Angiopoietin-like 4 antibodies and methods of use

Abstract

The present invention relates to monoclonal antibodies binding to human angiopoietin-like 4 protein (hereinafter, sometimes referred to as “ANGPTL4”), and pharmaceutical compositions and methods of treatment comprising the same.

1 . An isolated anti-ANGPTL4 antibody or fragment thereof. 
     
     
         2 - 28 . (canceled) 
     
     
         29 . A method of treating an ANGPTL4-disorder comprising administering to a patient afflicted with an ANGPTL4-disorder an effective amount of a pharmaceutical composition comprising an antibody or fragment of  claim 1 . 
     
     
         30 - 33 . (canceled) 
     
     
         34 . A nucleic acid encoding an anti-ANGPTL4 (angiopoietin-like 4) antibody or fragment thereof, wherein said antibody or fragment thereof comprises a CDR1, CDR2, and CDR3 from Table 1. 
     
     
         35 . The nucleic acid of  claim 34 , wherein the anti-ANGPTL4 antibody or fragment thereof comprises:
 (i) a heavy chain variable region CDR1 selected from the group consisting of SEQ ID NO: 10, 35, 55, 75, 95, 115, and 135; CDR2 selected from the group consisting of SEQ ID NO: 11, 36, 56, 76, 96, 116, and 136; CDR3 selected from the group consisting of 12, 37, 57, 77, 97, 117, and 137; a light chain variable region CDR1 selected from the group consisting of SEQ ID NO: 20, 45, 65, 85, 105, 125, and 145; CDR2 selected from the group consisting of SEQ ID NO: 21, 46, 66, 86, 106, 126, and 146; and CDR3 selected from the group consisting of SEQ ID NO: 22, 47, 67, 87, 107, 127, and 147; or   (ii) a heavy chain variable region CDR1 selected from the group consisting of SEQ ID NO: 10, 35, 55, 75, 95, 115, and 135; CDR2 selected from the group consisting of SEQ ID NO: 11, 36, 56, 76, 96, 116, and 136; CDR3 selected from the group consisting of 12, 37, 57, 77, 97, 117, and 137; a light chain variable region CDR1 selected from the group consisting of SEQ ID NO: 20, 45, 65, 85, 105, 125, and 145; CDR2 selected from the group consisting of SEQ ID NO: 21, 46, 66, 86, 106, 126, and 146; and CDR3 selected from the group consisting of SEQ ID NO: 22, 47, 67, 87, 107, 127, and 147.   
     
     
         36 . The nucleic acid of  claim 34 , wherein the anti-ANGPTL4 antibody or fragment thereof comprises a heavy chain variable region comprising HCDR1 of SEQ ID NO: 7, HCDR2 of SEQ ID NO: 8, HCDR3 of SEQ ID NO: 9, and a light chain variable region comprising LCDR1 of SEQ ID NO: 17, LCDR2 of SEQ ID NO: 18, and LCDR3 of SEQ ID NO: 19. 
     
     
         37 . The nucleic acid of  claim 34 , wherein the anti-ANGPTL4 antibody or fragment thereof comprises a heavy chain variable region comprising HCDR1 of SEQ ID NO: 10, HCDR2 of SEQ ID NO: 11, HCDR3 of SEQ ID NO: 12, and a light chain variable region comprising LCDR1 of SEQ ID NO: 20, LCDR2 of SEQ ID NO: 21, and LCDR3 of SEQ ID NO: 22. 
     
     
         38 . The nucleic acid of  claim 34 , wherein the anti-ANGPTL4 antibody or fragment thereof is a monoclonal antibody, humanized antibody, single chain antibody, Fab fragment, Fv fragment, F(ab) 2  fragment, or scFv fragment. 
     
     
         39 . The nucleic acid of  claim 34 , wherein the anti-ANGPTL4 antibody or fragment thereof is an IgG1 or IgG4 isotype antibody or fragment thereof. 
     
     
         40 . The nucleic acid of  claim 34 , wherein the anti-ANGPTL4 antibody or fragment thereof comprises a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 13, and a light chain variable region comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 23. 
     
     
         41 . The nucleic acid of  claim 34 , wherein the anti-ANGPTL4 antibody or fragment thereof comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 13, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 23. 
     
     
         42 . The nucleic acid of  claim 34 , wherein the anti-ANGPTL4 antibody or fragment thereof comprises a heavy chain comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 15, and a light chain comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 25. 
     
     
         43 . The nucleic acid of  claim 34 , wherein the antibody or fragment thereof comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 15, and a light chain comprising the amino acid sequence of SEQ ID NO: 25. 
     
     
         44 . The nucleic acid of  claim 34 , wherein the anti-ANGPTL4 antibody or fragment thereof comprises a heavy chain comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 28, and a light chain comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 25. 
     
     
         45 . The nucleic acid of  claim 34 , wherein the anti-ANGPTL4 antibody or fragment thereof comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 28, and a light chain comprising the amino acid sequence of SEQ ID NO: 25. 
     
     
         46 . The nucleic acid of  claim 34 , wherein the anti-ANGPTL4 antibody or fragment thereof is a bispecific antibody or fragment thereof. 
     
     
         47 . A vector comprising the nucleic acid of  claim 34 . 
     
     
         48 . A host cell comprising the nucleic acid molecule of  claim 34 . 
     
     
         49 . A host cell comprising the vector of  claim 47 . 
     
     
         50 . A method of producing an anti-ANGPTL4 antibody or fragment thereof, comprising culturing the host cell of  claim 48  under conditions suitable for expressing the antibody or fragment thereof. 
     
     
         51 . A method of producing an anti-ANGPTL4 antibody or fragment thereof, comprising culturing the host cell of  claim 49  under conditions suitable for expressing the antibody or fragment thereof.