JP-2022510276-A5 -

Dates

Publication Date

20221205

Application Date

20191127

Description

In some embodiments, the disease or condition is an inflammatory or autoimmune disease or condition. In some embodiments, the disease or condition is an anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, vasculitis, autoimmune skin disease, transplantation, rheumatic disease, inflammatory gastrointestinal disease, inflammatory eye disease, inflammatory neurological disease, inflammatory lung disease, inflammatory endocrine disease, or autoimmune hematological disease. In some embodiments, the disease or condition is selected from inflammatory bowel disease, transplantation, Crohn's disease, ulcerative colitis, multiple sclerosis, asthma, rheumatoid arthritis, or psoriasis. [Invention 1001] A variant CD86 polypeptide comprising an extracellular domain or an IgV domain or its specific binding fragment, with the positions indicated by SEQ ID NO: 29 being 13, 18, 25, 28, 33, 38, 39, 40, 43, 45, 52, 53, 60, 68, 71, 77, 79, 80, 82, 86, 88, 89, 90, 92, 93, 97, 102, 104, 113, 114, 123, 128, 129, 132, 133, 137, 141, 143, 144, 148, 153, 154, 158, 170 A variant CD86 polypeptide comprising one or more amino acid modifications in the unmodified CD86 polypeptide or its specific binding fragment, corresponding to a position selected from 172, 175, 178, 180, 181, 183, 185, 192, 193, 196, 197, 198, 205, 206, 207, 212, 215, 216, 222, 223, or 224. [Invention 1002] A variant CD86 polypeptide of the present invention 1001, wherein the amino acid modification includes amino acid substitution, deletion, or insertion. [Invention 1003] The unmodified CD86 polypeptide is a mammalian CD86 polypeptide or a specific binding fragment thereof, wherein the variant CD86 polypeptide of the present invention 1001 or 1002. [Invention 1004] The variant CD86 polypeptide of the present invention 1003, wherein the unmodified CD86 polypeptide is a human CD86 polypeptide or a specific binding fragment thereof. [Invention 1005] The variant CD86 polypeptide according to any one of the present inventions 1001 to 1004, wherein the variant CD86 polypeptide comprises the extracellular domain of human CD86, and the one or more amino acid modifications are located in one or more residues of the extracellular domain of the unmodified CD86 polypeptide. [Invention 1006] The aforementioned unmodified CD86 polypeptide (i) the amino acid sequence shown in SEQ ID NO: 29; (ii) an amino acid sequence having at least 95% sequence identity with SEQ ID NO: 29; or (iii) a portion thereof, which includes an IgV domain or a specific binding fragment of an IgV domain. A CD86 polypeptide variant of any of the invention 1001 to 1005, comprising the above. [Invention 1007] The unmodified CD86 comprises the amino acid sequence shown in SEQ ID NO: 29, and is a variant CD86 polypeptide of any of the present inventions 1001 to 1006. [Invention 1008] The CD86 polypeptide variant of the present invention 1006, wherein the aforementioned portion comprises the 33rd to 131st or 24th to 134th amino acid residues of the IgV domain or a specific binding fragment of the IgV domain. [Invention 1009] The aforementioned unmodified CD86 polypeptide (i) the amino acid sequence shown in SEQ ID NO: 123; (ii) an amino acid sequence having at least 95% sequence identity with SEQ ID NO: 123; or (iii) a portion thereof, which includes an IgV domain or a specific binding fragment of an IgV domain. A variant CD86 polypeptide comprising any of the inventions 1001-1006 and 1008. [Invention 1010] The unmodified CD86 comprises the amino acid sequence shown in SEQ ID NO: 123, and is a variant CD86 polypeptide according to any of the present inventions 1001 to 1006. [Invention 1011] The aforementioned unmodified CD86 polypeptide (i) the amino acid sequence shown in SEQ ID NO: 122; (ii) an amino acid sequence having at least 95% sequence identity with SEQ ID NO: 122; or (iii) a specific binding fragment thereof. A CD86 polypeptide variant of any of the present invention 1001-1006, 1008, and 1009, comprising: [Invention 1012] The unmodified CD86 comprises the amino acid sequence shown in SEQ ID NO: 122, and is a variant CD86 polypeptide of any of the present inventions 1001-1006, 1008, 1009, and 1011. [Invention 1013] The specific binding fragment has a length of at least 50, 60, 70, 80, 90, or 95 amino acids; or The specific binding fragment comprises at least 80% of the length of the IgV domain, which is represented as residues 33–131 of SEQ ID NO: 2. A CD86 polypeptide variant according to any of the invention 1001 to 1012. [Invention 1014] A variant CD86 polypeptide of any of the Invention 1001 to 1013, comprising up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid modifications, optionally amino acid substitutions, insertions, and/or deletions. [Invention 1015] The one or more amino acid modifications described above A variant CD86 polypeptide of any of the present invention 1001 to 1014, comprising one or more amino acid substitutions selected from,