Methods for the therapy of inflammatory bowel disease using a type-1 interferon antagonist
View Patent ↗Compositions and methods for the therapy of Inflammatory Bowel Disease (IBD), including Celiac Disease, Crohn's Disease, and Ulcerative Colitis, are disclosed. Illustrative compositions comprise one or more anti-type 1 interferon antagonists, such as anti-type 1 interferon receptor antibody antagonists and fragments thereof, as well as polypeptides and small molecules that inhibit the interaction of type 1 interferon with its receptor (IFNAR).
1. A method of treating a patient afflicted with Crohn's disease or ulcerative colitis, comprising (a) administering to said patient at a first time point a tolerizing dose of a first type 1 interferon antagonist which is a chimeric, humanized or human anti-type 1 interferon receptor antibody, and (b) administering to said patient at a second time point a therapeutically effective dose of a second type 1 interferon antagonist which is an anti-type 1 interferon alpha antibody.
2. The method of claim 1 , wherein said tolerizing dose of said anti-type 1 interferon receptor antibody is sufficient to reduce the induction of an IgG antibody response to repeat administration of the anti-type 1 interferon receptor antibody.
3. The method of claim 1 , wherein said tolerizing dose of said anti-type 1 interferon receptor antibody is between 10 mg/kg body weight to 50 mg/kg body weight, inclusive.
4. The method of claim 3 , wherein said tolerizing dose of said anti-type 1 interferon receptor antibody is between 20 mg/kg body weight and 40 mg/kg body weight, inclusive.
5. The method of claim 4 , wherein said tolerizing dose of said anti-type 1 interferon receptor antibody is between 20 mg/kg body weight and 25 mg/kg body weight, inclusive.
6. The method of claim 1 , wherein said therapeutically effective dose of said anti-type 1 interferon alpha antibody is administered in the range of 0.1 mg/kg body weight to 10 mg/kg body weight, inclusive.
7. The method of claim 6 , wherein said therapeutically effective dose of said anti-type 1 interferon alpha antibody is administered in the range of 0.2 mg/kg body weight to 5 mg/kg body weight, inclusive.
8. The method of claim 7 , wherein said therapeutically effective dose of said anti-type 1 interferon alpha antibody is administered in the range of 0.5 mg/kg body weight to 2 mg/kg body weight, inclusive.
9. The method of claim 1 , wherein said anti-type 1 interferon receptor antibody is administered by a route selected from the group consisting of intravenous bolus, intravenous slow bolus, and infusion.
10. The method of claim 1 , wherein said anti-type 1 interferon receptor antibody is administered by a route selected from the group consisting of subcutaneously, intramuscularly, transdermally, intradermally, and intravenously.
11. The method of claim 1 , wherein said anti-type 1 interferon receptor antibody is administered by a route of mucosal delivery selected from the group consisting of inhalation, nasopharyngeally, and orally.
12. The method of claim 1 , wherein said anti-type 1 interferon alpha antibody is administered by a route selected from the group consisting of intravenous bolus, intravenous slow bolus, and infusion.
13. The method of claim 1 , wherein said anti-type 1 interferon alpha antibody is administered by a route selected from the group consisting of subcutaneously, intramuscularly, transdermally, intradermally, and intravenously.
14. The method of claim 1 , wherein said anti-type 1 interferon alpha antibody is administered by a route of mucosal delivery selected from the group consisting of inhalation, nasopharyngeally, and orally.
15. The method of claim 1 , wherein said anti-type 1 interferon receptor antibody is a humanized antibody.
16. The method of claim 15 , wherein said humanized antibody comprises the variable region of CPI-1697 and a human IgG4 constant region.