Anti-IgE antibodies
First Claim
Patent Images
1. A human monoclonal antibody or antigen-binding portion thereof directed against human IgE, the antibody or portion having at least one additional property selected from the group consisting of:
- a) has an IC50 of 0.5 μ
g/mL or less as measured by its ability to reduce IgE cell binding assay using an RBL-2H3 cell line transfected with the human Fcε
R1;
b) has an IC50 of 0.5 μ
g/mL or less as measured by its ability to inhibit IgE-mediated degranulation of a RBL-2H3 cell line transfected with the human Fcε
R1;
c) does not crosslink receptor-bound IgE and does not stimulate IgE-dependent degranulation of RBL-2H3 (Fcε
R1) cells cultured with human IgE;
d) does not crosslink receptor-bound IgE and does not stimulate IgE-dependent degranulation of human blood basophils;
e) is highly selective for IgE over human IgA, IgG1 and IgG3;
f) binds to the full length of human IgE with an Affinity Constant, KD, of 15 nM or less as measured by surface plasmon resonance;
g) has an off rate (kOff) for human IgE of 2×
10−
4 s−
1 or smaller as measured by surface plasmon resonance; and
h) binds to the same epitope of human IgE as an antibody selected from the group consisting of recombinant 5.396.1;
5.396.1 Hc-S103N Lc-K61R;
recombinant 6.605.1;
6.605.1 (H3Q, M13K, D82E-T25A, T53S);
recombinant 5.948.1; and
5.948.1H100Y.
2 Assignments
0 Petitions
Accused Products
Abstract
The present invention relates to novel human antibodies specifically directed against human immunoglobulin E (anti-IgE). The present invention also relates to pharmaceutical compositions and methods for treating asthma, in particular allergic asthma, as well as other IgE-mediated disorders including allergic rhinitis and food allergies.
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Citations
47 Claims
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1. A human monoclonal antibody or antigen-binding portion thereof directed against human IgE, the antibody or portion having at least one additional property selected from the group consisting of:
-
a) has an IC50 of 0.5 μ
g/mL or less as measured by its ability to reduce IgE cell binding assay using an RBL-2H3 cell line transfected with the human Fcε
R1;b) has an IC50 of 0.5 μ
g/mL or less as measured by its ability to inhibit IgE-mediated degranulation of a RBL-2H3 cell line transfected with the human Fcε
R1;c) does not crosslink receptor-bound IgE and does not stimulate IgE-dependent degranulation of RBL-2H3 (Fcε
R1) cells cultured with human IgE;d) does not crosslink receptor-bound IgE and does not stimulate IgE-dependent degranulation of human blood basophils; e) is highly selective for IgE over human IgA, IgG1 and IgG3; f) binds to the full length of human IgE with an Affinity Constant, KD, of 15 nM or less as measured by surface plasmon resonance; g) has an off rate (kOff) for human IgE of 2×
10−
4 s−
1 or smaller as measured by surface plasmon resonance; andh) binds to the same epitope of human IgE as an antibody selected from the group consisting of recombinant 5.396.1;
5.396.1 Hc-S103N Lc-K61R;
recombinant 6.605.1;
6.605.1 (H3Q, M13K, D82E-T25A, T53S);
recombinant 5.948.1; and
5.948.1H100Y. - View Dependent Claims (4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 18, 19, 20, 46, 47)
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2. An isolated human antibody or antigen-binding portion thereof directed against human IgE, wherein said antibody has an IC25 ng/mL(100-5000 ng/mL) of about 0.1-30 μ
- g/mL, wherein the IC25 ng/mL(100-5000 ng/mL) is defined as the in vitro concentration of antibody required to reduce the free IgE concentration in a serum sample from an initial concentration in the range of about 100-5000 ng/mL to a concentration of about 25 ng/mL.
- View Dependent Claims (3)
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16. (canceled)
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17. (canceled)
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21. (canceled)
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22. A nucleic acid sequence selected from the group consisting of SEQ ID NOs:
- 1, 3, 11, 13, 21, 23, 31, 33, 41, 43, 51, 53, 61, 63, 71, 73, 81, 83, 91, 93, 101, 103, 105, 107, 109, 111, 121, 123, 131 and 133.
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23. An antibody or antigen-binding portion thereof directed against human IgE, wherein said antibody is selected from the group consisting of:
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an antibody comprising a H-variable domain having the sequence of SEQ ID NO;
4; and
a L-variable domain having the sequence of SEQ ID NO;
14;an antibody comprising a H-variable domain having the sequence of SEQ ID NO;
24; and
a L-variable domain having the sequence of SEQ ID NO;
34;an antibody comprising a H-variable domain having the sequence of SEQ ID NO;
44; and
a L-variable domain having the sequence of SEQ ID NO;
54;an antibody comprising a H-variable domain having the sequence of SEQ ID NO;
64; and
a L-variable domain having the sequence of SEQ ID NO;
74;an antibody comprising a H-variable domain having the sequence of SEQ ID NO;
84; and
a L-variable domain having the sequence of SEQ ID NO;
94;an antibody comprising a H-variable domain having the sequence of SEQ ID NO;
124; and
a L-variable domain having the sequence of SEQ ID NO;
134;an antibody comprising a H-chain having the sequence of SEQ ID NO;
2; and
a L-chain having the sequence of SEQ ID NO;
12;an antibody comprising a H-chain having the sequence of SEQ ID NO;
22; and
a L-chain having the sequence of SEQ ID NO;
32;an antibody comprising a H-chain having the sequence of SEQ ID NO;
42; and
a L-chain having the sequence of SEQ ID NO;
52;an antibody comprising a H-chain having the sequence of SEQ ID NO;
62; and
a L-chain having the sequence of SEQ ID NO;
72;an antibody comprising a H-chain having the sequence of SEQ ID NO;
82; and
a L-chain having the sequence of SEQ ID NO;
92;an antibody comprising a H-chain having the sequence of SEQ ID NO;
122; and
a L-chain having the sequence of SEQ ID NO;
132;an antibody comprising a H-chain encoded by the insert of ATCC deposit PTA-7977; and
a L-chain encoded by the insert of ATCC deposit PTA-7982;an antibody comprising a H-chain encoded by the insert of ATCC deposit PTA-7981; and
a L-chain encoded by the insert of ATCC deposit PTA-7980;an antibody comprising a H-chain encoded by the insert of ATCC deposit PTA-7985; and
a L-chain encoded by the insert of ATCC deposit PTA-7984;an antibody comprising a H-chain encoded by the insert of ATCC deposit PTA-7983; and
a L-chain encoded by the insert of ATCC deposit PTA-7978; andan antibody comprising a H-chain encoded by the insert of ATCC deposit PTA-7979; and
a L-chain encoded by the insert of ATCC deposit PTA-7986. - View Dependent Claims (37, 38, 39, 41, 42, 43, 44, 45)
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24-36. -36. (canceled)
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40. (canceled)
Specification