Humanized antibody compositions and methods for binding lysophosphatidic acid

Abstract

Compositions and methods for making and using humanized anti-LPA monoclonal antibodies, and fragments and derivatives thereof, are described.

What is claimed is: 
     
         1 . A compound selected from the group consisting of:
 a. anti-LPA agent, which agent specifically binds to LPA under physiological conditions and comprises a peptide amino acid sequence selected from the group consisting of SEQ ID NOs: 162, 163, 164, 165, 166, 167, 168, 169, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, and 189, optionally wherein said anti-LPA agent is selected from the group consisting of an antibody, an antibody derivative, and a non-antibody-derived moiety, wherein the antibody may be a full-length antibody or an antibody fragment, optionally wherein said anti-LPA agent is conjugated to a moiety selected from the group consisting of a polymer, a radionuclide, a chemotherapeutic agent, and a detection agent;   b. an isolated nucleic acid molecule that encodes an immunoglobulin heavy chain variable domain that comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188 and 189, optionally wherein said isolated nucleic acid molecule encodes a fragment of an immunoglobulin heavy chain or a full length immunoglobulin heavy chain;   c an isolated nucleic acid molecule that encodes an immunoglobulin light chain variable domain that comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 162, 163, 164, 165, 166, 167, 168 and 169, optionally wherein said isolated nucleic acid molecule encodes a fragment of an immunoglobulin light chain or a full length immunoglobulin light chain; and   d isolated polypeptide, which polypeptide specifically binds LPA in a physiological context and comprises an amino acid sequence that has a sequence identity of at least 50 percent with a peptide amino acid sequence selected from the group consisting of SEQ ID NO: 162, 163, 164, 165, 166, 167, 168, 169, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188 and 189, optionally wherein the isolated polypeptide is selected from the group consisting of a fragment of a variable domain of an animal immunoglobulin heavy chain, a full length variable domain of an animal immunoglobulin heavy chain, and a full length animal immunoglobulin heavy chain, a fragment of a variable domain of an animal immunoglobulin light chain, a full length variable domain of an animal immunoglobulin light chain and a full length animal immunoglobulin light chain.   
     
     
         2 . An anti-LPA agent according to  claim 1  that comprises an isolated anti-LPA antibody comprising two immunoglobulin heavy chains and two immunoglobulin light chains, wherein one or both of the immunoglobulin heavy chains comprises a variable domain having an amino acid sequence selected from the group consisting of SEQ ID NOs: 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188 and 189, and wherein said isolated anti-LPA antibody is optionally a humanized anti-LPA antibody. 
     
     
         3 . An anti-LPA agent according to  claim 1  that comprises an isolated anti-LPA antibody comprising two immunoglobulin heavy chains and two immunoglobulin light chains, wherein one or both of the immunoglobulin light chains comprises a variable domain having an amino acid sequence selected from the group consisting of SEQ ID NOs: 162, 163, 164, 165, 166, 167, 168 and 169, and wherein said isolated anti-LPA antibody is optionally a humanized anti-LPA antibody. 
     
     
         4 . An anti-LPA agent according to  claim 1  that comprises an isolated anti-LPA antibody comprising two immunoglobulin heavy chains and two immunoglobulin light chains, wherein one or both of the immunoglobulin heavy chains comprises a variable domain having an amino acid sequence independently selected from the group consisting of SEQ ID NOs: 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188 and 189, and wherein one or both of the immunoglobulin light chains comprises a variable domain having an amino acid sequence independently selected from the group consisting of SEQ ID NOs: 162, 163, 164, 165, 166, 167, 168 and 169, and wherein said isolated anti-LPA antibody is optionally a humanized anti-LPA antibody, optionally wherein both immunoglobulin heavy chains comprise a variable domain having the same amino acid sequence selected from the group consisting of SEQ ID NOs: 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188 and 189, optionally wherein both immunoglobulin light chains comprise a variable domain having the same amino acid sequence selected from the group consisting of SEQ ID NOs: 162, 163, 164, 165, 166, 167, 168 and 169. 
     
     
         5 . An anti-LPA agent according to  claim 1  that comprises an isolated anti-LPA antibody comprising two immunoglobulin heavy chains and two immunoglobulin light chains, wherein each immunoglobulin heavy chain comprises a variable domain having an amino acid sequence independently selected from the group consisting of SEQ ID NOs: 172, 179 and 180, and each immunoglobulin light chain comprises a variable domain having an amino acid sequence independently selected from the group consisting of SEQ ID NOs: 162 and 166, and wherein said isolated anti-LPA antibody is optionally a humanized anti-LPA antibody. 
     
     
         6 . A anti-LPA agent according to  claim 5  that comprises a humanized anti-LPA antibody comprising two immunoglobulin heavy chains and two immunoglobulin light chains, wherein each immunoglobulin heavy chain comprises a variable domain having an amino acid sequence consisting of SEQ ID NO: 172 and each immunoglobulin light chain comprises a variable domain having an amino acid sequence consisting of SEQ ID NO: 162. 
     
     
         7 . An isolated polypeptide according to  claim 1 , which polypeptide has a sequence identity of at least 65 percent, optionally at least 75 percent, at least 80 percent, at least 85 percent, at least 90 percent or at least 95 percent with a peptide amino acid sequence selected from the group consisting of SEQ ID NO: 162, 163, 164, 165, 166, 167, 168, 169, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188 and 189, optionally wherein the isolated polypeptide is selected from the group consisting of a fragment of a variable domain of an animal immunoglobulin heavy chain, a full length variable domain of an animal immunoglobulin heavy chain, and a full length animal immunoglobulin heavy chain, a fragment of a variable domain of an animal immunoglobulin light chain, a full length variable domain of an animal immunoglobulin light chain and a full length animal immunoglobulin light chain. 
     
     
         8 . A vector comprising an isolated nucleic acid molecule according to  claim 1 , wherein optionally said isolated nucleic acid molecule encodes (i) a fragment of an immunoglobulin heavy chain or a full length immunoglobulin heavy chain, (ii) a fragment of an immunoglobulin light chain or a full length immunoglobulin light chain, or (iii) a fragment of an immunoglobulin heavy chain or a full length immunoglobulin heavy chain and a fragment of an immunoglobulin light chain or a full length immunoglobulin light chain. 
     
     
         9 . A host cell transfected with an isolated nucleic acid molecule according to  claim 1 . 
     
     
         10 . A host cell transfected with a vector according to  claim 8 . 
     
     
         11 . A composition comprising a pharmaceutically acceptable carrier and an anti-LPA agent selected from the group consisting of:
 a. an isolated anti-LPA antibody which comprises two immunoglobulin heavy chains and two immunoglobulin light chains, wherein one or both of the immunoglobulin heavy chains comprises a variable domain having an amino acid sequence selected from the group consisting of SEQ ID NOs: 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188 and 189, and wherein said isolated anti-LPA antibody is optionally a humanized anti-LPA antibody;   b. an isolated anti-LPA antibody which comprises two immunoglobulin heavy chains and two immunoglobulin light chains, wherein one or both of the immunoglobulin light chains comprises a variable domain having an amino acid sequence selected from the group consisting of SEQ ID NOs: 162, 163, 164, 165, 166, 167, 168 and 169, and wherein said isolated anti-LPA antibody is optionally a humanized anti-LPA antibody;   c. an isolated anti-LPA antibody molecule which comprises two immunoglobulin heavy chains and two immunoglobulin light chains, wherein each immunoglobulin heavy chain comprises a variable domain having an amino acid sequence independently selected from the group consisting of SEQ ID NOs: 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188 and 189, and each immunoglobulin light chain comprises a variable domain having an amino acid sequence independently selected from the group consisting of SEQ ID NOs: 162, 163, 164, 165, 166, 167, 168 and 169, optionally wherein both immunoglobulin heavy chains comprise a variable domain having the same amino acid sequence selected from the group consisting of SEQ ID NOs: 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188 and 189, optionally wherein both immunoglobulin light chains comprise a variable domain having the same amino acid sequence selected from the group consisting of SEQ ID NOs: 162, 163, 164, 165, 166, 167, 168 and 169, and wherein said isolated anti-LPA antibody is optionally a humanized anti-LPA antibody;   d. an anti-LPA agent, which agent is reactive against LPA under physiological conditions and comprises a peptide amino acid sequence selected from the group consisting of SEQ ID NOs: 162, 163, 164, 165, 166, 167, 168, 169, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188 and 189, and   e. an anti-LPA agent that comprises an anti-LPA antibody which comprises two immunoglobulin heavy chains and two immunoglobulin light chains, wherein each immunoglobulin heavy chain comprises the same variable domain amino acid sequence selected from the group consisting of SEQ ID NOs: 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188 and 189, and each immunoglobulin light chain comprises the same variable domain amino acid sequence selected from the group consisting of 162, 163, 164, 165, 166, 167, 168 and 169;   optionally wherein said composition is packaged in a container, and optionally further comprising instructions for use of the composition.   
     
     
         12 . A method selected from the group consisting of:
 a. administering to a subject, optionally a human subject in need of such administration, an agent selected from the group consisting of:   (i) an anti-LPA agent which agent specifically binds LPA under physiological conditions and comprises a peptide amino acid sequence selected from the group consisting of SEQ ID NOs: 162, 163, 164, 165, 166, 167, 168, 169, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188 and 189;   (ii) an isolated polypeptide which specifically binds LPA in a physiological context and comprises an amino acid sequence that has a sequence identity of at least 65 percent, optionally at least 75 percent, at least 80 percent, at least 85 percent, at least 90 percent or at least 95 percent with a peptide amino acid sequence selected from the group consisting of SEQ ID NO: 162, 163, 164, 165, 166, 167, 168, 169, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188 and 189;   (iii) an isolated antibody molecule which specifically binds LPA in a physiological context, comprising:
 A. two immunoglobulin heavy chains, wherein each immunoglobulin heavy chain comprises a variable domain having an amino acid sequence selected from the group consisting of SEQ ID NOs: 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188 and 189; 
 B. two immunoglobulin light chains, wherein each immunoglobulin light chain comprises a variable domain having an amino acid sequence selected from the group consisting of SEQ ID NOs: 162, 163, 164, 165, 166, 167, 168 and 169; 
   (iv) a multivalent binding molecule that comprises at least first and second ligand binding elements, wherein the first ligand binding element specifically binds LPA and comprises a peptide amino acid sequence selected from the group consisting of SEQ ID NO: 162, 163, 164, 165, 166, 167, 168, 169, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188 and 189, wherein the second ligand binding element optionally also specifically binds LPA.   (v) an isolated anti-LPA antibody comprising a heavy chain which comprises a variable domain having an amino acid sequence selected from the group consisting of SEQ ID NOs: 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188 and 189;   (vi) an isolated anti-LPA antibody comprising a light chain which comprises a variable domain having an amino acid sequence selected from the group consisting of SEQ ID NOs: 162, 163, 164, 165, 166, 167, 168 and 169;   (vii) an isolated anti-LPA antibody, wherein each immunoglobulin heavy chain comprises a variable domain having an amino acid sequence selected from the group consisting of SEQ ID NOs: 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188 and 189, and each immunoglobulin light chain comprises a variable domain having an amino acid sequence selected from the group consisting of SEQ ID NOs: 162, 163, 164, 165, 166, 167, 168 and 169; and   (viii) a humanized anti-LPA antibody molecule which comprises two immunoglobulin heavy chains and two immunoglobulin light chains, wherein each immunoglobulin heavy chain comprises a variable domain having an amino acid sequence consisting of SEQ ID NO: 172 and each immunoglobulin light chain comprises a variable domain having an amino acid sequence consisting of SEQ ID NO: 162;   in an amount sufficient to have a desired effect, wherein the method consists of administering said agent to said subject systemically, parenterally, intravenously, intrathecally, epidurally, intramuscularly, subcutaneously, transdermally, intradermally, transmucosally, intraocularly, periocularly, mucosally, topically or by inhalation, wherein said desired effect is selected from the group consisting of decreasing the effective concentration of LPA in one or more bodily fluids or tissues and treating or preventing a disease or disorder correlated with aberrant levels of LPA, optionally elevated levels, of LPA;   b. treating or preventing a disease or disorder correlated with elevated levels of LPA, comprising administering to a subject, optionally a human subject in need of such treatment an agent selected from the group consisting of:   (i) an anti-LPA agent which agent specifically binds LPA under physiological conditions and comprises a peptide amino acid sequence selected from the group consisting of SEQ ID NOs: 162, 163, 164, 165, 166, 167, 168, 169, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188 and 189;   (ii) an isolated polypeptide which specifically binds LPA in a physiological context and comprises an amino acid sequence that has a sequence identity of at least 65 percent, optionally at least 75 percent, at least 80 percent, at least 85 percent, at least 90 percent or at least 95 percent with a peptide amino acid sequence selected from the group consisting of SEQ ID NO: 162, 163, 164, 165, 166, 167, 168, 169, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188 and 189;   (iii) an isolated antibody molecule which specifically binds LPA in a physiological context, comprising:
 A. two immunoglobulin heavy chains, wherein each immunoglobulin heavy chain comprises a variable domain having an amino acid sequence selected from the group consisting of SEQ ID NOs: 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188 and 189; 
 B. two immunoglobulin light chains, wherein each immunoglobulin light chain comprises a variable domain having an amino acid sequence selected from the group consisting of SEQ ID NOs: 162, 163, 164, 165, 166, 167, 168 and 169; 
   (iv) a multivalent binding molecule that comprises at least first and second ligand binding elements, wherein the first ligand binding element specifically binds LPA and comprises a peptide amino acid sequence selected from the group consisting of SEQ ID NO: 162, 163, 164, 165, 166, 167, 168, 169, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188 and 189, wherein the second ligand binding element optionally also specifically binds LPA.   (v) an isolated anti-LPA antibody comprising a heavy chain which comprises a variable domain having an amino acid sequence selected from the group consisting of SEQ ID NOs: 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188 and 189;   (vi) an isolated anti-LPA antibody comprising a light chain which comprises a variable domain having an amino acid sequence selected from the group consisting of SEQ ID NOs: 162, 163, 164, 165, 166, 167, 168 and 169; and   (vii) an isolated anti-LPA antibody, wherein each immunoglobulin heavy chain comprises a variable domain having an amino acid sequence selected from the group consisting of SEQ ID NOs: 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188 and 189, and each immunoglobulin light chain comprises a variable domain having an amino acid sequence selected from the group consisting of SEQ ID NOs: 162, 163, 164, 165, 166, 167, 168 and 169; and   (viii) a humanized anti-LPA antibody molecule which comprises two immunoglobulin heavy chains and two immunoglobulin light chains, wherein each immunoglobulin heavy chain comprises a variable domain having an amino acid sequence consisting of SEQ ID NO: 172 and each immunoglobulin light chain comprises a variable domain having an amino acid sequence consisting of SEQ ID NO: 162; in an amount effective to reduce in vivo the effective concentration of LPA, thereby effecting treatment or prevention of the disease or disorder,   optionally wherein the disease or disorder is selected from the group consisting of cancer, an inflammatory disorder, a cerebrovascular disease, a cardiovascular disease, an ocular disorder, a disease and disorder associated with excessive fibrogenesis, a disease or disorder associated with metastasis, a disease or disorder associated with tumor growth, and a disease or disorder associated with pathologic angiogenesis, and optionally wherein the anti-LPA agent, isolated polypeptide, isolated antibody or multivalent binding molecule is administered in combination with another therapeutic agent to effect treatment or prevention of the disease or disorder;   c. decreasing the effective concentration of LPA in at least one bodily fluid or tissue of a subject, optionally a human subject, comprising administering to a subject, optionally a human subject in need of such treatment, an agent selected from the group consisting of:   (i) an anti-LPA agent which specifically binds LPA under physiological conditions and comprises a peptide amino acid sequence selected from the group consisting of SEQ ID NOs: 162, 163, 164, 165, 166, 167, 168, 169, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188 and 189;   (ii) an isolated polypeptide which specifically binds LPA in a physiological context and comprises an amino acid sequence that has a sequence identity of at least 65 percent, optionally at least 75 percent, at least 80 percent, at least 85 percent, at least 90 percent or at least 95 percent with a peptide amino acid sequence selected from the group consisting of SEQ ID NO: 162, 163, 164, 165, 166, 167, 168, 169, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188 and 189;   (iii) an isolated antibody molecule which specifically binds LPA in a physiological context, comprising:   A. two immunoglobulin heavy chains, wherein each immunoglobulin heavy chain comprises a variable domain having an amino acid sequence selected from the group consisting of SEQ ID NOs: 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188 and 189;   B. two immunoglobulin light chains, wherein each immunoglobulin light chain comprises a variable domain having an amino acid sequence selected from the group consisting of SEQ ID NOs: 162, 163, 164, 165, 166, 167, 168 and 169;   (iv) a multivalent binding molecule that comprises at least first and second ligand binding elements, wherein the first ligand binding element specifically binds LPA and comprises a peptide amino acid sequence selected from the group consisting of SEQ ID NO: 162, 163, 164, 165, 166, 167, 168, 169, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188 and 189, wherein the second ligand binding element optionally also specifically binds LPA.   (v) an isolated anti-LPA antibody comprising a heavy chain which comprises a variable domain having an amino acid sequence selected from the group consisting of SEQ ID NOs: 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188 and 189;   (vi) an isolated anti-LPA antibody comprising a light chain which comprises a variable domain having an amino acid sequence selected from the group consisting of SEQ ID NOs: 162, 163, 164, 165, 166, 167, 168 and 169; and   (vii) an isolated anti-LPA antibody, wherein each immunoglobulin heavy chain comprises a variable domain having an amino acid sequence selected from the group consisting of SEQ ID NOs: 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188 and 189, and each immunoglobulin light chain comprises a variable domain having an amino acid sequence selected from the group consisting of SEQ ID NOs: 162, 163, 164, 165, 166, 167, 168 and 169; and   (viii) a humanized anti-LPA antibody molecule which comprises two immunoglobulin heavy chains and two immunoglobulin light chains, wherein each immunoglobulin heavy chain comprises a variable domain having an amino acid sequence consisting of SEQ ID NO: 172 and each immunoglobulin light chain comprises a variable domain having an amino acid sequence consisting of SEQ ID NO: 162;   in an amount effective to reduce the effective concentration of LPA in at least one bodily fluid or tissue of the subject; and   d. A method for detecting LPA or an LPA metabolite that comprises a native LPA epitope comprising exposing a sample suspected of containing LPA or an LPA metabolite that comprises a native LPA epitope to a compound which specifically binds a native LPA epitope, wherein said compound is selected from the group consisting of:   (i) an anti-LPA agent which agent specifically binds LPA under physiological conditions and comprises a peptide amino acid sequence selected from the group consisting of SEQ ID NOs: 162, 163, 164, 165, 166, 167, 168, 169, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188 and 189;   (ii) an isolated polypeptide which specifically binds LPA in a physiological context and comprises an amino acid sequence that has a sequence identity of at least 65 percent, optionally at least 75 percent, at least 80 percent, at least 85 percent, at least 90 percent or at least 95 percent with a peptide amino acid sequence selected from the group consisting of SEQ ID NO: 162, 163, 164, 165, 166, 167, 168, 169, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188 and 189;   (iii) an isolated antibody molecule which specifically binds LPA in a physiological context, comprising:
 A. two immunoglobulin heavy chains, wherein each immunoglobulin heavy chain comprises a variable domain having an amino acid sequence selected from the group consisting of SEQ ID NOs: 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188 and 189; 
 B. two immunoglobulin light chains, wherein each immunoglobulin light chain comprises a variable domain having an amino acid sequence selected from the group consisting of SEQ ID NOs: 162, 163, 164, 165, 166, 167, 168 and 169; 
   (iv) a multivalent binding molecule that comprises at least first and second ligand binding elements, wherein the first ligand binding element specifically binds LPA and comprises a peptide amino acid sequence selected from the group consisting of SEQ ID NOs: 162, 163, 164, 165, 166, 167, 168, 169, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188 and 189; wherein the second ligand binding element is optionally also specifically binds LPA.   (v) an isolated anti-LPA antibody comprising a heavy chain which comprises a variable domain having an amino acid sequence selected from the group consisting of SEQ ID NOs: 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188 and 189;   (vi) an isolated anti-LPA antibody comprising a light chain which comprises a variable domain having an amino acid sequence selected from the group consisting of SEQ ID NOs: 162, 163, 164, 165, 166, 167, 168 and 169; and   (vii) an isolated anti-LPA antibody, wherein each immunoglobulin heavy chain comprises a variable domain having an amino acid sequence selected from the group consisting of SEQ ID NOs: 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188 and 189, and each immunoglobulin light chain comprises a variable domain having an amino acid sequence selected from the group consisting of SEQ ID NO: 162, 163, 164, 165, 166, 167, 168 and 169;   
       and determining binding of the compound which specifically binds LPA to the sample, optionally wherein detecting binding results from exposing a sample known or suspected to contain the LPA or LPA metabolite with the compound which specifically binds LPA, under conditions that allow the compound which specifically binds LPA to bind to the LPA or LPA metabolite, if present in the sample, wherein the sample is optionally a tissue or liquid sample, optionally selected from the group consisting of whole blood, plasma, serum, urine, semen, bile, aqueous humor, vitreous humor, mucus, and sputum; wherein the compound which specifically binds LPA or LPA metabolite is optionally selected from the group consisting of a monoclonal antibody, an antibody fragment, an antibody variant, and an antibody derivative; wherein the compound which specifically binds LPA or LPA metabolite is optionally attached to a solid support; and wherein the method is optionally an ELISA assay.