LIPOPROTEIN-ASSOCIATED PHOSPHOLIPASE A2 ANTIBODY COMPOSITIONS AND METHODS OF USE
The invention provides isolated anti-Lp-PLA2 antibodies that bind to Lp-PLA2. The invention also encompasses compositions comprising an anti-Lp-PLA2 antibody. These compositions can be provided in an article of manufacture or a kit. Another aspect of the invention is an isolated nucleic acid encoding an anti-Lp-PLA2 antibody, as well as an expression vector comprising the isolated nucleic acid. Also provided are cells that produce the anti-Lp-PLA2 antibodies. The invention encompasses a method of producing the anti-Lp-PLA2 antibodies. Other aspects of the invention are a method of detecting an Lp-PLA2 in a subject.
1 . An isolated antibody, or antigen binding fragment thereof, wherein the antibody competes for binding to Lp-PLA2 with a reference antibody comprising:
(a) a light chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 2, 12, 22, 32 and 40; and
(b) a heavy chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 7, 17, 27, 37 and 40.
2 . The antibody of claim 1 , wherein the reference antibody comprises:
(a) a light chain variable region comprising the amino acid sequence of SEQ ID NOs: 2; and
(b) a heavy chain variable region comprising the amino acid sequence of SEQ ID NOs: 7.
3 . The antibody of claim 1 , wherein the reference antibody comprises:
(a) a light chain variable region comprising the amino acid sequence of SEQ ID NOs: 12; and
(b) a heavy chain variable region comprising the amino acid sequence of SEQ ID NOs: 17.
4 . The antibody of claim 1 , wherein the reference antibody comprises:
(a) a light chain variable region comprising the amino acid sequence of SEQ ID NOs: 22; and
(b) a heavy chain variable region comprising the amino acid sequence of SEQ ID NOs: 27.
5 . The antibody of claim 1 , wherein the reference antibody comprises:
(a) a light chain variable region comprising the amino acid sequence of SEQ ID NOs: 32; and
(b) a heavy chain variable region comprising the amino acid sequence of SEQ ID NOs: 37.
6 . The antibody of claim 1 , wherein the reference antibody comprises:
(a) a light chain variable region comprising the amino acid sequence of SEQ ID NOs: 40; and
(b) a heavy chain variable region comprising the amino acid sequence of SEQ ID NOs: 40.
7 . The antibody of claim 1 , wherein the antibody is a monoclonal antibody, a human antibody, a humanized antibody or a chimeric antibody.
8 . An isolated monoclonal antibody, or antigen binding fragment thereof, comprising: a light chain variable region comprising CDR1, CDR2 and CDR3 sequences; and a heavy chain variable region comprising CDR1, CDR2, CDR3 sequences, wherein:
(a) the light chain variable region CDR1 sequence comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 3, 13, 23, 33 and 40, and conservative modifications thereof;
(b) the heavy chain variable region CDR1 sequence comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 8, 18, 28, 38 and 40, and conservative modifications thereof; and
(c) the antibody binds to Lp-PLA2.
9 . The antibody of claim 8 , wherein the light chain variable region CDR2 sequence comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 4, 14, 24, 34 and 40, and conservative modifications thereof; and the heavy chain variable region CDR2 sequence comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 9, 19, 29, 39 and 40, and conservative modifications thereof.
10 . The antibody of claim 8 , wherein the light chain variable region CDR3 sequence comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 5, 15, 25, 35 and 40, and conservative modifications thereof; and the heavy chain variable region CDR3 sequence comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 10, 20, 30, and 40, and conservative modifications thereof.
11 . The antibody of claim 8 , wherein the antibody is a human antibody, a humanized antibody or a chimeric antibody.
12 . An article of manufacture comprising a container and a composition contained therein, wherein the composition comprises an antibody, or antigen binding fragment thereof, of claim 1 .
13 . An isolated nucleic acid molecule encoding the antibody, or antigen binding fragment thereof, of claim 1 .
14 . The isolated nucleic acid molecule of claim 13 , which comprises:
(a) a nucleic acid sequence encoding a light chain variable region selected from the group consisting of SEQ ID NO: 1, 11, 21, 31 and 40; and
(b) a nucleic acid sequence encoding a heavy chain variable region selected from the group consisting of SEQ ID NO: 6, 16, 26, 36 and 40.
15 . An expression vector comprising the nucleic acid molecule of claim 13 .
16 . A host cell comprising the expression vector of claim 15 .
17 . A transgenic mouse comprising human immunoglobulin light and heavy chain transgenes, wherein the mouse expresses the antibody of claim 1 .
18 . A hybridoma prepared from the mouse of claim 17 , wherein the hybridoma produces said antibody.
19 . A cell that produces the antibody of claim 1 .
20 . A method for detecting Lp-PLA2 in a subject comprising contacting a sample from the subject with an antibody, or antigen binding fragment thereof, of claim 1 under conditions suitable for binding; determining the level of Lp-PLA2 in the sample.
21 . The method of claim 20 wherein the sample is selected from the group comprising blood, serum, plasma, ascites, urine, peritoneal wash and tissue.