Peptide combinations and uses thereof for treating grass allergy
Inventors
Lundegaard, Claus • Gupta, Shashank • Peters, Bjoern • SØNDERKAER SUSANNE, null • Sønderkær, Susanne • Brimnes, Jens • Würtzen, Peter Adler • Henmar, Helene • Mygind, Thomas Christian • Maerkedahl, Lise Lund • Mærkedahl, Lise Lund, null • Sette, Alessandro
Assignees
ALK Abello AS • La Jolla Institute for Allergy and Immunology
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Publication Number
US-11013781-B2
Publication Date
2021-05-25
Expiration Date
Abstract
The invention relates to combinations of peptides derived from a portion of an amino sequence of a grass pollen allergen, e.g. the allergens Phl p 1, Phl p 2, Phl p 3, Phl p 4 and/or Phl p 5, or a peptide variant thereof. Such peptides comprise at least one T cell epitope mid a high number of patients in a worldwide population will have HLA Class II 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 grass pollen species.
Core Innovation
The invention concerns a composition comprising four peptide components, where a first peptide, a second peptide, a third peptide, and a fourth peptide are each defined by selecting specific amino acid sequences from groups of SEQ ID NOs. The peptide combinations comprise T-cell epitopes intended to induce T-cell-mediated immunological tolerance and are described in relation to HLA class II binding and qualitative coverage of HLA allele repertoire and donor coverage.
The disclosure describes peptide immunotherapy candidates derived from grass pollen allergens, including peptides associated with Phl p 1 through Phl p 5 and homologous peptides. It further describes cross-reactivity to homologous grass species, peptide group testing for T-cell cross-reactivity, and selection refinement of first choice peptides with peptide modification strategies.
The disclosure also connects the peptide combinations and peptide-variant substitutions to relief or reduction of grass allergy symptoms while minimizing IgE-mediated adverse events. It describes pharmaceutical, vaccine, and diagnostic kit concepts, parenteral administration, in vitro T cell recognition, and peptide variants and derivatives defined by selected amino-acid sequence alternatives and related peptide modifications and forms.
Claims Coverage
The claim coverage centers on a composition defined by four peptide components, with each peptide selected from specific SEQ ID NO sets. The dependent claims further specify additional peptides and narrower fixed peptide choices, characterize the composition as pharmaceutical, and add therapeutic and diagnostic use. Four inventive features are identified across the combined claims.
Four defined peptide selections by SEQ ID NO sets
A composition comprising a first peptide selected from SEQ ID NOs: 7, 212-214, 261, 262, 263 and 265; a second peptide selected from SEQ ID NOs: 71, 218-220, 224, 225, 288-291, 308 and 309; a third peptide selected from SEQ ID NOs: 72, 226, 227, 292-295; and a fourth peptide selected from SEQ ID NOs: 113, 186, 199, 228 and 229.
Additional specifically named peptides
The composition further includes an additional peptide defined by an amino acid sequence of an explicitly specified SEQ ID NO, and/or further adds additional explicitly specified peptides defined by particular SEQ ID NOs.
Pharmaceutical composition characterization
The composition is characterized as a pharmaceutical composition.
Therapeutic and diagnostic use of the composition
A method for relieving or reducing an immune response triggered by a grass pollen allergen from a grass species in a subject by administering a therapeutically effective amount of the composition, together with a diagnostic kit concept for contacting patient T cells with the composition or single peptides and detecting stimulation.
Overall, the claim coverage is directed to a defined four-peptide grass pollen allergen composition specified by SEQ ID NO sets, optionally narrowed to fixed sequences, characterized as a pharmaceutical composition, and used for therapeutic relief or reduction of allergen-triggered immune responses, with additional diagnostic use based on T-cell stimulation detection.
Stated Advantages
Induces T-cell-mediated immunological tolerance.
Relieves or reduces immune response and allergy symptoms triggered by a grass pollen allergen.
Minimizes IgE-mediated adverse events.
Relieves or reduces an immune response triggered by a grass pollen allergen.
Treating grass pollen-triggered immune responses with symptom-linked endpoints including allergic rhinitis symptoms, allergic conjunctivitis symptoms, allergic asthma symptoms, and atopic dermatitis symptoms.
Documented Applications
Use as a pharmaceutical composition or vaccine composition for grass allergy, including relieving or reducing an immune response triggered by a grass pollen allergen.
Use to relieve or reduce grass allergy immune responses and symptoms such as allergic rhinitis, allergic asthma, atopic dermatitis, and allergic conjunctivitis.
Kit-based pharmaceutical or vaccine delivery in connection with parenteral administration.
In vitro T cell recognition and diagnostic use involving contacting patient T cells with the composition or single peptides and detecting stimulation.
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