Humanized anti-factor D antibodies and uses thereof
AssigneeGenentech, Inc.
InventorsArthur Huang, Robert Kelley, Henry Lowman, Menno Van Lookeren Campagne, Charles Winter
Life of this patent
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Abstract
The invention relates to anti-Factor D antibodies, their nucleic acid and amino acid sequences, the cells and vectors that harbor these antibodies and their production and their use in the preparation of compositions and medicaments for treatment of diseases and disorders associated with excessive or uncontrolled complement activation. These antibodies are useful for diagnostics, prophylaxis and treatment of disease.
Claims35
An anti-Factor D antibody or an antigen-binding fragment thereof comprising:
- (a) a light chain variable domain comprising:
- (1) light chain HVR-1 (HVR-L1) comprising the sequence ITSTDIDDDMN (SEQ ID NO:
- 30) or a sequence that differs from SEQ ID NO:
- 30 by one or more amino acid substitutions, wherein said one or more substitutions are substitution of the amino acid residue at position 10 of SEQ ID NO:
- 30 to L or I and/or substitution of the amino acid at position 11 of SEQ ID NO:
- 30 to A or Q,
- (2) light chain HVR-2 (HVR-L2) comprising the sequence GGNTLRP (SEQ ID NO:
- 35) or a sequence that differs from SEQ ID NO:
- 35 by one amino acid substitution, wherein said one substitution is substitution of the amino acid residue at position 3 of SEQ ID NO:
- 35 to S or A, and,
- (3) light chain HVR-3 (HVR-L3) comprising the sequence LQSDSLPYT (SEQ ID NO:
- 38);
- and
- (b) a heavy chain variable domain comprising:
- (1) heavy chain HVR-1 (HVR-H1) comprising the sequence GYTFTNYGMN (SEQ ID NO:
- 39),
- (2) heavy chain HVR-2 (HVR-H2) comprising the sequence WINTYTGETTYADDFKG (SEQ ID NO:
- 40), and
- (3) heavy chain HVR-3 (HVR-H3) comprising the sequence EGGVNN (SEQ ID NO:
- 41) or a sequence that differs from SEQ ID NO:
- 41 by one or more amino acid substitutions, wherein said one or more substitutions are substitution of the amino acid residue at position 5 of SEQ ID NO:
- 41 with A or Q and/or substitution of the amino acid residue at position 6 of SEQ ID NO:
- 41 with A or Q,
- wherein said antibody or antigen-binding fragment thereof comprises at least one of the substitutions set forth in (a)(1), (a)(2), or (b)(3) above and/or the heavy chain variable domain comprises an E at position 1.
An anti-Factor D antibody or antigen-binding fragment thereof, comprising a polypeptide comprising the following amino acid sequence:
- X1VQLVQSGPELKKPGASVKVSCKASGYTFTNYGMNWVRQAPGQGLEWMGWINTYTG ETTYADDFKGRFVFSLDTSVSTAYLQISSLKAEDTAVYYCEREGGVX2X3WGQGTLVTVS S (SEQ ID NO:
- 74), wherein X1 is E;
- X2 is N, A or Q;
- and X3 is N, A or Q.
An anti-Factor D antibody or an antigen-binding fragment thereof, comprising the heavy chain variable domain sequence of SEQ ID NO:
- 19.
An anti-Factor D antibody or an antigen-binding fragment thereof, comprising the heavy chain sequence of SEQ ID NO:
- 63.
An anti-Factor D antibody or an antigen-binding fragment thereof, comprising:
- (a) a light chain variable domain comprising the amino acid sequence of SEQ ID NO:
- 1, wherein the amino acid residue at position 104 of SEQ ID NO:
- 1 is substituted with V;
- and
- (b) a heavy chain variable domain comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 39, an HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 40, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO:
- 41,
- wherein the amino acid residue at position 1 of the heavy chain variable domain is an E.
An anti-Factor D antibody or an antigen-binding fragment thereof made by the process of:
- (a) culturing a cell expressing an anti-Factor D antibody or an antigen-binding fragment thereof comprising the heavy chain variable domain sequence of SEQ ID NO:
- 19 and the light chain variable domain sequence of SEQ ID NO:
- 7;
- and
- (b) isolating the antibody or antigen-binding fragment from said cultured cell.
Dependencies are inferred from the claim text.