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 - 90 . (canceled) 
     
     
         91 . 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-I); 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.   
     
     
         92 . The method of  claim 91 , wherein the disorder is selected from the group consisting of 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. 
     
     
         93 . The method of  claim 91 , wherein the MMP is human MMP-1. 
     
     
         94 . The method of  claim 91 , wherein the TIMP-1 is a human TIMP-1. 
     
     
         95 . 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.   
     
     
         96 . The method of  claim 95 , wherein the disorder is selected from the group consisting of 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. 
     
     
         97 . The method of  claim 95 , wherein the MMP is human MMP-1. 
     
     
         98 . The method of  claim 95 , wherein the TIMP-1 is a human TIMP-1.