Remedies for hepatitis c
AssigneesMitsubishi Pharma Corporation, Japan as Represented by Director General of Agency of National Institute of Infectious Diseases
InventorsSeima Itami, Tatsurou Shibui, Makoto Seki, Yoshihisa Yotsumoto, Yoshiharu Matsuura, Tatsuo Miyamura
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Abstract
The present invention provides a substance which inhibits the binding between E2/NS1 protein of hepatitis C virus and a cell infectious with hepatitis C virus, a cell expressing CD81, or CD81. The present invention can provide a novel medicament which has an anti-viral effects such as an inhibitory action against HCV infection.
Claims74
A substance which inhibits the binding between E2/NS1 protein of hepatitis C virus and a cell infectious with hepatitis C virus, a cell expressing CD81, or CD81.
An antibody wherein CDR-1, CDR-2, and CDR-3 of a variable region of the H chain respectively comprise amino acid sequences shown by SEQ ID NOS:
- 1, 2, and 3 in the Sequence Listing or the amino acid sequences having a deletion, a substitution, or an addition of one or several amino acids in the amino acid sequences shown by SEQ ID NOS:
- 1, 2, and 3, and which has an affinity to E2/NS1 protein of hepatitis C virus.
An antibody wherein CDR-1, CDR-2, and CDR-3 of a variable region of the L chain respectively comprise amino acid sequences shown by SEQ ID NOS:
- 4, 5, and 6 in the Sequence Listing or the amino acid sequences having a deletion, a substitution, or an addition of one or several amino acids in the amino acid sequences shown by SEQ ID NOS:
- 4, 5, and 6, and which has an affinity to E2/NS1 protein of hepatitis C virus.
An antibody wherein CDR-1, CDR-2, and CDR-3 of a variable region of the L chain respectively comprise amino acid sequences shown by SEQ ID NOS:
- 7, 8, and 9 in the Sequence Listing or the amino acid sequences having a deletion, a substitution, or an addition of one or several amino acids in the amino acid sequences shown by SEQ ID NOS:
- 7, 8, and 9, and which has an affinity to E2/NS1 protein of hepatitis C virus.
An antibody wherein CDR-1, CDR-2, and CDR-3 of a variable region of the L chain respectively comprise amino acid sequences shown by SEQ ID NOS:
- 10, 11, and 12 in the Sequence Listing or the amino acid sequences having a deletion, a substitution, or an addition of one or several amino acids in the amino acid sequences shown by SEQ ID NOS:
- 10, 11, and 12, and which has an affinity to E2/NS1 protein of hepatitis C virus.
An antibody wherein CDR-1, CDR-2, and CDR-3 of a variable region of the L chain respectively comprise amino acid sequences shown by SEQ ID NOS:
- 13, 14, and 15 in the Sequence Listing or the amino acid sequences having a deletion, a substitution, or an addition of one or several amino acids in the amino acid sequences shown by SEQ ID NOS:
- 13, 14, and 15, and which has an affinity to E2/NS1 protein of hepatitis C virus.
An antibody wherein CDR-1, CDR-2, and CDR-3 of a variable region of the L chain respectively comprise amino acid sequences shown by SEQ ID NOS:
- 42, 43, and 44 in the Sequence Listing or the amino acid sequences having a deletion, a substitution, or an addition of one or several amino acids in the amino acid sequences shown by SEQ ID NOS:
- 42, 43, and 44, and which has an affinity to E2/NS1 protein of hepatitis C virus.
An antibody wherein CDR-1, CDR-2, and CDR-3 of a variable region of the L chain respectively comprise amino acid sequences shown by SEQ ID NOS:
- 45, 46, and 47 in the Sequence Listing or the amino acid sequences having a deletion, a substitution, or an addition of one or several amino acids in the amino acid sequences shown by SEQ ID NOS:
- 45, 46, and 47, and which has an affinity to E2/NS1 protein of hepatitis C virus.
An antibody wherein CDR-1, CDR-2, and CDR-3 of a variable region of the L chain respectively comprise amino acid sequences shown by SEQ ID NOS:
- 48, 49, and 50 in the Sequence Listing or the amino acid sequences having a deletion, a substitution, or an addition of one or several amino acids in the amino acid sequences shown by SEQ ID NOS:
- 48, 49, and 50, and which has an affinity to E2/NS1 protein of hepatitis C virus.
An antibody wherein CDR-1, CDR-2, and CDR-3 of a variable region of the L chain respectively comprise amino acid sequences shown by SEQ ID NOS:
- 51, 52, and 53 in the Sequence Listing or the amino acid sequences having a deletion, a substitution, or an addition of one or several amino acids in the amino acid sequences shown by SEQ ID NOS:
- 51, 52, and 53, and which has an affinity to E2/NS1 protein of hepatitis C virus.
An antibody which comprises, as an amino acid sequence of a heavy chain, an amino acid sequences shown by SEQ ID NO:
- 40 in the Sequence Listing or the amino acid sequences having a deletion, a substitution, or an addition of one or several amino acids in the amino acid sequences shown by SEQ ID NO:
- 40, and which has an affinity to E2/NS1 protein of hepatitis C virus.
An antibody which comprises, as an amino acid sequence of a light chain, an amino acid sequences shown by SEQ ID NO:
- 41 in the Sequence Listing or the amino acid sequences having a deletion, a substitution, or an addition of one or several amino acids in the amino acid sequences shown by SEQ ID NO:
- 41, and which has an affinity to E2/NS1 protein of hepatitis C virus.
A single-chain antibody having an affinity to E2/NS1 protein of hepatitis C virus, which comprises an amino acid sequence shown by SEQ ID NO:
- 26, 27, 28, or 29 in the Sequence Listing or the amino acid sequence having a deletion, a substitution, or an addition of one or several amino acids in the amino acid sequence shown by SEQ ID NO:
- 26, 27, 28, or 29.
A single-chain antibody having an affinity to E2/NS1 protein of hepatitis C virus, which comprises an amino acid sequence shown by SEQ ID NO:
- 36, 37, 38, or 39 in the Sequence Listing or the amino acid sequence having a deletion, a substitution, or an addition of one or several amino acids in the amino acid sequence shown by SEQ ID NO:
- 36, 37, 38, or 39.
A single-chain antibody having an affinity to E2/NS1 protein of hepatitis C virus, which comprises an amino acid sequence shown by SEQ ID NO:
- 62, 63, 64, or 65 in the Sequence Listing or the amino acid sequence having a deletion, a substitution, or an addition of one or several amino acids in the amino acid sequence shown by SEQ ID NO:
- 62, 63, 64, or 65.
A method for obtaining a sequence of the variable region of the antibody binding to E2/NS1 wherein the B cell of a patient who recovered from hepatitis C is stimulated to express mRNA of the antibody against E2/NS1 protein of hepatitis C virus, and thereby mRNA of the antibody and cDNA of the antibody are obtained from the B cell.
A method for screening a substance which inhibits the binding between E2/NS1 of hepatitis C virus and a cell infectious with hepatitis C, a cell expressing CD81, or CD81, which comprises steps of:
- contacting E2/NS1 of hepatitis C virus with a cell infectious with hepatitis C, a cell expressing CD81, or CD81 in the presence and absence of a test substance;
- and comparing the bindings between E2/NS1 of hepatitis C virus and the cell infectious with hepatitis C, the cell expressing CD81, or CD81 in the presence and absence of a test substance.
66 The screening method of any of claims 60 to 63 wherein CD81 is human CD81 and expressed by solubilized form.
A substance which inhibits a life cycle of hepatitis C virus, which is obtained by the screening method which comprises steps of assaying the binding between a cell infectious with HCV and a cell expressing HCV protein in the presence and absence of the test substance, and comparing it with the binding in the absence of the test substance.
A substance which inhibits a life cycle of hepatitis C virus, which is obtained by the screening method which comprises steps of, after the cell infectious with HCV has bound with the HCV protein expressing cell in the presence or absence of the test substance, assaying the fusion between the cell infectious with HCV and the HCV protein expressing cell, and comparing it with the fusion in the absence of the test substance.
Dependencies are inferred from the claim text.