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
Estimating the term…
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.
Claims76
An anti-Factor D antibody comprising light chain HVRs of a reference antibody, wherein said anti-Factor D antibody further comprises a substitution at one or more positions of said reference antibody, wherein said reference antibody comprises light chain HVR-1 comprising ITSTDIDDDMN (SEQ ID NO:
- 30), light chain HVR-2 comprising GGNTLRP (SEQ ID NO:
- 35), and light chain HVR-3 comprising LQSDSLPYT (SEQ ID NO:
- 38), and wherein said substitution is one or more of the following:
- (a) amino acid at position 33 of the light chain is L or I;
- (b) amino acid at position 34 of the light chain is A or Q;
- (c) amino acid at position 52 of the light chain is S or A;
- (d) amino acid at position 104 of the light chain is V;
- (e) amino acid at position 1 of the heavy chain is E;
- (f) amino acid at position 99 of the heavy chain is A or Q;
- or
- (g) amino acid at position 100 of the heavy chain is A or Q.
An anti-Factor D antibody comprising heavy chain HVRs of a reference antibody, wherein said anti-Factor D antibody further comprises a substitution at one or more positions of said reference antibody, wherein said reference antibody comprises heavy chain HVR-1 comprising GYTFTNYGMN (SEQ ID NO:
- 39), heavy chain HVR-2 comprising WINTYTGETTYADDFKG (SEQ ID NO:
- 40), and heavy chain HVR-3 comprising EGGVNN (SEQ ID NO:
- 41), and wherein said substitution is one or more of the following:
- (a) amino acid at position 33 of the light chain is L or I;
- (b) amino acid at position 34 of the light chain is A or Q;
- (c) amino acid at position 52 of the light chain is S or A;
- (d) amino acid at position 104 of the light chain is V′
- (e) amino acid at position 1 of the heavy chain is E;
- (f) amino acid at position 99 of the heavy chain is A or Q;
- or
- (g) amino acid at position 100 of the heavy chain is A or Q.
An anti-Factor D antibody comprising light chain HVRs and heavy chain HVRs of a reference antibody, wherein said anti-Factor D antibody further comprises a substitution at one or more positions of said reference antibody, wherein said reference antibody comprises light chain HVR-1 comprising ITSTDIDDDMN (SEQ ID NO:
- 30), light chain HVR-2 comprising GGNTLRP (SEQ ID NO:
- 35), and light chain HVR-3 comprising LQSDSLPYT (SEQ ID NO:
- 38), and heavy chain HVR-1 comprising GYTFTNYGMN (SEQ ID NO:
- 39), heavy chain HVR-2 comprising WINTYTGETTYADDFKG (SEQ ID NO:
- 40), and heavy chain HVR-3 comprising EGGVNN (SEQ ID NO:
- 41), and wherein said substitution is one or more of the following:
- (a) amino acid at position 33 of the light chain is L or I;
- (b) amino acid at position 34 of the light chain is A or Q;
- (c) amino acid at position 52 of the light chain is S or A;
- (d) amino acid at position 104 of the light chain is V;
- (e) amino acid at position 1 of the heavy chain is E;
- (f) amino acid at position 99 of the heavy chain is A or Q;
- or
- (g) amino acid at position 100 of the heavy chain is A or Q.
An anti-Factor D antibody comprising:
- (a) at least one, two, three, four, five or six HVRs selected from the group comprising:
- (i) an HVR-H1 comprising the amino acid sequence selected from SEQ ID NO:
- 39;
- (ii) an HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 40;
- (iii) an HVR-H3 comprising the amino acid sequence selected from SEQ ID NO:
- 41, SEQ ID NO:
- 42, SEQ ID NO:
- 43, SEQ ID NO:
- 44 and SEQ ID NO:
- 45;
- (iv) an HVR-L1 comprising the amino acid sequence selected from SEQ ID NO:
- 30, SEQ ID NO:
- 31, SEQ ID NO:
- 32, SEQ ID NO:
- 33 and SEQ ID NO:
- 34;
- (v) an HVR-L2 comprising the amino acid sequence selected from SEQ ID NO:
- 35, SEQ ID NO:
- 36 and SEQ ID NO:
- 37;
- and
- (vi) an HVR-L3 comprising the amino acid sequence selected from SEQ ID NO:
- 38;
- or
- (b) at least one variant HVR, wherein the variant HVR comprises modification of at least one residue of the sequence depicted in SEQ ID NO:
- 39, 40, 41, 42, 43, 44, 45, 30, 31, 32, 33, 34, 35, 36, 37 or 38.
A polypeptide comprising the following amino acid sequence:
- X1VQLVQSGPELKKPGASVKVSCKASGYTFTNYGMNWVRQAPGQGLEWMGWINTYTGETT YADDFKGRFVFSLDTSVSTAYLQISSLKAEDTAVYYCEREGGVX2X3WGQGTLVTVSS (SEQ ID NO:
- 74), wherein X1 is Q or E;
- X2 is N, A or Q;
- and X3 is N, A or Q.
A polypeptide comprising the following amino acid sequence:
- DIQVTQSPSSLSASVGDRVTITCITSTDIDDDX4X5WYQQKPGKVPKLLISGGX6TLRPGVPSRF SGSGSGTDFTLTISSLQPEDVATYYCLQSDSLPYTFGQGTKX7EIK (SEQ ID NO:
- 73), wherein X4 is M, L or I;
- X5 is N, A or Q;
- X6 is N, S or A;
- and X7 is L or V.
A polypeptide comprising an amino acid sequence selected from the group comprising SEQ ID NO:
- 18, SEQ ID NO:
- 19, SEQ ID NO:
- 20, SEQ ID NO:
- 21, SEQ ID NO:
- 22, SEQ ID NO:
- 23, SEQ ID NO:
- 24, SEQ ID NO:
- 25, SEQ ID NO:
- 26, SEQ ID NO:
- 27, SEQ ID NO:
- 28 and SEQ ID NO:
- 29.
A polypeptide comprising an amino acid sequence selected from the group comprising SEQ ID NO:
- 6, SEQ ID NO:
- 7, SEQ ID NO:
- 8, SEQ ID NO:
- 9, SEQ ID NO:
- 10, SEQ ID NO:
- 11, SEQ ID NO:
- 12, SEQ ID NO:
- 13, SEQ ID NO:
- 14, SEQ ID NO:
- 15, SEQ ID NO:
- 16 and SEQ ID NO:
- 17.
The polypeptide the comprising the amino acid selected from the group comprising SEQ ID NO:
- 47 and 61.
The polypeptide the comprising the amino acid selected from the group comprising SEQ ID NO:
- 54 and 63.
A method of treating a complement-associated disorder selected from the group comprising inflammatory disorders.
A method of treating a complement-associated disorder selected from the group comprising ocular diseases.
Dependencies are inferred from the claim text.