Human timp-1 antibodies

Abstract

Human antibodies that bind to TIMP-1 can be used as reagents to diagnose and treat disorders in which TIMP-1 is elevated, such as liver fibrosis, alcoholic liver disease, cardiac fibrosis, acute coronary syndrome, lupus nephritis, glomerulosclerotic renal disease, benign prostate hypertrophy, colon cancer, lung cancer, and idiopathic pulmonary fibrosis.

1 . A method of ameliorating symptoms of a disorder in which TIMP-1 is elevated, comprising the step of:
 administering to a patient having the disorder an effective amount of an antibody, wherein the antibody binds to a tissue inhibitor of metalloprotease-1 (TIMP-1); neutralizes a matrix metalloprotease (MMP)-inhibiting activity of the TIMP-1; and comprises:   a VHCDR1 region comprising an amino acid sequence as set forth in SEQ ID NO:356;   a VHCDR2 region comprising an amino acid sequence as set forth in SEQ ID NO:358;   a VHCDR3 region comprising an amino acid sequence as set forth in SEQ ID NO:3;   a VLCDR1 region comprising an amino acid sequence as set forth in SEQ ID NO:363;   a VLCDR2 region comprising an amino acid sequence as set forth in SEQ ID NO:364; and   a VLCDR3 region comprising an amino acid sequence as set forth in SEQ ID NO:365,   wherein the disorder is liver fibrosis.   
     
     
         2 . The method of  claim 1 , wherein the MMP is human MMP-1. 
     
     
         3 . The method of  claim 1 , wherein the TIMP-1 is a human TIMP-1. 
     
     
         4 . A method of ameliorating symptoms of a disorder in which TIMP-1 is elevated, comprising the step of:
 administering to a patient having the disorder an effective amount of a composition comprising   a human purified antibody which (1) binds to a TIMP-1; (2) neutralizes an MMP-inhibiting activity of the TIMP-1; and (3) comprises   a VHCDR1 region comprising an amino acid sequence as set forth in SEQ ID NO:356;   a VHCDR2 region comprising an amino acid sequence as set forth in SEQ ID NO:358;   a VHCDR3 region comprising an amino acid sequence as set forth in SEQ ID NO:3;   a VLCDR1 region comprising an amino acid sequence as set forth in SEQ ID NO:363;   a VLCDR2 region comprising an amino acid sequence as set forth in SEQ ID NO:364; and   a VLCDR3 region comprising an amino acid sequence as set forth in SEQ ID NO:365; and   a pharmaceutically acceptable carrier,   wherein the disorder is liver fibrosis.   
     
     
         5 . The method of  claim 4 , wherein the MMP is human MMP-1. 
     
     
         6 . The method of  claim 4 , wherein the TIMP-1 is a human TIMP-1.