PREVENTION AND TREATMENT OF PAIN USING MONOCLONAL ANTIBODIES AND ANTIBODY FRAGMENTS TO LYSOPHOSPHATIDIC ACID
Methods for preventing and treating pain are provided. These methods involve administering to a subject, including a human subject, an antibody or antibody fragment that binds LPA. Preferably, antibody is a humanized anti-LPA monoclonal antibody, or an antigen-binding fragment derived from such an antibody.
1 . A method of treating or preventing pain, the method comprising administering to a subject having or believed to be at risk of having pain a humanized monoclonal antibody or antibody fragment that binds and neutralizes LPA, thereby effecting treatment or prevention of pain, wherein the monoclonal antibody or antibody fragment comprises at least one light chain variable domain that comprises a first light chain complementarity determining region comprising an amino acid sequence selected from the group consisting of RSSQSLLKTNGNTYLH (SEQ ID NO: 4), TSGQSLVHINGNTYLH (SEQ ID NO: 11), RSSQSLVHSNGNTYLH (SEQ ID NO: 15), and SASSSLSYMH (SEQ ID NO: 20), a second light chain complementarity determining region comprising an amino acid sequence selected from the group consisting of KVSNRFS (SEQ ID NO: 5), KVSNLFS (SEQ ID NO: 12), and DTSKLAS (SEQ ID NO: 21), and a third light chain complementarity determining region comprising an amino acid sequence selected from the group consisting of SQSTHFPFT (SEQ ID NO: 6) and HRRSSYT (SEQ ID NO: 22), and at least one heavy chain variable domain that comprises a first heavy chain complementarity determining region comprising an amino acid sequence selected from the group consisting of NYLIE (SEQ ID NO: 7) and SGYYWT (SEQ ID NO: 23), a second heavy chain complementarity determining region comprising an amino acid sequence selected from the group consisting of LIYPDSGYINYNENFKG (SEQ ID NO: 2), LINPGSDYTNYNENFKG (SEQ ID NO: 9), LIIPGTGYTNYNENFKG (SEQ ID NO: 13), YIGYDGSNDSNPSLKN (SEQ ID NO: 18), and AINPGSDYTNYNENFKG (SEQ ID NO: 34), and a third heavy chain complementarity determining region comprising an amino acid sequence selected from the group consisting of RFAYYGSGYYFDY (SEQ ID NO: 3), RFGYYGSGNYFDY (SEQ ID NO: 10), RFGYYGSSNYFDY (SEQ ID NO: 14), RFGYYGSGYYFDY (SEQ ID NO: 16), and AMLRRGFDY (SEQ ID NO: 19).
2 . A method according to claim 1 wherein the monoclonal antibody or antibody fragment comprises at least one light chain variable domain that comprises a first light chain complementarity determining region comprising amino acid sequence TSGQSLVHINGNTYLH (SEQ ID NO: 11), a second light chain complementarity determining region comprising amino acid sequence KVSNLFS (SEQ ID NO: 12), and a third light chain complementarity determining region comprising amino acid sequence SQSTHFPFT (SEQ ID NO: 6), and at least one heavy chain variable domain that comprises a first heavy chain complementarity determining region comprising amino acid sequence NYLIE (SEQ ID NO: 7), a second heavy chain complementarity determining region comprising amino acid sequence LINPGSDYTNYNENFKG (SEQ ID NO: 9), and a third heavy chain complementarity determining region comprising amino acid sequence RFGYYGSGNYFDY (SEQ ID NO: 10).
3 . A method according to claim 1 wherein the monoclonal antibody or antibody fragment comprises at least one light chain variable domain that comprises a first light chain complementarity determining region comprising amino acid sequence RSSQSLLKTNGNTYLH (SEQ ID NO: 4), a second light chain complementarity determining region comprising amino acid sequence KVSNRFS (SEQ ID NO: 5), and a third light chain complementarity determining region comprising amino acid sequence SQSTHFPFT (SEQ ID NO: 6), and at least one heavy chain variable domain comprising a first heavy chain complementarity determining region comprising amino acid sequence NYLIE (SEQ ID NO: 7), a second heavy chain complementarity determining region comprising amino acid sequence LIYPDSGYINYNENFKG (SEQ ID NO: 2), and a third heavy chain complementarity determining region comprising amino acid sequence RFAYYGSGYYFDY (SEQ ID NO: 3).
4 . A method according to claim 1 wherein the monoclonal antibody or antibody fragment comprises at least one light chain polypeptide comprising a variable domain comprising an amino acid sequence having SEQ ID NO: 27, 35, 36, 37, 38, 39, 40, 41, 42, or 43, and at least one heavy chain polypeptide comprising a variable domain comprising an amino acid sequence having SEQ ID NO: 26, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, or 62.
5 . A method according to claim 1 wherein the pain is neuropathic pain.
6 . A method according to claim 1 wherein the subject is a human subject.