Peptide combinations and uses thereof in treating dust mite allergy
Inventors
Lundegaard, Claus • Christensen, Lars Harder • Wurtzen, Peter Adler • Sette, Alessandro • Sidney, John • Lund, Gitte • Andersen, Peter Sejer
Assignees
ALK Abello AS • La Jolla Institute for Allergy and Immunology
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Publication Number
US-10059751-B2
Publication Date
2018-08-28
Expiration Date
Abstract
The invention relates to combinations of peptides or variants thereof derived from a portion of an amino sequence of a house dust mite allergen, e.g. the allergens Der p 1, Der f 1, Der p 2 and/or Der f 2. Such peptides comprise at least one T cell epitope and a significant high number of patients in a worldwide population will have HLA alleles with the potential to bind the peptides of the peptide combinations. The invention also relates to the use of such peptide combinations in relieving an immune response caused by a dust mite.
Core Innovation
The invention relates to peptide immunotherapy compositions for dust mite allergy that comprise at least three peptides, with at least one peptide selected from each of multiple specified peptide groups derived from major dust mite allergens Der p 1/Der p 2 and Der f 1/Der f 2. The compositions center on parent peptides identified as SEQ ID NO: 82 (pep-110), SEQ ID NO: 271 (pep-131), and SEQ ID NO: 268 (pep-130), with variant peptides consisting of 15-25 amino acid residues and having at least 90% sequence identity over at least 15 contiguous amino acids to the corresponding parent peptide.
A core aspect is selecting peptides in combination such that the peptide sets cover broad HLA class II binding functions. The disclosure describes grouping peptides by HLA class II-binding function to achieve broad worldwide HLA coverage and states that the peptide combinations induce in vitro T-cell responses in large fractions of donor populations.
The compositions are associated with therapeutic and diagnostic uses for dust mite allergy and with vaccine-type pharmaceutical compositions for parenteral use. Therapeutic uses include relieving or reducing dust-mite allergen-triggered immune responses, inducing immunological tolerance, and modulating immune responses with immunologic endpoints such as IgG/IgE and T-cell response modulation. Diagnostic uses include in vitro T-cell recognition assays and diagnostic kits for recognizing T-cell responses to the peptide compositions.
Claims Coverage
The independent claims define a three-peptide composition framework and a therapeutic method claim. The inventive features focus on at least three peptides selected across three specified peptide groups, with variant peptide constraints on length and sequence identity, and on use to relieve or reduce dust-mite allergen-triggered immune responses.
Three-peptide composition with parent-peptide group selection
A composition comprising at least three peptides, wherein at least one of the three peptides is selected from each of the following peptide groups: a parent peptide consisting of SEQ ID NO: 82 (pep-110) or a variant thereof; a parent peptide consisting of SEQ ID NO: 271 (pep-131) or a variant thereof; and a parent peptide consisting of SEQ ID NO: 268 (pep-130) or a variant thereof; wherein the variant peptides each consist of 15-25 amino acid residues and each comprise an amino acid sequence having at least 90% sequence identity over at least 15 contiguous amino acids of the corresponding parent peptide.
Three-peptide composition with constrained variant group membership
A composition comprising at least three peptides, wherein at least one of the peptides is selected from each of the following peptide groups: a peptide consisting of SEQ ID NO: 82 (pep-110) or a variant thereof selected from the group consisting of SEQ ID NO: 70 and SEQ ID NO:269; a parent peptide consisting of SEQ ID NO: 271 (pep-131) or a variant thereof selected from the group consisting of peptides of SEQ ID NO: 67, SEQ ID NO: 79, SEQ ID NO: 256 and SEQ ID NO: 270; and a parent peptide consisting of SEQ ID NO: 268 (pep-130) or a variant thereof selected from the group consisting of SEQ ID NO: 22, SEQ ID NO: 283, SEQ ID NO: 284, SEQ ID NO: 285 and SEQ ID NO: 286.
Method for relieving or reducing dust-mite allergen-triggered immune response
A method of relieving or reducing an allergen-triggered immune response to a dust mite in a subject by administering a therapeutically effective amount of a composition as defined in claim 1.
Together, the independent claims cover dust-mite-derived peptide immunotherapy compositions requiring at least three peptides selected across three defined parent-peptide groups, with variant peptides constrained by defined sequence length and sequence identity. One independent claim framework additionally restricts allowable variant group membership, and a therapeutic method claim covers administration to relieve or reduce dust-mite allergen-triggered immune responses.
Stated Advantages
Relieving or reducing dust-mite allergen-triggered immune responses.
Inducing immunological tolerance.
Modulating immune responses with immunologic endpoints such as IgG/IgE and T-cell response modulation.
Broad worldwide HLA coverage.
Inducing in vitro T-cell responses in large fractions of donor populations.
Reducing symptoms across allergic rhinitis, allergic conjunctivitis, allergic asthma, and atopic dermatitis.
In vitro T-cell recognition assays and diagnostic kit use for recognizing responses to the peptide compositions.
Documented Applications
Therapeutic use to relieve or reduce an allergen-triggered immune response to a dust mite in a subject by administering a composition comprising at least three specified peptides.
Treatment or therapy for dust mite allergy.
Symptom reduction for allergic rhinitis, allergic conjunctivitis, allergic asthma, and atopic dermatitis.
Diagnostic use via in vitro T-cell recognition methods and diagnostic kits for dust mite allergy peptide responses.
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