Antagonizing interleukin-21 receptor activity
OwnerDeborah Young, Mary Collins +4inventors
InventorsDeborah Young, Mary Collins, Kyriaki Dunussi-Joannopoulos, Richard O'Hara, Marion Kasaian, Matthew Whitters
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Abstract
Methods and compositions for inhibiting interleukin-21 (IL-21)/IL-21 receptor (MU-1) activity using antagonists of IL-21 or IL-21 receptor (“IL-21R” or “MU-1”), are disclosed. IL-21/IL-21R antagonists can be used to induce immune suppression in vivo, e.g., for treating, ameliorating or preventing autoimmune or inflammatory disorders, including, e.g., inflammatory bowel disease (IBD), rheumatoid arthritis (RA), transplant/graft rejection, psoriasis, asthma, fibrosis, and systemic lupus erythematosus (SLE).
Claims32
A method of treating, ameliorating, or preventing an autoimmune or inflammatory disorder in a mammalian subject, comprising administering to the subject an IL-21/IL-21R antagonist selected from the group consisting of an anti-IL-21R antibody, an anti-IL-21 antibody, an antigen-binding fragment of an anti-IL-21R antibody, an antigen-binding fragment of an anti-IL-21 antibody, and an IL-21R soluble fragment, in an amount sufficient to treat, ameliorate, or prevent the disorder.
A method of treating, ameliorating, or preventing a disorder selected from the group consisting of an arthritic disorder, an atopic disorder, a respiratory disorder, a skin inflammatory disorder, an intestinal inflammatory disorder, a fibrotic disorder, systemic lupus erythematosus, transplant/graft rejection, and a disorder associated with transplant/graft rejection, in a mammalian subject, comprising administering to the subject an IL-21/IL-21R antagonist selected from the group consisting of an anti-IL-21R antibody, an anti-IL-21 antibody, an antigen-binding fragment of an anti-IL-21R antibody, an antigen-binding fragment of an anti-IL-21 antibody, and an IL-21R soluble fragment, in an amount sufficient to treat, ameliorate, or prevent the disorder.
A fusion protein comprised of an extracellular domain of an IL-21R and an Fc immunoglobulin fragment, wherein the IL-21R has an amino acid sequence at least 90% identical to the sequence set forth in SEQ ID NO:2, and wherein the fusion protein is capable of binding IL-21.
A pharmaceutical composition comprising an IL-21/IL-21R antagonist and a pharmaceutically acceptable carrier.
A method of transplanting/grafting an organ, tissue, cell or group of cells to a mammalian subject comprising the steps of:
- (a) administering to the subject an antagonist of IL-21/IL-21R selected from the group consisting of an anti-IL-21R antibody, an anti-IL-21 antibody, an antigen-binding fragment of an anti-IL-21R antibody, an antigen-binding fragment of an anti-IL-21 antibody, and an IL-21R soluble fragment, in an amount sufficient to reduce the risk of transplant/graft rejection;
- and
- (b) transplanting/grafting an organ, tissue, cell or group of cells to the subject,
- wherein the transplanting/grafting step (b) occurs either before, during, or after the administering step (a).
A method of treating, preventing or ameliorating transplant/graft rejection in a mammalian transplant/graft recipient comprising:
- (a) detecting a symptom of transplant/graft rejection in a transplant/graft recipient;
- and
- (b) administering to the transplant/graft recipient an IL-21/IL-21R antagonist selected from the group consisting of an anti-IL-21R antibody, an anti-IL-21 antibody, an antigen-binding fragment of an anti-IL-21R antibody, an antigen-binding fragment of an anti-IL-21 antibody, and an IL-21R soluble fragment.
Dependencies are inferred from the claim text.