Aqueous liquid formulation

Description

1 / 35 Aqueous liquid formulation FIELD OF THE INVENTION

[0001] The present invention relates to liquid formulations comprising a protein and methods for their preparation, which are useful, for example, in therapeutic applications. However, it should be noted that the invention is not limited to this specific field of use. More particularly, the invention relates to liquid formulations comprising an anti-TNFα antibody, in particular golimumab, a histidine buffer and a poloxamer. STATE OF THE ART

[0002] Any discussion of the state of the art throughout the description should in no way be considered as an admission that such state of the art is widely known or forms part of common general knowledge in the field.

[0003] Golimumab is a fully human monoclonal IgG antibody that binds with high affinity and specificity to the soluble and transmembrane forms of tumor necrosis factor alpha (TNFα). In the US, there are two commercial products of golimumab, Simponi® and Simponi Aria® (Janssen Biotech, Inc.), which contain 100 mg / ml and 12.5 mg / ml of golimumab, respectively. Simponi® and Simponi Aria® are parenteral formulations suitable for administration by subcutaneous (SC) or intravenous (IV) injection, respectively.

[0004] The subcutaneous product golimumab, Simponi®, is indicated (in the US) for the treatment of: moderate to severe rheumatoid arthritis (RA) in combination with methotrexate; active psoriatic arthritis (PsA), alone or in combination with methotrexate; active ankylosing spondylitis (AS); and active moderate to severe ulcerative colitis (UC). For RA, PsA, and AS, the dosing regimen for Simponi® is 50 mg, administered as a subcutaneous injection once a month. For UC, the dosing regimen for Simponi® is three initial subcutaneous injections (two 100 mg injections on the first day of treatment, followed by one 100 mg injection two weeks later) and, Petition 870250078565, dated 03 / 09 / 2025, page 9 / 69 2 / 35 subsequently, a 100 mg injection every four weeks. The subcutaneous injection of Simponi® can be self-administered by the patient.

[0005] The intravenous golimumab product, Simponi Aria®, is indicated (in the US) for the treatment of: moderate to severe rheumatoid arthritis (RA) in adults, in combination with methotrexate; active psoriatic arthritis (PsA) in people two years of age and older; active ankylosing spondylitis (AS) in adults; and active polyarticular juvenile idiopathic arthritis (pJIA) in people two years of age and older. Simponi Aria® is administered by intravenous injection (infusion), usually four weeks after the first treatment and then every eight weeks.

[0006] In Europe, Simponi® is approved for rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), psoriatic arthritis (PsA), axial spondyloarthritis (AS), and ulcerative colitis (UC). RA, PsA, AS, and UC are available in 50 mg or 100 mg pens or in PFS, and as a pre-filled variable-dose pen (45 mg / 0.45 mL), delivering 0.1 to 0.45 mL in 0.05 mL increments for JIA.

[0007] Each 1 mL dose of Simponi® contains 100 mg of golimumab, 41 mg of sorbitol, 0.87 mg of L-histidine, and 0.15 mg of polysorbate 80, pH adjusted to 5.5 in water for injection. Each 1 mL dose of Simponi Aria® contains 12.5 mg of golimumab, 45 mg of sorbitol, 0.285 mg of L-histidine, 1.605 mg of L-histidine monohydrochloride monohydrate, and 0.15 mg of polysorbate 80, pH adjusted to 5.5 in water for injection.

[0008] Product stability is an essential quality attribute for pharmaceutical formulations, important for both efficacy and safety, and is a regulatory requirement for approval by health authorities. This refers to the retention of chemical, physical, and biological properties and characteristics after manufacturing, formulation, transportation, storage, and administration.Stability can be particularly challenging for biological products, which are prone to aggregation, degradation, oxidation, isomerization, adsorption, and denaturation, all of which can be accelerated by environmental stresses such as agitation and variations in pH and temperature.

[0009] Surfactants play a vital role in stabilizing biological products. This function may include protection against interfacial stresses, such as Petition 870250078565, dated 03 / 09 / 2025, page 10 / 69 3 / 35 aggregation, precipitation and adsorption induced by the interface, due to exposure to a liquid-air interface and contact with purification equipment and other processing, storage and distribution equipment.

[0010] One objective of the present invention is to provide stable formulations of golimumab. BRIEF DESCRIPTION OF THE INVENTION

[0011] Polyoxyethylene (PEO) surfactants, including polysorbates, have been identified as promising surfactants for use in biological formulations. However, the present inventors have found that, surprisingly, polysorbates can be unstable and were apparently the source of particulate matter and turbidity during the identification and evaluation of golimumab formulations, especially when co-formulated with a histidine buffer. The present inventors have found that stable golimumab formulations can be produced with a poloxamer surfactant, optionally in combination with a histidine buffer.

[0012] The present invention relates to liquid formulations comprising an anti-TNFα antibody and, more specifically, stable liquid formulations comprising golimumab.

[0013] In a first aspect, the invention provides an aqueous liquid formulation comprising: from 5 to 200 mg / mL of golimumab; 20 to 50 mg / mL of a sugar and / or a sugar alcohol; 0.6 to 1.6 mg / mL of a histidine buffer; and 0.005 to 0.1% (w / v) of a poloxamer; where the liquid formulation has a pH of 5.0 to 6.0.

[0014] In a second aspect, the invention provides an aqueous liquid formulation consisting essentially of: from 5 to 200 mg / mL of golimumab; 20 to 50 mg / mL of a sugar and / or a sugar alcohol; Petition 870250078565, dated 03 / 09 / 2025, page 11 / 69 4 / 35 of 0.6 to 1.6 mg / mL of a histidine buffer; 0.005 to 0.1% (w / v) of a poloxamer; and water; where the liquid formulation has a pH of 5.0 to 6.0.

[0015] In a third aspect, the invention provides an aqueous liquid formulation comprising: approximately 12.5 mg / mL of golimumab or approximately 100 mg / mL of golimumab; approximately 40 to 50 mg / mL of sorbitol; approximately 0.8 to 1.5 mg / mL of a histidine buffer; and approximately 0.015% (w / v) of a poloxamer; where the liquid formulation has a pH of approximately 5.0 to approximately 6.0.

[0016] In a fourth aspect, the invention provides an aqueous liquid formulation comprising: approximately 12.5 mg / mL of golimumab or approximately 100 mg / mL of golimumab; approximately 41 to 45 mg / mL of sorbitol; approximately 0.8 to 1.5 mg / mL of a histidine buffer; and approximately 0.015% (w / v) of poloxamer 188; where the liquid formulation has a pH of approximately 5.5.

[0017] In a fifth aspect, the invention provides an aqueous liquid formulation comprising: (1) approximately 12.5 mg / mL of golimumab; and (2) one of the following: a) approximately 45 mg / mL of sorbitol, approximately 1.47 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.2; b) approximately 45 mg / mL of sorbitol, approximately 1.47 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.5; Petition 870250078565, dated 03 / 09 / 2025, page 12 / 69 5 / 35 c) approximately 45 mg / mL of sorbitol, approximately 1.47 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.8; d) approximately 45 mg / mL of sorbitol, approximately 1.47 mg / mL of histidine buffer and approximately 0.010% (w / v) of poloxamer 188, with a pH of approximately 5.2; (e) approximately 45 mg / mL of sorbitol, approximately 1.47 mg / mL of histidine buffer and approximately 0.010% (w / v) of poloxamer 188, with a pH of approximately 5.5; f) approximately 45 mg / mL of sorbitol, approximately 1.47 mg / mL of histidine buffer and approximately 0.010% (w / v) of poloxamer 188, with a pH of approximately 5.8; (g) approximately 45 mg / mL of sorbitol, approximately 1.47 mg / mL of histidine buffer and approximately 0.020% (w / v) of poloxamer 188, with a pH of approximately 5.2; h) approximately 45 mg / mL of sorbitol, approximately 1.47 mg / mL of histidine buffer and approximately 0.020% (w / v) of poloxamer 188, with a pH of approximately 5.5; i) approximately 45 mg / mL of sorbitol, approximately 1.47 mg / mL of histidine buffer and approximately 0.020% (w / v) of poloxamer 188, with a pH of approximately 5.8; j) approximately 45 mg / mL of sorbitol, approximately 1.30 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.2; k) approximately 45 mg / mL of sorbitol, approximately 1.30 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.5; Petition 870250078565, dated 03 / 09 / 2025, page 13 / 69 6 / 35 l) approximately 45 mg / mL of sorbitol, approximately 1.30 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.8; m) approximately 45 mg / mL of sorbitol, approximately 1.60 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.2; n) approximately 45 mg / mL of sorbitol, approximately 1.60 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.5; or o) approximately 45 mg / mL of sorbitol, approximately 1.60 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.8.

[0018] In a sixth aspect, the invention provides an aqueous liquid formulation comprising: (1) approximately 100 mg / ml of golimumab; and (2) one of the following: a) approximately 41 mg / mL of sorbitol, approximately 0.87 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.2; b) approximately 41 mg / mL of sorbitol, approximately 0.87 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.5; c) approximately 41 mg / mL of sorbitol, approximately 0.87 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.8; d) approximately 41 mg / mL of sorbitol, approximately 0.87 mg / mL of histidine buffer and approximately 0.010% (w / v) of poloxamer 188, with a pH of approximately 5.2; Petition 870250078565, dated 03 / 09 / 2025, page 14 / 69 7 / 35 (e) approximately 41 mg / mL of sorbitol, approximately 0.87 mg / mL of histidine buffer and approximately 0.010% (w / v) of poloxamer 188, with a pH of approximately 5.5; f) approximately 41 mg / mL of sorbitol, approximately 0.87 mg / mL of histidine buffer and approximately 0.010% (w / v) of poloxamer 188, with a pH of approximately 5.8; (g) approximately 41 mg / mL of sorbitol, approximately 0.87 mg / mL of histidine buffer and approximately 0.020% (w / v) of poloxamer 188, with a pH of approximately 5.2; h) approximately 41 mg / mL of sorbitol, approximately 0.87 mg / mL of histidine buffer and approximately 0.020% (w / v) of poloxamer 188, with a pH of approximately 5.5; i) approximately 41 mg / mL of sorbitol, approximately 0.87 mg / mL of histidine buffer and approximately 0.020% (w / v) of poloxamer 188, with a pH of approximately 5.8; j) approximately 41 mg / mL of sorbitol, approximately 0.60 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.2; k) approximately 41 mg / mL of sorbitol, approximately 0.60 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.5; l) approximately 41 mg / mL of sorbitol, approximately 0.60 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.8; m) approximately 41 mg / mL of sorbitol, approximately 1.00 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH around 5.2; Petition 870250078565, dated 03 / 09 / 2025, p. 15 / 69 8 / 35 n) approximately 41 mg / mL of sorbitol, approximately 1.00 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH around 5.5; or o) approximately 41 mg / mL of sorbitol, approximately 1.00 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH around 5.8.

[0019] In a seventh aspect, the invention provides an aqueous liquid formulation comprising golimumab and a surfactant. The formulation exhibits a surfactant concentration loss of 40% or less when stored for one month at 25°C and / or a surfactant concentration loss of 50% or less when stored for one month at 40°C.

[0020] In an eighth aspect, the invention provides an aqueous liquid formulation comprising golimumab and a poloxamer.

[0021] In a ninth aspect, the invention provides a golimumab formulation for parenteral injection, comprising a sugar and / or a sugar alcohol, a buffer and a surfactant, wherein the surfactant is a poloxamer.

[0022] In a tenth aspect, the invention provides a liquid formulation of the invention for use in the treatment or prevention of rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis, active ulcerative colitis, or active polyarticular juvenile idiopathic arthritis.

[0023] In an eleventh aspect, the invention provides a method of treating or preventing rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis, active ulcerative colitis, or active polyarticular juvenile idiopathic arthritis in a subject, comprising administering to the subject a liquid formulation of the invention.

[0024] In a twelfth aspect, the invention provides the use of a liquid formulation of the invention in the manufacture of a medicament for treating or preventing rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis, active ulcerative colitis or active polyarticular juvenile idiopathic arthritis. Petition 870250078565, dated 03 / 09 / 2025, page 16 / 69 9 / 35

[0025] In a thirteenth aspect, the invention provides a liquid formulation of the invention for use in the treatment or prevention of rheumatoid arthritis or active psoriatic arthritis, in combination with methotrexate.

[0026] In a fourteenth aspect, the invention provides a method of treating or preventing active rheumatoid arthritis or psoriatic arthritis, in combination with the administration of methotrexate.

[0027] In a fifteenth aspect, the invention provides the use of a liquid formulation of the invention in the manufacture of a medicament for treating or preventing rheumatoid arthritis or active psoriatic arthritis, in combination with methotrexate.

[0028] The following features can be used alone or in combination with aspects one through fifteen above. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Preferred embodiments of the invention will now be described, by way of example only, with reference to the accompanying drawings, in which:

[0030] FIG. 1 shows the surfactant concentration (polysorbate 80) over time under different storage conditions, for various comparative formulations.

[0031] FIG. 2 shows the surfactant concentration (poloxamer 188) over time, under different storage conditions, for various inventive formulations. DEFINITIONS

[0032] In describing and claiming the present invention, the following terminology shall be used in accordance with the definitions set forth below. It should also be understood that the terminology used herein is intended only to describe specific embodiments of the invention and is not intended to be limiting. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by someone with common knowledge of the art to which the invention relates.

[0033] Unless the context clearly requires otherwise, throughout the description and claims, the words understand, comprehending, and similar words should be Petition 870250078565, dated 03 / 09 / 2025, p. 17 / 69 10 / 35 interpreted in an inclusive sense, as opposed to an exclusive or exhaustive sense; that is, in the sense of including, but not being limited to.

[0034] Except in operational examples, or where otherwise indicated, all numbers expressing quantities of ingredients or reaction conditions used herein should be understood as modified in all cases by the term 'about'.

[0035] Hereafter, unless otherwise indicated, '%' shall mean '% (w / v)', calculated as [100 x mx / vtot ], where mx is the mass of component x in grams and vtot is the total volume of all components in mL.

[0036] The term substantially, as used herein, means comprising more than 50% by weight, where relevant, unless otherwise indicated.

[0037] The recitation of a numerical range using commas includes the commas and all the numbers subsumed within that range (for example, from 1 to 10 includes 1, 1.5, 2, 5, 5.75, 7.1, 8.5, 9, 10, etc.).

[0038] As used herein and in the claims, the singular form of “a”, “an” and “the” may include plural references, unless the context clearly indicates otherwise.

[0039] As used herein, the terms “about” and “approximately” are used synonymously. Both terms are intended to encompass any normal fluctuations or variations understood by those skilled in the art. In some embodiments, “about” and “approximately” refer to ± 10% of the reference value, or ± 5%, or ± 2%, or ± 1%, or ± 0.1% of the reference value.

[0040] As used herein, the term “an effective amount” or “therapeutically effective amount” refers to an amount of golimumab that will elicit a biological or medical response in a subject, for example, by inhibiting a disease and its progression (e.g., inhibiting a disease, condition, or disorder in an individual who is experiencing or exhibiting the pathology or symptomatology of the disease, condition, or disorder, including halting the further development of the pathology and / or symptomatology of the disease); and / or improving a disease (e.g., improving a disease, condition, or disorder in an individual who is experiencing or exhibiting the Petition 870250078565, dated 03 / 09 / 2025, page 18 / 69 11 / 35 pathology or symptomatology of the disease, condition or disorder, such as reducing the pathology, reversing the pathology and / or symptomatology of the disease).

[0041] As used herein, the phrase treating, treating, and treatment and the like includes inhibiting a disease and / or its progression (e.g., inhibiting a disease, condition, or disorder in an individual who is presenting or manifesting the pathology or symptomatology of the disease, condition, or disorder, including blocking the progression or further development of the pathology and / or symptomatology of the disease); and / or improving a disease (e.g., improving a disease, condition, or disorder in an individual who is presenting or manifesting the pathology or symptomatology of the disease, condition, or disorder, including blocking the progression or further development of the pathology and / or symptomatology of the disease).

[0042] As used herein, the term prevention, prevent and prevention and the like, includes the prevention of the recurrence and / or onset of one or more symptoms of a disorder or disease, especially in a subject who has been assessed as susceptible or likely to develop the disease.

[0043] As used here, the phrase "a subject who needs this" means that the subject has been identified as needing the treatment described here.

[0044] As used herein, the terms subject and patient are interchangeable and can be understood as any living organism that can be treated with compounds of the present invention. Thus, the terms patient and subject can include an adult or a child. DETAILED DESCRIPTION OF THE INVENTION

[0045] All references cited herein, including patents, patent applications, publications and databases, are incorporated herein by reference in their entirety, whether or not they have been specifically incorporated previously.

[0046] Those skilled in the art will understand that the liquid formulations described herein comprise the embodiments and characteristics disclosed herein, as well as all combinations and / or permutations of the embodiments and characteristics disclosed. Petition 870250078565, dated 03 / 09 / 2025, p. 19 / 69 12 / 35

[0047] The present inventors have surprisingly discovered that golimumab formulations containing a poloxamer instead of a polysorbate as a surfactant exhibit improved stability (in particular, surfactant stability) over long periods of time, especially at relatively high temperatures. This allows for the production of golimumab formulations that are stable throughout the periods during which a treatment must be administered. The inventors believe that the stability of the surfactant in golimumab formulations can be positively influenced by the use of a poloxamer surfactant along with a histidine buffer.Furthermore, the surfactant stability of the golimumab formations described here may result, in part, from increased resistance to oxidation and hydrolysis, both enzymatically from residual host cell proteins (e.g., lipases) that are not removed during clarification and purification, and from histidine (e.g., in combination with trace metals).

[0048] An aqueous liquid formulation comprising golimumab and a surfactant is described herein. The formulation preferably comprises: 5 to 200 mg / mL of golimumab; 20 to 50 mg / mL of a sugar and / or a sugar alcohol; 0.6 to 1.6 mg / mL of a histidine buffer; and 0.005 to 0.1% (w / v) of a surfactant which is a poloxamer; wherein the liquid formulation has a pH of 5.0 to 6.0. In one embodiment, an aqueous liquid formulation consisting essentially of: 5 to 200 mg / mL of golimumab; 20 to 50 mg / mL of a sugar and / or a sugar alcohol; 0.6 to 1.6 mg / mL of a histidine buffer; and from 0.005 to 0.1% (w / v) of a poloxamer; wherein the liquid formulation has a pH of 5.0 to 6.0.In another embodiment, a liquid formulation is described herein comprising: approximately 12.5 mg / mL of golimumab or approximately 100 mg / mL of golimumab; approximately 40 to 50 mg / mL of sorbitol; approximately 0.8 to 1.5 mg / mL of a histidine buffer; and approximately 0.015% (w / v) of a poloxamer; wherein the liquid formulation has a pH of approximately 5.0 to approximately 6.0. In another embodiment, a liquid formulation is described herein comprising: approximately 12.5 mg / mL of golimumab or approximately 100 mg / mL of golimumab; approximately 41 to 45 mg / mL of sorbitol; approximately 0.8 to 1.5 mg / mL of... Petition 870250078565, dated 03 / 09 / 2025, page 20 / 69 13 / 35 a histidine buffer; and about 0.015% (w / v) poloxamer 188; wherein the liquid formulation has a pH of about 5.5.

[0049] The present invention is based, in part, on the discovery that golimumab formulations containing a poloxamer instead of a polysorbate as a surfactant exhibit improved stability over long periods, especially at relatively high temperatures. More particularly, the formulation exhibits enhanced surfactant stability.

[0050] The liquid formulations described here are suitable for pharmaceutical administration, such as parenteral administration, and especially for subcutaneous injection, such as by means of a single-use pre-filled syringe or autoinjector. Water

[0051] The principal component (or vehicle) of liquid formulations is pharmaceutical-grade water. 'Pharmaceutical-grade water' refers to water that meets, at a minimum, the purity and quality requirements suitable for the preparation of a parenteral liquid formulation, as established in the USP for 'water for injection' (or WFI). As understood by those skilled in the art, WFI is potable water purified by distillation or by a purification process equivalent to or superior to distillation, resulting in the removal of chemicals and microorganisms. WFI contains no added substances. Pharmaceutical-grade water may be sterilized before and / or after being combined with other components of the liquid formulation, but sterilization is not required.

[0052] The liquid formulations described herein comprise several components that are dissolved and / or dispersed, but normally completely dissolved, in pharmaceutical-grade water. These include: golimumab, a sugar and / or a sugar alcohol, a histidine buffer, and a poloxamer. anti-TNFa antibody

[0053] The antibody used in the liquid formulations is the golimumab antibody, whose encoded amino acid sequence contains 1342 amino acids, including any accepted variations or biosimilars. In one embodiment, golimumab is produced from Petition 870250078565, dated 03 / 09 / 2025, page 21 / 69 14 / 35 of one or more vectors encoding amino acid sequences that comprise the golimumab light chain sequence: EIVLTQSPATLSLSPGERATLSCRASQSVYSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSG SGTDFTLTISSLEPEDFAVYYCQQRSNWPPFTFGPGTKVDIKRTVAAPSVFIFPPSDEQLKSGTAS VVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACE VTHQGLSSPVTKSFNRGEC (SEQ ID NO: 1) and the golimumab heavy chain sequence: QVQLVESGGGVVQPGRSLRLSCAASGFIFSSYAMHWVRQAPGNGLEWVAFMSYDGSNKKYA DSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDRGIAAGGNYYYYGMDVWGQGTTVT VSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL YSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTV LHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFY PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNH YTQKSLSLSPGK (SEQ ID NO: 2).

[0054] In another embodiment, golimumab is produced from one or more vectors that encode amino acid sequences comprising the variable light chain sequence of golimumab: EIVLTQSPATLSLSPGERATLSCRASQSVYSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSG SGTDFTLTISSLEPEDFAVYYCQQRSNWPPFTFGPGTKVDIK (SEQ ID NO: 3) and the variable sequence of the golimumab heavy chain: QVQLVESGGGVVQPGRSLRLSCAASGFIFSSYAMHWVRQAPGNGLEWVAFMSYDGSNKKYA DSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDRGIAAGGNYYYYGMDVWGQGTTVT VSS (SEQ ID NO: 4)

[0055] Because golimumab is produced by a biological process, certain minor variations may occur from batch to batch, including, but not limited to, lysine clipping, in which the C-terminal lysine of the constant region of the heavy chain is cut off; these variations are considered golimumab and have no clinically significant effect. A biosimilar, as understood by those skilled in the art, refers to a biological product that is Petition 870250078565, dated 03 / 09 / 2025, page 22 / 69 15 / 35 highly similar to the reference product (in this case, golimumab produced by Janssen Biotech, Inc.) and does not exhibit clinically significant differences in terms of efficacy and safety. The high degree of similarity between the biosimilar and the reference product generally includes physical, chemical, and biological properties, and the small permitted differences are not clinically significant. This understanding is used by the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA), as well as by pharmaceutical companies seeking permission to market a biosimilar of a reference product. In the US, a biosimilar may be denoted with an extension after the name of the reference product. In the context of the present invention, for the avoidance of doubt, all golimumab extension names should be considered within the scope of the term golimumab, as used herein.The concentration of golimumab in the liquid formulations described herein may vary from 5 mg / mL to 200 mg / mL, as well as from 10 mg / mL to 110 mg / mL, and in particular, it may be 12.5 mg / mL or 100 mg / mL. Sugar and Sugar Alcohol

[0056] The liquid formulations described herein may comprise from 20 to 50 mg / mL of a sugar or sugar alcohol. The primary purpose of the sugar or sugar alcohol is to stabilize the protein and / or modify the osmolality of the formulations to an iso-osmotic level. The sugar or sugar alcohol may be any suitable sugar or sugar alcohol. In some embodiments, the sugar or sugar alcohol is selected from sucrose, trehalose, maltose, lactose, or sorbitol, individually or in any suitable combination of two or more. In one embodiment, the sugar alcohol is sorbitol.

[0057] The sugar or sugar alcohol may be present in the liquid formulations described herein at any suitable concentration from 20 to 50 mg / mL. In some embodiments, the sugar or sugar alcohol is present at a concentration of 30 to 50 mg / mL, or 40 to 50 mg / mL, or 41 to 45 mg / mL.In some embodiments, sugar is present in the liquid formulations described herein at a concentration of approximately 41 mg / mL, or at a concentration of approximately 45 mg / mL. Petition 870250078565, dated 03 / 09 / 2025, p. 23 / 69 16 / 35 Poloxamer

[0058] The liquid formulations described herein comprise a poloxamer as a surfactant. Poloxamers are nonionic triblock copolymers composed of a central hydrophobic polyoxypropylene (poly(propylene oxide)) chain flanked by two hydrophilic polyoxyethylene (poly(ethylene oxide)) chains. Poloxamers can protect protein formulations against stress induced by agitation and / or exposure of proteins to air-liquid surfaces and / or interfaces. The poloxamer used herein is not intended to be particularly limited. In one specific embodiment, the poloxamer may be poloxamer 188, also known as P188, where the first two digits (18) multiplied by 100 give the approximate molecular mass of the polyoxypropylene core (i.e., 1800) and the last digit (8) multiplied by 10 gives the percentage of polyoxyethylene content (i.e., 80%).

[0059] As described above, commercial formulations of Simponi® and Simponi Aria® do not include poloxamer. Instead, these formulations use polysorbate 80 (polyoxyethylene (80) sorbitan monolaurate) as a surfactant, at a concentration of 0.15 mg / mL, or 0.015% (w / v).

[0060] The liquid formulations described herein preferably comprise a poloxamer in an amount of 0.005 to 0.1% (w / v) based on the total formulation. In some embodiments, poloxamer is present in an amount of 0.005 to 0.05% (w / v), or 0.01 to 0.05% (w / v), or 0.015 to 0.1% (w / v), or 0.0075 to 0.02% (w / v), or 0.01 to 0.075% (w / v), or 0.01 to 0.04% (w / v), or an amount of approximately 0.005% (w / v), 0.0075% (w / v), 0.01% (w / v), 0.015% (w / v), 0.02% (w / v), 0.03% (w / v), 0.04% (w / v), 0.05% (w / v), 0.06% (w / v), 0.07% (w / v), 0.08% (w / v), 0.09% (w / v) or 0.1% (w / v). Osmolality

[0061] The liquid formulations described herein exhibit an osmolality within a parenterally acceptable range, generally between 200 and 600 mOsm / kg. Typically, the osmolality of the liquid formulations described herein is within the range of 240 to 420 mOsm / kg. In some embodiments, the liquid formulations exhibit an osmolality within the range of 300 to 400 mOsm / kg, and typically between 330 and 380 Petition 870250078565, dated 03 / 09 / 2025, page 24 / 69 17 / 35 mOsm / kg. In other modalities, osmolality is within the range of 270 to 325 mOsm / kg. Values ​​within these ranges can be obtained by balancing the type and amount of stabilizer, the type and amount of buffer, and, to a lesser extent, the type and amount of poloxamer, considering the amount of golimumab in pharmaceutical-grade water. Osmolality can also be adjusted by adding additional agents, such as salts (e.g., NaCl). pH

[0062] The liquid formulations described herein preferably have a pH in the range of 5.0 to 6.0. In some embodiments, the pH is in the range of 5.2 to 5.8. In some embodiments, the pH is about 5.2, or about 5.5, or about 5.8. The pH can be adjusted, if necessary, by adding pH adjusting agents. In some embodiments, the pH adjusting agents can be an acid or a base. In some embodiments, the acid is HCl or acetic acid. In some embodiments, the base is NaOH. Histidine buffer

[0063] The liquid formulations described herein may comprise a buffer, preferably a histidine buffer, and preferably 0.6 to 1.6 mg / mL of a histidine buffer. The concentration of the histidine buffer does not necessarily refer to the concentration of the initial ingredients used to prepare the buffered solution. Instead, it refers to the concentration of histidine in the buffered solution after the initial ingredients have been added and have undergone ionic dissociation in the balanced buffered solution. For example, the product Simponi Aria® includes L-histidine and L-histidine monohydrate hydrochloride as initial ingredients, at concentrations of 0.285 and 1.605 mg / mL, respectively. After dissociation in the buffered solution, these ingredient concentrations result in a histidine buffer concentration of 1.473 mg / mL. Similarly, the product Simponi® has a reported histidine concentration of 0.87 mg / mL.This histidine concentration in the buffered solution can be obtained by including 0.148 mg / mL of L-histidine and 0.974 mg / mL of L-histidine monohydrochloride monohydrate as ingredients, at a pH of 5.5. Petition 870250078565, dated 03 / 09 / 2025, page 25 / 69 18 / 35

[0064] In some embodiments, the liquid formulations described herein comprise 0.6 to 1.6 mg / mL of histidine buffer. In other embodiments, the formulations comprise 0.8 to 1.5 mg / mL of histidine buffer. In other embodiments, the formulations comprise 1.3 to 1.6 mg / mL of histidine buffer. In some embodiments, the formulations comprise 1.30 mg / mL, 1.47 mg / mL, or 1.60 mg / mL of histidine buffer. As noted above, a histidine buffer concentration of 1.473 mg / mL can be obtained by including L-histidine and L-histidine monohydrochloride monohydrate as ingredients, at concentrations of 0.285 and 1.605 mg / mL, respectively. Similarly, a histidine buffer concentration of 0.87 mg / mL can be obtained by including L-histidine and L-histidine monohydrochloride as ingredients, at concentrations of 0.148 and 0.974 mg / mL, respectively. Finally, it is understood that an antibody such as golimumab can contribute to the buffering capacity of a liquid formulation. Formulations

[0065] In one embodiment, the aqueous liquid formulations described herein may comprise from 5 to 200 mg / mL of golimumab; from 20 to 50 mg / mL of a sugar and / or a sugar alcohol; from 0.6 to 1.6 mg / mL of a histidine buffer; and from 0.005 to 0.1% (w / v) of a poloxamer; wherein the liquid formulation has a pH of 5.0 to 6.0.

[0066] In another embodiment, the aqueous liquid formulations described herein may consist essentially of 5 to 200 mg / mL of golimumab; 20 to 50 mg / mL of a sugar and / or a sugar alcohol; 0.6 to 1.6 mg / mL of a histidine buffer; and 0.005 to 0.1% (w / v) of a poloxamer; wherein the liquid formulation has a pH of 5.0 to 6.0. Consisting essentially of in this context serves to exclude the addition of other buffers or salts, but would allow the addition of secondary agents such as pH adjusters, antioxidants or preservatives.

[0067] In a further embodiment, the aqueous liquid formulation described herein may consist of water, 5 to 200 mg / mL of golimumab; 20 to 50 mg / mL of a sugar and / or a sugar alcohol; 0.6 to 1.6 mg / mL of a histidine buffer; and 0.005 to 0.1% (w / v) of a poloxamer; wherein the liquid formulation has a pH of 5.0 to 6.0. In this context, Petition 870250078565, dated 03 / 09 / 2025, page 26 / 69 19 / 35 consists of excluding all other pharmaceutical excipients and therefore additional buffers or salts are excluded, as well as antioxidants and preservatives. For clarity, impurities at a level low enough to be pharmaceutically acceptable are not excluded.

[0068] Exemplary liquid stabilizing formulations of golimumab are formulations comprising the following, in combination with approximately 12.5 mg / mL of golimumab: a) approximately 45 mg / mL of sorbitol, approximately 1.47 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.2; b) approximately 45 mg / mL of sorbitol, approximately 1.47 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.5; c) approximately 45 mg / mL of sorbitol, approximately 1.47 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.8; d) approximately 45 mg / mL of sorbitol, approximately 1.47 mg / mL of histidine buffer and approximately 0.010% (w / v) of poloxamer 188, with a pH of approximately 5.2; (e) approximately 45 mg / mL of sorbitol, approximately 1.47 mg / mL of histidine buffer and approximately 0.010% (w / v) of poloxamer 188, with a pH of approximately 5.5; f) approximately 45 mg / mL of sorbitol, approximately 1.47 mg / mL of histidine buffer and approximately 0.010% (w / v) of poloxamer 188, with a pH of approximately 5.8; (g) approximately 45 mg / mL of sorbitol, approximately 1.47 mg / mL of histidine buffer and approximately 0.020% (w / v) of poloxamer 188, with a pH of approximately 5.2; Petition 870250078565, dated 03 / 09 / 2025, page 27 / 69 20 / 35 h) approximately 45 mg / mL of sorbitol, approximately 1.47 mg / mL of histidine buffer and approximately 0.020% (w / v) of poloxamer 188, with a pH of approximately 5.5; i) approximately 45 mg / mL of sorbitol, approximately 1.47 mg / mL of histidine buffer and approximately 0.020% (w / v) of poloxamer 188, with a pH of approximately 5.8; j) approximately 45 mg / mL of sorbitol, approximately 1.30 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.2; k) approximately 45 mg / mL of sorbitol, approximately 1.30 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.5; l) approximately 45 mg / mL of sorbitol, approximately 1.30 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.8; m) approximately 45 mg / mL of sorbitol, approximately 1.60 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.2; n) approximately 45 mg / mL of sorbitol, approximately 1.60 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.5; o) approximately 45 mg / mL of sorbitol, approximately 1.60 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.8.

[0069] Exemplary liquid stabilizing formulations of golimumab are formulations comprising the following, in combination with approximately 100 mg / mL of golimumab: Petition 870250078565, dated 03 / 09 / 2025, page 28 / 69 21 / 35 a) approximately 41 mg / mL of sorbitol, approximately 0.87 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.2; b) approximately 41 mg / mL of sorbitol, approximately 0.87 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.5; c) approximately 41 mg / mL of sorbitol, approximately 0.87 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.8; d) approximately 41 mg / mL of sorbitol, approximately 0.87 mg / mL of histidine buffer and approximately 0.010% (w / v) of poloxamer 188, with a pH of approximately 5.2; (e) approximately 41 mg / mL of sorbitol, approximately 0.87 mg / mL of histidine buffer and approximately 0.010% (w / v) of poloxamer 188, with a pH of approximately 5.5; f) approximately 41 mg / mL of sorbitol, approximately 0.87 mg / mL of histidine buffer and approximately 0.010% (w / v) of poloxamer 188, with a pH of approximately 5.8; (g) approximately 41 mg / mL of sorbitol, approximately 0.87 mg / mL of histidine buffer and approximately 0.020% (w / v) of poloxamer 188, with a pH of approximately 5.2; h) approximately 41 mg / mL of sorbitol, approximately 0.87 mg / mL of histidine buffer and approximately 0.020% (w / v) of poloxamer 188, with a pH of approximately 5.5; i) approximately 41 mg / mL of sorbitol, approximately 0.87 mg / mL of histidine buffer and approximately 0.020% (w / v) of poloxamer 188, with a pH of approximately 5.8; Petition 870250078565, dated 03 / 09 / 2025, page 29 / 69 22 / 35 j) approximately 41 mg / mL of sorbitol, approximately 0.60 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.2; k) approximately 41 mg / mL of sorbitol, approximately 0.60 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.5; l) approximately 41 mg / mL of sorbitol, approximately 0.60 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.8; m) approximately 41 mg / mL of sorbitol, approximately 1.00 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.2; n) approximately 41 mg / mL of sorbitol, approximately 1.00 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.5; or o) approximately 41 mg / mL of sorbitol, approximately 1.00 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.8. Stability

[0070] The liquid formulations described herein are relatively stable. Typically, the formulation exhibits satisfactory bulk stability for at least 36 months, or at least 24 months, or at least 12 months, or at least 6 months, or at least 3 months. In general, this stability includes the chemical and physical stability of golimumab, such that only small amounts of antibody fragmentation and aggregation are observed, as well as the stability of the surfactant, such that only small amounts of surfactant degradation are observed.

[0071] The golimumab formulations described here exhibit remarkable stability in surfactant concentration or, in other words, resistance to surfactant degradation. In some embodiments, a golimumab formulation exhibits loss Petition 870250078565, dated 03 / 09 / 2025, p. 30 / 69 23 / 35 minimum surfactant concentration during storage. The loss of surfactant concentration can be expressed as a percentage of the original surfactant concentration, determined by comparing the surfactant concentration after storage under specific conditions with the concentration of the golimumab formulation as prepared. The surfactant concentration can be measured after storage, for example, by ultra-high performance liquid chromatography coupled to evaporative light scattering detection (UPLC / ELSD).

[0072] As an exemplary and non-limiting explanation, the surfactant stability of the golimumab formulations described herein may result, in part, from increased resistance to oxidation and hydrolysis, both enzymatically from residual host cell proteins (e.g., lipases) that are not removed during clarification and purification and / or histidine (e.g., in combination with trace metals).

[0073] In some embodiments, golimumab formulations exhibit a surfactant concentration loss after storage at 5°C for 1 month of 15% or less. In some embodiments, golimumab formulations exhibit a surfactant concentration loss after storage at 25°C for 1 month of 40% or less, 35% or less, 25% or less, 20% or less, 15% or less, or 10% or less. In some embodiments, golimumab formulations exhibit a surfactant concentration loss after storage at 40°C for 1 month of 55% or less, 50% or less, 40% or less, 35% or less, 30% or less, 25% or less, 20% or less, or 15% or less. Surfactant concentration loss can be measured, for example, as described in the examples below. Formulation manufacturing

[0074] The liquid formulation of the present invention can be prepared by combining golimumab, stabilizer, poloxamer, and histidine buffer in pharmaceutical-grade water to form a solution and / or suspension. The order of addition and the method of combination are usually not of particular importance. For convenience and commercial practicality, golimumab can be formulated into the formulations described herein using well-known ultrafiltration / diafiltration (UF / DF) techniques. In general, the Petition 870250078565, dated 03 / 09 / 2025, page 31 / 69 24 / 35 Golimumab Express is captured and purified by various processes and then subjected to UF / DF for further purification, concentration, and modification of the liquid medium. The golimumab solution resulting from the previous purification process steps can be replaced by diafiltration, as is well known in the art. In the preparation of the formulations described herein, golimumab can be diafiltered with a stabilizer and histidine buffer solution in WFI, with poloxamer being added during or after completion of the UF / DF process. Poloxamer can be added as a solution in WFI or in the diafiltration solution. The pH can be adjusted, if necessary, before, during, or after the UF / DF operations, such as by the introduction of HCl or another pH adjusting agent suitable for a parenteral formulation.The formation of the liquid is not limited, however, to the use of UF / DF, and any suitable process or means for combining the aforementioned ingredients at the desired concentrations may be used to prepare the liquid formulations described herein. Uses of the Formulation

[0075] The liquid formulations described herein are useful for treating a variety of diseases and disorders or symptoms thereof that respond to treatment with golimumab or anti-TNFα antibody. These include rheumatoid arthritis (RA), active psoriatic arthritis (PsA), active ankylosing spondylitis (AS), moderate to severe active ulcerative colitis (UC), and active polyarticular juvenile idiopathic arthritis (pJIA). The dosage amount and regimen are well known from the administration of Simponi® and Simponi Aria® as, for example, approved by the US FDA or EMA. The liquid formulations described herein can be loaded into a pre-filled syringe to deliver 0.5 mL of a 100 mg / mL formulation, corresponding to a golimumab dose of 50 mg, or they can be delivered in a vial for injection in a quantity of 1.0 mL of a 12.5 mg / mL formulation, corresponding to a golimumab dose of 12.5 mg.

[0076] In several exemplary forms, the present disclosure refers to the following items and all combinations thereof: 1. An aqueous liquid formulation comprising: from 5 to 200 mg / mL of golimumab; Petition 870250078565, dated 03 / 09 / 2025, page 32 / 69 25 / 35 from 20 to 50 mg / mL of a sugar and / or a sugar alcohol; 0.6 to 1.6 mg / mL of a histidine buffer; and 0.005 to 0.1% (w / v) of a poloxamer; where the liquid formulation has a pH of 5.0 to 6.0. 2. The aqueous liquid formulation of item 1, consisting essentially of: from 5 to 200 mg / mL of golimumab; 20 to 50 mg / mL of a sugar and / or a sugar alcohol; 0.6 to 1.6 mg / mL of a histidine buffer; 0.005 to 0.1% (w / v) of a poloxamer; and water; where the liquid formulation has a pH of 5.0 to 6.0. 3. The aqueous liquid formulation of item 1 or item 2, comprising a sugar alcohol comprising sorbitol. 4. The aqueous liquid formulation of any of items 1 to 3, wherein the poloxamer comprises poloxamer 188. 5. The aqueous liquid formulation of any of items 1 to 4, where the pH is from 5.2 to 5.8. 6. The aqueous liquid formulation of any of items 1 to 5, where the pH is approximately 5.5. 7. An aqueous liquid formulation of any of items 1 to 3, comprising approximately 12.5 mg / mL of golimumab or approximately 100 mg / mL of golimumab; approximately 40 to 50 mg / mL of sorbitol; approximately 0.8 to 1.5 mg / mL of a histidine buffer; and approximately 0.015% (w / v) of a poloxamer; where the liquid formulation has a pH of 5.0 to 6.0. 8. The aqueous liquid formulation of any of items 1 to 5, comprising: Petition 870250078565, dated 03 / 09 / 2025, page 33 / 69 26 / 35 (i) approximately 12.5 mg / mL of golimumab; and (ii) one of the following: a) approximately 45 mg / mL of sorbitol, approximately 1.47 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.2; b) approximately 45 mg / mL of sorbitol, approximately 1.47 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.5; c) approximately 45 mg / mL of sorbitol, approximately 1.47 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.8; d) approximately 45 mg / mL of sorbitol, approximately 1.47 mg / mL of histidine buffer and approximately 0.010% (w / v) of poloxamer 188, with a pH of approximately 5.2; (e) approximately 45 mg / mL of sorbitol, approximately 1.47 mg / mL of histidine buffer and approximately 0.010% (w / v) of poloxamer 188, with a pH of approximately 5.5; f) approximately 45 mg / mL of sorbitol, approximately 1.47 mg / mL of histidine buffer and approximately 0.010% (w / v) of poloxamer 188, with a pH of approximately 5.8; (g) approximately 45 mg / mL of sorbitol, approximately 1.47 mg / mL of histidine buffer and approximately 0.020% (w / v) of poloxamer 188, with a pH of approximately 5.2; h) approximately 45 mg / mL of sorbitol, approximately 1.47 mg / mL of histidine buffer and approximately 0.020% (w / v) of poloxamer 188, with a pH of approximately 5.5; i) approximately 45 mg / mL of sorbitol, approximately 1.47 mg / mL of histidine buffer and approximately 0.020% (w / v) of poloxamer 188, with a pH of approximately 5.8; Petition 870250078565, dated 03 / 09 / 2025, page 34 / 69 27 / 35 j) approximately 45 mg / mL of sorbitol, approximately 1.30 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.2; k) approximately 45 mg / mL of sorbitol, approximately 1.30 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.5; l) approximately 45 mg / mL of sorbitol, approximately 1.30 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.8; m) approximately 45 mg / mL of sorbitol, approximately 1.60 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.2; n) approximately 45 mg / mL of sorbitol, approximately 1.60 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.5; or o) approximately 45 mg / mL of sorbitol, approximately 1.60 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.8. 9. The aqueous liquid formulation of any of items 1 to 5, comprising: (i) approximately 100 mg / mL of golimumab; and (ii) one of the following: a) approximately 41 mg / mL of sorbitol, approximately 0.87 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.2; b) approximately 41 mg / mL of sorbitol, approximately 0.87 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.5; Petition 870250078565, dated 03 / 09 / 2025, page 35 / 69 28 / 35 c) approximately 41 mg / mL of sorbitol, approximately 0.87 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.8; d) approximately 41 mg / mL of sorbitol, approximately 0.87 mg / mL of histidine buffer and approximately 0.010% (w / v) of poloxamer 188, with a pH of approximately 5.2; (e) approximately 41 mg / mL of sorbitol, approximately 0.87 mg / mL of histidine buffer and approximately 0.010% (w / v) of poloxamer 188, with a pH of approximately 5.5; f) approximately 41 mg / mL of sorbitol, approximately 0.87 mg / mL of histidine buffer and approximately 0.010% (w / v) of poloxamer 188, with a pH of approximately 5.8; g) approximately 41 mg / mL of sorbitol, approximately 0.87 mg / mL of histidine buffer and approximately 0.020% (w / v) of poloxamer 188, with a pH of approximately 5.2; h) approximately 41 mg / mL of sorbitol, approximately 0.87 mg / mL of histidine buffer and approximately 0.020% (w / v) of poloxamer 188, with a pH of approximately 5.5; i) approximately 41 mg / mL of sorbitol, approximately 0.87 mg / mL of histidine buffer and approximately 0.020% (w / v) of poloxamer 188, with a pH of approximately 5.8; j) approximately 41 mg / mL of sorbitol, approximately 0.60 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.2; k) approximately 41 mg / mL of sorbitol, approximately 0.60 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.5; Petition 870250078565, dated 03 / 09 / 2025, pp. 36 / 69 29 / 35 l) approximately 41 mg / mL of sorbitol, approximately 0.60 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH around 5.8; m) approximately 41 mg / mL of sorbitol, approximately 1.00 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH around 5.2; n) approximately 41 mg / mL of sorbitol, approximately 1.00 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH around 5.5; or o) approximately 41 mg / mL of sorbitol, approximately 1.00 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH around 5.8. 10. An aqueous liquid formulation comprising golimumab and a surfactant, wherein the formulation exhibits a surfactant concentration loss of 40% or less when stored for one month at 25°C. 11. The aqueous liquid formulation of item 10, where the surfactant concentration loss is 15% or less. 12. The aqueous liquid formulation of item 10 or 11, wherein the surfactant comprises a poloxamer. 13. The aqueous liquid formulation of any of items 10 to 12, further comprising a histidine buffer. 14. The aqueous liquid formulation of any of items 10 to 13, comprising: from 5 to 200 mg / mL of golimumab; 20 to 50 mg / mL of a sugar and / or a sugar alcohol; 0.6 to 1.6 mg / mL of a histidine buffer; and 0.005 to 0.1% (w / v) of a poloxamer; where the liquid formulation has a pH of 5.0 to 6.0. Petition 870250078565, dated 03 / 09 / 2025, pp. 37 / 69 30 / 35 15. The aqueous liquid formulation of any of items 10 to 14, consisting essentially of: from 5 to 200 mg / mL of golimumab; 20 to 50 mg / mL of a sugar and / or a sugar alcohol; 0.6 to 1.6 mg / mL of a histidine buffer; 0.005 to 0.1% (w / v) of a poloxamer; and water; where the liquid formulation has a pH of 5.0 to 6.0. 16. An aqueous liquid formulation comprising golimumab and a poloxamer. 17. The aqueous liquid formulation of item 16, comprising 5 to 200 mg / mL of golimumab. 18. The aqueous liquid formulation of item 16 or 17, wherein the poloxamer is poloxamer 188. 19. The aqueous liquid formulation of any of items 16 to 18, comprising 0.005 to 0.1% (w / v) of poloxamer. 20. The aqueous liquid formulation of any of items 16 to 19, further comprising a histidine buffer. 21. The aqueous liquid formulation of item 20, comprising 0.6 to 1.6 mg / mL of histidine buffer. 22. The aqueous liquid formulation of any of items 16 to 21, further comprising a sugar and / or a sugar alcohol. 23. The aqueous liquid formulation of item 22, comprising a sugar alcohol containing sorbitol. 24. The aqueous liquid formulation of item 22 or 23, comprising 20 to 50 mg / mL of sugar and / or sugar alcohol. 25. The aqueous liquid formulation of any of items 16 to 24, with a pH of 5.0 to 6.0. Petition 870250078565, dated 03 / 09 / 2025, pp. 38 / 69 31 / 35 26. A golimumab formulation for parenteral injection, comprising a sugar and / or a sugar alcohol, a buffer and a surfactant, wherein the surfactant is a poloxamer. 27. The golimumab formulation of item 26, comprising 5 to 200 mg / mL of golimumab. 28. The golimumab formulation of item 26 or 27, wherein the poloxamer is poloxamer 188. 29. The golimumab formulation of any of items 26 to 28, comprising 0.005 to 0.1% (w / v) of poloxamer. 30. The golimumab formulation of any of items 26 to 29, wherein the buffer is a histidine buffer. 31. The golimumab formulation of item 30, comprising 0.6 to 1.6 mg / mL of histidine buffer. 32. The golimumab formulation of any of items 26 to 31, comprising a sugar alcohol comprising sorbitol. 33. The golimumab formulation of any of items 26 to 32, comprising 20 to 50 mg / mL of sugar and / or sugar alcohol. 34. The golimumab formulation of any of the items 26 to 33, with a pH of 5.0 to 6.0. 35. An aqueous liquid formulation comprising golimumab and a surfactant, wherein the formulation exhibits a surfactant concentration loss of 50% or less when stored for one month at 40°C. 36. The aqueous liquid formulation of item 35, in which the surfactant concentration loss is 15% or less. 37. The aqueous liquid formulation of item 35 or 36, wherein the surfactant comprises a poloxamer. 38. The aqueous liquid formulation of any of items 35 to 37, further comprising a histidine buffer. Petition 870250078565, dated 03 / 09 / 2025, pp. 39 / 69 32 / 35 39. The aqueous liquid formulation of any of items 35 to 38, comprising: from 5 to 200 mg / mL of golimumab; 20 to 50 mg / mL of a sugar and / or a sugar alcohol; 0.6 to 1.6 mg / mL of a histidine buffer; and 0.005 to 0.1% (w / v) of a poloxamer; where the liquid formulation has a pH of 5.0 to 6.0. 40. The aqueous liquid formulation of any of items 35 to 39, consisting essentially of: from 5 to 200 mg / mL of golimumab; 20 to 50 mg / mL of a sugar and / or a sugar alcohol; 0.6 to 1.6 mg / mL of a histidine buffer; 0.005 to 0.1% (w / v) of a poloxamer; and water; where the liquid formulation has a pH of 5.0 to 6.0. 41. The formulation of any of items 1 to 40, for use in the treatment or prevention of rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis, moderate to severe active ulcerative colitis, or active polyarticular juvenile idiopathic arthritis. 42. A method for treating or preventing rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis, moderate to severe active ulcerative colitis, or active polyarticular juvenile idiopathic arthritis in a subject, comprising administering to the subject the formulation of any one of items 1 to 41. 43. Use of a formulation of any of items 1 to 41 in the manufacture of a medicament to treat or prevent rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis, moderate to severe active ulcerative colitis, or active polyarticular juvenile idiopathic arthritis. Petition 870250078565, dated 03 / 09 / 2025, pages 40 / 69 33 / 35 EXAMPLES

[0077] The present invention will now be described with reference to the following examples, which should be regarded in all respects as illustrative and not restrictive.

[0078] Surfactant concentration over time, under a range of storage temperatures, was measured for the following inventive and comparative formulations in Table 1. Table 1: Comparison between comparative and inventive examples Component Example Comparative 1 Inventive Example 1 Comparative Example 2 Inventive Example 2 Golimumab (mg / mL) 100 100 12.5 12.5 L-histidine (mg / mL) 0.148* 0.148* 0.285 0.285 L-histidine monohydrochloride monohydrate (mg / mL) 0.974* 0.974* 1.605 1.605 Histidine buffer concentration (mg / mL) 0.87* 0.87* 1.473 1.473 Sorbitol (mg / mL) 41 41 45 45 Surfactant type Polysorbate 80 Poloxamer 188 Polysorbate 80 Poloxamer 188 Surfactant concentration (% (w / v)) 0.015 0.015 0.015 0.015 pH 5.5 5.5 5.5 5.5 * The concentration of L-histidine and L-histidine monohydrate hydrochloride in the Simponi® formulation is collectively reported as 0.87 mg / mL. It is presumed that the value Petition 870250078565, dated 03 / 09 / 2025, pp. 41 / 69 34 / 35 refers to the total L-histidine concentration of both components of the histidine buffering system. The concentration of each component ingredient was calculated according to the target pH.

[0079] In these examples, Comparative Example 1 corresponds to the Simponi® formulation, and Comparative Example 2 corresponds to the Simponi Aria® formulation. Inventive Example 1 corresponds to Comparative Example 1, except for the use of poloxamer 188 instead of polysorbate 80 as a surfactant. Similarly, Inventive Example 2 corresponds to Comparative Example 2, except for the use of poloxamer 188 instead of polysorbate 80 as a surfactant.

[0080] Surfactant concentrations for these four exemplary formulations were monitored under storage conditions of 5°C, 25°C, and 40°C for three months. Figure 1 shows the results for the comparative examples. After three months of storage at 25°C (green lines) and 40°C (red lines), the polysorbate 80 concentration of these comparative formulations decreased substantially (approximately 24 to 62% surfactant remaining). After three months of storage at 5°C (blue lines), the polysorbate 80 concentration was somewhat more stable, with approximately 93% surfactant remaining.

[0081] FIG. 2 shows the results for the examples of the invention. After three months of storage at 5°C (blue lines), 25°C (green lines) and 40°C (red lines), the concentration of poloxamer 188 in these formulations of the invention remained remarkably stable (approximately 87 to 100% of the remaining surfactant).

[0082] As can be seen in Figures 1 and 2, the liquid formulations described here, containing a poloxamer surfactant, showed better surfactant stability compared to formulations containing a polysorbate surfactant. This effect was particularly pronounced at storage temperatures of 25°C and 40°C.

[0083] Although the invention has been described with reference to specific examples, it will be understood by those skilled in the art that the invention can be embodied in many other forms, in which particular features of any of the various Petition 870250078565, dated 03 / 09 / 2025, p. 42 / 69 The 35 / 35 examples described can be provided in any combination with any of the other examples described. Petition 870250078565, dated 03 / 09 / 2025, pp. 43 / 69

Claims

1 / 6 CLAIMS 1. Aqueous liquid formulation characterized by comprising golimumab and a poloxamer.

2. Aqueous liquid formulation, according to claim 1, characterized by comprising from 5 to 200 mg / mL of golimumab.

3. Aqueous liquid formulation according to claims 1 or 2, characterized in that the poloxamer is poloxamer 188.

4. Aqueous liquid formulation, according to any one of claims 1 to 3, characterized by comprising from 0.005 to 0.1% (w / v) of poloxamer.

5. Aqueous liquid formulation, according to any one of claims 1 to 4, characterized by further comprising a histidine buffer, preferably comprising 0.6 to 1.6 mg / mL of histidine buffer.

6. Aqueous liquid formulation, according to any one of claims 1 to 5, characterized by further comprising a sugar and / or a sugar alcohol, preferably comprising sorbitol.

7. Aqueous liquid formulation as described in claim 6, characterized by comprising sugar and / or sugar alcohol in an amount of 20 to 50 mg / mL.

8. Aqueous liquid formulation, according to any one of claims 1 to 7, characterized by having a pH of 5.0 to 6.

0.

9. Aqueous liquid formulation, according to claim 1, characterized by comprising: Petition 870250078565, dated 03 / 09 / 2025, page 44 / 69 2 / 6 approximately 12.5 mg / mL of golimumab; approximately 40 to 50 mg / mL of sorbitol, preferably 45 mg / mL of sorbitol; approximately 0.8 to 1.5 mg / mL of a histidine buffer; and approximately 0.015% (w / v) of a poloxamer, preferably poloxamer 188; wherein the liquid formulation has a pH of 5.0 to 6.

0.

10. Aqueous liquid formulation, according to claim 1, characterized by comprising: about 100 mg / mL of golimumab; about 40 to 50 mg / mL of sorbitol, preferably 41 mg / mL of sorbitol; about 0.8 to 1.5 mg / mL of a histidine buffer; and about 0.015% (w / v) of a poloxamer, preferably poloxamer 188; wherein the liquid formulation has a pH of 5.0 to 6.

0.

11. Aqueous liquid formulation according to any one of claims 1 to 9, characterized by comprising: (i) about 12.5 mg / mL of golimumab; and (ii) one of the following: a) about 45 mg / mL of sorbitol, about 1.47 mg / mL of histidine buffer and about 0.015% (w / v) of poloxamer 188, with a pH of about 5.2; b) about 45 mg / mL of sorbitol, about 1.47 mg / mL of histidine buffer and about 0.015% (w / v) of poloxamer 188, with a pH of about 5.5; c) approximately 45 mg / mL of sorbitol, approximately 1.47 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.8; d) approximately 45 mg / mL of sorbitol, approximately 1.47 mg / mL of histidine buffer and approximately 0.010% (w / v) of poloxamer 188, with a pH of approximately 5.2; Petition 870250078565, dated 03 / 09 / 2025, page. 45 / 69 3 / 6 e) approximately 45 mg / mL of sorbitol, approximately 1.47 mg / mL of histidine buffer and approximately 0.010% (w / v) of poloxamer 188, with a pH of approximately 5.5;f) approximately 45 mg / mL of sorbitol, approximately 1.47 mg / mL of histidine buffer and approximately 0.010% (w / v) of poloxamer 188, with a pH of approximately 5.8; g) approximately 45 mg / mL of sorbitol, approximately 1.47 mg / mL of histidine buffer and approximately 0.020% (w / v) of poloxamer 188, with a pH of approximately 5.2; h) approximately 45 mg / mL of sorbitol, approximately 1.47 mg / mL of histidine buffer and approximately 0.020% (w / v) of poloxamer 188, with a pH of approximately 5.5; i) approximately 45 mg / mL of sorbitol, approximately 1.47 mg / mL of histidine buffer and approximately 0.020% (w / v) of poloxamer 188, with a pH of approximately 5.8; j) approximately 45 mg / mL of sorbitol, approximately 1.30 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.2; k) approximately 45 mg / mL of sorbitol, approximately 1.30 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.5;l) approximately 45 mg / mL of sorbitol, approximately 1.30 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.8; m) approximately 45 mg / mL of sorbitol, approximately 1.60 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.2; n) approximately 45 mg / mL of sorbitol, approximately 1.60 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.5; or Petition 870250078565, dated 03 / 09 / 2025, p. 46 / 69 4 / 6 o) approximately 45 mg / mL of sorbitol, approximately 1.60 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.

8.

12. Aqueous liquid formulation according to any one of claims 1 to 8 and 10, characterized by comprising: (i) about 100 mg / mL of golimumab; and (ii) one of the following: a) about 41 mg / mL of sorbitol, about 0.87 mg / mL of histidine buffer and about 0.015% (w / v) of poloxamer 188, with a pH of about 5.2; b) about 41 mg / mL of sorbitol, about 0.87 mg / mL of histidine buffer and about 0.015% (w / v) of poloxamer 188, with a pH of about 5.5; c) approximately 41 mg / mL of sorbitol, approximately 0.87 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.8; d) approximately 41 mg / mL of sorbitol, approximately 0.87 mg / mL of histidine buffer and approximately 0.010% (w / v) of poloxamer 188, with a pH of approximately 5.2; e) approximately 41 mg / mL of sorbitol, approximately 0.87 mg / mL of histidine buffer and approximately 0.010% (w / v) of poloxamer 188, with a pH of approximately 5.5;f) approximately 41 mg / mL of sorbitol, approximately 0.87 mg / mL of histidine buffer and approximately 0.010% (w / v) of poloxamer 188, with a pH of approximately 5.8; g) approximately 41 mg / mL of sorbitol, approximately 0.87 mg / mL of histidine buffer and approximately 0.020% (w / v) of poloxamer 188, with a pH of approximately 5.2; Petition 870250078565, dated 03 / 09 / 2025, p. 47 / 69 5 / 6 h) approximately 41 mg / mL of sorbitol, approximately 0.87 mg / mL of histidine buffer and approximately 0.020% (w / v) of poloxamer 188, with a pH of approximately 5.5; i) approximately 41 mg / mL of sorbitol, approximately 0.87 mg / mL of histidine buffer and approximately 0.020% (w / v) of poloxamer 188, with a pH of approximately 5.8; j) approximately 41 mg / mL of sorbitol, approximately 0.60 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.2; k) approximately 41 mg / mL of sorbitol, approximately 0.60 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH of approximately 5.5;l) approximately 41 mg / mL of sorbitol, approximately 0.60 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH around 5.8; m) approximately 41 mg / mL of sorbitol, approximately 1.00 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH around 5.2; n) approximately 41 mg / mL of sorbitol, approximately 1.00 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH around 5.5; or o) approximately 41 mg / mL of sorbitol, approximately 1.00 mg / mL of histidine buffer and approximately 0.015% (w / v) of poloxamer 188, with a pH around 5.

8.

13. Aqueous liquid formulation, according to any one of claims 1 to 12, characterized in that the formulation exhibits a surfactant concentration loss of 40% or less when stored for one month at 25°C, preferably a surfactant concentration loss of 15% or less. Petition 870250078565, dated 03 / 09 / 2025, p. 48 / 69 6 / 6 14. Aqueous liquid formulation, according to any one of claims 1 to 13, characterized in that the formulation exhibits a surfactant concentration loss of 50% or less when stored for one month at 40°C, preferably a surfactant concentration loss of 15% or less.

15. Aqueous liquid formulation, according to any one of claims 1 to 14, characterized by being for use in the treatment or prevention of rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis, moderate to severe active ulcerative colitis, active polyarticular juvenile idiopathic arthritis. Petition 870250078565, dated 03 / 09 / 2025, p. 49 / 69

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