US2014141011A1PendingUtilityA1

Engineered anti-tslp antibody

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Assignee: PRESTA LEONARD GPriority: Dec 14, 2006Filed: Oct 8, 2013Published: May 22, 2014
Est. expiryDec 14, 2026(~0.4 yrs left)· nominal 20-yr term from priority
Inventors:Leonard G. PrestaRene De Waal Malefyt
A61P 37/06A61P 37/08A61P 37/00A61P 29/00A61P 27/02C07K 2317/76A61P 17/00A61P 17/04A61P 11/06C07K 2317/565C07K 2317/73C07K 2317/92C07K 2317/567C07K 16/24C07K 16/244C07K 2317/56C07K 2317/52C07K 2317/24A61K 2039/505A61K 39/395A61P 11/02C12N 15/11
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Claims

Abstract

The invention relates to binding compounds that specifically bind to human TSLP, as well as uses thereof, e.g., in the treatment of inflammatory disorders.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A binding compound that specifically binds human and cyno TSLP, comprising:
 at least one antibody heavy chain variable region, or a TSLP-binding fragment thereof, said heavy chain variable region comprising at least one CDR sequence selected from the group consisting of SEQ ID NOs: 1, 2 and 3; or   at least one antibody light chain variable region, or a TSLP-binding fragment thereof, said light chain variable region comprising at least one CDR sequence selected from the group consisting of SEQ ID NOs: 4, 5 and 6.   
     
     
         2 . The binding compound of  claim 1 , wherein the binding compound comprises:
 at least one antibody heavy chain variable region, or a TSLP-binding fragment thereof, said heavy chain variable region comprising at least one CDR sequence selected from the group consisting of SEQ ID NOs: 1, 2 and 3; and   at least one antibody light chain variable region, or a TSLP-binding fragment thereof, said light chain variable region comprising at least one CDR sequence selected from the group consisting of SEQ ID NOs: 4, 5 and 6.   
     
     
         3 . The binding compound of  claim 2 , wherein:
 the antibody heavy chain variable region, or TSLP-binding fragment thereof, comprises at least two CDR sequences selected from the group consisting of SEQ ID NOs: 1, 2 an 3; and   the antibody light chain variable region, or TSLP-binding fragment thereof, comprises at least two CDR sequences selected from the group consisting of SEQ ID NOs: 4, 5 and 6.   
     
     
         4 . The binding compound of  claim 2 , wherein:
 the antibody heavy chain variable region, or TSLP-binding fragment thereof, has the three CDR sequences set forth in SEQ ID NOs: 1, 2 and 3; and   the antibody light chain variable region, or TSLP-binding fragment thereof, has the three CDR sequences set forth in SEQ ID NOs: 4, 5 and 6.   
     
     
         5 . A binding compound that specifically binds human and cyno TSLP, comprising:
 at least one antibody heavy chain variable region, or a TSLP-binding fragment thereof, said heavy chain variable region comprising: the CDR-H1 of SEQ ID NO. 1, or a variant thereof; the CDR-H2 of SEQ ID NO. 2, or a variant thereof; and the CDR-H3 of SEQ ID NO. 3, or a variant thereof; or   at least one antibody light chain variable region, or a TSLP-binding fragment thereof, said light chain variable region comprising: the CDR-L1 of SEQ ID NO. 4, or a variant thereof; the CDR-L2 of SEQ ID NO. 5, or a variant thereof; and the CDR-L3 of SEQ ID NO. 6, or a variant thereof.   
     
     
         6 . The binding compound of  claim 5 , wherein said binding compound comprises:
 at least one antibody heavy chain variable region, or a TSLP-binding fragment thereof, said heavy chain variable region comprising: the CDR-H1 of SEQ ID NO. 1, or a variant thereof; the CDR-H2 of SEQ ID NO. 2, or a variant thereof; and the CDR-H3 of SEQ ID NO. 3, or a variant thereof; and   at least one antibody light chain variable region, or a TSLP-binding fragment thereof, said light chain variable region comprising: the CDR-L1 of SEQ ID NO. 4, or a variant thereof; the CDR-L2 of SEQ ID NO. 5, or a variant thereof; and the CDR-L3 of SEQ ID NO. 6, or a variant thereof.   
     
     
         7 . A binding compound that specifically binds human and cyno TSLP, comprising:
 a heavy chain variable region comprising residues 1-116 of SEQ ID NO: 10 or a variant thereof; and   a light chain variable region comprising residues 1-108 of SEQ ID NO: 12, or a variant thereof,   wherein the variant comprises up to 20 conservatively modified amino acid residues.   
     
     
         8 . The binding compound of  claim 7 , comprising:
 a heavy chain variable region comprising residues 1-116 of SEQ ID NO: 10; and   a light chain variable region comprising residues 1-108 of SEQ ID NO: 12.   
     
     
         9 . A binding compound that specifically binds human and cyno TSLP, comprising:
 a heavy chain variable region having at least 90% homology to residues 1-116 of SEQ ID NO: 10; and   a light chain variable region having at least 90% homology to residues 1-108 of SEQ ID NO: 12.   
     
     
         10 . An isolated nucleic acid encoding at least one of the heavy chain variable region or light chain variable region of the binding compound of  claim 1 . 
     
     
         11 . An expression vector comprising the nucleic acid of  claim 10  operably linked to control sequences that are recognized by a host cell when the host cell is transfected with the vector. 
     
     
         12 . A host cell comprising the expression vector of  claim 11 . 
     
     
         13 . A method of producing a polypeptide comprising:
 culturing the host cell of  claim 8  in culture medium under conditions wherein the nucleic acid sequence is expressed, thereby producing polypeptides comprising the light and heavy chain variable regions; and   recovering the polypeptides from the host cell or culture medium.   
     
     
         14 . The binding compound of  claim 1 , further comprising:
 a human heavy chain constant region or a variant thereof, wherein the variant comprises up to 20 conservatively modified amino acid substitutions; or   a human light chain constant region or a variant thereof, wherein the variant comprises up to 20 conservatively modified amino acid substitutions.   
     
     
         15 . The binding compound of  claim 14 , wherein the human heavy chain constant region comprises a γ4 or γ1 human heavy chain constant region or a variant thereof, wherein the variant comprises up to 20 conservatively modified amino acid substitutions. 
     
     
         16 . The binding compound of  claim 2 , further comprising:
 a human heavy chain constant region or a variant thereof, wherein the variant comprises up to 20 conservatively modified amino acid substitutions; or   a human light chain constant region or a variant thereof, wherein the variant comprises up to 20 conservatively modified amino acid substitutions.   
     
     
         17 . The binding compound of  claim 16 , wherein the human heavy chain constant region comprises a γ4 or γ1 human heavy chain constant region or a variant thereof, wherein the variant comprises up to 20 conservatively modified amino acid substitutions. 
     
     
         18 . The binding compound of  claim 1 , wherein the binding compound is a humanized antibody or a TSLP-binding fragment thereof. 
     
     
         19 . The binding compound of  claim 1 , wherein the binding compound is a TSLP-binding antibody fragment selected from the group consisting of Fab, Fab′, Fab′-SH, Fv, scFv, F(ab′) 2 , and a diabody. 
     
     
         20 . A method of suppressing an immune response in a human subject comprising administering to a subject in need thereof the binding compound of  claim 1 , or a TSLP-binding fragment thereof, in an amount effective to block the biological activity of TSLP. 
     
     
         21 . The method of  claim 20 , wherein the immune response is an inflammatory response. 
     
     
         22 . The method of  claim 20 , wherein the subject has a disorder selected from the group consisting of allergic rhinosinusitis, allergic asthma, allergic conjunctivitis, or atopic dermatitis. 
     
     
         23 . The method of  claim 20 , wherein the subject has asthma. 
     
     
         24 . A composition comprising the binding compound of  claim 1  in combination with a pharmaceutically acceptable carrier or diluent. 
     
     
         25 . An antibody that specifically binds to the epitope on human TSLP that is bound by the antibody produced by the hybridoma deposited as PTA-7951, wherein the antibody that specifically binds to the epitope on human TSLP is not the antibody produced by the hybridoma deposited as PTA-7951. 
     
     
         26 . An antibody that competitively inhibits binding by the antibody produced by the hybridoma deposited as PTA-7951 to human TSLP, wherein the antibody that competitively inhibits binding is not the antibody produced by the hybridoma deposited as PTA-7951. 
     
     
         27 . The binding compound of  claim 1 , wherein the binding compound blocks TSLP-mediated activity. 
     
     
         28 . The binding compound of  claim 1 , wherein said binding compound is able to block the binding of TSLP to TSLPR in a cross-blocking assay. 
     
     
         29 . The use of the binding compound of  claim 1 , or a TSLP-binding fragment thereof, for the preparation of a medicament to suppress an immune response. 
     
     
         30 . The use of the binding compound of  claim 1 , or a TSLP-binding fragment thereof, for the preparation of a medicament to treat inflammation. 
     
     
         31 . The use of the binding compound of  claim 1 , or a TSLP-binding fragment thereof, for the preparation of a medicament to treat allergic inflammation. 
     
     
         32 . The use of the binding compound of  claim 1 , or a TSLP-binding fragment thereof, for the preparation of a medicament to treat allergic rhinosinusitis, allergic asthma, allergic conjunctivitis, or atopic dermatitis. 
     
     
         33 . The use of the binding compound of  claim 1 , or a TSLP-binding fragment thereof, for the preparation of a medicament to treat asthma.

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