, capable of eliciting protective immunity against toxic shock induced by a pyrogenic exotoxin or by a mixture of pyrogenic exotoxins. Preferred peptides comprise an amino acid sequence homologous to the amino sequence of a fragment ofenterotoxin B (SEB). The invention also relates to broad spectrum pharmaceutical compositions for the treatment, protection against or short term prophylaxis of toxin-mediated activation of T cells, comprising as active ingredient at least one peptide according to the invention or derivative thereof, and to broad spectrum vaccines for conferring long term immunity against toxic shock induced by at least one pyrogenic exotoxin are provided. The vaccines comprising as active ingredient at least one peptide according to the invention, or derivative thereof.

Broad spectrum antagonists and vaccines directed against pyrogenic exotoxins

A cis-acting nucleotide sequence which is capable of rendering the removal of introns from a precursor transcript encoded by a gene, which gene harbors at least one such cis-acting nucleotide sequence, occurring during the production of mRNA of a gene, dependent upon activation of a trans-acting factor. The trans-acting factor is an RNA-activated protein kinase which is capable of phosphorylating the &#x3b1;-subunit of eukaryotic initiation factor 2. The trans-acting factor is preferably, the RNA-activated protein kinase (PKR). The cis-acting nucleotide sequence can be derived from the 3' untranslated region of the human tumor necrosis factor &#x3b1; gene (TNF-&#x3b1;3&#x2032;-UTR) and may comprise the nucleotide sequence as denoted by SEQ ID NO:1 or biologically functional fragments, derivatives, mutants and homologues thereof.

Regulation of gene expression through manipulation of mRNA splicing and its uses

The invention relates to a method and kit for the prediction of the response of a patient suffering from superficial bladder carcinoma to treatment with bacillus Calmette-Guerin (BCG), by calculating the inducibility of the Interleukin-2 (IL-2) gene of the patient in a sample of peripheral blood mononuclear (PBM) cells from the patient receiving BCG. The method includes the steps of culturing at least two aliquots of PBM from the patient where the cells in a first aliquot are cultured in the presence of an inducing agent for inducing expression of the IL-2 gene and the cells in the second aliquot are cultured in the absence of the inducing agent. The extent of expression of the IL-2 gene is quantitatively determined for each aliquot. The ratio of the extent of the expression of the IL-2 gene in the first aliquot to the extent of the expression of the IL-2 gene in the second aliquot is calculated, the ratio providing a measure of the inducibility of the IL-2 gene. The inducibility is in a direct relationship with the probability of entering remission, relapse or persistence of bladder carcinoma in the patient. Patients with a ratio below about 1.5 can be treated either with a cytokine preparation, a second course of treatment with the BCG or a second course of treatment with the BCG in combination with a cytokine preparation to improve response.

Growing community of inventors

Jerusalem, Israel

Raymond Kaempfer