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NZ739899B2 - Biopharmaceutical compositions - Google Patents

Biopharmaceutical compositions

Info

Publication number
NZ739899B2
NZ739899B2 NZ739899A NZ73989916A NZ739899B2 NZ 739899 B2 NZ739899 B2 NZ 739899B2 NZ 739899 A NZ739899 A NZ 739899A NZ 73989916 A NZ73989916 A NZ 73989916A NZ 739899 B2 NZ739899 B2 NZ 739899B2
Authority
NZ
New Zealand
Prior art keywords
amino acid
acid sequence
chain amino
heavy chain
antibody variant
Prior art date
Application number
NZ739899A
Other versions
NZ739899A (en
Inventor
Narendra B Bam
Jennifer Dally
Myrna A Monck
Michelle Spatara
Original Assignee
) Limited
Filing date
Publication date
Application filed by ) Limited filed Critical ) Limited
Priority claimed from PCT/IB2016/055012 external-priority patent/WO2017033121A1/en
Publication of NZ739899A publication Critical patent/NZ739899A/en
Publication of NZ739899B2 publication Critical patent/NZ739899B2/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/02—Nasal agents, e.g. decongestants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
    • C07K16/244—Interleukins [IL]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/40—Immunoglobulins specific features characterized by post-translational modification
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance

Abstract

The present disclosure relates to compositions, for treating interleukin 5 (IL-5) mediated diseases, and related methods. In particular, the invention provides a composition comprising an IL-5 antibody comprising SEQ ID NO: 1 and 2, wherein the composition comprises =25% deamidated antibody variant at N31 of the light chain amino acid sequence, =3% oxidised antibody variant at W52 of the heavy chain amino acid sequence, =55% oxidised antibody variant at M64 of the heavy chain amino acid sequence, =35% deamidated antibody variant at N386 of the heavy chain amino acid sequence, =55% oxidised antibody variant at M254 of the heavy chain amino acid sequence, =50% oxidised antibody variant at M360 of the heavy chain amino acid sequence, and =55% oxidised antibody variant at M430 of the heavy chain amino acid sequence; and wherein the composition comprises 20% to 72% acidic antibody variants as measured using capillary isoelectric focusing.

Claims (23)

1. A composition comprising an anti-IL-5 antibody having a heavy chain amino acid 5 sequence as shown in SEQ ID NO: 1 and a light chain amino acid sequence as shown in SEQ ID NO: 2, wherein the composition comprises deamidated antibody variant at N31 of the light chain amino acid sequence, oxidised antibody variant at W52 of the heavy chain amino acid sequence, oxidised antibody variant at M64 of the heavy chain amino acid sequence, 10 deamidated antibody variant at N386 of the heavy chain amino acid sequence, oxidised antibody variant at M254 of the heavy chain amino acid sequence, oxidised antibody variant at M360 of the heavy chain amino acid sequence, and oxidised antibody variant at M430 of the heavy chain amino acid sequence; wherein the composition comprises =25% deamidated antibody variant at N31 of the light chain amino acid sequence, =3% oxidised antibody variant at W52 of the heavy chain amino acid sequence, =55% oxidised antibody variant at M64 of the heavy chain amino acid sequence, =35% deamidated antibody variant at N386 of the heavy chain amino acid sequence, =55% oxidised antibody variant at M254 of the heavy chain amino acid sequence, =50% oxidised antibody variant at M360 of the heavy chain amino acid sequence, and =55% 20 oxidised antibody variant at M430 of the heavy chain amino acid sequence; and wherein the composition comprises 20% to 72% acidic antibody variants as measured using capillary isoelectric focusing.
2. The composition according to claim 1, comprising =50% heavy chain C-terminal lysine 25 K449 deleted antibody variant.
3. The composition according to claim 1 or 2, comprising =50% heavy chain amino acid sequence pyro-glutamate N-terminal antibody variant. 30
4. The composition according to any one of claims 1-3 comprising =20% aggregated antibody variant.
5. A composition comprising a population of anti-IL-5 antibodies, wherein the composition comprises: 35 a) an anti-IL-5 antibody comprising a heavy chain sequence having the amino acid sequence shown in SEQ ID NO: 1 and a light chain sequence having the amino acid sequence shown in SEQ ID NO: 2; b) 3.3% to 6.6% deamidated antibody variants at N31 of the light chain amino acid sequence; c) 0.3% to 1.5% deamidated antibody variants at N317 of the heavy chain amino acid sequence; d) 1.5% to 4.5% deamidated antibody variants at N386 of the heavy chain amino acid 5 sequence; and e) 55% or less oxidised antibody variant at M64 of the heavy chain amino acid sequence, 55% or less oxidised antibody variant at M254 of the heavy chain amino acid sequence, 50% or less oxidised antibody variant at M360 of the heavy chain sequence, 55% or less oxidised antibody variant at M430 of the heavy chain amino acid sequence, and 3% or less oxidised 10 antibody variant at W52 of the heavy chain amino acid sequence.
6. The composition according to claim 5, comprising: 0.5% to 1.5% oxidised antibody variant at M64, 2.5% to 3.5% oxidised antibody variant at M254, 0.4% to 0.8% oxidised antibody variant at M430, 0.2% to 1.5% oxidised antibody variant at M82 and 0.1% to 1.0% oxidised antibody variant at M4 of the light chain amino acid sequence.
7. A composition according to any one of claims 1-6 wherein the antibody is at a concentration of between 75 mg/ml to 100 mg/ml. 20
8. A composition according to any one of claims 1-7 wherein the composition further comprises one or a combination of: (a) a buffering agent selected from the group consisting of sodium phosphate dibasic heptahydrate, phosphate, citrate, sodium phosphate, potassium phosphate, sodium citrate, and histidine, providing a pH of between 6.8 and 7.2; and/or 25 (b) a sugar; and/or (c) polysorbate 80; and/or (d) EDTA.
9. A composition according to any one of claims 1 to 7 wherein the composition is an 30 aqueous liquid formulation comprising 100 mg/mL antibody and: (a) 15.5 mM sodium phosphate dibasic heptahydrate and 4.5 mM citric acid monohydrate at pH 6.3, (b) 12% weight of sucrose to volume, (c) 0.02% weight of polysorbate 80 to volume, and 35 (d) 0.05 mM EDTA.
10. A composition according to any one of claims 1 to 7 wherein the composition is a lyophilizate which may be reconstituted by the addition of water to produce a composition comprising: 75 mg/mL antibody and: (a) 20 mM sodium phosphate dibasic heptahydrate at pH 6.8 to 7.2, 5 (b) 12% weight of sucrose to volume, and (c) 0.05% weight of polysorbate 80 to volume.
11. A composition according to any one of claims 1-10 wherein the composition has at least 0.70 IL-5 specific antigen binding activity; and/or at least 70% FcRn binding activity, 10 compared with a reference standard comprising SEQ ID NO: 1 and SEQ ID NO:2 and 98% or more HC C-terminal lysine deleted variant, 95% or more HC N-terminal pyro-glutamate variant, 6% or less deamidated variant, 4% or less methionine or cysteine oxidated variant, 0.1 % or less tryptophan oxidated variant, and 0.4% or less aggregated variant.
12. A pharmaceutical composition comprising a composition according to any of claims 1-11 and a pharmaceutically acceptable carrier.
13. A composition according to any of claims 1-12 for use in treating asthma, severe eosinophilic asthma, severe asthma, uncontrolled eosinophilic asthma, eosinophilic asthma, 20 sub-eosinophilic asthma, chronic obstructive pulmonary disease, eosinophilic granulomatosis with polyangiitis, hypereosinophilic syndrome, nasal polyposis, bullous pemphigoid and eosinophilic esophagitis.
14. The composition according to claim 13, wherein the composition is to be administered at 25 a dose of 100 mg once every 4 weeks.
15. The composition according to claim 13, wherein the composition is for use in treating eosinophilic granulomatosis with polyangiitis (EGPA) and is to be administered to an EGPA patient in an amount of 300 mg once every 4 weeks.
16. The composition according to claim 13, wherein the composition is for use in treating hypereosinophilic syndrome (HES) and is to be administered to an HES patient in an amount of 300 mg once every 4 weeks. 35
17. Use of a composition according to any of claims 1-12 in the manufacture of a medicament for the treatment of asthma, severe eosinophilic asthma, severe asthma, uncontrolled eosinophilic asthma, eosinophilic asthma, sub-eosinophilic asthma, chronic obstructive pulmonary disease, eosinophilic granulomatosis with polyangiitis, hypereosinophilic syndrome, nasal polyposis, bullous pemphigoid and eosinophilic esophagitis.
18. The use according to claim 17, wherein the medicament is to be administered at a dose of 5 100 mg once every 4 weeks.
19. The use according to claim 17, wherein the medicament is for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA) and is to be administered to an EGPA patient in an amount of 300 mg once every 4 weeks.
20. The use according to claim 17, wherein the medicament is for the treatment of hypereosinophilic syndrome (HES) and is to be administered to an HES patient in an amount of 300 mg once every 4 weeks.
21. The composition according to claim 1 or 5, substantially as herein described with reference to any example thereof.
22. The pharmaceutical composition according to claim 12, substantially as herein described with reference to any example thereof.
23. The use according to claim 17, substantially as herein described with reference to any example thereof.
NZ739899A 2016-08-22 Biopharmaceutical compositions NZ739899B2 (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201562209000P 2015-08-24 2015-08-24
US201562240131P 2015-10-12 2015-10-12
US201562247906P 2015-10-29 2015-10-29
US201562249497P 2015-11-02 2015-11-02
PCT/IB2016/055012 WO2017033121A1 (en) 2015-08-24 2016-08-22 Biopharmaceutical compositions

Publications (2)

Publication Number Publication Date
NZ739899A NZ739899A (en) 2025-05-02
NZ739899B2 true NZ739899B2 (en) 2025-08-05

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