US2011300157A1PendingUtilityA1

Metalloproteinase 9 and metalloproteinase 2 binding proteins

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Assignee: DEVY LAETITIAPriority: Mar 3, 2008Filed: Aug 1, 2011Published: Dec 8, 2011
Est. expiryMar 3, 2028(~1.6 yrs left)· nominal 20-yr term from priority
Inventors:Laetitia Devy
A61P 35/00A61P 35/04A61P 43/00A61P 9/04A61P 27/02A61P 25/00A61P 29/00A61K 49/0002C07K 2317/92C07K 16/40C07K 2317/76A61K 2039/505A61K 47/6871A61K 47/6817A61P 11/06A61P 11/00A61P 1/00C07K 2317/56A61K 47/6809C07K 2317/21C07K 2317/55A61K 47/6803
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Claims

Abstract

Proteins that bind to matrix metalloproteinase 9 and to matrix metalloproteinase 2 and methods of using such proteins are described.

Claims

exact text as granted — not AI-modified
1 .- 51 . (canceled) 
     
     
         52 . An isolated protein that binds to Matrix Metalloproteinase-9 (MMP-9) and Matrix Metalloproteinase-2 (MMP-2), wherein the protein comprises an immunoglobulin heavy chain (HC) variable domain sequence and an immunoglobulin light chain (LC) variable domain sequence. 
     
     
         53 . The protein of  claim 52 , wherein the protein competes for binding with an antibody selected from the group consisting of 539-M0237-D02, 539A-M0276-F11, 539A-M0256-D11, 539A-M0274-G08, 539A-M0275-D03, 539A-M0307-F04, 539A-M0256-G09, 539A-M0256-A04, 539A-M0256-D03, 539A-M0265-A07, 539A-M0263-F01, 539A-M0263-F05, 539A-M0256-C09, 539A-M0256-B03, 539A-M0265-A04, 539A-M0256-A07, 539A-M0264-A09, 539A-M0265-C07, 539A-M0266-E02, 539A-M0256-E10, 539A-M0256-C07, 539A-M0266-D03, and 539A-M0256-E03. 
     
     
         54 . The protein of  claim 52 , wherein the protein binds the same epitope as an antibody selected from the group consisting of 539-M0237-D02, 539A-M0276-F11, 539A-M0256-D11, 539A-M0274-G08, 539A-M0275-D03, 539A-M0307-F04, 539A-M0256-G09, 539A-M0256-A04, 539A-M0256-D03, 539A-M0265-A07, 539A-M0263-F01, 539A-M0263-F05, 539A-M0256-C09, 539A-M0256-B03, 539A-M0265-A04, 539A-M0256-A07, 539A-M0264-A09, 539A-M0265-C07, 539A-M0266-E02, 539A-M0256-E10, 539A-M0256-C07, 539A-M0266-D03, and 539A-M0256-E03. 
     
     
         55 . The protein of  claim 52 , wherein the protein comprises a heavy chain variable domain comprising a HC-CDR1, a HC-CDR1, and a HC-CDR3, and a LC-CDR1, a LC-CDR2, and a LC-CDR3 of an antibody selected from the group consisting of 539-M0237-D02, 539A-M0276-F11, 539A-M0256-D11, 539A-M0274-G08, 539A-M0275-D03, 539A-M0307-F04, 539A-M0256-G09, 539A-M0256-A04, 539A-M0256-D03, 539A-M0265-A07, 539A-M0263-F01, 539A-M0263-F05, 539A-M0256-C09, 539A-M0256-B03, 539A-M0265-A04, 539A-M0256-A07, 539A-M0264-A09, 539A-M0265-C07, 539A-M0266-E02, 539A-M0256-E10, 539A-M0256-C07, 539A-M0266-D03, and 539A-M0256-E03. 
     
     
         56 . The protein of  claim 52 , wherein the MMP-9 is human MMP-9 and the MMP-2 is human MMP-2. 
     
     
         57 . The protein of  claim 52 , wherein the protein is a Fab fragment or an IgG. 
     
     
         58 . The protein of  claim 52 , wherein the protein is a human or humanized antibody, a primate or primatized antibody or an antibody that is non-immunogenic in a human. 
     
     
         59 . The protein of  claim 52 , wherein the protein inhibits the catalytic activity of MMP-9 and/or MMP-2. 
     
     
         60 . The protein of  claim 52 , wherein the protein is conjugated to a drug. 
     
     
         61 . The protein of  claim 60 , wherein the drug is a cytotoxic or cytostatic agent. 
     
     
         62 . The protein of  claim 52 , wherein the protein comprises one or more of the following characteristics:
 (a) a human CDR or human framework region,   (b) the HC immunoglobulin variable domain comprises CDR sequences CDR1, CDR2, and CDR3 of an antibody selected from the group consisting of 539-M0237-D02, 539A-M0276-F11, 539A-M0256-D11, 539A-M0274-G08, 539A-M0275-D03, 539A-M0307-F04, 539A-M0256-G09, 539A-M0256-A04, 539A-M0256-D03, 539A-M0265-A07, 539A-M0263-F01, 539A-M0263-F05, 539A-M0256-C09, 539A-M0256-B03, 539A-M0265-A04, 539A-M0256-A07, 539A-M0264-A09, 539A-M0265-C07, 539A-M0266-E02, 539A-M0256-E10, 539A-M0256-C07, 539A-M0266-D03, and 539A-M0256-E03,   (c) the LC immunoglobulin variable domain sequence comprises CDR sequences CDR1, CDR2, and CDR3 of an antibody selected from the group consisting of 539-M0237-D02, 539A-M0276-F11, 539A-M0256-D11, 539A-M0274-G08, 539A-M0275-D03, 539A-M0307-F04, 539A-M0256-G09, 539A-M0256-A04, 539A-M0256-D03, 539A-M0265-A07, 539A-M0263-F01, 539A-M0263-F05, 539A-M0256-C09, 539A-M0256-B03, 539A-M0265-A04, 539A-M0256-A07, 539A-M0264-A09, 539A-M0265-C07, 539A-M0266-E02, 539A-M0256-E10, 539A-M0256-C07, 539A-M0266-D03, and 539A-M0256-E03,   (d) the LC immunoglobulin variable domain sequence is at least 90% identical to a LC variable domain sequence of an antibody selected from the group consisting of 539-M0237-D02, 539A-M0276-F11, 539A-M0256-D11, 539A-M0274-G08, 539A-M0275-D03, 539A-M0307-F04, 539A-M0256-G09, 539A-M0256-A04, 539A-M0256-D03, 539A-M0265-A07, 539A-M0263-F01, 539A-M0263-F05, 539A-M0256-C09, 539A-M0256-B03, 539A-M0265-A04, 539A-M0256-A07, 539A-M0264-A09, 539A-M0265-C07, 539A-M0266-E02, 539A-M0256-E10, 539A-M0256-C07, 539A-M0266-D03, and 539A-M0256-E03, or   (e) the HC immunoglobulin variable domain sequence is at least 90% identical to a HC variable domain sequence of an antibody selected from the group consisting of 539-M0237-D02, 539A-M0276-F11, 539A-M0256-D11, 539A-M0274-G08, 539A-M0275-D03, 539A-M0307-F04, 539A-M0256-G09, 539A-M0256-A04, 539A-M0256-D03, 539A-M0265-A07, 539A-M0263-F01, 539A-M0263-F05, 539A-M0256-C09, 539A-M0256-B03, 539A-M0265-A04, 539A-M0256-A07, 539A-M0264-A09, 539A-M0265-C07, 539A-M0266-E02, 539A-M0256-E10, 539A-M0256-C07, 539A-M0266-D03, and 539A-M0256-E03.   
     
     
         63 . The protein of  claim 52 , wherein the protein comprises an affinity for MMP-9 and/or MMP-2 characterized by a K D  of less than 100 nM. 
     
     
         64 . The protein of  claim 52 , wherein the protein comprises an affinity for MMP-9 and/or MMP-2 characterized by a K D  of less than 10 nM. 
     
     
         65 . The protein of  claim 52 , wherein the protein has a Ki for MMP-9 and/or MMP-2 of less than 1 nM. 
     
     
         66 . The protein of  claim 59 , wherein the protein comprises a HC CDR1, CDR2, and CDR3 sequence of an antibody selected from the group consisting of 539-M0237-D02, 539A-M0276-F11, 539A-M0256-D11, 539A-M0274-G08, 539A-M0275-D03, 539A-M0307-F04, 539A-M0256-G09, 539A-M0256-A04, 539A-M0256-D03, 539A-M0265-A07, 539A-M0263-F01, 539A-M0263-F05, 539A-M0256-C09, 539A-M0256-B03, 539A-M0265-A04, 539A-M0256-A07, 539A-M0264-A09, 539A-M0265-C07, 539A-M0266-E02, 539A-M0256-E10, 539A-M0256-C07, 539A-M0266-D03, and 539A-M0256-E03. 
     
     
         67 . The protein of  claim 59 , wherein the protein comprises an LC CDR1, CDR2, and CDR3 sequence of an antibody selected from the group consisting of 539-M0237-D02, 539A-M0276-F11, 539A-M0256-D11, 539A-M0274-G08, 539A-M0275-D03, 539A-M0307-F04, 539A-M0256-G09, 539A-M0256-A04, 539A-M0256-D03, 539A-M0265-A07, 539A-M0263-F01, 539A-M0263-F05, 539A-M0256-C09, 539A-M0256-B03, 539A-M0265-A04, 539A-M0256-A07, 539A-M0264-A09, 539A-M0265-C07, 539A-M0266-E02, 539A-M0256-E10, 539A-M0256-C07, 539A-M0266-D03, and 539A-M0256-E03. 
     
     
         68 . A pharmaceutical composition comprising an isolated protein of  claim 52  and a pharmaceutically acceptable carrier.

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