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Novel mutant allergens

A technology for allergens and allergies, applied in the field of preparing such recombinant allergen mutants, vaccines, and novel recombinant allergens, and can solve problems such as reducing IgE binding

Inactive Publication Date: 2010-01-06
ALK ABELLO SA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0029] None of the studies mentioned above addressed the reduction of IgE binding by replacing surface-exposed amino acids while maintaining the tertiary structure of the α-carbon backbone.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 4

[0144] Ala16Pro, (Asn28Thr, Lys32Gln), Lys103Thr, Pro108Gly, (Leu152Lys, Ala153Gly, Ser155Pro).

[0145] Mutant 2724:

[0146] N28T, K32Q, N78K, K103V, P108G, R145E, D156H, +160N.

[0147] Mutant 2733 (Example 4):

[0148] (Tyr5Val, Lys134Glu), (Asn28Thr, Lys32Gln), Glu45Ser, Lys65Asn, (Asn78Lys, Lys103Val), Lys97Ser, Pro108Gly, Arg145Glu, (Asp156His, +160Asn).

[0149] Mutant 2744: (Tyr5Val, Lys134Glu), (Glu42Ser, Glu45Ser), (Asn78Lys, Lys103Val), Lys123Ile, (Asp156His, +160Asn).

[0150] Mutant 2753 (Example 4):

[0151] (Asn28Thr, Lys32Gln), Lys65Asn, (Glu96Leu, Lys97Ser), (Pro108Gly, Asp109Asn), (Asp125Tyr, Glu127Ser), Arg145Glu.

[0152] Mutant 2744+2595:

[0153] Y5V, N28T, K32Q, E42S, E45S, N78K, K103V, P108G, K123I, K134E, D156H, +160N.

[0154] Mutant 2744+2628:

[0155] Y5V, E42S, E45S, K65N, N78K, K97S, K103V, K123I, K134E, D156H, +160N.

[0156] Mutant 2744+2595+2628:

[0157] Y5V, N28T, K32Q, E42S, E45S, K65N, N78K, K97S, K103V, P108G, K123I, K134E, D156H...

Embodiment 1

[0217] Example 1 describes the preparation of recombinant allergen mutants with 1 or 3 primary mutations. Recombinant allergen mutants according to the invention, ie allergens comprising at least 4 primary mutations, can be prepared using the same procedure.

[0218] Determination of Common Epitopes in Fagales Pollen Allergens

[0219] The major birch pollen allergen Bet v 1 shows about 90% amino acid sequence identity with the major allergens from taxonomically related tree pollen, which Fagales (e.g. hazelnut and hornbeam) and birch pollen allergies often show Clinical symptoms of allergic cross-reactivity to these Bet v 1 homologous proteins.

[0220] Bet v 1 also shows approximately 50-60% sequence identity with allergenic proteins found in certain fruits (eg, apples and cherries) and vegetables (eg, celery and carrots), and there is clinical evidence that Bet v 1 and Allergic cross-reactivity between these food-associated proteins.

[0221] In addition, Bet v 1 share...

Embodiment 2

[0297] Example 2 describes the preparation of recombinant allergen mutants with 1 primary mutation. Recombinant allergen mutants according to the invention, ie allergens comprising at least 4 primary mutations, can be prepared using the same procedure.

[0298] Common Epitope in Major Allergen Antigen 5 of Vespula Vulgaris Venom bit determination

[0299]Antigen 5 is one of 3 wasp venom proteins that are known human allergens. Wasps include hornets, hornets, and wasps. 2 other known wasp venom allergens are phospholipase A 1 and hyaluronidase. Antigen 5 from Vespula Vulgaris (Ves v5) has been cloned and expressed as a recombinant protein in yeast systems (Monsalve et al. 1999, ref. 22). Recently it has been updated with 1.8 Resolution determination of the 3D crystal structure of recombinant Vesv 5 (in preparation). The main feature of this structure consists of 4 β-strands and 4 α-helices arranged in 3 stacked layers to form an "α-β-α sandwich". The sequence identi...

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PUM

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Abstract

Novel recombinant allergens with multiple mutations and reduced IgE binding affinity are disclosed. The allergens are non-naturally occurring mutants of naturally-occurring allergens. The overall PROPORTIONAL -carbon backbone tertiary structure is essentially preserved. Also disclosed is a method for preparing such recombinant allergens as well as uses thereof.

Description

field of invention [0001] The present invention relates to mutants of natural allergens and novel recombinant allergens. The invention also relates to compositions comprising mixtures of the novel recombinant allergen mutants. Still further, the invention relates to methods for preparing such recombinant allergen mutants and pharmaceutical compositions, including vaccines, comprising such recombinant allergen mutants. In further embodiments, the invention relates to methods of generating an immune response in a subject, of vaccinating or treating a subject and of preparing the compositions of the invention. Background of the invention [0002] A genetically induced individual becomes sensitized (allergic) to antigens derived from various environmental sources as well as to allergens to which the individual is exposed. Allergic reactions occur when a previously allergic individual is re-exposed to the same or homologous allergen. Allergic reactions range from hay fever, rh...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12N15/29C12N15/12C07K14/415C07K14/435A61K39/35A61K39/36C12N5/10A61P37/08G01N33/53A61K38/095A61K39/00C07K14/00C07K16/16C12N1/15C12N1/19C12N1/21C12N15/09C12P21/02
CPCA61K2039/57C07K2299/00C07K14/415C07K14/43563C07K14/43568A61K38/00C07K16/16A61K39/00C07K14/43572A61P37/06A61P37/08C12N15/11
Inventor J·霍尔姆H·伊普森J·尼得加德拉尔森M·D·斯潘格福特
Owner ALK ABELLO SA
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