Peptides for treating and preventing immune-related disorders, including treating and preventing infection by modulating innate immunity
Inventors
Donini, Oreola • Rozek, Annett • Lentz, Shannon Wayne
Assignees
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Publication Number
US-8791061-B2
Publication Date
2014-07-29
Expiration Date
Abstract
In one aspect, the present invention provides isolated novel peptides that can be used to modulate innate immunity in a subject and/or for the treatment of an immune-related disorder, including treating and preventing infection by modulating innate immunity. Also provided are an agent reactive with the peptide, a pharmaceutical composition that includes the peptide, an isolated nucleic acid molecule encoding the peptide, a recombinant nucleic acid construct that includes the nucleic acid molecule, at least one host cell comprising the recombinant nucleic acid construct, and a method of producing the peptide using the host cell. The present invention further provides a method for treating and/or preventing infection in a subject by administering the peptide of the invention to the subject, thereby modulating innate immunity in the subject. Additionally, the present invention provides a method for predicting whether a subject would be responsive to treatment with a peptide of the invention.
Core Innovation
The invention relates to an isolated immunomodulatory peptide class that modulates innate immunity without direct antimicrobial activity and improves survival in infected hosts. The peptides comprise amino acid sequences, including SEQ ID NOs in TABLE 1, and reduce activity of dipeptidyl peptidase IV (DPPIV/CD26). The document connects DPPIV/CD26 to immune-related disorders and inflammation, and positions the peptides as therapeutic agents that act through immunomodulation rather than direct antimicrobial mechanisms.
The core peptide member RRVP (SEQ. ID. NO: 62) is claimed in isolated form, including pharmaceutical salt, ester or amide forms. The disclosed peptide scope includes truncations and termini modifications, and amino acid substitutions such as D-amino acid substitutions, backbone modifications such as N-methyl, and cyclic or derivatized variants. The disclosure further includes isolated nucleic acids encoding the peptides, recombinant nucleic acid constructs, and host cells for producing the peptides.
The document states therapeutic and prophylactic uses for treating and preventing infections across bacteria, fungi, parasites, and viruses. It also discloses optional combination use with antibiotics, including enhanced antibiotic efficacy in MRSA models. In addition, it discloses diagnostic and predictive methods based on assaying DPPIV activity and other biomarkers to identify patient responsiveness, including methods that relate to human and animal contexts.
Claims Coverage
The independent claim is directed to an isolated peptide RRVP (SEQ. ID. NO: 62), including pharmaceutical salt, ester, or amide forms, and it is supported by formulation-focused dependent claims that add excipients and optionally an antibiotic. The inventive features across the claim set focus on the defined RRVP peptide identity and its conversion to pharmaceutically acceptable chemical forms, plus pharmaceutical composition formulations with selected carriers/excipients and optional antibiotic co-administration.
Isolated RRVP peptide and pharmaceutically acceptable forms
An isolated peptide consisting of the amino acid sequence of RRVP (SEQ. ID. NO: 62), or a pharmaceutical salt, ester or amide thereof.
Pharmaceutical composition with acceptable carrier, diluent, or excipient
A pharmaceutical composition comprising the isolated peptide and a pharmaceutically-acceptable carrier, diluent, or excipient.
Pharmaceutical composition further comprising an antibiotic
The pharmaceutical composition further comprising an antibiotic.
Selected excipients from a defined excipient group
The pharmaceutical composition wherein the pharmaceutical carrier, diluent, or excipient is one or more selected from the group consisting of carboxymethyl cellulose, crystalline cellulose, glycerin, gum arabic, lactose, magnesium stearate, methyl cellulose, powders, saline, sodium alginate, sucrose, starch, talc, and water.
Saline as the pharmaceutical carrier
The pharmaceutical composition wherein the pharmaceutical carrier is saline.
Overall, the claims cover the isolated RRVP (SEQ. ID. NO: 62) peptide in salt, ester, or amide forms and pharmaceutical compositions containing it. The dependents further specify formulation with selected excipients, including saline, and optionally include an antibiotic as a co-administered component.
Stated Advantages
Modulates innate immunity.
Improves survival in infected hosts.
Acts without direct antimicrobial activity.
Reduces activity of dipeptidyl peptidase IV (DPPIV/CD26), linked to immune-related disorders and inflammation.
Decreases LPS-stimulated cytokine response.
Provides protection against S. aureus in vivo.
Shows efficacy in an ex vivo human blood infection model.
Demonstrates dose-response reduction of DPPIV activity in mouse and human blood.
Enhances antibiotic efficacy in MRSA models.
Documented Applications
Therapeutic and prophylactic treatment and prevention of infections (bacteria, fungi, parasites, viruses) using the disclosed immunomodulatory peptides.
Combination therapy with antibiotics, including enhanced antibiotic efficacy in MRSA models.
Diagnostic and predictive methods using assaying DPPIV activity and other biomarkers to identify patient responsiveness.
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