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US 7,351,816 B2Granted
Nucleic acid encoding anti-IgE antibodies
AssigneeGenentech, Inc.
InventorsPaula M. Jardieu, Leonard G. Presta
Life of this patent
Estimating the term…
Abstract
The present invention describes IgE antagonists (including variant anti-IgE antibodies) and their use in diagnosis, therapy or prophylaxis of allergic and other IgE-mediated disorders, including asthma, food allergies, hypersensitivity and anaphylactic reactions.
Claims53
An isolated nucleic acid molecule encoding a humanized antibody that specifically binds IgE comprising:
- (a) a VH domain and a VL domain, wherein:
- (i) the VH domain comprises the VH domain of SEQ ID NO:8 in which the alanine residue at position 61 of SEQ ID NO:8 is replaced by an asparagine residue, the aspartic acid residue at position 62 of SEQ ID NO:8 is replaced by a proline residue, the valine residue at position 64 of SEQ ID NO:8 is replaced by a leucine residue, and the phenylalanine residue at position 68 of SEQ ID NO:8 is replaced by an isoleucine residue, in which said positions correspond to Kabat numbering 60, 61, 63 and 67, respectively, and
- (ii) the VL domain comprises the VL domain of SEQ ID NO:9;
- or
- (b) a VH domain and a VL domain, wherein:
- (i) the VH domain comprises the VH domain of SEQ ID NO:8 in which the alanine residue at position 61 of SEQ ID NO:8 is replaced by an asparagine residue, the aspartic acid residue at position 62 of SEQ ID NO:8 is replaced by a proline residue, and the phenylalanine residue at position 68 of SEQ ID NO:8 is replaced by an isoleucine residue, in which said positions correspond to Kabat numbering 60, 61 and 67, respectively, and
- (ii) the VL domain comprises the VL domain of SEQ ID NO:9;
- or
- (c) a VH domain and a VL domain, wherein:
- (i) the VH domain comprises the VH domain of SEQ ID NO:8 in which the valine residue at position 49 of SEQ ID NO:8 is replaced by a methionine residue, the alanine residue at position 50 of SEQ ID NO:8 is replaced by a isoleucine residue, the alanine residue at position 61 of SEQ ID NO:8 is replaced by an asparagine residue, the valine residue at position 64 of SEQ ID NO:8 is replaced by an leucine residue, the phenylalanine residue at position 68 of SEQ ID NO:8 is replaced by an isoleucine residue, the isoleucine residue at position 70 of SEQ ID NO:8 is replaced by a valine residue, the methionine residue at position 83 of SEQ ID NO:8 is replaced by a leucine residue, and the leucine residue at position 86 of SEQ ID NO:8 is replaced by an alanine residue, in which said positions correspond to Kabat numbering 48, 49, 60, 63, 67, 69, 82 and 82c, respectively, and
- (ii) the VL domain comprises the VL domain of SEQ ID NO:9 in which the alanine residue at position 13 of SEQ ID NO:9 is replaced by a valine residue, the valine residue at position 19 of SEQ ID NO:9 is replaced by an alanine residue, the valine residue at position 62 of SEQ ID NO:9 is replaced by an isoleucine residue, the leucine residue at position 82 of SEQ ID NO:9 is replaced by a valine residue, and the valine residue at position 108 of SEQ ID NO:9 is replaced by a leucine residue, in which said positions correspond to Kabat numbering 13, 19, 58, 78 and 104, respectively.
8 more elements
An isolated nucleic acid molecule encoding a humanized antibody that specifically binds to IgE comprising a VH domain and a VL domain, wherein:
- (a) the VH domain comprises the VH domain of SEQ ID NO:8 in which the alanine residue at position 61 of SEQ ID NO:8 is replaced by an asparagine residue, the aspartic acid residue at position 62 of SEQ ID NO:8 is replaced by a proline residue, the valine residue at position 64 of SEQ ID NO:8 is replaced by a leucine residue, and the phenylalanine residue at position 68 of SEQ ID NO:8 is replaced by an isoleucine residue, in which said positions correspond to Kabat numbering 60, 61, 63 and 67, respectively and
- (b) the VL domain comprises the VL domain of SEQ ID NO:9.
An isolated nucleic acid molecule encoding a polypeptide comprising a VH domain and a VL domain, wherein:
- (a) the VH domain comprises the VH domain of SEQ ID NO:8 in which the alanine residue at position 61 of SEQ ID NO:8 is replaced by an asparagine residue, the aspartic acid residue at position 62 of SEQ ID NO:8 is replaced by a proline residue, the valine residue at position 64 of SEQ ID NO:8 is replaced by a leucine residue, and the phenylalanine residue at position 68 of SEQ ID NO:8 is replaced by an isoleucine residue, in which said positions correspond to Kabat numbering 60, 61, 63 and 67, respectively and
- (b) the VL domain comprises the VL domain of SEQ ID NO:9.
An isolated nucleic acid molecule encoding a humanized antibody that specifically binds to IgE comprising a VH domain and a VL domain, wherein:
- (a) the VH domain comprises the VH domain of SEQ ID NO:8 in which the alanine residue at position 61 of SEQ ID NO:8 is replaced by an asparagine residue, the aspartic acid residue at position 62 of SEQ ID NO:8 is replaced by a proline residue, and the phenylalanine residue at position 68 of SEQ ID NO:8 is replaced by an isoleucine residue, in which said positions correspond to Kabat numbering 60, 61 and 67, respectively, and
- (b) the VL domain comprising the VL domain of SEQ ID NO:9.
An isolated nucleic acid molecule encoding a polypeptide comprising a VH domain and a VL domain, wherein:
- (a) the VH domain comprises the VH domain of SEQ ID NO:8 in which the alanine residue at position 61 of SEQ ID NO:8 is replaced by an asparagine residue, the aspartic acid residue at position 62 of SEQ ID NO:8 is replaced by a proline residue, and the phenylalanine residue at position 68 of SEQ ID NO:8 is replaced by an isoleucine residue, in which said positions correspond to Kabat numbering 60, 61 and 67, respectively, and
- (b) the VL domain comprising the VL domain of SEQ ID NO:9.
An isolated nucleic acid molecule encoding a humanized antibody that specifically binds to IgE comprising a VH domain and a VL domain, wherein:
- (a) the VH domain comprises the VH domain of SEQ ID NO:8 in which the valine residue at position 49 of SEQ ID NO:8 is replaced by a methionine residue, the alanine residue at position 50 of SEQ ID NO:8 is replaced by a glycine residue, the alanine residue at position 61 of SEQ ID NO:8 is replaced by an asparagine residue, the valine residue at position 64 of SEQ ID NO:8 is replaced by a leucine residue, the phenylalanine residue at position 68 of SEQ ID NO:8 is replaced by an isoleucine residue, the isoleucine residue at position 70 of SEQ ID NO:8 is replaced by a valine residue, the methionine residue at position 83 of SEQ ID NO:8 is replaced by a leucine residue, and the leucine residue, at position 86 of SEQ ID NO:8 is replaced by an alanine residue, in which said positions correspond to Kabat numbering 48, 49, 60, 63, 67, 69, 82 and 82c, respectively, and
- (b) the VL domain comprises the VL domain of SEQ ID NO:9 in which the alanine residue at position 13 of SEQ ID NO:9 is replaced by a valine residue, the valine residue at position 19 of SEQ ID NO:9 is replaced by an alanine residue, the valine residue at position 62 of SEQ ID NO:9 is replaced by an isoleucine residue, the leucine residue at position 82 of SEQ ID NO:9 is replaced by a valine residue, and the valine residue at position 108 of SEQ ID NO:9 is replaced by a leucine residue, in which said positions correspond to Kabat numbering 10, 19, 58, 78 and 104, respectively.
An isolated nucleic acid molecule encoding a polypeptide comprising a VH domain and a VL domain, wherein:
- (a) the VH domain comprises the VH domain of SEQ ID NO:8 in which the valine residue at position 49 of SEQ ID NO:8 is replaced by a methionine residue, the alanine residue at position 50 of SEQ ID NO:8 is replaced by a glycine residue, the alanine residue at position 61 of SEQ ID NO:8 is replaced by an asparagine residue, the valine residue at position 64 of SEQ ID NO:8 is replaced by a leucine residue, the phenylalanine residue at position 68 of SEQ ID NO:8 is replaced by an isoleucine residue, the isoleucine residue at position 70 of SEQ ID NO:8 is replaced by a valine residue, the methionine residue at position 83 of SEQ ID NO:8 is replaced by a leucine residue, and the leucine residue at position 86 of SEQ ID NO:8 is replaced by an alanine residue, in which said positions correspond to Kabat numbering 48, 49, 60, 63, 67, 69, 82 and 82c, respectively, and
- (b) the VL domain comprises the VL domain of SEQ ID NO:9 in which the alanine residue at position 13 of SEQ ID NO:9 is replaced by a valine residue, the valine residue at position 19 of SEQ ID NO:9 is replaced by an alanine residue, the valine residue at position 62 of SEQ ID NO:9 is replaced by an isoleucine residue, the leucine residue at position 82 of SEQ ID NO:9 is replaced by a valine residue, and the valine residue at position 108 of SEQ ID NQ:9 is replaced by a leucine residue, in which said positions correspond to Kabat numbering 13, 19, 58, 78 and 104, respectively.
Dependencies are inferred from the claim text.