Substance specific to pd-1

Abstract

Substances comprising a substance that recognizes PD-1, a substance that recognizes a membrane protein co-existing with PD-1 on a cell membrane, and a linker. As the substances that specifically recognizes PD-1 by the present invention can recognize selectively both PD-1 and a membrane protein co-existing with PD-1 on a cell membrane, and can transmit the suppressive signal of PD-1, they are useful for the medical treatment and/or prevention of the diseases caused by immune abnormality.

1 . A substance comprising a substance that recognizes PD-1, a substance that recognizes a membrane protein co-existing with PD-1 on a cell membrane, and a linker.  
     
     
         2 . The substance according to  claim 1 , which is a divalent substance comprising a substance that recognizes PD-1, a substance that recognizes a membrane protein co-existing with PD-1 on a cell membrane, and a linker.  
     
     
         3 . The substance according to  claim 1 , in which a membrane protein is a protein existing on a T cell membrane or B cell membrane.  
     
     
         4 . The substance according to  claim 1 , which comprises a substance that recognizes PD-1, a substance that recognizes a protein constituting T cell receptor complex or a substance that recognizes a protein constituting B cell receptor complex, and a linker.  
     
     
         5 . The substance according to  claim 1 , in which a substance that recognizes PD-1 and in which a substance that recognizes a protein is dimer to pentamer, respectively.  
     
     
         6 . The substance according to  claim 1 , in which one of or both substance that recognizes PD-1 and substance that recognizes a protein are an antibody.  
     
     
         7 . The substance according to  claim 1 , in which one of the two or both substance that recognizes PD-1 and substance that recognizes a protein are a Fab portion of antibody.  
     
     
         8 . The substance according to  claim 1 , in which a linker comprises an organic compound.  
     
     
         9 . The substance according to  claim 1 , in which a linker comprises a peptide.  
     
     
         10 . The substance according to  claim 1 , in which a substance that recognizes PD-1 and in which a substance that recognizes a protein is a peptide, respectively.  
     
     
         11 . The substance according to  claim 1 , in which a substance that recognizes PD-1 and in which a substance that recognizes a protein comprises two or more peptides including a heavy chain variable region and a light chain variable region of antibody, respectively.  
     
     
         12 . The substance according to  claim 1 , in which a substance that recognizes PD-1, in which a substance that recognizes a protein, and in which a linker is a peptide, respectively.  
     
     
         13 . A pharmaceutical composition containing an effective dose of the substance according to  claim 1  for the medical treatment and/or prevention of a disease in which PD-1 participates.  
     
     
         14 . The pharmaceutical composition according to  claim 13 , in which disease is selected from the group consisting of neurodegenerative disease, autoimmune disease, organ transplant rejection, neoplasm and infection.  
     
     
         15 . The pharmaceutical composition according to  claim 14 , in which neulodegenerative disease is selected from the group consisting of Parkinson's disease, parkinsonian syndrome, Huntington's disease, Machado-Joseph disease, amyotrophic lateral sclerosis and Creutzfeldt-Jakob disease.  
     
     
         16 . The pharmaceutical composition according to  claim 14 , in which autoimmune disease is selected from the group consisting of glomerular nephritis, arthritis, dilated cardiomyopathy-like disease, ulcerative colitis, Sjogren's syndrome, Crohn's disease, systemic lupus erythematosus, chronic rheumatoid arthritis, multiple sclerosis, Psoriasis, allergic contact dermatitis, polymyositis, scleroderma, periarteritis nodosa, rheumatic fever, vitiligo vulgaris, insulin-dependent diabetes mellitus, Behcet's Syndrome and chronic thyroiditis.  
     
     
         17 . A method for the medical treatment and/or prevention of a disease in which PD-1 participates which comprises administering to a subject in need thereof an effective amount of the substance according to  claim 1 .  
     
     
         18 . The method according to  claim 17 , in which disease is selected from the group consisting of neurodegenerative disease, autoimmune disease, organ transplant rejection, neoplasm and infection.  
     
     
         19 . The method according to  claim 18 , in which neurodegenerative disease is selected from the group consisting of Parkinson's disease, parkinsonian syndrome, Huntington's disease, Machado-Joseph disease, amyotrophic lateral sclerosis and Creutzfeldt-Jakob disease.  
     
     
         20 . The method according to  claim 18 , in which autoimmune disease is selected from the group consisting of glomerular nephritis, arthritis, dilated cardiomyopathy-like disease, ulcerative colitis, Sjogren's syndrome, Crohn's disease, systemic lupus erythematosus, chronic rheumatoid arthritis, multiple sclerosis, Psoriasis, allergic contact dermatitis, polymyositis, scleroderma, periarteritis nodosa, rheumatic fever, vitiligo vulgaris, insulin-dependent diabetes mellitus, Behcet's Syndrome and chronic thyroiditis.