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BR-112022016456-B1 - Human Anti-TSLP Antibody Compositions, Articles of Manufacture, Use, Method of Manufacture, Solution for Injection, Pre-filled Syringe and Kit

BR112022016456B1BR 112022016456 B1BR112022016456 B1BR 112022016456B1BR-112022016456-B1

Abstract

FORMULATIONS OF HUMAN ANTI-TSLP ANTIBODIES AND METHODS OF USE THEREOF. Compositions comprising more than about 100 mg/mL of an anti-TSLP antibody, a surfactant, proline, and a buffer are provided in this document. Methods for treating an inflammatory disease in a subject are also provided.

Inventors

  • Lauren Roschen
  • Jennifer Litowski

Assignees

  • AMGEN INC

Dates

Publication Date
20260317
Application Date
20210218
Priority Date
20200218

Claims (20)

  1. 1. A composition comprising more than 100 mg/mL of an anti-TSLP antibody, a surfactant, proline and a buffer, wherein the composition comprises less than or equal to 3.0% (w/v) of proline, characterized in that the anti-TSLP antibody comprises (A) a variable light chain domain comprising: (i) a CDR1 light chain sequence comprising the amino acid sequence presented in SEQ ID NO: 3; (ii) a CDR2 light chain sequence comprising the amino acid sequence presented in SEQ ID NO: 4; and (iii) a CDR3 light chain sequence comprising the amino acid sequence presented in SEQ ID NO: 5; and (B) a variable heavy chain domain comprising: (i) a CDR1 heavy chain sequence comprising the amino acid sequence presented in SEQ ID NO: 6; (ii) a heavy chain CDR2 sequence comprising the amino acid sequence presented in SEQ ID NO: 7, and (iii) a heavy chain CDR3 sequence comprising the amino acid sequence presented in SEQ ID NO: 8.
  2. 2. Composition according to claim 1, characterized in that the anti-TSLP antibody comprises: (A) a variable light chain domain selected from the group consisting of: i. an amino acid sequence that is established at SEQ ID NO: 12; ii. an amino acid sequence encoded by a polynucleotide sequence that is established at SEQ ID NO: 11; or (B) a variable heavy chain domain selected from the group consisting of: i. an amino acid sequence that is established at SEQ ID NO: 10; ii. an amino acid sequence encoded by a polynucleotide sequence that is established at SEQ ID NO: 9; or (C) a variable light chain domain of (A) and a variable heavy chain domain of (B).
  3. 3. Composition according to claim 1 or 2, characterized in that the anti-TSLP antibody is an IgG2 antibody.
  4. 4. Composition, according to any one of claims 1 to 3, characterized in that the anti-TSLP antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 13, a light chain comprising the amino acid sequence of SEQ ID NO: 14, or a heavy chain comprising the amino acid sequence of SEQ ID NO: 13 and a light chain comprising the amino acid sequence of SEQ ID NO: 14.
  5. 5. Composition, according to any one of claims 1 to 4, characterized in that the anti-TSLP antibody is present in the composition at a concentration of less than 200 mg/mL, or less than 150 mg/mL, or at a concentration of 110 mg/mL to 140 mg/mL, or at a concentration of 110 mg/mL ± 10%, or at a concentration of 140 mg/mL ± 10%.
  6. 6. Composition according to claim 5, characterized in that it comprises a surfactant in a concentration of less than or from 0.005% (w/v) to 0.015% (w/v), or comprising 0.010% (w/v) to 0.0025% (w/v) of surfactant, or comprising 0.005% (w/v) to 0.010% (w/v) of surfactant or 0.015% (w/v) of surfactant.
  7. 7. Composition, according to any one of claims 1 to 6, characterized in that it comprises less than 3.0% (w/v) of proline, optionally comprising 2.4% (w/v) to 2.8% (w/v) of proline or 2.5% (w/v) to 2.8% (w/v) of proline.
  8. 8. Composition, according to any one of claims 1 to 7, characterized in that proline is the only amino acid present in the composition.
  9. 9. Composition, according to any one of claims 1 to 8, characterized in that the buffer is selected from the group consisting of: succinate, glutamate, histidine and acetate.
  10. 10. Composition, according to any one of claims 1 to 9, characterized in that it comprises 10 mM to 30 mM of buffer, or comprising 20 mM to 28 mM of buffer, optionally 23 mM to 28 mM of buffer, 24 mM to 28 mM, or 24 mM to 26 mM of buffer.
  11. 11. Composition, according to any one of claims 1 to 10, characterized in that it comprises not more than 0.001% (w/v) of a sugar or citrate, optionally, wherein the sugar is a disaccharide, for example, trehalose and sucrose.
  12. 12. Composition, according to any one of claims 1 to 11, characterized in that the composition is a liquid.
  13. 13. Composition according to claim 12, characterized in that the pH is less than 6.0, optionally less than 5.5.
  14. 14. Composition according to claim 13, characterized in that the pH is 4.5 to 5.5, or 4.8 to 5.4, or 4.9, 5.2 or 5.4.
  15. 15. Composition according to claim 13, characterized in that it has a viscosity of 5 cP to 20 cP, optionally 15 cP.
  16. 16. Composition, according to any one of claims 12 to 15, characterized in that the composition is isotonic or has an osmolarity in a range of 200 mOsm/kg to 500 mOsm/kg, or 225 mOsm/kg to 400 mOsm/kg, or 250 mOsm/kg to 350 mOsm/kg.
  17. 17. Composition, characterized in that it comprises 110 mg/mL to 140 mg/mL of tezepelumab, 0.01% (w/v) ± 0.005% (w/v) of polysorbate 80, 2.4% (w/v) to 2.8% (w/v) of L-proline and 20 mM to 28 mM of acetate, wherein the viscosity of the composition is less than 20 cP and the pH is less than 5.5.
  18. 18. Composition according to claim 17, characterized in that the pH is 5.2, optionally, in which the viscosity is 15 cP at 20 °C up to 25 °C.
  19. 19. Composition, characterized in that it comprises 110 mg/mL of an anti-TSLP antibody, 0.01% (w/v) polysorbate 80, 2.4% (w/v) to 2.8% (w/v) L-proline and 20 mM to 28 mM acetate, wherein the composition has a pH of 5.2, wherein the anti-TSLP antibody comprises: (A) a variable light chain domain comprising: (i) a CDR1 light chain sequence comprising the amino acid sequence presented in SEQ ID NO: 3; (ii) a CDR2 light chain sequence comprising the amino acid sequence presented in SEQ ID NO: 4; and (iii) a CDR3 light chain sequence comprising the amino acid sequence presented in SEQ ID NO: 5; and (B) a variable heavy chain domain comprising: (i) a CDR1 heavy chain sequence comprising the amino acid sequence presented in SEQ ID NO: 6; (ii) a CDR2 heavy chain sequence comprising the amino acid sequence presented in SEQ ID NO: 7; and (iii) a CDR3 heavy chain sequence comprising the amino acid sequence presented in SEQ ID NO: 8.
  20. 20. Composition according to claim 19, characterized in that it comprises 22 mM to 26 mM of acetate.

Description

CROSS-REFERENCE TO RELATED REQUESTS [0001] This application claims the benefit of priority of U.S. Provisional Patent Application No. 62/978,201, filed February 18, 2020, which is incorporated herein by reference in its entirety. FIELD OF DISSEMINATION [0002] The invention relates to human anti-TSLP monoclonal antibodies, including high-concentration aqueous formulations of tezepelumab and its biosimilars. Incorporation by reference of material submitted electronically. [0003] Incorporated by reference in its entirety is a computer-readable listing of nucleotide/amino acid sequences submitted concurrently with this document and identified as follows: ASCII (Text) file of 9856 bytes named “55238_Seqlisting.txt”; created on February 16, 2021. BACKGROUND Brief Description of Related Technology [0004] In a recent randomized, double-blind, placebo-controlled, phase 2 clinical trial, tezepelumab (also known as AMG 157 and MED9929) was administered to humans at doses ranging from 70 mg to 280 mg. Subjects who received tezepelumab demonstrated lower rates of clinically significant asthma exacerbations than those who received placebo. [0005] Increasing protein concentrations in drug formulations can cause stability problems, for example protein aggregation resulting in the formation of high molecular weight species (HMWS). HMWS, particularly those that retain most of the native configuration of the monomer counterpart, can be particularly concerning in some protein formulations. Aggregation can also potentially affect the subcutaneous bioavailability and pharmacokinetics of a therapeutic protein. [0006] Filling and finishing operations, as well as administration of the pharmaceutical product, may involve flow steps of protein solutions through piston pumps, peristaltic pumps, or injection needles. Such processes may impart shear and mechanical stresses, which can cause protein denaturation and result in aggregation. This phenomenon may be exacerbated as protein solutions become more concentrated. SUMMARY [0007] An improved formulation for anti-TSLP antibodies is provided in this document, having increased stability and low viscosity while containing a high antibody concentration. [0008] One aspect of the disclosure is a composition comprising more than about 100 mg/mL of an anti-TSLP antibody, a surfactant, proline, and a buffer. By way of example, the anti-TSLP antibody is present in the composition at a concentration of less than about 200 mg/mL or less than about 150 mg/mL. By way of example, the anti-TSLP antibody is present in the composition at a concentration of about 110 mg/mL to about 140 mg/mL. By way of example, the anti-TSLP antibody is present in the composition at a concentration of about 110 mg/mL ± 10% or about 140 mg/mL ± 10%. Optionally, the anti-TSLP antibody is present in the composition at a concentration of about 105 mg/mL to about 115 mg/mL. In exemplary aspects, the surfactant is amphipathic and non-ionic. In many aspects, the surfactant is a polysorbate, for example, polysorbate 20 or polysorbate 80 or a mixture thereof. In exemplary cases, the surfactant is present in the composition at a concentration of less than or about 0.015% (w/v) ± 0.005% (w/v), for example, about 0.005% (w/v) to about 0.015% (w/v) of surfactant. In some cases, the surfactant concentration is about 0.005% (w/v), 0.010% (w/v) or 0.015% (w/v). In exemplary aspects, the composition comprises less than about 3.0% (w/v) proline, for example, about 2.4% (w/v) to about 2.8% (w/v) proline or about 2.5% (w/v) to about 2.8% (w/v) proline. In exemplary cases, the proline is L-proline. In certain aspects, proline is the only amino acid present in the composition. In exemplary aspects, the buffer is selected from the group consisting of: succinate, glutamate, histidine, and acetate. In preferred cases, the buffer is acetate. By way of example, the composition comprises about 1 mM to about 50 mM of buffer, for example, about 10 mM to about 30 mM of buffer, optionally about 15 mM to about 30 mM of buffer, about 20 mM to about 30 mM of buffer or about 10 mM to about 25 mM of buffer. Optionally, the buffer comprises about 20 mM to about 2 mM of buffer (for example, about 20 mM to about 28 mM of buffer, about 23 mM to about 28 mM, about 24 mM to about 28 mM). By way of example, the composition comprises not more than 0.001% (w/v) of a sugar or citrate, optionally, wherein the sugar is a disaccharide, for example, trehalose and sucrose. By way of example, the composition is a liquid and, optionally, the pH is less than about 6.0, optionally less than about 5.5. In certain aspects, the pH is from about 4.5 to about 5.5 or from about 4.8 to about 5.4 or about 4.9, about 5.2 or about 5.4. By way of example, the composition is characterized by reduced viscosity, relative to the liquid composition that does not comprise proline. For example, the composition, in some cases, is characterized by a viscosity of less than about 24 cP at about 20