Non-Anaphylactogenic IgE Fusion Proteins

a fusion protein and non-anaphylaxis technology, applied in the field of non-anaphylaxis ige fusion proteins, can solve the problems of conflicting approaches, inconsistent and conflicting, and little information on bona fide ige receptor binding sites, and achieve the effect of enhancing the immune response to an antigen

Inactive Publication Date: 2008-08-14
PFIZER INC +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The peptides effectively induce high titers of anti-IgE antibodies that prevent IgE from binding to its receptors on mast cells and basophils without causing anaphylaxis, providing a safer and more effective treatment for IgE-mediated allergic disorders.

Problems solved by technology

The results of Basu et al. and Vangelista et al. are inconsistent and conflict with those of Helm et al. cited abo
However, the anti-CH3 peptide antibodies induced in response to the CH3 peptide released histamine from IgE-loaded mast cells indicating that the amino acids defined by the CH3peptide did not define the bona fide IgE receptor-binding site and that anti-CH3 peptide antibodies could cause anaphylaxis.
However, Schwartzbaum's conclusion contradict Weetall et al.
However, the conclusions by Nissim et al. and Vangelista et al. contradict the conclusions of Weetall et al. and Robertson et al.
Unfortunately, when these IgGEL variants were tested for receptor binding, they exhibited minimal binding compared to the native IgE or the IgG in which the full length IgE CH3 domain replaced the full length CγH2 domain.
Although many monoclonal antibodies have been developed, they have provided little information on the bona fide IgE receptor-binding site because in many cases the amino acid sequence recognized by these monoclonal antibodies have not or could not be identified.
It is apparent from the above discussion that approaches that have been devised to identify the receptor binding site on IgE have produced conflicting results.
The difficulty in the identification of the amino acid residues of IgE responsible for receptor binding could be further complicated by the possibility that the site on IgE used for binding to the receptor may not be a linear sequence of amino acids, which could be mimicked by a synthetic peptide.
High doses of antihistamines and corticosteroids have deleterious side effects such as renal and gastrointestinal toicities.
Second, the cost of treatment with these antibodies will be very high since high doses of these monoclonal antibodies are required to induce a therapeutic effect.
Moreover, the frequency and administration routes with which these antibodies have to be administered are inconvenient.
However, this peptide has been shown not to induce the production of antibodies that react with native soluble IgE.
A major obstacle facing the development of an anti-IgE vaccine is the lack of information regarding the precise amino acids representing non-anaphylactogenic IgE determinants that could be safely used to immunize allergic subjects and induce non-anaphylactogenic polyclonal antibodies (i.e., polyclonal anti-IgE antibodies that do not bind to receptor-bound IgE).

Method used

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  • Non-Anaphylactogenic IgE Fusion Proteins
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[0096]1. Selection of antigenic peptides and cloning of corresponding polyneucleotide sequences

[0097]A major obstacle facing the development of an anti-IgE vaccine is the lack of information regarding the precise amino acids representing non-anaphylactogenic IgE determinants that could be safely used to immunize allergic subjects and induce non-anaphylactogenic polyclonal antibodies (i.e. polyclonal anti-IgE antibodies that do not bind to receptor-bound IgE). By definition, those determinants ideally correspond to only those IgE amino acid sequences that physically contact the IgE receptor. Clearly, there is no information in the prior art on the precise identity of those sequences. Indeed, the prior art is inconsistent on even the region or domain of IgE within which those sequences may reside. Furthermore, the identity of non-anaphylactogenic determinants could be correctly elucidated from only solving the crystal structure of IgE-IgE receptor complex which, unfortunately, has not...

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Abstract

The present invention provides compositions and methods for the use of antigenic peptides derived from the Fc portion of the epsilon heavy chain of IgE molecules from two unrelated species as vaccines for the treatment and prevention of IgE-mediated allergic disorders, in particular, the invention provides compositions for the treatment and prevention of IgE-mediated allergic disorders comprising an immunogenic amount of one or more antigenic peptides.

Description

FIELD OF THE INVENTION[0001]The present invention relates to compositions and methods for the use of antigenic peptides derived from the Fc portion of the epsilon heavy chain of IgE molecules as vaccines for the treatment and prevention of IgE-mediated allergic disorders. In particular, the present invention relates to compositions comprising at least one antigenic peptide comprising an amino acid sequence derived from the CH3 domain of IgE molecules from two different species for the treatment or prevention of an IgE-mediated allergic disorder. The present invention also relates to compositions comprising antigenic peptides coupled to heterologous carrier proteins and optionally further comprising an adjuvant. The compositions of the present invention induce anti-IgE antibodies which bind to soluble (free) IgE in serum and other bodily fluids, prevent IgE from binding to its high affinity receptors on mast cells and basophils, and do not cross-link receptor-bound IgE. The present i...

Claims

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Application Information

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Patent Type & AuthorityApplications(United States)
IPC IPC(8): A61K39/395C07K16/18A61P37/00A61K39/00C12N15/09A61P37/04A61P37/08C07K16/00C12N1/15C12N1/19C12N1/21C12N5/10C12N15/13
CPCA61K39/00A61K2039/505A61K2039/53C07K16/00C07K2317/52C07K2317/24C07K2319/00C12N2799/026C07K2317/21A61P31/12A61P37/00A61P37/04A61P37/08
InventorMORSEY, MOHAMAD A.BROWN, TRACY M.
OwnerPFIZER INC