Recombinant protein variants
AssigneeALK-Abello A/S
InventorsJens Holm, Jorgen N. Larsen
Life of this patent
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Abstract
The present invention relates to novel recombinant protein variants that are useful as immunotherapeutic components. Also the present invention relates to DNA sequences encoding said protein variants as well as compositions comprising said protein variants.
Claims75
A recombinant protein variant with the ability to induce a protective immune response to a naturally occurring allergen, wherein the protein variant
- is a variant of a scaffold protein, said scaffold protein has a three-dimensional folding pattern that is structurally similar to that of the naturally occurring allergen,
- compared to the scaffold protein, comprises two or more primary mutations spaced by at least one non-mutated amino acid residue, each primary mutation introducing into the scaffold protein at least one amino acid residue identical or homologous to the amino acid residue or residues in corresponding position in the naturally occurring allergen, and
- has, compared to the scaffold protein, an increased affinity and/or binding capacity to IgE antibodies that are specific to the naturally occurring allergen.
A method of producing a recombinant protein variant with the ability to induce a protective immune response to a naturally occurring allergen, comprising the steps of:
- selecting a scaffold protein, said scaffold protein having a three-dimensional folding pattern that is structurally similar to that of the naturally occurring allergen,
- introducing two or more primary mutations, that are spaced by at least one non-mutated amino acid residue, into the scaffold protein, each primary mutation introducing into the scaffold protein at least one amino acid residue identical or homologous to the corresponding amino acid residue or residues in the naturally occurring allergen, and
- the protein variant having, compared to the scaffold protein, an increased affinity and/or binding capacity to IgE antibodies that are specific to the naturally occurring protein.
A recombinant protein variant with the ability to modulate an immune response to a naturally occurring allergen, wherein
- the naturally occurring allergen is selected from the group consisting of plant, grass, food, and mite allergens,
- the protein variant is a variant of a scaffold protein, said scaffold protein has a three-dimensional folding pattern that is similar to that of a naturally occurring allergen, the protein variant compared to the scaffold protein comprises at least one primary mutation introducing into the scaffold protein at least one amino acid residue identical or homologous to at least one amino acid residue present in the corresponding position in the natural occurring allergen, and
- the protein variant has, compared to the scaffold protein, an increased affinity and/or binding capacity to IgE antibodies that are specific to the naturally occurring protein.
A recombinant protein variant with the ability to modulate an immune response to a naturally occurring allergen, wherein
- the protein variant is a variant of a scaffold protein, said scaffold protein has a three-dimensional folding pattern that is similar to that of the naturally occurring allergen,
- the scaffold protein having a level of sequence identity with the naturally occurring allergen of between 30 and 50%,
- the protein variant compared to the scaffold protein comprises at least one primary mutation introducing into the scaffold protein at least one amino acid residue identical or homologous to at least one amino acid residue present in the corresponding position in the natural occurring allergen, and
- the protein variant has, compared to the scaffold protein, an increased affinity and/or binding capacity to IgE antibodies that are specific to the naturally occurring.
A recombinant protein variant with the ability to modulate an immune response to a naturally occurring allergen, wherein
- the protein variant is a variant of a scaffold protein, said scaffold protein has a three-dimensional folding pattern that is similar to that of a naturally occurring allergen,
- the deconvoluted CD-spectra of the protein variant deviates less than 30%, preferably less than 20%, and even more preferably less than 10% compared to the deconvoluted CD-spectra of the naturally occurring allergen,
- the protein variant compared to the scaffold protein comprises at least one primary mutation introducing into the scaffold protein at least one amino acid residue identical or homologous to at least one amino acid residue present in the corresponding position in the natural occurring allergen, and
- the protein variant has, compared to the scaffold protein, an increased affinity and/or binding capacity to IgE antibodies that are specific to the naturally occurring protein.
Dependencies are inferred from the claim text.