Polynucleotide encoding anti-CD14 antibody fusion protein
AssigneeMochida Pharmaceutical Co., Ltd.
InventorsShoji Furusako, Kazuyuki Nakayama, Yoshitaka Hosaka, Tetsushi Kawahara, Masaki Nakamura, Takashi Takeuchi
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Abstract
A protein comprising (I) an anti-CD14 antibody or its active fragment, or a derivative thereof and (II) an inhibitor for a protease, or its active fragment, or a derivative thereof is provided.
Claims30
At least a first polynucleotide and a second polynucleotide which together encode a fusion protein, wherein said first and second polynucleotides are a part of the same nucleic acid molecule or a different nucleic acid molecule, and wherein said first polynucleotide encodes a polypeptide comprising (Ia) and (II), below, and said second polynucleotide encodes a polypeptide comprising (Ib), below, or said first polynucleotide encodes a polypeptide comprising (Ia), below, and said second polynucleotide encodes a polypeptide comprising (Ib) and (II), below,
- wherein (Ia) is
- a heavy chain of an anti-CD14 antibody or its CD14 binding fragment, wherein said antibody or the fragment has an antigen binding activity and an inhibitory activity for LPS-induced IL-6 production in a TLR expressing cell, and
- wherein (Ib) is
- a light chain of an anti-CD14 antibody or its CD14 binding fragment, wherein said antibody or the fragment has an antigen binding activity and an inhibitory activity for LPS-induced IL-6 production in a TLR expressing cell, and
- wherein (II) is
- an inhibitor for a protease recited in 1), 2) or 3) below;
- 1) a polypeptide consisting of any one of amino acid sequences selected from the group consisting of a human UTI domain 2 (hereinafter referred to “UTI-D2”) represented by from 474th to 543rd amino acid residues of SEQ ID NO 10 and a mutant of human UTI domain 2 with 3 amino acid substitutions (R11S/Q19K/Y46D) (hereinafter referred to “UTI-D2(3)”) represented by from 474th to 543rd amino acid residues of SEQ ID NO 12,
- 2) a mutant of UTI-D2, wherein the mutant has one or more mutations, and wherein the one or more mutations are selected from the group consisting of:
- a deletion of the 474th amino acid of SEQ ID NO:
- 10,
- a deletion of the 475th amino acid of SEQ ID NO:
- 10,
- a substitution of the 484th amino acid of SEQ ID NO:
- 10,
- a substitution of the 492nd amino acid of SEQ ID NO:
- 10, and
- a substitution of the 519th amino acid of SEQ ID NO:
- 10
- to the amino acid sequence recited in 1) above, wherein said mutant has an anticoagulant action, or an inhibitory action for a blood coagulation factor,
- 3) a polypeptide consisting of any one of amino acid sequences selected from the group consisting of the amino acid sequences of the mutant UTI domain 2 of SEQ ID NOS:
- 34, 36, 42, 43, 46, 47, 48, 49, 62 and 63.
A polynucleotide comprising a polynucleotide, which encodes for a polypeptide comprising:
- (Ia) a heavy chain of an anti-CD 14 antibody or its CD14 binding fragment, wherein said antibody or the fragment has an antigen binding activity and an inhibitory activity for LPS-induced IL-6 production in a TLR expressing cell, and
- (II) an inhibitor for a protease recited in 1), 2) or 3) below;
- 1) a polypeptide consisting of any one of amino acid sequences selected from the group consisting of UTI-D2 and UTI-D2(3),
- 2) a mutant of UTI-D2, wherein the mutant has one or more mutations, and wherein the one or more mutations are selected from the group consisting of:
- a deletion of the 474th amino acid of SEQ ID NO:10,
- a deletion of the 475th amino acid of SEQ ID NO:10,
- a substitution of the 484th amino acid of SEQ ID NO:10,
- a substitution of the 492nd amino acid of SEQ ID NO:10, and
- a substitution of the 519th amino acid of SEQ ID NO:10
- to the amino acid sequence recited in 1) above, wherein said mutant has an anticoagulant action, or an inhibitory action for a blood coagulation factor,
- 3) a polypeptide consisting of any one of amino acid sequences selected from the group consisting of the amino acid sequences of the mutant UTI domain 2 of SEQ ID NOS:27-106.
Dependencies are inferred from the claim text.