Methods of treatment comprising antibodies binding to alpha7beta1 integrin antibodies
AssigneePliant Therapeutics, Inc.
InventorsPatrick ANDRE, Chun CHEN, Scott TURNER
Life of this patent
Estimating the term…
Abstract
Disclosed herein are pharmaceutical agents and compositions that activate integrin heterodimers that contain beta-1 integrin protein that specifically bind laminin protein. Such agents and compositions are useful for treating diseases related to muscle malfunction, including muscular dystrophies.
Claims68
A pharmaceutical agent that is an agonist of at least one of α7β1 integrin, α6β1 integrin and α3β1 integrin and that binds to the extracellular domain of at least one of α7 protein, α6 protein and α3 protein.
A monoclonal antibody that is an agonist of α7β1 integrin, or an antibody fragment thereof, wherein the antibody or the antibody fragment binds specifically to an epitope of α7 protein, wherein the epitope comprises, consists essentially of, or consists of:
- (i) the amino acid sequence of SEQ ID NO:
- 10 or SEQ ID NO:
- 1;
- (ii) 5-10, 10-15, 15-20, 20-25, 25-30, 30-35 or 35-40 amino acids of SEQ ID NO:
- 10 or SEQ ID NO:
- 1;
- or
- (iii) 5-10, 10-15, 15-20, 20-25, 25-30, 30-35 or 35-40 amino acids of SEQ ID NO:
- 24.
A monoclonal antibody that is an agonist of α7β1 integrin, or an antibody fragment thereof, wherein the antibody or the antibody fragment binds specifically to an epitope of α7 protein, wherein the epitope comprises SWWP (SEQ ID NO:
- 25).
A monoclonal antibody that is an agonist of α7β1 integrin, or an antibody fragment thereof, wherein the antibody or the antibody fragment binds specifically to an epitope comprising the residues S977, W978, W979 and P980 of SEQ ID NO:
- 24.
A monoclonal antibody that is an agonist of α7β1 integrin, or an antibody fragment thereof, wherein the antibody or the antibody fragment binds specifically to an epitope comprising the residues R958, M976, S977, W978, W979 and P980 of SEQ ID NO:
- 24.
A monoclonal antibody that is an agonist of α7β1 integrin, or an antibody fragment thereof, wherein the antibody or the antibody fragment comprises a heavy chain variable (VH) region and a light chain variable (VL) region,
- wherein the VH region amino acid sequence comprises HCDR1 of SEQ ID NO:
- 2, HCDR2 of SEQ ID NO:
- 3 and HCDR3 of SEQ ID NO:
- 4, or a variant thereof having 5 or fewer conservative amino acid substitutions in HCDR1, HCDR2, and/or HCDR3;
- wherein the VH region amino acid sequence comprises HCDR1 of SEQ ID NO:
- 14, HCDR2 of SEQ ID NO:
- 3 and HCDR3 of SEQ ID NO:
- 15, or a variant thereof having 5 or fewer conservative amino acid substitutions in HCDR1, HCDR2, and/or HCDR3;
- wherein the VH region amino acid sequence comprises HCDR1 of SEQ ID NO:
- 65, HCDR2 of SEQ ID NO:
- 3 and HCDR3 of SEQ ID NO:
- 66, or a variant thereof having 5 or fewer conservative amino acid substitutions in HCDR1, HCDR2, and/or HCDR3;
- or
- wherein the VH region amino acid sequence comprises HCDR1 of SEQ ID NO:
- 14, HCDR2 of SEQ ID NO:
- 3 and HCDR3 of SEQ ID NO:
- 68, or a variant thereof having 5 or fewer conservative amino acid substitutions in HCDR1, HCDR2, and/or HCDR3.
A monoclonal antibody that is an agonist of α7β1 integrin, or an antibody fragment thereof, wherein the antibody or the antibody fragment comprises a light chain variable (VL) region and a heavy chain variable (VH) region,
- wherein the VL region amino acid sequence comprises LCDR1 of SEQ ID NO:
- 5, LCDR2 of SEQ ID NO:
- 6 and LCDR3 of SEQ ID NO:
- 7, or a variant thereof having 5 or fewer conservative amino acid substitutions in LCDR1, LCDR2, and/or LCDR3;
- wherein the VL region amino acid sequence comprises LCDR1 of SEQ ID NO:
- 69, LCDR2 of SEQ ID NO:
- 6 and LCDR3 of SEQ ID NO:
- 7, or a variant thereof having 5 or fewer conservative amino acid substitutions in LCDR1, LCDR2, and/or LCDR3;
- or
- wherein the VL region amino acid sequence comprises LCDR1 of SEQ ID NO:
- 71, LCDR2 of SEQ ID NO:
- 6 and LCDR3 of SEQ ID NO:
- 7, or a variant thereof having 5 or fewer conservative amino acid substitutions in LCDR1, LCDR2, and/or LCDR3.
A monoclonal antibody that is an agonist of α7β1 integrin, or an antibody fragment thereof, wherein the antibody or the antibody fragment comprises a heavy chain variable (VH) region and a light chain variable (VL) region, wherein:
- (i) the VH region amino acid sequence comprises HCDR1 of SEQ ID NO:
- 2, HCDR2 of SEQ ID NO:
- 3 and HCDR3 of SEQ ID NO:
- 4, or a variant thereof having 5 or fewer conservative amino acid substitutions in HCDR1, HCDR2, and/or HCDR3;
- and the VL region amino acid sequence comprises LCDR1 of SEQ ID NO:
- 5, LCDR2 of SEQ ID NO:
- 6 and LCDR3 of SEQ ID NO:
- 7, or a variant thereof having 5 or fewer conservative amino acid substitutions in LCDR1, LCDR2, and/or LCDR3;
- (ii) the VH region amino acid sequence comprises HCDR1 of SEQ ID NO:
- 14, HCDR2 of SEQ ID NO:
- 3 and HCDR3 of SEQ ID NO:
- 15, or a variant thereof having 5 or fewer conservative amino acid substitutions in HCDR1, HCDR2, and/or HCDR3;
- and the VL region amino acid sequence comprises LCDR1 of SEQ ID NO:
- 5, LCDR2 of SEQ ID NO:
- 6 and LCDR3 of SEQ ID NO:
- 7, or a variant thereof having 5 or fewer conservative amino acid substitutions in LCDR1, LCDR2, and/or LCDR3;
- (iii) the VH region amino acid sequence comprises HCDR1 of SEQ ID NO:
- 65, HCDR2 of SEQ ID NO:
- 3 and HCDR3 of SEQ ID NO:
- 66, or a variant thereof having 5 or fewer conservative amino acid substitutions in HCDR1, HCDR2, and/or HCDR3;
- and the VL region amino acid sequence comprises LCDR1 of SEQ ID NO:
- 5, LCDR2 of SEQ ID NO:
- 6 and LCDR3 of SEQ ID NO:
- 7, or a variant thereof having 5 or fewer conservative amino acid substitutions in LCDR1, LCDR2, and/or LCDR3;
- (iv) the VH region amino acid sequence comprises HCDR1 of SEQ ID NO:
- 14, HCDR2 of SEQ ID NO:
- 3 and HCDR3 of SEQ ID NO:
- 68, or a variant thereof having 5 or fewer conservative amino acid substitutions in HCDR1, HCDR2, and/or HCDR3;
- and the VL region amino acid sequence comprises LCDR1 of SEQ ID NO:
- 69, LCDR2 of SEQ ID NO:
- 6 and LCDR3 of SEQ ID NO:
- 7, or a variant thereof having 5 or fewer conservative amino acid substitutions in LCDR1, LCDR2, and/or LCDR3;
- or
- (v) the VH region amino acid sequence comprises HCDR1 of SEQ ID NO:
- 14, HCDR2 of SEQ ID NO:
- 3 and HCDR3 of SEQ ID NO:
- 68, or a variant thereof having 5 or fewer conservative amino acid substitutions in HCDR1, HCDR2, and/or HCDR3;
- and the VL region amino acid sequence comprises LCDR1 of SEQ ID NO:
- 71, LCDR2 of SEQ ID NO:
- 6 and LCDR3 of SEQ ID NO:
- 7, or a variant thereof having 5 or fewer conservative amino acid substitutions in LCDR1, LCDR2, and/or LCDR3.
A monoclonal antibody that is an agonist of α7β1 integrin, or an antibody fragment thereof, wherein the antibody comprises a heavy chain and a light chain,
- (i) wherein the heavy chain amino acid sequence comprises SEQ ID NO:
- 18, and the light chain amino acid sequence comprises SEQ ID NO:
- 19;
- (ii) wherein the heavy chain amino acid sequence comprises SEQ ID NO:
- 45, and the light chain amino acid sequence comprises SEQ ID NO:
- 53;
- (iii) wherein the heavy chain amino acid sequence comprises SEQ ID NO:
- 18, and the light chain amino acid sequence comprises SEQ ID NO:
- 62;
- or
- (iv) wherein the heavy chain amino acid sequence comprises SEQ ID NO:
- 18, and the light chain amino acid sequence comprises SEQ ID NO:
- 63.
Dependencies are inferred from the claim text.