IL303833A

Anti-respiratory syncytial virus antibodies, and methods of their generation and use

Abstract

This record has no abstract on file.

IL303833A, drawing sheet 1
Sheet 1 of 14

Term

No projected expiry on record.

  1. Priority
  2. Filed
  3. Published
  4. Today

22 claims: 8 independent, 14 dependent

  1. 1
    An isolated antibody or an antigen-binding fragment thereor that specifically binds to Respiratory Syncytial Virus (RSV) F protein (F), wherein at least one of the CDRH1, a CDRH2, a CDRH3, a CDRL1, a CDRL2, and CDRL3 amino acid sequence of the antibody or the antigen-binding fragment thereof is at least 70% identical; at least 75% identical; 80% identical; at least 85% identical; at least 90% identical; at least 95% identical; at least 96% identical; at least 97% identical; at least 98% identical; at least 99%; and/or all percentages of identity in between; to at least one the CDRH1, a CDRH2, a CDRH3, a CDRL1, a CDRL2, and/or a CDRL3 amino acid sequences as disclosed in Table 6 of an antibody selected from Antibody Number 124 through Antibody Number 244 as disclosed in Table 6; and wherein said antibody or the antigen-binding fragment thereof also has one or more of the following characteristics:a) the antibody or antigen-binding fragment thereof cross-competes with said antibody ar antigen-binding fragment thereof for binding to RSV-F;b) the antibody or antigen-binding fragment thereof displays better binding affinity for the PreF form of RSV-F relative to the PostF form;c) the antibody or antigen-binding fragment thereof displays a clean or low polyreactivity profile;d) the antibody or antigen-binding fragment thereof displays neutralization activity towoard RSV suptype A and RSV subtype B in vitro;e) the antibody or antigen-binding fragment thereof displays antigenic site specificity for RSV-F at Site 0, Site I, Site II, Site III, Site IV, or Site V;f) the antibody or antigen-binding fragment thereof displays antigenic site specificity for RSV-F Site 0, Site V, or Site III relative to RSV-F Site I, Site II, or Site IV;g) at least a portion of the epitope with which the antibody or antigen-binding fragment thereof interacts comprises the a3 helix and β3/β4 hairpin of PreF;h) the antibody or antigen-binding fragment thereof displays an in vitro neutralization potency (IC50) of between about 0.5 microgram/milliliter (ug/ml) to about 5 ug/ml;between about 0.05 ug/ml to about 0.5 ug/ml;or less than about 0.05 mg/ml;i) the binding affinity and/or epitopic specificity of the antibody or antigen-binding fragment thereof for any one of the RSV-F variants designated as 1, 2, 3, 4, 5, 6, 7, 8, 9, and DG in Figure 7A is reduced or eliminated relative to the binding affinity and/or epitopic specificity of said antibody or antigen-binding fragment thereof for the RSV-F or RSV-F DS-Cavl;j) the antibody or antigen-binding fragment thereof of displays a cross-neutalization potency (IC50) against human metapneumovirus (HMPV);k) the antibody or antigen-binding fragment thereof does not complete with D25, MPE8, palivisumab, motavizumab, or AM-14;or 1) the the antibody or antigen-binding fragment thereof displays at least about 2-fold;at least about 3-fold;at least about 4-fold;at least about 5-fold;at least about 6-fold;at least about 7-fold;at least about 8-fold;at least about 9-fold;at least about 10-fold;at least about 15-fold;at least about 20-fold;at least about 25-fold;at least about 30-fold;at least about 35-fold;at least about 40-fold;at least about 50-fold;at least about 55-fold;at least about 60-fold;at least about 70-fold;at least about 80-fold;at least about 90-fold;at least about 100-fold;greater than about 100-fold;and folds in between any of the foregoing;greater neutralization potency (IC50) than D25 and/or palivizumab.
  2. 4
    The isolated antibody or antigen-binding fragment thereof of any one of claims 1 through 3, wherein the antibody or antigen-binding fragment thereof comprises:a) a heavy chain (HC) amino acid sequence of any one of the antibodies designated Antibody Number 124 through Antibody Number 244 as disclosed in Table 6;and/or b) a light chain (LC) amino acid sequence of any one of the antibodies designated Antibody Number 124 through Antibody Number 244 as disclosed in Table 6.
  3. 5
    The isolated antibody or antigen-binding fragment thereof of any one of claims 1 through 4, wherein the antibody is selected from the group consisting antibodies that are at least 70% identical;at least 75% identical;80% identical;at least 85% identical;at least 90% identical;at least 95% identical;at least 96% identical;at least 97% identical;at least 98% identical;at least 99%;and/or all percentages of identity in between;to any one of the antibodies designated as Antibody Number 124 through Antibody Number 244 as disclosed in Table 6.
  4. 6
    The isolated antibody or antigen-binding fragment thereof of any one of claims 1 through 5, wherein the antibody is selected from the group consisting of the antibodies designated as Antibody Number 124 through Antibody Number 244 as disclosed in Table 6.
  5. 7
    An isolated nucleic acid sequence encoding an antibody or antigen-binding fragment thereof according to any one of claims 1 through 6.
  6. 10
    A pharmaceutical composition comprising:one or more of the isolated antibodies or antigen-binding fragments thereof according to any one of claims 1 through 6;and a pharmaceutically acceptable carrier and/or excipient.
  7. 13
    A method of treating or preventing a Respiratory Syncytial Virus (RSV) infection, ar at least one symptom associated with RSV infection, comprising administering to a patient in need thereof or suspected of being in need thereof:a) one or more antibodies or antigen-binding fragments thereof according to any of claims 1 thorugh 6;b) a nucleic acid sequences according to claim 7;c) an expression vector according to claim 8;d) a host cell according to claim 9;or e) a pharmaceutical composition according claim 10 or claim 11;such that the RSV infection is treated or prevented, or the at least on symptom associated with RSV infection is treated, alleviated, or reduced in severity.
  8. 14
    A method of treating or preventing either a Respiratory Syncytial Virus (RSV) infection or a human metapneumovirus (HMPV) infection, ar at least one symptom associated with said RSV infection or said HMPV infection, comprising administering to a patient in need thereof or suspected of being in need thereof:a) one or more antibodies or antigen-binding fragments thereof according to any of claims 1 through 6;b) a nucleic acid sequences according to claim 7;c) an expression vector according to claim 8;d) a host cell according to claim 9;or e) a pharmaceutical composition according claim 10 or claim 11;such that the RSV infection is treated or prevented, or the at least on symptom associated with RSV infection is treated, alleviated, or reduced in severity.
  9. 16
    The method according to any one of claims 13 through 15, wherein the method further comprises administering to the patient a second therapeutic agent.
  10. 18
    A pharmacueitcal composition comprising any one or more of the isolated antibodies or antigen-binding fragments thereof of any one of claims 1 through 7 and a pharmaceutically acceptable carrier and/oror excipient.