Anti-Polyubiquitin Multispecific Antibodies
AssigneeGenentech, Inc.
InventorsVishva Dixit, Marissa Matsumoto, Erick Castellanos
Life of this patent
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Abstract
The invention provides antibodies that bind mixed-topology polyubiquitin and multispecific anti-polyubiquitin antibodies, and methods of using the same.
Claims88
An antibody with a greater avidity for a mixed-topology polyubiquitin than a single-topology polyubiquitin, wherein the mixed-topology polyubiquitin comprises a first linkage and a second linkage, wherein the first linkage and the second linkage differ from one another.
A multispecific antibody that binds a mixed-topology polyubiquitin comprising a first linkage and a second linkage, the antibody comprising a first antigen recognition site specific for the first linkage, and a second antigen recognition site specific for the second linkage, wherein the first linkage and the second linkage differ from one another.
The antibody of any one of the preceding claims, comprising a first VH/VL unit specific for the first linkage, and a second VH/VL unit specific for the second linkage.
The antibody of any one of the preceding claims, which is a knob-in-hole bispecific antibody;
- a bispecific antibody comprising a leucine zipper;
- a cross-linked pair of antibodies;
- an antibody Fc-heterodimeric molecule;
- a diabody;
- a triabody;
- a tetrabody;
- a single-chain Fv dimer;
- a trispecific antibody;
- an octopus antibody;
- or a dual acting FAb.
The antibody of any one of the preceding claims, wherein the first linkage or the second linkage is a K11 linkage.
The antibody of any one of the preceding claims, wherein the first linkage or the second linkage is a K48 linkage.
The antibody of any one of the preceding claims, wherein the first linkage or the second linkage is a K63-linkage.
The antibody of any one of the preceding claims, wherein the first linkage or the second linkage is a C-terminal to N-terminal-linkage.
The antibody of any one of the preceding claims, wherein the first linkage and the second linkage are:
- a) a K11 linkage and a K48 linkage;
- b) a K11 linkage and a K63 linkage;
- c) a K11 linkage and a C- to N-terminal linkage;
- d) a K48 linkage and a K63 linkage;
- e) a K48 linkage and a C- to N-terminal linkage;
- or
- f) a K63 linkage and a C- to N-terminal linkage.
The antibody of any one of the preceding claims, comprising a first half antibody that comprises:
- a) (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
- 9,
- (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
- 10,
- (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 11,
- (iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 12,
- (v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 13, and
- (vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
- 14;
- b) (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
- 23,
- (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
- 24,
- (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 25,
- (iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 26,
- (v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 27, and
- (vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
- 28;
- c) (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
- 37,
- (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
- 38,
- (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 39,
- (iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 40,
- (v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 41, and
- (vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
- 42;
- or
- d) (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
- 51,
- (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
- 52,
- (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 53,
- (iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 54,
- (v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 55, and
- (vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
- 56.
The antibody of any one of the preceding claims, comprising a second half antibody that comprises:
- a) (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
- 9,
- (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
- 10,
- (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 11,
- (iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 12,
- (v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 13, and
- (vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
- 14;
- b) (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
- 23,
- (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
- 24,
- (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 25,
- (iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 26,
- (v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 27, and
- (vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
- 28;
- c) (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
- 37,
- (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
- 38,
- (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 39,
- (iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 40,
- (v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 41, and
- (vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
- 42;
- or
- d) (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
- 51,
- (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
- 52,
- (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 53,
- (iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 54,
- (v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 55, and
- (vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
- 56,
- wherein the HVRs of the second half antibody are not identical to the HVRs of the first half antibody.
The antibody of any one of the preceding claims, comprising first and second half antibodies, wherein:
- a) one of the first and second half antibodies comprises
- (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
- 9,
- (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
- 10,
- (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 11,
- (iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 12,
- (v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 13, and
- (vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
- 14, and the other of the first and second half antibodies comprises
- (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
- 23,
- (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
- 24,
- (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 25,
- (iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 26,
- (v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 27, and
- (vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
- 28;
- b) one of the first and second half antibodies comprises
- (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
- 9,
- (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
- 10,
- (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 11,
- (iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 12,
- (v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 13, and
- (vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
- 14, and the other of the first and second half antibodies comprises
- (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
- 37,
- (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
- 38,
- (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 39,
- (iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 40,
- (v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 41, and
- (vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
- 42;
- c) one of the first and second half antibodies comprises
- (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
- 9,
- (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
- 10,
- (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 11,
- (iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 12,
- (v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 13, and
- (vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
- 14, and the other of the first and second half antibodies comprises
- (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
- 51,
- (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
- 52,
- (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 53,
- (iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 54,
- (v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 55, and
- (vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
- 56;
- d) one of the first and second half antibodies comprises
- (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
- 23,
- (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
- 24,
- (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 25,
- (iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 26,
- (v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 27, and
- (vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
- 28, and the other of the first and second half antibodies comprises
- (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
- 37,
- (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
- 38,
- (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 39,
- (iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 40,
- (v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 41, and
- (vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
- 42;
- e) one of the first and second half antibodies comprises
- (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
- 23,
- (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
- 24,
- (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 25,
- (iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 26,
- (v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 27, and
- (vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
- 28, and the other of the first and second half antibodies comprises
- (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
- 51,
- (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
- 52,
- (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 53,
- (iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 54,
- (v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 55, and
- (vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
- 56;
- or
- f) one of the first and second half antibodies comprises
- (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
- 37,
- (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
- 38,
- (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 39,
- (iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 40,
- (v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 41, and
- (vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
- 42, and the other of the first and second half antibodies comprises
- (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
- 51,
- (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
- 52,
- (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 53,
- (iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 54,
- (v) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 55, and
- (vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
- 56.
The antibody of any one of the preceding claims, comprising first and second half antibodies, wherein the first half antibody comprises
- a) a VL sequence with at least about 95% sequence identity to SEQ ID NO:
- 7 and a VH sequence with at least about 95% sequence identity to SEQ ID NO:
- 8;
- b) a VL sequence with at least about 95% sequence identity to SEQ ID NO:
- 21 and a VH sequence with at least about 95% sequence identity to SEQ ID NO:
- 22;
- c) a VL sequence with at least about 95% sequence identity to SEQ ID NO:
- 35 and a VH sequence with at least about 95% sequence identity to SEQ ID NO:
- 36;
- or
- d) a VL sequence with at least about 95% sequence identity to SEQ ID NO:
- 49 and a VH sequence with at least about 95% sequence identity to SEQ ID NO:
- 50.
The antibody of any one of the preceding claims, comprising first and second half antibodies, wherein the second half antibody comprises
- a) a VL sequence with at least about 95% sequence identity to SEQ ID NO:
- 7 and a VH sequence with at least about 95% sequence identity to SEQ ID NO:
- 8;
- b) a VL sequence with at least about 95% sequence identity to SEQ ID NO:
- 21 and a VH sequence with at least about 95% sequence identity to SEQ ID NO:
- 22;
- c) a VL sequence with at least about 95% sequence identity to SEQ ID NO:
- 35 and a VH sequence with at least about 95% sequence identity to SEQ ID NO:
- 36;
- or
- d) a VL sequence with at least about 95% sequence identity to SEQ ID NO:
- 49 and a VH sequence with at least about 95% sequence identity to SEQ ID NO:
- 50;
- wherein the VL and VH sequences of the second half antibody are not identical to the VL and VH sequences of the first half antibody.
The antibody of any one of the preceding claims, comprising first and second half antibodies, wherein:
- a) one of the first and second half antibodies comprises a VL sequence with at least about 95% sequence identity to SEQ ID NO:
- 7 and a VH sequence with at least about 95% sequence identity to SEQ ID NO:
- 8,
- and the other of the first and second half antibodies comprises a VL sequence with at least about 95% sequence identity to SEQ ID NO:
- 21 and a VH sequence with at least about 95% sequence identity to SEQ ID NO:
- 22;
- b) one of the first and second half antibodies comprises a VL sequence with at least about 95% sequence identity to SEQ ID NO:
- 7 and a VH sequence with at least about 95% sequence identity to SEQ ID NO:
- 8,
- and the other of the first and second half antibodies comprises a VL sequence with at least about 95% sequence identity to SEQ ID NO:
- 35 and a VH sequence with at least about 95% sequence identity to SEQ ID NO:
- 36;
- c) one of the first and second half antibodies comprises a VL sequence with at least about 95% sequence identity to SEQ ID NO:
- 7 and a VH sequence with at least about 95% sequence identity to SEQ ID NO:
- 8,
- and the other of the first and second half antibodies comprises a VL sequence with at least about 95% sequence identity to SEQ ID NO:
- 49 and a VH sequence with at least about 95% sequence identity to SEQ ID NO:
- 50;
- d) one of the first and second half antibodies comprises a VL sequence with at least about 95% sequence identity to SEQ ID NO:
- 21 and a VH sequence with at least about 95% sequence identity to SEQ ID NO:
- 22,
- and the other of the first and second half antibodies comprises a VL sequence with at least about 95% sequence identity to SEQ ID NO:
- 35 and a VH sequence with at least about 95% sequence identity to SEQ ID NO:
- 36;
- e) one of the first and second half antibodies comprises a VL sequence with at least about 95% sequence identity to SEQ ID NO:
- 21 and a VH sequence with at least about 95% sequence identity to SEQ ID NO:
- 22,
- and the other of the first and second half antibodies comprises a VL sequence with at least about 95% sequence identity to SEQ ID NO:
- 49 and a VH sequence with at least about 95% sequence identity to SEQ ID NO:
- 50;
- or
- f) one of the first and second half antibodies comprises a VL sequence with at least about 95% sequence identity to SEQ ID NO:
- 35 and a VH sequence with at least about 95% sequence identity to SEQ ID NO:
- 36,
- and the other of the first and second half antibodies comprises a VL sequence with at least about 95% sequence identity to SEQ ID NO:
- 49 and a VH sequence with at least about 95% sequence identity to SEQ ID NO:
- 50.
The antibody of any one of the preceding claims, comprising first and second half antibodies, wherein the first half antibody comprises
- a) a VL sequence of SEQ ID NO:
- 7 and a VH sequence of SEQ ID NO:
- 8;
- b) a VL sequence of SEQ ID NO:
- 21 and a VH sequence of SEQ ID NO:
- 22;
- c) a VL sequence of SEQ ID NO:
- 35 and a VH sequence of SEQ ID NO:
- 36;
- or
- d) a VL sequence of SEQ ID NO:
- 49 and a VH sequence of SEQ ID NO:
- 50.
The antibody of any one of the preceding claims, comprising first and second half antibodies, wherein the second half antibody comprises
- a) a VL sequence of SEQ ID NO:
- 7 and a VH sequence of SEQ ID NO:
- 8;
- b) a VL sequence of SEQ ID NO:
- 21 and a VH sequence of SEQ ID NO:
- 22;
- c) a VL sequence of SEQ ID NO:
- 35 and a VH sequence of SEQ ID NO:
- 36;
- or
- d) a VL sequence of SEQ ID NO:
- 49 and a VH sequence of SEQ ID NO:
- 50;
- wherein the VL and VH sequences of the second half antibody are not identical to the VL and VH sequences of the first half antibody.
The antibody of any one of the preceding claims, comprising first and second half antibodies, wherein:
- a) one of the first and second half antibodies comprises a VL sequence of SEQ ID NO:
- 7 and a VH sequence of SEQ ID NO:
- 8,
- and the other of the first and second half antibodies comprises a VL sequence of SEQ ID NO:
- 21 and a VH sequence of SEQ ID NO:
- 22;
- b) one of the first and second half antibodies comprises a VL sequence of SEQ ID NO:
- 7 and a VH sequence of SEQ ID NO:
- 8,
- and the other of the first and second half antibodies comprises a VL sequence of SEQ ID NO:
- 35 and a VH sequence of SEQ ID NO:
- 36;
- c) one of the first and second half antibodies comprises a VL sequence of SEQ ID NO:
- 7 and a VH sequence of SEQ ID NO:
- 8,
- and the other of the first and second half antibodies comprises a VL sequence of SEQ ID NO:
- 49 and a VH sequence of SEQ ID NO:
- 50;
- d) one of the first and second half antibodies comprises a VL sequence of SEQ ID NO:
- 21 and a VH sequence of SEQ ID NO:
- 22,
- and the other of the first and second half antibodies comprises a VL sequence of SEQ ID NO:
- 35 and a VH sequence of SEQ ID NO:
- 36;
- e) one of the first and second half antibodies comprises a VL sequence of SEQ ID NO:
- 21 and a VH sequence of SEQ ID NO:
- 22,
- and the other of the first and second half antibodies comprises a VL sequence of SEQ ID NO:
- 49 and a VH sequence of SEQ ID NO:
- 50;
- or
- f) one of the first and second half antibodies comprises a VL sequence of SEQ ID NO:
- 35 and a VH sequence of SEQ ID NO:
- 36,
- and the other of the first and second half antibodies comprises a VL sequence of SEQ ID NO:
- 49 and a VH sequence of SEQ ID NO:
- 50.
The antibody of any one of the preceding claims, which is a monoclonal antibody.
The antibody of any one of the preceding claims, which is a mouse, rabbit, human, humanized, or chimeric antibody.
The antibody of any one of the preceding claims, wherein the antibody is an IgG antibody.
The antibody of any one of the preceding claims, wherein the antibody is an IgG1, IgG2a, IgG2b, IgG3, or IgG4 antibody.
The antibody of any one of the preceding claims, wherein the antibody is an IgG1 or IgG4 antibody.
The antibody of any one of the preceding claims, comprising first and second half antibodies, wherein the first half antibody comprises a first heavy chain constant region comprising a knob mutation and the second half antibody comprises a second heavy chain constant region comprising a hole mutation;
- or wherein the first half antibody comprises a first heavy chain constant region comprising a hole mutation and the second half antibody comprises a second heavy chain constant region comprising a knob mutation.
The antibody of any one of the preceding claims, comprising first and second half antibodies, wherein the first half antibody comprises
- a) a light chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 2;
- b) a light chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 16;
- c) a light chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 30;
- or
- d) a light chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 44.
The antibody of any one of the preceding claims, comprising first and second half antibodies, wherein the first half antibody comprises
- a) a heavy chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 4;
- b) a heavy chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 18;
- c) a heavy chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 32;
- or
- d) a heavy chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 46,
- optionally wherein a C-terminal lysine is missing from one or more heavy chains.
The antibody of any one of the preceding claims, comprising first and second half antibodies, wherein the first half antibody comprises
- a) a light chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 2 and a heavy chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 4;
- b) a light chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 16 and a heavy chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 18;
- c) a light chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 30 and a heavy chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 32;
- or
- d) a light chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 44 and a heavy chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 46,
- optionally wherein a C-terminal lysine is missing from one or more heavy chains.
The antibody of any one of the preceding claims, comprising first and second half antibodies, wherein the second half antibody comprises
- a) a light chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 2;
- b) a light chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 16;
- c) a light chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 30;
- or
- d) a light chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 44;
- wherein the light chain and heavy chain sequences of the second half antibody are not identical to the light chain and heavy chain sequences of the first half antibody.
The antibody of any one of the preceding claims, comprising first and second half antibodies, wherein:
- a) one of the first and second half antibodies comprises a light chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 2 and a heavy chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 4,
- and the other of the first and second half antibodies comprises a light chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 16 and a heavy chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 20;
- b) one of the first and second half antibodies comprises a light chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 2 and a heavy chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 4,
- and the other of the first and second half antibodies comprises a light chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 30 and a heavy chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 34;
- c) one of the first and second half antibodies comprises a light chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 2 and a heavy chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 4,
- and the other of the first and second half antibodies comprises a light chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 44 and a heavy chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 48;
- d) one of the first and second half antibodies comprises a light chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 2 and a heavy chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 6,
- and the other of the first and second half antibodies comprises a light chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 16 and a heavy chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 18;
- e) one of the first and second half antibodies comprises a light chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 2 and a heavy chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 6,
- and the other of the first and second half antibodies comprises a light chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 30 and a heavy chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 32;
- f) one of the first and second half antibodies comprises a light chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 2 and a heavy chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 6,
- and the other of the first and second half antibodies comprises a light chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 44 and a heavy chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 46;
- g) one of the first and second half antibodies comprises a light chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 16 and a heavy chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 18,
- and the other of the first and second half antibodies comprises a light chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 30 and a heavy chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 34;
- h) one of the first and second half antibodies comprises a light chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 16 and a heavy chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 18,
- and the other of the first and second half antibodies comprises a light chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 44 and a heavy chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 48;
- i) one of the first and second half antibodies comprises a light chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 30 and a heavy chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 32,
- and the other of the first and second half antibodies comprises a light chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 44 and a heavy chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 48;
- j) one of the first and second half antibodies comprises a light chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 16 and a heavy chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 20,
- and the other of the first and second half antibodies comprises a light chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 30 and a heavy chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 32;
- k) one of the first and second half antibodies comprises a light chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 16 and a heavy chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 20,
- and the other of the first and second half antibodies comprises a light chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 44 and a heavy chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 46;
- or
- l) one of the first and second half antibodies comprises a light chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 30 and a heavy chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 34,
- and the other of the first and second half antibodies comprises a light chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 44 and a heavy chain sequence having at least about 95% sequence identity to SEQ ID NO:
- 46,
- optionally wherein a C-terminal lysine is missing from one or more heavy chains.
The antibody of any one of the preceding claims, comprising first and second half antibodies, wherein the first half antibody comprises
- a) a light chain sequence of SEQ ID NO:
- 2;
- b) a light chain sequence of SEQ ID NO:
- 16;
- c) a light chain sequence of SEQ ID NO:
- 30;
- or
- d) a light chain sequence of SEQ ID NO:
- 44.
The antibody of any one of the preceding claims, comprising first and second half antibodies, wherein the second half antibody comprises
- a) a light chain sequence of SEQ ID NO:
- 2;
- b) a light chain sequence of SEQ ID NO:
- 16;
- c) a light chain sequence of SEQ ID NO:
- 30;
- or
- d) a light chain sequence of SEQ ID NO:
- 44;
- wherein the light chain and heavy chain sequences of the second half antibody are not identical to the light chain and heavy chain sequences of the first half antibody, optionally wherein a C-terminal lysine is missing from one or more heavy chains.
The antibody of any one of the preceding claims, comprising first and second half antibodies, wherein:
- a) the first half antibody comprises a light chain sequence of SEQ ID NO:
- 2 and a heavy chain sequence of SEQ ID NO:
- 4,
- and the second half antibody comprises a light chain sequence of SEQ ID NO:
- 16 and a heavy chain sequence of SEQ ID NO:
- 20;
- b) the first half antibody comprises a light chain sequence of SEQ ID NO:
- 2 and a heavy chain sequence of SEQ ID NO:
- 4,
- and the second half antibody comprises a light chain sequence of SEQ ID NO:
- 30 and a heavy chain sequence of SEQ ID NO:
- 34;
- c) the first half antibody comprises a light chain sequence of SEQ ID NO:
- 2 and a heavy chain sequence of SEQ ID NO:
- 4,
- and the second half antibody comprises a light chain sequence of SEQ ID NO:
- 44 and a heavy chain sequence of SEQ ID NO:
- 48;
- d) the first half antibody comprises a light chain sequence of SEQ ID NO:
- 2 and a heavy chain sequence of SEQ ID NO:
- 6,
- and the second half antibody comprises a light chain sequence of SEQ ID NO:
- 16 and a heavy chain sequence of SEQ ID NO:
- 18;
- e) the first half antibody comprises a light chain sequence of SEQ ID NO:
- 2 and a heavy chain sequence of SEQ ID NO:
- 6,
- and the second half antibody comprises a light chain sequence of SEQ ID NO:
- 30 and a heavy chain sequence of SEQ ID NO:
- 32;
- f) the first half antibody comprises a light chain sequence of SEQ ID NO:
- 2 and a heavy chain sequence of SEQ ID NO:
- 6,
- and the second half antibody comprises a light chain sequence of SEQ ID NO:
- 44 and a heavy chain sequence of SEQ ID NO:
- 46;
- g) the first half antibody comprises a light chain sequence of SEQ ID NO:
- 16 and a heavy chain sequence of SEQ ID NO:
- 18,
- and the second half antibody comprises a light chain sequence of SEQ ID NO:
- 30 and a heavy chain sequence of SEQ ID NO:
- 34;
- h) the first half antibody comprises a light chain sequence of SEQ ID NO:
- 16 and a heavy chain sequence of SEQ ID NO:
- 18,
- and the second half antibody comprises a light chain sequence of SEQ ID NO:
- 44 and a heavy chain sequence of SEQ ID NO:
- 48;
- i) the first half antibody comprises a light chain sequence of SEQ ID NO:
- 30 and a heavy chain sequence of SEQ ID NO:
- 32,
- and the second half antibody comprises a light chain sequence of SEQ ID NO:
- 44 and a heavy chain sequence of SEQ ID NO:
- 48;
- j) the first half antibody comprises a light chain sequence of SEQ ID NO:
- 16 and a heavy chain sequence of SEQ ID NO:
- 20,
- and the second half antibody comprises a light chain sequence of SEQ ID NO:
- 30 and a heavy chain sequence of SEQ ID NO:
- 32;
- k) the first half antibody comprises a light chain sequence of SEQ ID NO:
- 16 and a heavy chain sequence of SEQ ID NO:
- 20,
- and the second half antibody comprises a light chain sequence of SEQ ID NO:
- 44 and a heavy chain sequence of SEQ ID NO:
- 46;
- or
- l) the first half antibody comprises a light chain sequence of SEQ ID NO:
- 30 and a heavy chain sequence of SEQ ID NO:
- 34,
- and the second half antibody comprises a light chain sequence of SEQ ID NO:
- 44 and a heavy chain sequence of SEQ ID NO:
- 46;
- optionally wherein a C-terminal lysine is missing from one or more heavy chains.
The antibody of any one of the preceding claims, comprising first and second half antibodies, wherein the first half antibody comprises a light chain sequence of SEQ ID NO:
- 2 and a heavy chain sequence of SEQ ID NO:
- 4, and the second half antibody comprises a light chain sequence of SEQ ID NO:
- 16 and a heavy chain sequence of SEQ ID NO:
- 20, and optionally wherein a C-terminal lysine is missing from one or more heavy chains.
An antibody that competes with the antibody of any one of the preceding claims for binding to a mixed-topology polyubiquitin.
An antibody that binds the same epitopes of a mixed-topology polyubiquitin as the antibody of any one of the preceding claims.
The antibody of any one of the preceding claims, which is a bispecific antibody.
The antibody of any one of the preceding claims, which is a diabody, triabody, or tetrabody.
The antibody of any one of the preceding claims, conjugated to a label.
Dependencies are inferred from the claim text.