# US 2015/0147337 A1 · Crystalline anti-human il-23 antibodies

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- Number: US 2015/0147337 A1
- Document ID: US20150147337A1
- Status: Published application
- Kind: A1
- Application number: 14/407,319
- Filed: 2013-06-25
- Published: 2015-05-28
- Earliest claimed: 2012-06-27
- Assignees: Merck Sharp & Dohme Corp.
- Applicants: Merck Sharp & Dohme Corp.
- Inventors: Paul Reichert; Winifred W. Prosise; Peter Orth; Chakravarthy Nachu Narasimhan; Ramesh S. Kashi
- Web page: https://patentgrep.com/patent/US20150147337A1

## CPC

- C07K 16/244: {Interleukins [IL]}
- A61K 39/39591: {Stabilisation, fragmentation}
- C07K 2299/00: Coordinates from 3D structures of peptides, e.g. proteins or enzymes
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

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.

## Claims

### Claim 1

A crystalline anti-human IL-23 antibody.

### Claim 2 (depends on 1)

The crystalline anti-human IL-23 antibody of claim 1 wherein the antibody binds to the p19 subunit of IL-23.

### Claim 3 (depends on 1)

The crystalline anti-human IL-23 antibody of claim 1 comprising crystalline particles with an average particle size between five and 200 microns.

### Claim 4 (depends on 1)

The crystalline anti-human IL-23 antibody of claim 1 characterized by unit cell dimensions a=b=192 Å, c=106 Å, α=β=γ=90° and in space group 14.

### Claim 5 (depends on 1)

A suspension of the crystalline anti-human IL-23 antibody of claim 1 in which the antibody is at a concentration of at least 150 mg/ml.

### Claim 6 (depends on 5)

The suspension of claim 5 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.

### Claim 7 (depends on 2)

The crystalline anti-human IL-23p19 antibody of claim 2, comprising:
a) an antibody light chain variable domain, or antigen binding fragment thereof, 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, or antigen binding fragment thereof, 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 NOs: 6-8; and
iii) CDRH3 comprises the sequence of SEQ ID NO: 9.

### Claim 8 (depends on 7)

The crystalline anti-human IL-23p19 antibody of claim 7 wherein CDRH2 comprises the sequence of SEQ ID NO: 7.

### Claim 9 (depends on 7)

The crystalline anti-human IL-23p19 antibody of claim 7 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: 1, SEQ ID NO: 2 or SEQ ID NO: 3.

### Claim 10 (depends on 9)

The crystalline anti-human IL-23p19 antibody of claim 9 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.

### Claim 11 (depends on 9)

The crystalline anti-human IL-23p19 antibody of claim 9 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: 1, SEQ ID NO: 2 or SEQ ID NO: 3.

### Claim 12 (depends on 11)

The crystalline anti-human IL-23p19 antibody of claim 11 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.

### Claim at position 13

13-14. (canceled)

### Claim 15 (depends on 7)

The crystalline anti-human IL-23p19 antibody of claim 7, further comprising a heavy chain constant region comprising a γ1 human heavy chain constant region.

### Claim 16

(canceled)

### Claim 17 (depends on 1)

A pharmaceutical composition comprising the crystalline anti-human IL-23 antibody of claim 1 in combination with a pharmaceutically acceptable carrier or diluent.

### Claim at position 17

18-22. (canceled)

### Claim 23 (depends on 1)

A method for treatment of a disorder in a subject, comprising administering to said subject an effective amount of the crystalline anti-human IL-23 antibody of claim 1.

### Claim at position 19

24-25. (canceled)

### Claim 26

A method of producing a crystalline anti-huIL-23 antibody, said method comprising:
a) mixing a solution of anti-human IL-23 antibody and a precipitant solution to obtain a crystallization solution;
b) incubating that crystallization solution for a period of time sufficient for crystal formation; and
c) harvesting the crystals from the crystallization solution.

### Claim 27 (depends on 26)

The method of claim 26 wherein the anti-human IL-23 antibody is at a concentration of 5-70 mg/ml prior to addition of the precipitant solution.

### Claim 28 (depends on 26)

The method of claim 26 wherein the anti-human IL-23 antibody is at a concentration of about 100 mg/ml prior to addition of the precipitant solution.

### Claim 29 (depends on 26)

The method claim 26 in which the crystallization solution comprises:
a) an anti-human IL-23p19 antibody;
b) a buffer (pH 4.0-8.0);
c) 5-70% (v/v) 1,2 propanediol; and
d) PEG 300 or 400.

### Claim at position 24

30-32. (canceled)

### Claim 33 (depends on 26)

The method of claim 26 in which the crystallization solution comprises:
a) an anti-human IL-23p19 antibody;
b) a buffer (pH 4.0-6.0);
c) 2-5% (wt/v) sucrose;
c) 0.1-0.5% (v/v) polysorbate 80; and
d) PEG 300 or 400.

### Claim at position 26

34-44. (canceled)