Dual-specific il-1a/ il-1b antibodies
AssigneeAbbott Laboratories
InventorsChung-ming Hsieh, Bradford L. McRae, Yuliya Kutskova, John E. Memmott, Michael Roguska, Ian Tomlinson, Carrie Enever, Steven Grant, Mihriban Tuna
Life of this patent
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Abstract
The invention provides an isolated, dual-specific antibody, or an antigen-binding portion thereof, which is specific for human IL-1α and human IL-1β. The dual specific antibodies of the invention also neutralize both human IL-1α and human IL-1β. The invention also provides domain antibodies (dAbs) specific for human IL-1α and human IL-1β.
Claims57
An isolated, dual-specific antibody, or an antigen-binding portion thereof, with the following characteristics:
- a) dissociates from human IL-1α with a KD of 3×10−7 M or less;
- b) dissociates from human IL-1β with a KD of 5×10−5 M or less;
- and
- c) does not bind mouse IL-1α or mouse IL-1β.
3-12. (canceled)
(canceled)
An isolated antibody, or an antigen-binding portion thereof, having dual-specificity for human IL-1α and human IL-1β comprising
- a variable light chain comprising complementary determining regions (CDRs) as set forth in an amino acid sequence selected from the group consisting of SEQ ID NO:
- 12, SEQ ID NO:
- 24, and SEQ ID NO:
- 28, or
- a variable heavy chain comprising CDRS as set forth in an amino acid sequence selected from the group consisting of SEQ ID NO:
- 4, SEQ ID NO:
- 8, SEQ ID NO:
- 16, and SEQ ID NO:
- 20.
17-21. (canceled)
An isolated antibody, or an antigen-binding portion thereof, having dual-specificity for human IL-1α and human IL-1β comprising either
- a variable light chain comprising CDRs as set forth in an amino acid sequence selected from the group consisting of SEQ ID NO:
- 36, SEQ ID NO:
- 40, and SEQ ID NO:
- 48, or
- a variable heavy chain comprising CDRs as set forth in an amino acid sequence selected from the group consisting of SEQ ID NO:
- 32, SEQ ID NO:
- 44, SEQ ID NO:
- 52.
25-28. (canceled)
An isolated antibody, or an antigen-binding portion thereof, having dual-specificity for human IL-1α and human IL-1β, comprising
- an IL-1α antigen binding region having either a light chain variable sequence comprising a CDR3 selected from the group consisting of SEQ ID NO:
- 11, SEQ ID NO:
- 23, and SEQ ID NO:
- 27 or a heavy chain variable sequence comprising a CDR3 selected from the group consisting of SEQ ID NO:
- 3, SEQ ID NO:
- 7, SEQ ID NO:
- 15, SEQ ID NO:
- 19, and
- an IL-1β antigen binding region having either a light chain variable sequence comprising a CDR3 selected from the group consisting of SEQ ID NO:
- 35, SEQ ID NO:
- 39, and SEQ ID NO:
- 47 or a heavy chain variable sequence comprising a CDR3 selected from the group consisting of SEQ ID NO:
- 31, SEQ ID NO:
- 43, and SEQ ID NO:
- 51.
32-38. (canceled)
A dual-specific, isolated antibody, or antigen-binding portion thereof, comprising an IL-1α antigen binding region and an IL-1β antigen binding region, wherein the antibody, or antigen-binding portion thereof, comprises a heavy chain variable region and a light chain variable region combination selected from the group consisting of
- a) a heavy chain variable region comprising CDRs as set forth in SEQ ID NO:
- 16 (ABT1-96) and a light chain variable region comprising CDRs as set forth in SEQ ID NO:
- 40 (ABT2-46);
- b) light chain variable region comprising CDRs as set forth in SEQ ID NO:
- 24 (ABT1-122) and a heavy chain variable region comprising CDRs as set forth in SEQ ID NO:
- 52 (ABT2-108);
- c) a light chain variable region comprising CDRs as set forth in SEQ ID NO:
- 28 (ABT1-141) and a heavy chain variable region comprising CDRs as set forth in SEQ ID NO:
- 52 (ABT2-108);
- d) a light chain variable region comprising CDRs as set forth in SEQ ID NO:
- 28 (ABT1-141) and a heavy chain variable region comprising CDRs as set forth in SEQ ID NO:
- 44 (ABT2-65);
- e) a heavy chain variable region comprising CDRs as set forth in SEQ ID NO:
- 16 (ABT1-96) and a light chain variable region comprising CDRs as set forth in SEQ ID NO:
- 36 (ABT2-42);
- f) a light chain variable region comprising CDRs as set forth in SEQ ID NO:
- 12 (ABT1-95) and a heavy chain variable region comprising CDRs as set forth in SEQ ID NO:
- 32 (ABT2-13);
- g) a light chain variable region comprising CDRs as set forth in SEQ ID NO:
- 24 (ABT1-122) and a heavy chain variable region comprising CDRs as set forth in SEQ ID NO:
- 44 (ABT2-65);
- and
- h) a heavy chain variable region comprising CDRs as set forth in SEQ ID NO:
- 20 (ABT1-98) and a light chain variable region comprising CDRs as set forth in SEQ ID NO:
- 48 (ABT2-76).
(canceled)
A single domain antibody (dAb) comprising an amino acid sequence selected from the group consisting of SEQ ID NO:
- 4, SEQ ID NO:
- 8, SEQ ID NO:
- 12, SEQ ID NO:
- 16, SEQ ID NO:
- 20, SEQ ID NO:
- 24, SEQ ID NO:
- 28, SEQ ID NO:
- 32, SEQ ID NO:
- 36, SEQ ID NO:
- 40, SEQ ID NO:
- 44, SEQ ID NO:
- 48, SEQ ID NO:
- 52, SEQ ID NO:
- 53, SEQ ID NO:
- 54, SEQ ID NO:
- 55, SEQ ID NO:
- 56, SEQ ID NO:
- 57, SEQ ID NO:
- 58, SEQ ID NO:
- 59, SEQ ID NO:
- 60, SEQ ID NO:
- 61, SEQ ID NO:
- 62, SEQ ID NO:
- 63, SEQ ID NO:
- 64, SEQ ID NO:
- 65, SEQ ID NO:
- 66, SEQ ID NO:
- 67, SEQ ID NO:
- 68, SEQ ID NO:
- 69, SEQ ID NO:
- 70, SEQ ID NO:
- 71, SEQ ID NO:
- 72, SEQ ID NO:
- 73, SEQ ID NO:
- 74, SEQ ID NO:
- 75, SEQ ID NO:
- 76, SEQ ID NO:
- 77, SEQ ID NO:
- 78, SEQ ID NO:
- 79, SEQ ID NO:
- 80, SEQ ID NO:
- 81, SEQ ID NO:
- 82, SEQ ID NO:
- 83, SEQ ID NO:
- 84, SEQ ID NO:
- 85, SEQ ID NO:
- 86, SEQ ID NO:
- 87, SEQ ID NO:
- 88, SEQ ID NO:
- 89, SEQ ID NO:
- 90, SEQ ID NO:
- 91, SEQ ID NO:
- 92, SEQ ID NO:
- 93, SEQ ID NO:
- 94, SEQ ID NO:
- 95, SEQ ID NO:
- 96, SEQ ID NO:
- 97, SEQ ID NO:
- 98, SEQ ID NO:
- 99, SEQ ID NO:
- 100, SEQ ID NO:
- 101, SEQ ID NO:
- 102, SEQ ID NO:
- 103, SEQ ID NO:
- 104, SEQ ID NO:
- 105, SEQ ID NO:
- 106, SEQ ID NO:
- 107, SEQ ID NO:
- 108, SEQ ID NO:
- 109, SEQ ID NO:
- 110, SEQ ID NO:
- 111, SEQ ID NO:
- 112, SEQ ID NO:
- 113, SEQ ID NO:
- 114, SEQ ID NO:
- 115, SEQ ID NO:
- 116, SEQ ID NO:
- 117, SEQ ID NO:
- 118, SEQ ID NO:
- 119, SEQ ID NO:
- 120, SEQ ID NO:
- 121, SEQ ID NO:
- 122, SEQ ID NO:
- 123, SEQ ID NO:
- 124, SEQ ID NO:
- 125, SEQ ID NO:
- 126, SEQ ID NO:
- 127, SEQ ID NO:
- 128, SEQ ID NO:
- 129, SEQ ID NO:
- 130, SEQ ID NO:
- 131, SEQ ID NO:
- 132, and SEQ ID NO:
- 133.
An isolated nucleic acid encoding a light chain CDR3 domain selected from the group consisting of SEQ ID NO:
- 11, SEQ ID NO:
- 23, and SEQ ID NO:
- 27.
(canceled)
An isolated nucleic acid encoding a heavy chain CDR3 domain selected from the group consisting of SEQ ID NO:
- 3, SEQ ID NO:
- 7, SEQ ID NO:
- 15, and SEQ ID NO:
- 19.
(canceled)
An isolated nucleic acid encoding a light chain CDR3 domain selected from the group consisting of SEQ ID NO:
- 35, SEQ ID NO:
- 39, and SEQ ID NO:
- 47.
(canceled)
An isolated nucleic acid encoding a heavy chain CDR3 domain selected from the group consisting of SEQ ID NO:
- 31, SEQ ID NO:
- 43, and SEQ ID NO:
- 51.
(canceled)
An isolated nucleic acid
- (a) encoding an antibody light chain variable region comprising the amino acid sequence selected from the group consisting of SEQ ID NO:
- 12, SEQ ID NO:
- 24, SEQ ID NO:
- 28, SEQ ID NO:
- 36, SEQ ID NO:
- 40, SEQ ID NO:
- 48, SEQ ID NO:
- 94, SEQ ID NO:
- 95, SEQ ID NO:
- 96, SEQ ID NO:
- 97, SEQ ID NO:
- 98, SEQ ID NO:
- 99, SEQ ID NO:
- 100, SEQ ID NO:
- 101, SEQ ID NO:
- 102, SEQ ID NO:
- 103, SEQ ID NO:
- 104, SEQ ID NO:
- 105, SEQ ID NO:
- 106, SEQ ID NO:
- 107, SEQ ID NO:
- 108, SEQ ID NO:
- 109, SEQ ID NO:
- 110, SEQ ID NO:
- 111, SEQ ID NO:
- 112, SEQ ID NO:
- 113, SEQ ID NO:
- 114, SEQ ID NO:
- 115, SEQ ID NO:
- 116, SEQ ID NO:
- 117, SEQ ID NO:
- 118, SEQ ID NO:
- 119, SEQ ID NO:
- 120, SEQ ID NO:
- 121, SEQ ID NO:
- 122, SEQ ID NO:
- 123, SEQ ID NO:
- 124, SEQ ID NO:
- 125, SEQ ID NO:
- 126, SEQ ID NO:
- 127, SEQ ID NO:
- 128, SEQ ID NO:
- 129, SEQ ID NO:
- 130, SEQ ID NO:
- 131, SEQ ID NO:
- 132, and SEQ ID NO:
- 133;
- (b) encoding an antibody heavy chain variable region comprising the amino acid sequence selected from the group consisting of SEQ ID NO:
- 4, SEQ ID NO 8, SEQ ID NO:
- 16, SEQ ID NO:
- 20, SEQ ID NO:
- 32, SEQ ID NO:
- 44, SEQ ID NO:
- 52, SEQ ID NO:
- 54, SEQ ID NO:
- 55, SEQ ID NO:
- 56, SEQ ID NO:
- 57, SEQ ID NO:
- 58, SEQ ID NO:
- 59, SEQ ID NO:
- 60, SEQ ID NO:
- 61, SEQ ID NO:
- 62, SEQ ID NO:
- 63, SEQ ID NO:
- 64, SEQ ID NO:
- 65, SEQ ID NO:
- 66, SEQ ID NO:
- 67, SEQ ID NO:
- 68, SEQ ID NO:
- 69, SEQ ID NO:
- 70, SEQ ID NO:
- 71, SEQ ID NO:
- 72, SEQ ID NO:
- 73, SEQ ID NO:
- 74, SEQ ID NO:
- 75, SEQ ID NO:
- 76, SEQ ID NO:
- 77, SEQ ID NO:
- 78, SEQ ID NO:
- 79, SEQ ID NO:
- 80, SEQ ID NO:
- 81, SEQ ID NO:
- 82, SEQ ID NO:
- 83, SEQ ID NO:
- 84, SEQ ID NO:
- 85, SEQ ID NO:
- 86, SEQ ID NO:
- 87, SEQ ID NO:
- 88, SEQ ID NO:
- 89, SEQ ID NO:
- 90, SEQ ID NO:
- 91, and SEQ ID NO:
- 92;
- or
- (c) selected from the group consisting of SEQ ID NO:
- 134 to SEQ ID NO:
- 843.
68-69. (canceled)
An expression vector comprising:
- a) an episomal origin of replication;
- b) an insertion site for inserting a nucleic acid sequence encoding a gene of interest;
- c) a stuffer sequence at the insertion site;
- and
- d) a nucleic acid encoding an antibody heavy or light chain constant region.
(canceled)
Dependencies are inferred from the claim text.