JPWO2019207122A5 - - Google Patents

Claims (35)

A pharmaceutical composition for treating or preventing fibrosis, comprising an antagonist of IL-11-mediated signaling and an antagonist of angiogenic factors. A combination of an IL-11-mediated signaling antagonist and an angiogenic factor antagonist for use in methods of treating or preventing fibrosis. Use of IL-11-mediated signaling antagonists and angiogenic factor antagonists in the manufacture of pharmaceuticals for use in methods of treating or preventing fibrosis. The composition according to claim 1, the combination for use according to claim 2, or the use according to claim 3, wherein the fibrosis is fibrosis in the eye , heart, liver, or kidney . The fibrosis is Graves ophthalmopathy, supretinal fibrosis, retinal fibrosis, idiopathic premacular fibrosis, subretinal fibrosis , exudative age-related macular degeneration (AMD ), diabetic retina, glaucoma, and map. The composition , combination for use, or use according to any one of claims 1-4, selected from atrophy, macular fibrosis, postoperative fibrosis , conjunctival fibrosis, and subconjunctival fibrosis. The fibrosis
It is in the liver and is associated with chronic liver disease or cirrhosis;
Any of claims 1-4 , which are in the kidney and are associated with chronic kidney disease; or in the heart and are associated with dysfunction of the muscular tissue or electrical properties of the heart, or thickening of the walls or valves of the heart. Or the composition according to paragraph 1 , combination for use, or use. The composition according to any one of claims 1 to 6 , wherein the angiogenic factor is selected from vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF). Things , combinations for use, or use. The agent according to any one of claims 1 to 7 , wherein the IL-11-mediated signaling antagonist is an agent capable of preventing or reducing the binding of IL-11 to the IL-11 receptor. Composition , combination for use, or use. The composition according to any one of claims 1 to 8 , wherein the IL-11-mediated signaling antagonist is an agent capable of binding to a receptor for IL-11 or IL-11. Combination or use for. The composition of claim 9 , wherein the IL-11-mediated signaling antagonist is selected from the group consisting of antibodies or antigen-binding fragments thereof, polypeptides, peptides, oligonucleotides, aptamers , and small molecules. Combination for use, or use. The composition , combination for use, or combination according to claim 10 , wherein the IL-11-mediated signaling antagonist is an anti-IL-11 antibody , an anti- IL-11Rα antibody , or a decoy IL-11 receptor. use. The composition according to any one of claims 1 to 7 , wherein the IL-11-mediated signaling antagonist can reduce the expression of the IL-11 or IL-11 receptor, for use. Combination or use. 12. The composition , combination for use, or use of claim 12 , wherein the IL-11-mediated signaling antagonist is an oligonucleotide or small molecule. The agent according to any one of claims 1 to 13 , wherein the antagonist of the angiogenic factor is an agent capable of preventing or reducing the binding of the angiogenic factor to an interacting partner of the angiogenic factor. Composition , combination for use, or use. The composition according to any one of claims 1 to 14 , a combination for use, wherein the antagonist of the angiogenic factor is an agent capable of binding to the angiogenic factor or an interacting partner of the angiogenic factor. , Or use. The composition according to claim 15 , a combination for use, wherein the antagonist of the angiogenic factor is selected from the group consisting of an antibody or an antigen-binding fragment thereof, a polypeptide, a peptide, an oligonucleotide, an aptamer and a small molecule. , Or use. The composition , combination for use, or use according to claim 16 , wherein the antagonist of the angiogenic factor is an anti-VEGF antibody , an anti- VEGF receptor antibody , a decoy VEGF receptor, or an aflibercept . The composition according to any one of claims 1 to 13 , a combination for use, wherein the antagonist of the angiogenic factor can reduce the expression of the angiogenic factor or the interaction partner of the angiogenic factor. Or use. The composition , combination for use, or use according to claim 18 , wherein the antagonist of the angiogenic factor is an oligonucleotide or a small molecule. A combination comprising an IL-11-mediated signaling antagonist and an angiogenic factor antagonist. A pharmaceutical composition comprising an IL-11-mediated signaling antagonist and an angiogenic factor antagonist. A kit of elements comprising a predetermined amount of an IL-11-mediated signaling antagonist and an angiogenic factor antagonist, the combination of claim 20 , or the pharmaceutical composition of claim 21 . 21. The combination of claim 20 , wherein the angiogenic factor is selected from vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF). A pharmaceutical composition or a kit of elements according to claim 22 . The agent according to any one of claims 20 to 23 , wherein the IL-11-mediated signaling antagonist is an agent capable of preventing or reducing the binding of IL-11 to the IL-11 receptor. Combinations, pharmaceutical compositions or kits of elements. The combination, pharmaceutical composition according to any one of claims 20 to 24 , wherein the IL-11-mediated signaling antagonist is an agent capable of binding to a receptor for IL-11 or IL-11. Or a kit of elements. 25. The combination according to claim 25 , wherein the IL-11-mediated signaling antagonist is selected from the group consisting of antibodies or antigen-binding fragments thereof, polypeptides, peptides, oligonucleotides, aptamers , and small molecules. A kit of compositions or elements. The kit of a combination, pharmaceutical composition or element according to claim 26 , wherein the IL-11-mediated signaling antagonist is an anti-IL-11 antibody , an anti- IL-11Rα antibody , or a decoy IL-11 receptor . The combination, pharmaceutical composition or pharmaceutical composition according to any one of claims 20 to 23 , wherein the IL-11-mediated signaling antagonist can reduce the expression of the IL-11 or IL-11 receptor. Element kit. 28. A kit of combinations, pharmaceutical compositions or elements according to claim 28 , wherein the IL-11-mediated signaling antagonist is an oligonucleotide or a small molecule. The agent according to any one of claims 20 to 29 , wherein the antagonist of the angiogenic factor is an agent capable of preventing or reducing the binding of the angiogenic factor to an interacting partner of the angiogenic factor. Combinations, pharmaceutical compositions or kits of elements. The combination, pharmaceutical composition or element of any one of claims 20-30 , wherein the antagonist of the angiogenic factor is an agent capable of binding to the angiogenic factor or an interacting partner of the angiogenic factor. kit. 31. The combination, pharmaceutical composition or element of claim 31 , wherein the angiogenic factor antagonist is selected from the group consisting of antibodies or antigen-binding fragments thereof, polypeptides, peptides, oligonucleotides, aptamers , and small molecules. Kit. 23. The combination, pharmaceutical composition or kit of elements according to claim 32 , wherein the antagonist of the angiogenic factor is an anti-VEGF antibody , an anti- VEGF receptor antibody , a decoy VEGF receptor, or an aflibercept . The kit of a combination, pharmaceutical composition or element according to any one of claims 20 to 29 , wherein the antagonist of the angiogenic factor can reduce the expression of the interacting partner of the angiogenic factor. The kit of a combination, pharmaceutical composition or element according to claim 34 , wherein the antagonist of the angiogenic factor is an oligonucleotide or a small molecule.