JPWO2019191563A5

JPWO2019191563A5 -

Info

Publication number: JPWO2019191563A5
Application number: JP2020552838A
Authority: JP
Publication date: 2022-03-29

Claims

It specifically binds to human interleukin 17A (IL-17A) and
(A) Light chain CDR1, CDR2, CDR3 sequences represented by SEQ ID NOs: 18, 22, 25, and heavy chain CDR1, CDR2, CDR3 sequences represented by SEQ ID NOs: 2, 7, 13;
(B) Light chain CDR1, CDR2, CDR3 sequences represented by SEQ ID NOs: 19, 23, 26, and heavy chain CDR1, CDR2, CDR3 sequences represented by SEQ ID NOs: 3, 8, 14;
(C) The light chain CDR1, CDR2, CDR3 sequences represented by SEQ ID NOs: 20, 22, 27, and the heavy chain CDR1, CDR2, CDR3 sequences represented by SEQ ID NOs: 4, 9, 15;
(D) The light chain CDR1, CDR2, CDR3 sequences represented by SEQ ID NOs: 21, 24, 28, and the heavy chain CDR1, CDR2, CDR3 sequences represented by SEQ ID NOs: 5, 10 and 16;
(E) The light chain CDR1, CDR2, CDR3 sequences represented by SEQ ID NOs: 20, 22, 27, and the heavy chain CDR1, CDR2, CDR3 sequences represented by SEQ ID NOs: 6, 11, 17; or
(F) Light chain CDR1, CDR2, CDR3 sequences shown by SEQ ID NOs: 19, 22, 29, and heavy chain CDR1, CDR2, CDR3 sequences shown by SEQ ID NOs: 4, 12, 17
An isolated antibody or antigen-binding fragment thereof, comprising any of the above.

It specifically binds to human IL-17A and
(A) (i) Light chain CDR1, CDR2, CDR3 sequences represented by SEQ ID NOs: 18, 22, 25, and heavy chain CDR1, CDR2, CDR3 sequences represented by SEQ ID NOs: 2, 7, 13;
(Ii) The light chain CDR1, CDR2, CDR3 sequences represented by SEQ ID NOs: 19, 23, 26, and the heavy chain CDR1, CDR2, CDR3 sequences represented by SEQ ID NOs: 3, 8, 14;
(Iii) The light chain CDR1, CDR2, CDR3 sequences set forth in SEQ ID NOs: 20, 22, 27, and the heavy chain CDR1, CDR2, CDR3 sequences set forth in SEQ ID NOs: 4, 9, 15;
(Iv) The light chain CDR1, CDR2, CDR3 sequences set forth in SEQ ID NOs: 21, 24, 28, and the heavy chain CDR1, CDR2, CDR3 sequences set forth in SEQ ID NOs: 5, 10 and 16;
(V) The light chain CDR1, CDR2, CDR3 sequences set forth in SEQ ID NOs: 20, 22, 27, and the heavy chain CDR1, CDR2, CDR3 sequences set forth in SEQ ID NOs: 6, 11, 17; or
(Vi) Light chain CDR1, CDR2, CDR3 sequences set forth in SEQ ID NOs: 19, 22, 29, and heavy chain CDR1, CDR2, CDR3 sequences set forth in SEQ ID NOs: 4, 12, 17; and (b) human immunoglobulin ( An isolated antibody or antigen-binding fragment thereof, comprising any of four sets of variable region framework regions from IgG).

See above for binding to human IL-17A at the same or greater Kd as the reference antibody comprising the heavy chain sequence of SEQ ID NO: 66 and the light chain sequence of SEQ ID NO: 68 , (b) binding to human IL-17A. An isolated antibody or antigen-binding fragment thereof that competes with the antibody or (c) is less immunogenic in a human subject than the reference antibody.

IL-17A protein at least 1 x ^10-6 M, at least 1 x ^10-7 M, at least 1 x ^10-8 M, at least 1 x ^10-9 M, at least 1 The invention according to any one of claims 1 to 3 , which binds with a dissociation constant (KD) of × ^10-10 _M , at least 1 × ^10-11 M, or at least 1 × ^10-12 M. An isolated antibody or antigen-binding fragment thereof.

Human antibody, humanized antibody, chimeric antibody, monoclonal antibody , recombinant antibody, antigen-binding antibody fragment, single-stranded antibody, diabody, triabody, tetrabody, Fab fragment, Fab'fragment , F (ab) ' ₂ From a fragment , IgD antibody, IgE antibody, IgM antibody, IgG1 antibody, IgG2 antibody, IgG3 antibody, IgG4 antibody, or IgG4 antibody having at least one mutation in the hinge region that reduces the tendency to form disulfide bonds within the H chain. The isolated antibody or antigen-binding fragment thereof according to any one of claims 1 to 4 , which is selected.

Heavy chain variable region sequences specifically bound to human IL-17A and selected from the group consisting of the sequences set forth in SEQ ID NOs: 58, 60, 62, and 64 , as well as SEQ ID NOs: 59, 61, 63, and 65. An isolated humanized antibody or antigen-binding fragment thereof comprising a light chain variable region sequence selected from the group consisting of the sequences shown .

An isolated humanized antibody or antigen-binding fragment thereof that specifically binds to human IL-17A and comprises the heavy chain sequence of SEQ ID NO: 66 and the light chain sequence of SEQ ID NO: 68 .

An isolated humanized antibody or antigen-binding fragment thereof that specifically binds to human IL-17A and comprises the heavy chain sequence of SEQ ID NO: 66 and the light chain sequence of SEQ ID NO: 72 .

An isolated humanized antibody or antigen-binding fragment thereof that specifically binds to human IL-17A and comprises the heavy chain sequence of SEQ ID NO: 66 and the light chain sequence of SEQ ID NO: 80 .

A pharmaceutical composition comprising the isolated antibody according to any one of claims 1 to 9 or an antigen-binding fragment thereof, which is mixed with a pharmaceutically acceptable carrier.

An isolated immune complex or fusion protein comprising the antibody according to any one of claims 1 to 9 or an antigen-binding fragment thereof bound to an effector molecule.

An isolated nucleic acid comprising a polynucleotide sequence encoding the antibody according to any one of claims 1 to 9 or an antigen-binding fragment thereof.

A recombinant expression vector comprising the isolated nucleic acid of claim 12 .

A host cell comprising the vector of claim 13 .