MONOCLONAL ANTIBODY AND ANTIGENS FOR DIAGNOSING AND TREATING LUNG DISEASE AND INJURY
The present invention provides methods for diagnosing a patient with emphysema, COPD of lung injury caused by tobacco use by detecting the levels of EMAP II in a sample. Disclosed herein are the hypervariable regions for a rat monoclonal antibody that binds to a form of EMAP II. This disclosure also includes a polypeptide sequence included in EMAP II that is the target for the binding of the antibody to its target protein. This epitope serves as the basis for a humanized antibody that can be used to treat patients that suffer from pathologies that exhibit elevated levels of EMAP II expression.
1 . An antibody, comprising:
a heavy chain variable region, wherein said heavy chain variable reg10n includes at least a portion of a first polypeptide according to SEQ. ID. NO. 2; and
a light chain variable region, wherein said light chain variable region includes at least a portion of a second polypeptide according to SEQ. ID. NO. 3, wherein said antibody is humanized and the humanized antibody binds to human EMAPII.
2 . The antibody according to claim 1 , wherein said first polypeptide has at least 99 percent homology to SEQ. ID. NO. 2, and said second polypeptide has at least 99 percent homology to SEQ. ID. NO. 3.
3 . The antibody according to claim 1 , wherein said first polypeptide has at least 95 percent identity to SEQ. ID. NO. 2 and said second polypeptide has at least 95 percent identity to SEQ. ID. NO. 3.
4 . The antibody according to claim 1 , wherein said first polypeptide has at least 99 percent identity to SEQ. ID. NO. 2 and said second polypeptide has at least 99 percent identity to SEQ. ID. NO. 3.
5 . The antibody according to claim 1 , wherein said first polypeptide is SEQ. ID. NO. 2 and said second polypeptide is SEQ. ID. NO. 3.
6 . An antibody, comprising:
a heavy chain, wherein said heavy chain includes the heavy chain hypervariable regions CDR1, CDR2 and CDR3, wherein CDR1 includes at least a portion of the polypeptide according to SEQ. ID. NO. 5, CDR2 includes at least a portion of the polypeptide according to SEQ. ID. NO. 6, and CDR3 includes at least a portion of the polypeptide according to SEQ. ID. NO. 7; and
a light chain, wherein said light chain includes the light chain hypervariable regions CDR1L, CDR2 L, and CDR3 L, wherein CDR1L includes at least a portion of the polypeptide according to SEQ. ID. NO. 8, CDR2 L includes at least a portion of the polypeptide according to SEQ. ID. NO. 9 and CDR3 L includes at least a portion of the polypeptide according to SEQ. ID. NO. 10, wherein the heavy chain and the light chain form a portion of a humanized antibody, that binds to human EMAPII.
7 . The humanized antibody according to claim 6 , wherein: CDR1 is SEQ. ID. NO. 5, CDR2 is SEQ. ID. NO. 6, and CDR3 is SEQ. ID. NO. 7; CDR1L his SEQ. ID. NO. 8, CDR2 L is SEQ. ID. NO. 9, and CDR3 L is SEQ. ID. NO. 10.
8 . An epitope, comprising:
an epitope of human EMAP II, wherein said epitope includes at least a portion of an isolated polypeptide according to SEQ. ID. NO. 12.
9 . The epitope, according to claim 8 , wherein said isolated polypeptide has at least 95 percent homology to SEQ. ID. NO. 12.
10 . The epitope, according to claim 8 , wherein said isolated polypeptide has at least 99 percent homology to SEQ. ID. NO. 12.
11 . The epitope, according to claim 8 , wherein said isolated polypeptide has at least 95 percent identity to SEQ. ID. NO. 12.
12 . The epitope, according to claim 8 , wherein said isolated polypeptide has at least 99 percent identity to SEQ. ID. NO. 12.
13 . The epitope, according to claim 8 , wherein said isolated polypeptide is SEQ. ID. NO.12.
14 . The epitope, according to claim 8 , wherein said isolated polypeptide has at least 95 percent identity to SEQ. ID. NO. 11.
15 . The epitope, according to claim 8 , wherein said isolated polypeptide has at least 99 percent identity to SEQ. ID. NO. 11.
16 . The epitope, according to claim 8 , wherein said isolated polypeptide is SEQ. ID. NO.11.
17 . A method of making an antibody, comprising the steps of:
producing a synthetic polypeptide wherein at least one portion of the synthetic polypeptide includes at least a portion of the polypeptide according to SEQ. ID. NO. 12.
18 . The method according to claim 17 , wherein said at least one portion of the synthetic polypeptide has at least 95 percent homology to SEQ. ID. NO. 12.
19 . The method according to claim 17 , wherein said at least one portion of the synthetic polypeptide has at least 99 percent homology to SEQ. ID. NO. 12.
20 . The method according to claim 17 , wherein said at least one portion of the synthetic polypeptide has at least 95 percent identity to SEQ. ID. NO. 12.
21 . The method according to claim 17 , wherein said at least one portion of the synthetic polypeptide has at least 99 percent identity to SEQ. ID. NO. 12.
22 . The method according to claim 17 , wherein said at least one portion of the synthetic polypeptide is SEQ. ID. NO. 12.
23 . The method according to claim 17 , wherein at least one portion of the synthetic polypeptide has at least 95 percent homology to SEQ. ID. NO. 11.
24 . The method according to claim 17 , wherein at least one portion of the synthetic polypeptide has at least 99 percent homology to SEQ. ID. NO. 11.
25 . The method according to claim 17 , wherein at least one portion of the synthetic polypeptide has at least 95 percent identity to SEQ. ID. NO. 11.
26 . The method according to claim 17 , wherein at least one portion of the synthetic polypeptide has at least 99 percent identity to SEQ. ID. NO. 11.
27 . The method according to claim 17 , wherein at least one portion of the synthetic polypeptide is SEQ. ID. NO. 11.
28 . The method according to claim 17 , further including the step of: contacting said synthetic polypeptide with the immune system of a mammal.
29 . The method according to claim 28 , further including the step of selecting a B-cell from said mammal contacted with said synthetic polypeptide, wherein said B-cell produces antibody that binds with high affinity to EMAPII.