Patent Application: US-31281207-A

Abstract:
the invention relates to compositions for the treatment of th2 mediated inflammatory conditions . the compositions are vaccines comprising a non - primate tslp or fragments thereof to be used as a vaccine to treat humans with excessive mediated inflammatory conditions . for the treatment of th2 mediate inflammatory conditions in other non - human mammals the tslp of the species to be vaccinated is being used as antigen .

Description:
anti tslp antibodies are produced in the host by active immunization , so called vaccination . by injecting a modified tslp molecule into the host the immune system of the host produces a polyclonal antibody response directed against its own tslp thereby down regulating the effects of its potentially excessive tslp production . it is of major importance to modify the antigen so that the immune system of the host recognize the modified self - protein as a non - self protein . this can be achieved by covalent coupling of non - self amino acid regions to tslp or a selected region of tslp from the species to be treated . the peptides within the non - self region then attract and activate non - tolerized t cells , which give help for the potentially auto - reactive b cells . there are at least four possible strategies to do this modification of the self - protein . one method is to produce a fusion protein between a non - self protein , and the entire or a selected fragment of more than 5 amino acids of self - tslp in a prokaryotic or eukaryotic expression system . the open reading frame of tslp , as exemplified by canine and human tslp in fig1 , is then first being cloned into a bacterial , fungal or eukaryotic fusion protein vector . this fusion protein construct is then transfected into a mammalian or prokaryotic host for production of the desired fusion protein . the fusion partner can here be any non - self protein of any size from 10 amino acids to several hundred kd . however , it is usually favorable to use a fusion partner of approximately the same size as the self - protein . alternatively , an immunodominant peptide can be inserted into the tslp structure giving rise to a fusion protein with self - tslp sequences on both sides of the foreign peptide . as a third alternative , a non - modified tslp can be produced in a mammalian or prokaryotic host or host cell line and then covalently attached to a carrier protein by chemical coupling . the fourth alternative , which in our mind less favorable , is to produce selected regions of the tslp sequence as synthetic peptides and then to couple these peptides to a foreign carrier molecule by chemical coupling . this fourth alternative usually results , after injection into the patient , in antibody responses that show low binding activity against the native properly folded protein and thereby in lower clinical effect . following production the vaccine antigen is then purified and tested for pyrogen content and potential content of other contaminants . in order to obtain sufficiently strong immune response against the self - epitopes the vaccine antigen is then ( optionally ) mixed with an adjuvant before injection into the patient . after administration in the patient the vaccine induces an immune response against the vaccine antigen . due to the presence of self - epitopes in the vaccine antigen this protein also induces an antibody response against the target molecule , here tslp , thereby reducing the levels of this protein in the patient . 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