Delivering biological drugs to tissues
Disclosed herein are fusion proteins for use in treating an inflammatory or immune disorder and methods of use. In some examples, the fusion proteins include an anchor domain and a therapeutic polypeptide. In some examples, the fusion proteins and methods herein can be used to treat inflammatory or immune disorders.
1. A fusion protein comprising an anchor domain and a therapeutic polypeptide, wherein
the anchor domain comprises a wheat germ agglutinin (WGA) anchor domain, and
the therapeutic polypeptide comprises
an antibody that specifically binds to, and is an antagonist of, interleukin (IL)-17A.
2. The fusion protein of claim 1 , wherein:
the WGA anchor binding domain comprises the amino acid sequence of SEQ ID NO: 7.
3. The fusion protein of claim 1 , further comprising a linker between the anchor binding domain and the therapeutic domain.
4. The fusion protein of claim 3 , wherein linker has the amino acid sequence of SEQ ID NO:9 or SEQ ID NO: 19.
5. The fusion protein of claim 1 , further comprising a label, solubility enhancing sequence, purification tag, or combinations thereof.
6. The fusion protein of claim 1 , wherein the anchor domain, therapeutic peptide or combination thereof are benzylated, glycosylated, acetylated, phosphorylated, amidated, pegylated, and combinations thereof.
7. A method for treating an inflammation of tissue in a subject, comprising administering to the tissue of the subject a therapeutically effective amount of the fusion protein of claim 1 thereby treating the inflammation of the tissue in the subject.
8. The method of claim 7 , wherein the tissue is in a mouth, a bladder, a nasal cavity, a gastrointestinal tract, a lung, a joint, an eye, or the reproductive system of a subject.
9. A pharmaceutical composition comprising a therapeutically effective amount of the fusion protein of claim 1 and a pharmaceutically acceptable carrier formulated for external and/or topical administration to a tissue.
10. A unit dose dispenser comprising the pharmaceutical composition claim 9 .
11. The pharmaceutical composition of claim 9 , wherein the pharmaceutical composition is formulated as a gel, cream, lotion, or ointment.
12. A method for treating an inflammation of an eye in a subject, comprising administering to the eye of the subject a therapeutically effective amount of the fusion protein of claim 1 , thereby treating the inflammation of the eye in the subject.
13. The method of claim 12 , wherein the subject has dry eye.
14. The method of claim 12 , wherein the subject has Sjögren's syndrome.