Crystalline anti-human IL-23p19 antibodies
Crystalline forms of antibodies to human IL-23, such as antibodies to human IL-23p19 , are provided, as well as methods of producing such crystalline forms, and uses of such crystalline forms, e.g. in treatment of inflammatory, autoimmune, and proliferative disorders. In various embodiments, the anti-hulL-23 antibody crystals, such as anti-hulL-23p19 antibody crystals of the present invention are obtainable by batch crystallization methods, vapor diffusion methods, liquid-liquid diffusion methods, and dialysis. In other aspects, the invention relates to suspensions of the crystalline anti-hulL-23 antibodies of the present invention, including those at higher concentrations and lower viscosities than would be possible with a corresponding non-crystalline solution at the same concentration of antibody. In other embodiments, the anti-huiL-23 antibody crystals of the present invention have increased stability, i.e. they maintain biological activity of the anti-huiL-23 antibody, such as anti-huiL-23p 19 antibody, longer than corresponding solution formulations.
1. A crystalline anti-human IL-23p19 antibody comprising:
a) an antibody light chain variable domain comprising CDRL1, CDRL2 and CDRL3, wherein:
i) CDRL1 comprises the sequence of SEQ ID NO: 10;
ii) CDRL2 comprises the sequence of SEQ ID NO: 11; and
iii) CDRL3 comprises the sequence of SEQ ID NO: 12; and
b) an antibody heavy chain variable domain comprising CDRH1, CDRH2 and CDRH3, wherein:
i) CDRH1 comprises the sequence of SEQ ID NO: 5;
ii) CDRH2 comprises a sequence selected from the group consisting of SEQ ID NO: 7; and
iii) CDRH3 comprises the sequence of SEQ ID NO: 9;
wherein the crystalline antibody neutralizes human IL-23 and wherein the crystalline anti-human IL-23p19 antibody is characterized by unit cell dimensions a=b=192Å, c=106Å, α=β=γ=90° and in space group I4.
2. The crystalline anti-human IL-23p19 antibody of claim 1 comprising crystalline particles with an average particle size between five and 200 microns.
3. A suspension of the crystalline anti-human IL-23p19 antibody of claim 1 in which the antibody is at a concentration of at least 150 mg/ml.
4. The suspension of claim 3 in which the viscosity of the suspension is less than about half the viscosity of a solution formulation of the same antibody at the same concentration.
5. The crystalline anti-human IL-23p19 antibody of claim 1 comprising:
a) an antibody light chain variable domain comprising residues 1-108 of SEQ ID NO: 4; and
b) an antibody heavy chain variable domain comprising residues 1-116 of SEQ ID NO: 2.
6. The crystalline anti-human IL-23p19 antibody of claim 1 comprising an
antibody light chain and an antibody heavy chain, wherein:
a) the antibody light chain comprises the sequence of SEQ ID NO: 4; and
b) the antibody heavy chain comprises the sequence of SEQ ID NO: 2.
7. The crystalline anti-human IL-23p19 antibody of claim 1 , further comprising a heavy chain constant region comprising a γ1 human heavy chain constant region.
8. A pharmaceutical composition comprising the crystalline anti-human IL-23p19 antibody of claim 1 in combination with a pharmaceutically acceptable carrier or diluent.