NZ757874B2 - Stable antibody formulation - Google Patents
Stable antibody formulationInfo
- Publication number
- NZ757874B2 NZ757874B2 NZ757874A NZ75787418A NZ757874B2 NZ 757874 B2 NZ757874 B2 NZ 757874B2 NZ 757874 A NZ757874 A NZ 757874A NZ 75787418 A NZ75787418 A NZ 75787418A NZ 757874 B2 NZ757874 B2 NZ 757874B2
- Authority
- NZ
- New Zealand
- Prior art keywords
- pharmaceutical formulation
- histidine
- antibody
- polysorbate
- sucrose
- Prior art date
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
- 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
- A61K47/06—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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- 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
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- 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
- 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 invention provides stable pharmaceutical formulations comprising an antibody which binds specifically to human programmed death-1 (PD-1) comprising a HCVR and a LCVR of SEQ ID NOs: 1 and 2, respectively, histidine buffer, polysorbate, sucrose and proline in defined concentrations, and having a pH of 6.0 ± 0.3. The pharmaceutical formulations of the present invention exhibit a substantial degree of antibody stability upon stress and storage. Kits comprising said formulations are also included.
Claims (15)
1. A stable liquid pharmaceutical formulation comprising: (a) 5 mg/mL ± 0.75 mg/mL to 250 mg/mL ± 37.5 mg/mL of an antibody which binds ically to human programmed death-1 (PD-1), wherein the antibody comprises a heavy chain variable region (HCVR) of SEQ ID NO: 1 and a light chain variable region (LCVR) of SEQ ID NO: 2; (b) 10 mM ± 2 mM histidine ; (c) 0.2% ± 0.1% w/v polysorbate; (d) 5% ± 1% w/v sucrose; and (e) 1.5% ± 0.3% w/v proline; wherein the stable liquid pharmaceutical formulation has a pH of 6.0 ? 0.3.
2. The pharmaceutical formulation of claim 1, wherein the dy concentration is: a. 25 mg/mL ? 3.75 mg/mL; b. 50 mg/mL ? 7.5 mg/mL; c. 150 mg/mL ? 22.5 mg/mL; or d. 175 mg/mL ? 26.25 mg/mL.
3. The pharmaceutical formulation of claim 1 or 2, wherein the polysorbate is polysorbate 80.
4. The pharmaceutical formulation of any one of claims 1-3, wherein the formulation has a viscosity of less than 20 cP at 25°C.
5. The pharmaceutical formulation of claim 1, sing: 175 mg/mL ? 26.25 mg/mL antibody.
6. The pharmaceutical formulation of claim 1, comprising: 150 mg/mL ? 22.5 mg/mL antibody.
7. The pharmaceutical formulation of claim 1, comprising: 50 mg/mL ? 7.5 mg/mL antibody.
8. The pharmaceutical formulation of claim 1, comprising: 25 mg/mL ? 3.75 mg/mL antibody. 21515022_1 ters) P45499NZ00
9. The pharmaceutical formulation of any one of claims 1-8, wherein the histidine buffer is prepared from 4.8 mM ± 0.96 mM L-histidine and 5.2 mM ± 1.04 mM L- histidine monohydrochloride monohydrate.
10. The pharmaceutical formulation of claim 9, wherein the L-histidine concentration is 4.8 mM ± 0.96 mM and the L-histidine monohydrochloride monohydrate concentration is 5.2 mM ± 1.04 mM.
11. The ceutical formulation of claim 5, comprising: (a) 175 mg/mL ? 26.25 mg/mL antibody, (b) 0.74 mg/mL of L-histidine, (c) 1.1 mg/mL of L-histidine monohydrochloride monohydrate, (d) 2 mg/mL of polysorbate, (e) 50 mg/mL of sucrose, and (f) 15 mg/mL of w/v e.
12. The pharmaceutical formulation of claim 6, comprising: (a) 150 mg/mL ? 22.5 mg/mL dy, (b) 0.74 mg/mL of L-histidine, (c) 1.1 mg/mL of L-histidine monohydrochloride monohydrate, (d) 2 mg/mL of polysorbate, (e) 50 mg/mL of sucrose, and (f) 15 mg/mL of proline.
13. The pharmaceutical formulation of claim 7, comprising: (a) 50 mg/mL ? 7.5 mg/mL antibody, (b) 0.74 mg/mL of idine, (c) 1.1 mg/mL of L-histidine monohydrochloride monohydrate, (d) 2 mg/mL of rbate, (e) 50 mg/mL of sucrose, and (f) 15 mg/mL of proline.
14. The pharmaceutical formulation of claim 8, comprising: (a) 25 mg/mL ? 3.75 mg/mL antibody, (b) 0.74 mg/mL of L-histidine, 21515022_1 (GHMatters) P45499NZ00 (c) 1.1 mg/mL of L-histidine monohydrochloride monohydrate, (d) 2 mg/mL of polysorbate, (e) 50 mg/mL of sucrose, and (f) 15 mg/mL of proline.
15. The pharmaceutical formulation of any one of claims 1-14, wherein the antibody comprises: a. a heavy chain and light chain, wherein the heavy chain comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 9 and b. a heavy chain and light chain, wherein the light chain comprises the amino acid sequence of SEQ ID NO: 10; or c. a heavy chain/light chain comprising amino acid sequences ed from the group ting of SEQ ID NOs:
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762482270P | 2017-04-06 | 2017-04-06 | |
| PCT/US2018/024032 WO2018187057A1 (en) | 2017-04-06 | 2018-03-23 | Stable antibody formulation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NZ757874A NZ757874A (en) | 2025-02-28 |
| NZ757874B2 true NZ757874B2 (en) | 2025-06-04 |
Family
ID=
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