US2021355206A1PendingUtilityA1

Compositions and methods for antibodies targeting epo

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Assignee: NOVARTIS AGPriority: Dec 5, 2012Filed: Jul 22, 2021Published: Nov 18, 2021
Est. expiryDec 5, 2032(~6.3 yrs left)· nominal 20-yr term from priority
Inventors:Joy GhoshMichael RoguskaMark RutzIgor SplawskiKathrin Ulrike Tissot-Daguette
C07K 2317/21A61K 2039/505C07K 2317/55C07K 16/26C07K 2317/73C07K 2317/34A61K 45/06A61K 2039/507C07K 2317/92A61P 3/10A61K 39/3955A61P 27/02C07K 16/22A61K 39/395A61P 43/00A61P 27/00A61P 9/10C07K 2317/76
74
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Claims

Abstract

The present invention relates to compositions and methods for the inhibition of EPO. The invention provides antibodies and antigen binding fragments thereof that bind to EPO and are able to inhibit EPO-dependent cell proliferation and/or EPO-dependent cell signaling.

Claims

exact text as granted — not AI-modified
1 . An isolated antibody, or antigen binding fragment thereof, that binds Epo with a K D  less than or equal to 50 pM. 
     
     
         2 . The isolated antibody or antigen binding fragment of  claim 1  that binds the Helix D domain of Epo. 
     
     
         3 . The isolated antibody or antigen binding fragment of  claim 1  or  claim 2  that further binds the Loop A-B domain of Epo. 
     
     
         4 . The isolated antibody or antigen binding fragment of any of  claim 2  or  claim 3  that further binds the Helix A domain of Epo. 
     
     
         5 . The isolated antibody or antigen binding fragment of any of the preceding claims wherein said antibody binds human Epo. 
     
     
         6 . The isolated antibody, or antigen binding fragment, of  claim 1 , that binds a conformational epitope comprising amino acids within Epo Helix D and Loop A-B. 
     
     
         7 . The antibody, or antigen binding fragment, of  claim 6 , that binds a conformational epitope further comprising amino acids within Epo Helix A. 
     
     
         8 . The isolated antibody, or antigen binding fragment of  claim 1  that binds a conformational epitope comprising amino acids at positions, 44-50, 52, 53, 147, 150, 151, 154, 155, 159, and 162 of SEQ ID NO: 81. 
     
     
         9 . The isolated antibody, or antigen binding fragment, of any of the preceding claims, that binds a conformational epitope comprising amino acids at positions, 9, 13, 44-53, 147, 150, 151, 154, 155, 158, 159, and 162 of SEQ ID NO: 81. 
     
     
         10 . The isolated antibody, or antigen binding fragment, of any of the preceding claims, that binds a conformational epitope comprising amino acids at positions, 23, 43-50, 52, 53, 131, 143, 147, 150, 151, 154, 155, 159, and 162 of SEQ ID NO: 81. 
     
     
         11 . The isolated antibody, or antigen binding fragment, of any of the preceding claims that also binds cynomologous, mouse or rat Epo. 
     
     
         12 . The isolated antibody, or antigen binding fragment, of any of the preceding claims that further inhibits EPO-dependent cell proliferation with an EC 50  less than or equal to 350 pM. 
     
     
         13 . The isolated antibody, or antigen binding fragment, of any of the preceding claims that inhibits EPO-dependent cell proliferation in B-cells expressing the EPO receptor. 
     
     
         14 . An isolated antibody, or antigen binding fragment thereof, that binds the same epitope as an antibody described in Table 1 or competes with an antibody described in Table 1. 
     
     
         15 . An isolated antibody, or antigen binding fragment, of any of the preceding claims that binds EPO, and comprises:
 a) heavy chain variable region HCDR1, HCDR2 and HCDR3 as set forth in SEQ ID NOs: 1, 2, and 3, respectively, and light chain variable region LCDR1, LCDR2, and LCDR3 as set forth in SEQ ID NOs: 4, 5, and 6, respectively;   b) heavy chain variable region HCDR1, HCDR2 and HCDR3 as set forth in SEQ ID NOs: 21, 22, and 23, respectively, and light chain variable region LCDR1, LCDR2, and LCDR3 as set forth in SEQ ID NOs: 24, 25, and 26, respectively;   c) heavy chain variable region HCDR1, HCDR2 and HCDR3 as set forth in SEQ ID NOs: 41, 42, and 43, respectively, and light chain variable region LCDR1, LCDR2, and LCDR3 as set forth in SEQ ID NOs: 44, 45, and 46, respectively; or   d) heavy chain variable region HCDR1, HCDR2 and HCDR3 as set forth in SEQ ID NOs: 61, 62, and 63, respectively, and light chain variable region LCDR1, LCDR2, and LCDR3 as set forth in SEQ ID NOs: 64, 65, and 66, respectively.   
     
     
         16 . The isolated antibody, or antigen binding fragment, of any of the preceding lcaimiclaims comprising heavy and light chain variable regions having amino acid sequences at least 90% identical to SEQ ID NOs: 13 and 14; SEQ ID NOs: 33 and 34; SEQ ID NOs: 53 and 54; or SEQ ID NOs: 73 and 74, respectively. 
     
     
         17 . The isolated antibody, or antigen binding fragment, of any of the preceding claims that binds Epo comprising a heavy chain and a light chain with an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 15 and 16, 35 and 36, 55 and 56, or 75 and 76. 
     
     
         18 . The antibody or antigen binding fragment of any of the preceding claims, wherein said antibody is a human antibody, a chimeric antibody, a monoclonal antibody, a single chain antibody, Fab, Fab′, F(ab′)2, Fv or scFv. 
     
     
         19 . The antibody or antigen binding fragment of any of the preceding claims, wherein said antibody is an IgG isotype. 
     
     
         20 . An isolated nucleic acid molecule comprising a nucleotide sequence encoding the antibody or fragment as claimed in any of the preceding claims. 
     
     
         21 . The nucleic acid molecule of  claim 20 , wherein said nucleic acid comprises a sequence encoding a heavy chain variable domain and said sequence has at least 95% sequence identity to a sequence selected from SEQ ID NOs: 17, 37, 57, and 77. 
     
     
         22 . The nucleic acid molecule of  claim 20  wherein said nucleic acid comprises a sequence encoding a light chain variable domain and said sequence has at least 95% sequence identity to a sequence selected from SEQ ID NO: 18, 38, 58, and 78. 
     
     
         23 . A vector comprising the nucleic acid molecule of any of  claims 20  to  22 . 
     
     
         24 . An isolated host cell comprising the nucleic acid as claimed in any of  claims 20  to  22  or the vector of  claim 23 . 
     
     
         25 . A composition comprising the antibody or antigen binding fragment of any of  claims 1  to  19  and a pharmaceutically acceptable diluent or carrier. 
     
     
         26 . A method of treating retinal vascular disease in a subject comprising administering to said subject, an effective amount of a composition comprising the antibody or antigen binding fragment of any of  claims 1  to  19 . 
     
     
         27 . The method of  claim 26 , wherein the retinal vascular disease in the subject is associated with a disease or condition selected from: diabetic retinopathy, diabetic macular edema, proliferative diabetic retinopathy, non-proliferative diabetic retinopathy, age-related macular degeneration, retinal vein occlusion, multifocal choroiditis, myopic choroidal neovascularization, and retinopathy of prematurity. 
     
     
         28 . A method of treating macular edema in a subject comprising administering to said subject, an effective amount of a composition comprising the antibody or antigen binding fragment of any of  claims 1  to  19 . 
     
     
         29 . A method of treating diabetic retinopathy in a subject comprising administering to said subject, an effective amount of a composition comprising the antibody or antigen binding fragment of any of  claims 1  to  19 . 
     
     
         30 . A method of treating diabetic macular edema in a subject comprising administering to said subject an effective amount of a composition comprising the antibody or antigen binding fragment of any of  claims 1  to  19 . 
     
     
         31 . A method of treating proliferative diabetic retinopathy, comprising contacting EPO with a composition comprising the antibody or antigen binding fragment of any of  claims 1  to  19 . 
     
     
         32 . A method of inhibiting EPO-dependent cell proliferation, comprising contacting EPO with a composition comprising the antibody or antigen binding fragment of any of  claims 1  to  19 . 
     
     
         33 . A method of inhibiting EPO-dependent cell proliferation in a cell expressing an Epo receptor, comprising contacting said cell with a composition comprising the antibody or antigen binding fragment of any of  claims 1  to  19 . 
     
     
         34 . The method of  claim 33  wherein the cell is a B-cell. 
     
     
         35 . A method of inhibiting diabetic macular edema, comprising administering to the eye of a subject a composition comprising the antibody or antigen binding fragment of any of  claims 1  to  19 , wherein administration of said composition decreases retinal vein dilation, decreases vascular leakage and/or increases blood flow in the eye. 
     
     
         36 . A method of inhibiting EPO binding to the EPO receptor on a cell, comprising contacting EPO with a composition comprising the antibody or antigen binding fragment of any of  claims 1  to  19 . 
     
     
         37 . The method of  claim 36  wherein the cell is in a subject.

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