Oral administration compositions comprising an OB-fold protein variant
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Publication Number
US-10293025-B2
Publication Date
2019-05-21
Expiration Date
Abstract
The invention relates to an oral administration composition containing an OB-fold protein variant, and to the method for preparing the same.
Core Innovation
The invention relates to an oral administration composition comprising a variant of a wild-type OB-fold protein. The variant has between 5 and 32 mutated residues in the interface of binding of the wild-type OB-fold protein to its natural ligand, and the composition is based on OB-fold protein variants described as nanofitins, including variants within a Sac7d-family.
The described OB-fold includes binding interfaces defined as the binding interface of the wild-type OB-fold protein to its natural ligand, and the binding interface is modified through between 5 and 32 mutated residues. Optional loop insertions are described in connection with the OB-fold protein variants, and the rationale is provided for oral delivery despite gastric degradation by using OB-fold protein variants intended to remain functional during passage into the intestine.
The composition is formulated for oral administration with pharmaceutically acceptable excipients and oral dosage forms such as gel capsules, tablets, pills, lozenges, and liquid/syrup forms, including slow-release matrices and lyophilized proteins. Target of interest binding is described broadly, and therapeutic use is described for gastrointestinal or systemic diseases, with possible diagnostic implementations involving fusions and tracer coupling.
Experimental support described in the document includes nanofitins A1/A2/A3 tested in a TNBS-induced murine model of colitis using preventive and curative regimens. Evaluation is described macroscopically and histologically using Wallace and Ameho criteria, and the results are described as showing efficacy and demonstrating gastric resistance and intestinal/site action after oral administration, including comparability to Pentasa®.
Claims Coverage
The independent claim covers an oral administration composition defined by an OB-fold protein variant with a specified range of interface mutations relative to a wild-type OB-fold protein binding to its natural ligand. The claim set specifies multiple inventive features through dependent refinements, including definition of the wild-type OB-fold protein sources, the binding target-of-interest group, oral dosage forms, and delivery outcomes.
Oral composition with interface-mutated OB-fold variant
An oral administration composition comprising a variant of a wild-type OB-fold protein, said variant having between 5 and 32 mutated residues in the interface of binding of said wild-type OB-fold protein to its natural ligand.
Selected wild-type OB-fold proteins from Sac7/Sso7/DBP7/Ssh7/p7ss family
The wild-type OB-fold protein is selected from Sac7d or Sac7e (Sulfolobus acidocaldarius), Sso7d (Sulfolobus solfataricus), DBP 7 (Sulfolobus tokodaii), Ssh7b/Ssh7a (Sulfolobus shibatae), and p7ss (Sulfolobus solfataricus).
Binding to a defined target of interest
The variant binds to a target of interest selected from antigens, antibodies, cell proteins, circulating proteins, peptides, active ingredients of medicaments, nucleic acids, interleukins, cytokines, cytokine or interleukin receptors, proteins encoded by oncogenes, surface proteins of microorganisms, and microorganism lipopolysaccharides.
Oral dosage forms as gel/capsules/tablets/lozenges/pills
The composition is in the form of gel, capsules, tablets, lozenges or pills.
Delivery to the intestine and/or crossing the intestinal barrier
A pharmacologically effective amount of the variant is delivered to the intestine and/or crosses the barrier of the intestine.
Overall, the claim coverage centers on an oral administration composition using an OB-fold protein variant with between 5 and 32 mutated residues in the binding interface of the wild-type OB-fold protein to its natural ligand, further restricted by defined OB-fold sources, a specified target-of-interest group, particular oral dosage forms, and delivery outcomes to the intestine and/or intestinal barrier.
Stated Advantages
Demonstrates gastric resistance and intestinal/site action after oral administration.
Shows efficacy in a TNBS-induced murine model of colitis with preventive and curative regimens.
Described as comparable to Pentasa®.
Documented Applications
Therapeutic use for gastrointestinal or systemic diseases using oral administration compositions containing OB-fold protein variants.
Use in a TNBS-induced murine model of colitis with preventive and curative dosing, evaluated macroscopically and histologically using Wallace and Ameho criteria.
Diagnostic use via fusions and tracer coupling, including diagnostic tracers and radiotracers.
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