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NZ794917B2 - Stable formulation for recombinant anti-pd-1 monoclonal antibody - Google Patents
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NZ794917B2 - Stable formulation for recombinant anti-pd-1 monoclonal antibody - Google Patents

Stable formulation for recombinant anti-pd-1 monoclonal antibody

Info

Publication number
NZ794917B2
NZ794917B2 NZ794917A NZ79491721A NZ794917B2 NZ 794917 B2 NZ794917 B2 NZ 794917B2 NZ 794917 A NZ794917 A NZ 794917A NZ 79491721 A NZ79491721 A NZ 79491721A NZ 794917 B2 NZ794917 B2 NZ 794917B2
Authority
NZ
New Zealand
Prior art keywords
buffer
formulation
monoclonal antibody
amino acid
acid sequence
Prior art date
Application number
NZ794917A
Other versions
NZ794917A (en
Inventor
Ping Hu
Qingru Huai
Yan Liu
Chunyun Sun
Mingzhen Tao
Shaomei Tian
Original Assignee
Sinocelltech Ltd
Filing date
Publication date
Application filed by Sinocelltech Ltd filed Critical Sinocelltech Ltd
Priority claimed from PCT/CN2021/100658 external-priority patent/WO2021254447A1/en
Publication of NZ794917A publication Critical patent/NZ794917A/en
Publication of NZ794917B2 publication Critical patent/NZ794917B2/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
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39591—Stabilisation, fragmentation
    • 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
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
    • 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
    • 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
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2818—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against CD28 or CD152
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2896—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565—Complementarity determining region [CDR]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • 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
    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Abstract

Provided is a stable formulation for a recombinant monoclonal antibody, consisting of a recombinant anti-PD-1 monoclonal antibody at a concentration of 10-25 mg/mL (PD1-H944), a buffer at 10-50 nM (citric acid buffer, acetate buffer, or histidine buffer), an osmotic pressure regulator at 20-200 nM (sodium chloride), a stabilizer at 10-250 nM (sucrose, trehalose, or arginine hydrochloride), and a surfactant at 0.005-0.05% (polysorbate 80). The pharmaceutical formulation may enhance the stability of the antibody and prolongs a validity period of the antibody in aqueous formulations.

Claims (5)

THE CLAIMS DEFINING THE INVENTION ARE AS FOLLOWS:
1. A stable formulation comprising a recombinant anti-PD-1 monoclonal antibody of 10-25 mg/mL; a buffer of 10-50 mM, wherein the buffer is selected from one or more of citric acid buffer, acetate buffer, and histidine buffer; an osmolality regulator of 20-200 mM, wherein the osmolality regulator is selected from sodium chloride; a stabilizer of 10-250 mM, wherein the stabilizer is one or more selected from the group consisting of sucrose, trehalose, and arginine hydrochloride; a surfactant of 0.005-0.05 wt%, wherein the surfactant is polysorbate 80; the pH of the formulation is 5.5-6.5; wherein the recombinant anti-PD-1 monoclonal antibody comprises a light chain variable region and a heavy chain variable region, wherein the light chain variable region comprises a light chain CDR1 with amino acid sequence SEQ ID NO:1, a light chain CDR2 with amino acid sequence SEQ ID NO:2 and a light chain CDR3 with amino acid sequence SEQ ID NO:3; and the heavy chain variable region comprises heavy chain CDR1 with amino acid sequence SEQ ID NO:4, heavy chain CDR2 with amino acid sequence SEQ ID NO:5, and heavy chain CDR3 with amino acid sequence SEQ ID NO:6.
2. The formulation according to claim 1, wherein the concentration of the stabilizer is 205 mM sucrose, or 20 mM-80 mM arginine hydrochloride, or 200 mM trehalose.
3. The formulation according to either claim 1 or claim 2, wherein the concentration of the buffer is 20-40 mM; the concentration of the osmolality regulator of an osmolality regulator is 80-160 mM; the concentration of the stabilizer is 20-205 mM; the concentration of the surfactant is 0.02-0.04 wt%; and/or the pH of the formulation is 5.8-6.2.
4. The formulation according to any one of claims 1 to 3, wherein the formulation has a pH of
5. The formulation according to any one of claims 1 to 4, wherein the formulation comprises 25 mg/mL recombinant anti-PD-1 monoclonal antibody, 20 mM histidine buffer,
NZ794917A 2021-06-17 Stable formulation for recombinant anti-pd-1 monoclonal antibody NZ794917B2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN202010566153 2020-06-19
PCT/CN2021/100658 WO2021254447A1 (en) 2020-06-19 2021-06-17 Stable formulation for recombinant anti-pd-1 monoclonal antibody

Publications (2)

Publication Number Publication Date
NZ794917A NZ794917A (en) 2025-06-27
NZ794917B2 true NZ794917B2 (en) 2025-09-30

Family

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