Stable Liquid Pharmaceutical Formulation, Container, and Kit

Abstract

The present disclosure provides pharmaceutical formulations comprising one or more antibodies or antigen-binding fragments thereof that bind to the cat allergen Fel d1. The formulations may contain, in addition to the anti-Fel d1 antibody, a buffer, a thermal stabilizer, a viscosity reducer, and a surfactant. In one aspect, co-formulations comprising two anti-Fel d1 antibodies are provided that have acceptable stability and optimal viscosity.

Description

104 Stable Liquid Pharmaceutical Formulation, Container, and Kit CROSS-REFERENCE TO RELATED REQUESTS

[001] This application claims priority over the Patent Application United States Provisional Order No. 63 / 487,791, filed March 1, 2023, the contents of which are incorporated herein by reference. SEQUENCE LISTING

[002] An official copy of the sequence listing is sent simultaneously with the specification electronically via the Patent Office. The contents of the electronic sequence listing (10852WO01_Sequence_Listing_ST26.xml; Size: 32,768 bytes; and Creation Date: February 29, 2024) are incorporated herein by reference in their entirety. FIELD OF THE INVENTION

[003] This disclosure relates to therapeutic antibody formulations. More specifically, this disclosure relates to the field of pharmaceutical formulations comprising one or more human antibodies that bind specifically to the cat allergen Fel d1. FUNDAMENTALS

[004] Cat allergens are among the most significant indoor allergens and are a common cause of IgE-mediated allergic diseases worldwide. The most dominant allergen in cats is Felis domesticus allergen 1 (Fel dl); it is estimated that approximately 90% to 95% of individuals allergic to cats are sensitized to Fel d1 (van Ree et al., J. Allergy Clin. Immunol. 1999, 104:1223-1230). Fel d1 is produced by the cat's skin and salivary and lacrimal glands (Kleine-Tebbe et al., Int Arch Allergy Immunol 1993, 100:256-62). Dried saliva and dander are spread by the cat's fur into the surrounding environment as small airborne particles that readily adhere to surfaces such as Petition 870250097901, dated 10 / 27 / 2025, page 6 / 139 / 104 walls, carpets, and furniture. Although the largest amount of the Fel dl allergen is found in households with cats, the allergen can also be transported to locations without cats, such as cars, schools, and homes, and can persist in these areas for months to years (see, for example, Neisler et al., Aerobiology 2016, 32:571-580). Therefore, Fel dl is an attractive therapeutic target for the treatment of patients allergic to cats. Antibodies to Fel dl are described, for example, in US Patents Nos. 9,079,948, 10,047,153, and 11,174,305.

[005] Therapeutic macromolecules, such as antibodies, must be formulated in a way that not only makes them suitable for administration to patients but also maintains their stability during storage. For example, therapeutic antibodies in liquid solution are prone to degradation, aggregation, and / or undesirable chemical modifications unless the solution is formulated correctly. The stability of an antibody in a liquid formulation depends not only on the types of excipients used in the formulation but also on the amounts and proportions of the excipients relative to each other. Furthermore, considerations beyond stability must be taken into account when preparing a liquid antibody formulation. Examples of such additional considerations include the viscosity of the solution and the antibody concentration that can be accommodated by a given formulation, and the visual quality or appeal of the formulation.Co-formulating two or more therapeutic antibodies in the same formulation is even more challenging, as each antibody may have very different requirements for pH, excipients, and / or appropriate ionic strength. SUMMARY

[006] In one aspect, stable liquid pharmaceutical formulations are provided comprising at least one antibody that specifically binds to Fel d1. In some embodiments, the formulation Petition 870250097901, dated 10 / 27 / 2025, page 7 / 139 / 104 includes: (a) at least one antibody that binds specifically to Fel dl, wherein the antibody is selected from the group consisting of: (i) an antibody comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:4, an HCDR2 comprising the amino acid sequence of SEQ ID NO:6, an HCDR3 comprising the amino acid sequence of SEQ ID NO:8, an LCDR1 comprising the amino acid sequence of SEQ ID NO:12, an LCDR2 comprising the amino acid sequence AAS and an LCDR3 comprising the amino acid sequence of SEQ ID NO:14; and (ii) an antibody comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:18, an HCDR2 comprising the amino acid sequence of SEQ ID NO:20, an HCDR3 comprising the amino acid sequence of SEQ ID NO:22, an LCDR1 comprising the amino acid sequence of SEQ ID NO:26, an LCDR2 comprising the amino acid sequence KAS and an LCDR3 comprising the amino acid sequence of SEQ ID NO:28; (b) a buffer containing histidine; (c) a thermal stabilizer; and (d) a surfactant; where the formulation has a pH of 6.0 ± 0.3.

[007] In some embodiments, the stable liquid pharmaceutical formulation comprises (i) a first antibody that specifically binds to Fel d1, wherein the first antibody comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO:4, an HCDR2 comprising the amino acid sequence of SEQ ID NO:6, an HCDR3 comprising the amino acid sequence of SEQ ID NO:8, an LCDR1 comprising the amino acid sequence of SEQ ID NO:12, an LCDR2 comprising the amino acid sequence AAS, and an LCDR3 comprising the sequence of Petition 870250097901, dated 10 / 27 / 2025, p. 8 / 139 / 104 amino acids of SEQ ID NO:14; and (ii) a second antibody that specifically binds to Fel d1, wherein the second antibody comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO:18, a HCDR2 comprising the amino acid sequence of SEQ ID NO:20,um HCDR3 comprising the amino acid sequence of SEQ ID NO:22,um LCDR1 comprising the amino acid sequence of SEQ ID NO:26,um LCDR2 comprising the amino acid sequence KAS, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:28.

[008] In some embodiments, the first antibody comprises a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO:2 and a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO:10.

[009] In some embodiments, the second antibody comprises an HCVR comprising the amino acid sequence of SEQ ID NO:16 and an LCVR comprising the amino acid sequence of SEQ ID NO:24.

[0010] In some embodiments, the total antibody concentration is up to 200 mg / mL (e.g., up to 50 mg / mL, up to 100 mg / mL, or up to 150 mg / mL). In some embodiments, the total antibody concentration is from 5 mg / mL to 200 mg / mL. In some embodiments, the total antibody concentration is from 50 mg / mL to 200 mg / mL. In some embodiments, the total antibody concentration is 150 mg / mL ± 15 mg / mL. In some embodiments, where the formulation comprises two antibodies, the first antibody and the second antibody are present in the formulation in a molecular ratio of 1:1 or about 1:1. In some embodiments, the first antibody is present at a concentration of 75 mg / mL ± 7.5 mg / mL and the second antibody is present at a concentration of 75 mg / mL ± 7.5 mg / mL.

[0011] In some embodiments, the buffer comprises histidine at a concentration of 5 mM to 25 mM. Petition 870250097901, dated 10 / 27 / 2025, p. 9 / 139 / 104

[0012] In some embodiments, histidine is present at a concentration of 10 mM ± 2 mM.

[0013] In some embodiments, the thermal stabilizer comprises sucrose, trehalose, proline or sorbitol.

[0014] In some embodiments, the thermal stabilizer comprises sucrose at a concentration of 2.5% w / v ± 7.5% w / v. In some embodiments, sucrose is present at a concentration of 5% w / v ± 1% w / v.

[0015] In some embodiments, the stable liquid pharmaceutical formulation also includes a viscosity reducer.

[0016] In some embodiments, the viscosity reducer comprises arginine. In some embodiments, arginine is present at a concentration of 60 mM to 130 mM. In some embodiments, arginine is present at a concentration of at least 70 mM. In some embodiments, arginine is present at a concentration of 70 mM ± 14 mM.

[0017] In some embodiments, the surfactant comprises polysorbate 20 or polysorbate 80. In some embodiments, polysorbate 20 or polysorbate 80 is present at a concentration of 0.05% w / v ± 0.25% w / v, for example, 0.05% w / v ± 0.2% w / v or 0.075% w / v ± 0.2% w / v. In some embodiments, the surfactant comprises polysorbate 80 at a concentration of 0.15% w / v ± 0.075% w / v.

[0018] In some embodiments, the stable liquid pharmaceutical formulation comprises: histidine at a concentration of 10 mM ± 2 mM; sucrose at a concentration of 5% w / v ± 1% w / v; arginine at a concentration of 70 mM ± 14 mM; polysorbate 80 at a concentration of 0.15% w / v ± 0.075% w / v; where the total concentration of antibodies in the formulation is Petition 870250097901, dated 10 / 27 / 2025, page 10 / 139 / 104 150 mg / mL ± 15 mg / mL, and where the formulation has a pH of 6.0 ± 0.3.

[0019] In some embodiments, the stable liquid pharmaceutical formulation has a viscosity < 30 cP at 20°C. In some embodiments, the stable liquid pharmaceutical formulation has a viscosity < 25 cP at 20°C. In some embodiments, the stable liquid pharmaceutical formulation has a viscosity < 20 cP at 20°C. In some embodiments, the stable liquid pharmaceutical formulation has a viscosity < 15 cP at 20°C.

[0020] In some embodiments, the stable liquid pharmaceutical formulation comprises: an anti-Fel D1 antibody comprising an HCVR comprising the amino acid sequence of SEQ ID NO:2 and an LCVR comprising the amino acid sequence of SEQ ID NO:10, wherein the antibody concentration is from 50 mg / mL to 190 mg / mL; histidine at a concentration of 10 mM ± 2 mM; sucrose at a concentration of 5% w / v ± 1% w / v; arginine at a concentration of 70 mM ± 14 mM; and polysorbate 80 at a concentration of 0.15% w / v ± 0.075% w / v; wherein the formulation has a pH of 6.0 ± 0.3.

[0021] In some embodiments, the stable liquid pharmaceutical formulation comprises: an anti-Fel D1 antibody comprising an HCVR comprising the amino acid sequence of SEQ ID NO:16 and an LCVR comprising the amino acid sequence of SEQ ID NO:24, wherein the antibody concentration is from 50 mg / mL to 190 mg / mL; histidine at a concentration of 10 mM ± 2 mM; sucrose at a concentration of 5% w / v ± 1% w / v; and polysorbate 20 or polysorbate 80 at a concentration of 0.15% w / v ± 0.075% w / v; Petition 870250097901, dated 10 / 27 / 2025, page 11 / 139 / 104, in which the formulation has a pH of 6.0 ± 0.3.

[0022] In some embodiments, the stable liquid pharmaceutical formulation further comprises a viscosity reducer. In some embodiments, the viscosity reducer is arginine at a concentration of 70 mM ± 14 mM.

[0023] In some embodiments, the stable liquid pharmaceutical formulation comprises: a first antibody that binds specifically to Fel d1, wherein the first antibody comprises an HCVR comprising the amino acid sequence of SEQ ID NO:2 and an LCVR comprising the amino acid sequence of SEQ ID NO:10, wherein the concentration of the first antibody is 75 mg / mL ± 10 mg / mL; a second antibody that binds specifically to Fel d1, wherein the second antibody comprises an HCVR comprising the amino acid sequence of SEQ ID NO:16 and an LCVR comprising the amino acid sequence of SEQ ID NO:24, wherein the concentration of the second antibody is 75 mg / mL ± 10 mg / mL; histidine at a concentration of 10 mM ± 2 mM; sucrose at a concentration of 5% w / v ± 1% w / v; arginine at a concentration of 70 mM ± 14 mM; and polysorbate 80 at a concentration of 0.15% w / v ± 0.075% w / v; wherein the formulation has a pH of 6.0 ± 0.3.

[0024] In some embodiments, the stable liquid pharmaceutical formulation is contained in a container selected from the group consisting of a glass vial, a syringe, a pre-filled syringe, a pen-type administration device, and an autoinjector administration device. In some embodiments, the stable liquid pharmaceutical formulation is contained in a large-volume device or bolus injector.

[0025] In another aspect, a container is provided containing a Petition 870250097901, dated 10 / 27 / 2025, page 12 / 139 / 104 stable liquid pharmaceutical formulation, as described herein.

[0026] In another aspect, a kit is provided. In some models, the kit includes: (i) a container containing a stable liquid pharmaceutical formulation, as described herein; and (ii) marking for use of the pharmaceutical formulation. In some embodiments, the labeling indicates subcutaneous or intravenous administration of the pharmaceutical formulation.

[0027] In some embodiments, the kit comprises a stable liquid pharmaceutical formulation comprising: (a) an antibody that specifically binds to Fel d1, wherein the antibody comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO:4, an HCDR2 comprising the amino acid sequence of SEQ ID NO:6, an HCDR3 comprising the amino acid sequence of SEQ ID NO:8, an LCDR1 comprising the amino acid sequence of SEQ ID NO:12, an LCDR2 comprising the amino acid sequence AAS and an LCDR3 comprising the amino acid sequence of SEQ ID NO:14; (b) a buffer containing histidine; (c) a thermal stabilizer; and (d) a surfactant; where the formulation has a pH of 6.0 ± 0.3.

[0028] In some embodiments, the kit comprises an antibody comprising an HCVR comprising the amino acid sequence of SEQ ID NO:2 and an LCVR comprising the amino acid sequence of SEQ ID NO:10.

[0029] In some embodiments, the kit comprises a stable liquid pharmaceutical formulation comprising: an anti-Fel D1 antibody comprising an HCVR Petition 870250097901, dated 10 / 27 / 2025, page 13 / 139 / 104 comprising the amino acid sequence of SEQ ID NO:2 and an LCVR comprising the amino acid sequence of SEQ ID NO:10, in which the antibody concentration is from 50 mg / mL to 190 mg / mL; histidine at a concentration of 10 mM ± 2 mM; Sucrose at a concentration of 5% w / v ± 1% w / v; and polysorbate 80 at a concentration of 0.15% w / v ± 0.075% w / v; wherein the formulation has a pH of 6.0 ± 0.3.

[0030] In some embodiments, the kit comprises a stable liquid pharmaceutical formulation comprising: (a) an antibody that specifically binds to Fel d1, wherein the antibody comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO:18, an HCDR2 comprising the amino acid sequence of SEQ ID NO:20, an HCDR3 comprising the amino acid sequence of SEQ ID NO:22, an LCDR1 comprising the amino acid sequence of SEQ ID NO:26, an LCDR2 comprising the amino acid sequence KAS and an LCDR3 comprising the amino acid sequence of SEQ ID NO:28; (b) a buffer containing histidine; (c) a thermal stabilizer; and (d) a surfactant; where the formulation has a pH of 6.0 ± 0.3.

[0031] In some embodiments, the kit comprises an antibody comprising an HCVR comprising the amino acid sequence of SEQ ID NO:16 and an LCVR comprising the amino acid sequence of SEQ ID NO:24.

[0032] In some embodiments, the kit comprises a stable liquid pharmaceutical formulation comprising: an anti-Fel D1 antibody comprising an HCVR comprising the amino acid sequence of SEQ ID NO:16 and an LCVR Petition 870250097901, dated 10 / 27 / 2025, page 14 / 139 / 104 comprising the amino acid sequence of SEQ ID NO: 24, in which the antibody concentration is from 50 mg / mL to 190 mg / mL; histidine at a concentration of 10 mM ± 2 mM; sucrose at a concentration of 5% w / v ± 1% w / v; and polysorbate 20 or polysorbate 80 at a concentration of 0.15% w / v ± 0.075% w / v; where the formulation has a pH of 6.0 ± 0.3.

[0033] In some embodiments, the kit comprises a stable liquid pharmaceutical formulation, as described above, and further comprises a viscosity reducer. In some embodiments, the viscosity reducer is arginine at a concentration of 70 mM ± 14 mM.

[0034] In some embodiments, the kit comprises a stable liquid pharmaceutical formulation comprising: a first antibody that binds specifically to Fel d1, wherein the first antibody comprises an HCVR comprising the amino acid sequence of SEQ ID NO:2 and an LCVR comprising the amino acid sequence of SEQ ID NO:10, wherein the concentration of the first antibody is 75 mg / mL ± 10 mg / mL; a second antibody that binds specifically to Fel d1, wherein the second antibody comprises an HCVR comprising the amino acid sequence of SEQ ID NO:16 and an LCVR comprising the amino acid sequence of SEQ ID NO:24, wherein the concentration of the second antibody is 75 mg / mL ± 10 mg / mL; histidine at a concentration of 10 mM ± 2 mM; sucrose at a concentration of 5% w / v ± 1% w / v; arginine at a concentration of 70 mM ± 14 mM; and polysorbate 80 at a concentration of 0.15% w / v ± 0.075% w / v; where the formulation has a pH of 6.0 ± 0.3.

[0035] Other modalities will become apparent from a review Petition 870250097901, dated 10 / 27 / 2025, page 15 / 139 / 104 of the detailed description below. BRIEF DESCRIPTION OF THE FIGURES

[0036] FIG. 1A. Percent increase in HMW species of 150 mg / mL REGN1908 () or REGN1909 (♦) formulations in 10 mM histidine buffer at different pHs after incubation at 45°C for 28 days.

[0037] FIG. 1B. Percent increase in HMW species of 150 mg / mL REGN1908 () or REGN1909 (♦) formulations in 10 mM histidine buffer at different pHs after incubation at 25°C for 2 months.

[0038] FIG. 2. Viscosity (cP at 20°C) of 150 mg / mL REGN1908 () or REGN1909 (·) formulations in 10 mM histidine buffer at different pHs.

[0039] FIG. 3. Viscosity (cP at 20°C) of formulations containing 10 mM histidine, pH 6.0 and REGN1908 () or REGN1909 (·) at different concentrations.

[0040] FIG. 4. Effect of excipients on viscosity (cP at 20°C) for formulations comprising a target concentration of 150 mg / mL of REGN1908 or REGN1909, and 10 mM histidine pH 6.0, 10 mM histidine pH 6.0 + 70 mM arginine, 100 mM histidine pH 6.0, 10 mM histidine pH 6.0 + 3% proline, or 10 mM histidine pH 6.0 + 70 mM NaCl.

[0041] FIG. 5. Effect of sucrose cryoprotectant on viscosity (cP at 20°C) for formulations comprising a target concentration of 150 mg / mL REGN1908 (♦) or REGN1909 (), 10 mM histidine, pH 6.0.

[0042] FIG. 6. Effect of viscosity reducer and cryoprotectant on viscosity (cP at 20°C) for a formulation comprising a target concentration of 150 mg / mL of REGN1908, 10 mM, pH 6.2, in the absence of viscosity reducer and cryoprotectant or in the presence of 70 mM arginine + 5% sucrose.

[0043] FIG. 7A. Average viscosity (mPa-s / cP) of formulations Petition 870250097901, dated 10 / 27 / 2025, p. 16 / 139 / 104 containing a target concentration of 150 mg / mL REGN1908, 10 mM histidine, 5% sucrose, pH 6.1 with different amounts of viscosity reducer arginine.

[0044] FIG. 7B. Average viscosity (mPa-s / cP) of formulations containing a target concentration of 150 mg / mL REGN1909, 10 mM histidine, 5% sucrose, pH 6.1 with different amounts of arginine viscosity reducer.

[0045] FIG. 7C. Average viscosity (mPa-s / cP) of formulations containing a target concentration of 150 mg / mL of total antibody (REGN1908 + REGN1909), 10 mM histidine, 5% sucrose, pH 6.1 with different amounts of arginine viscosity reducer.

[0046] FIG. 8A. The REGN1908-REGN1909 co-formulations without polysorbate 20 (PS20) or with 0.01%, 0.025%, 0.05%, 0.075%, 0.1% or 0.2% (w / v) PS20 were evaluated in a shaking assay for aggregation suppression, measured by the percentage change in HMW at time 0 (·), 24 hours (▲) or 48 hours (▼). Inset graph = an enlarged / exploded view of the data, allowing visualization of the minimum amount of PS20 surfactant needed to cause little or no change in the percentage of HMW species (aggregates). LSL = Lower Specification Limit.

[0047] FIG. 8B. The REGN1908-REGN1909 co-formulations without polysorbate 80 (PS80) or with 0.01%, 0.025%, 0.05%, 0.075%, 0.1% or 0.2% (w / v) of PS80 were evaluated in a shaking assay for aggregation suppression, measured by the percentage change in HMW at time 0 (·), 24 hours (▲) or 48 hours (▼). Inserted graph = an enlarged / exploded view of the data, allowing visualization of the minimum amount of PS80 surfactant needed to cause little or no change in the percentage of HMW species (aggregates). LSL = Lower Specification Limit.

[0048] FIG. 9. The formation of subvisible particles was evaluated using microfluidic images (>10 μM and >25 μM) at time 0 or 48 hours, Petition 870250097901, dated 10 / 27 / 2025, page 17 / 139 / 104 for co-formulations REGN1908-REGN1909 without polysorbate 20 (PS20) or polysorbate 80 (PS80) or with 0.01%, 0.025%, 0.05%, 0.075%, 0.1% or 0.2% (w / v) of PS20 or PS80.

[0049] FIG. 10A. Accelerated stability study for coformulations comprising REGN1908-REGN1909 (150 mg / mL total antibody), 10 mM histidine, 70 mM arginine, 0.15% (w / v) polysorbate 20, pH 6.0 and 2.5% sorbitol (·), 3% proline (▲), 5% sucrose (▼), 5% trehalose (), or no cryoprotectant (♦).

[0050] FIG. 10B. Freeze / thaw stability study for coformulations comprising REGN1908-REGN1909 (150 mg / mL total antibody), 10 mM histidine, 70 mM arginine, 0.15% (w / v) polysorbate 20, pH 6.0 and 2.5% sorbitol (•), 3% proline (▲), 5% sucrose (▼), 5% trehalose (), or no cryoprotectant (♦).

[0051] FIG. 10C. Accelerated stability study for coformulations comprising REGN1908-REGN1909 (150 mg / mL total antibody), 10 mM histidine, 70 mM arginine, 0.15% (w / v) polysorbate 80, pH 6.0 and 2.5% sorbitol (·), 3% proline (▲), 5% sucrose (▼), 5% trehalose (), or no cryoprotectant (♦).

[0052] FIG. 10D. Freeze / thaw stability study for coformulations comprising REGN1908-REGN1909 (150 mg / mL total antibody), 10 mM histidine, 70 mM arginine, 0.15% (w / v) polysorbate 80, pH 6.0 and 2.5% sorbitol (•), 3% proline (▲), 5% sucrose (▼), 5% trehalose (), or no cryoprotectant (♦).

[0053] FIG. 11 The thermal profiler demonstrates the predicted formulation responses at 40°C as a function of the variation of the formulation components. The columns describe the formulation components: Concentration of REGN1908-REGN1909 (from 135 mg / mL to 165 mg / mL), pH Petition 870250097901, dated 10 / 27 / 2025, page 18 / 139 / 104 (from 5.5 to 6.5), histidine (from 6 mM to 14 mM), polysorbate 80 (from 0.075% to 0.2% w / v), arginine (from 42 mM to 98 mM) and sucrose (from 3% to 7% w / v). The lines describe the predicted responses of a formulation attribute: change in total protein recovery percentage, change in total HMW percentage, change in total acidic species percentage, change in total basic species percentage, change in particle formation (10 micron compartment) and change in particle formation (25 micron compartment).

[0054] FIG. 12 The agitation profiler demonstrates the predicted responses of the formulation under agitation stress as a function of the variation of the formulation components. The columns describe the formulation components: REGN1908-REGN1909 concentration (from 135 mg / mL to 165 mg / mL), pH (from 5.5 to 6.5), histidine (from 6 mM to 14 mM), polysorbate 80 (from 0.075% to 0.2% w / v), arginine (from 42 mM to 98 mM), and sucrose (from 3% to 7% w / v). The rows describe the predicted responses of a formulation attribute: change in total protein recovery percentage, change in total HMW percentage, change in particle formation (10 micron compartment), and change in particle formation (25 micron compartment).

[0055] FIG. 13 The freeze-thaw profiler demonstrates the predicted responses of the formulation under freeze-thaw stress as a function of the variation of the formulation components. The columns describe the formulation components: REGN1908-REGN1909 concentration (from 135 mg / mL to 165 mg / mL), pH (from 5.5 to 6.5), histidine (from 6 mM to 14 mM), polysorbate 80 (from 0.075% to 0.2% w / v), arginine (from 42 mM to 98 mM), and sucrose (from 3% to 7% w / v). The rows describe the predicted responses of a formulation attribute: change in total protein recovery percentage, change in total HMW percentage, change in particle formation. Petition 870250097901, dated 10 / 27 / 2025, page 19 / 139 / 104 (10 micron compartment) and alteration in particle formation (25 micron compartment).

[0056] FIG. 14. The T=0 profiler demonstrates the predicted viscosity and osmolality responses as a function of the variation of the formulation components. The columns describe the formulation components: REGN1908-REGN1909 concentration (from 135 mg / mL to 165 mg / mL), pH (from 5.5 to 6.5), histidine (from 6 mM to 14 mM), polysorbate 80 (from 0.075% to 0.2% w / v), arginine (from 42 mM to 98 mM), and sucrose (from 3% to 7% w / v). The rows represent the predicted responses of a formulation attribute: viscosity at t=0 and osmolality at t=0. DETAILED DESCRIPTION Definitions

[0057] Before describing the present invention, it should be understood that the invention is not limited to the particular experimental methods and conditions described, as such methods and conditions may vary. Furthermore, it should be understood that the terminology used in this document is intended only to describe specific embodiments and is not intended to be a limiting factor, since the scope of the present invention will be limited only by the appended claims.

[0058] Unless otherwise defined, all technical and scientific terms used in this document have the same meaning as commonly understood by a person skilled in the art to which this invention pertains.

[0059] As used in this document, the term approximately, when used in reference to a given quoted numerical value, means that the value may vary from the quoted value by no more than 1%. For example, as used in this document, the expression approximately 100 includes 99 and 101 and all intermediate values ​​(e.g., 99.1, 99.2, 99.3, 99.4, etc.).

[0060] As used herein, the expression pharmaceutical formulation Petition 870250097901, dated 10 / 27 / 2025, p. 20 / 139 / 104, means a combination of at least one active ingredient (e.g., an antibody, small molecule, compound, etc. that is capable of exerting a biological effect on a human or non-human animal) and at least one inactive ingredient that, when combined with the active ingredient and / or one or more additional inactive ingredients, is suitable for therapeutic administration to a human or non-human animal. The term formulation, as used herein, means pharmaceutical formulation unless specifically indicated otherwise. This disclosure provides pharmaceutical formulations comprising at least one therapeutic polypeptide. According to certain embodiments of this disclosure, the therapeutic polypeptide is an antibody, or an antigen-binding fragment thereof, that specifically binds to Fel d1.In some embodiments, this disclosure includes pharmaceutical formulations comprising: (i) one or more human antibodies that bind specifically to Fel d1; (ii) one or more buffers; (iii) a thermal stabilizer; (iv) a viscosity reducer; and optionally (v) a surfactant. In some embodiments, this disclosure includes pharmaceutical formulations comprising: (i) one or more human antibodies that bind specifically to Fel d1; (ii) one or more buffers; (iii) a thermal stabilizer; (iv) a surfactant; and optionally (v) a viscosity reducer. In a specific embodiment, the pharmaceutical formulation comprises: (i) two human antibodies that bind specifically to Fel d1; (ii) one or more buffers; (iii) a thermal stabilizer; (iv) a viscosity reducer; and (v) a surfactant.Additional components may be included in the formulations of this disclosure if such components do not significantly interfere with the viscosity and stability of the formulation. Specific exemplary components and formulations included in this disclosure are described in detail below.

[0061] The term excipient, as used herein, means any Petition 870250097901, dated 10 / 27 / 2025, page 21 / 139 / 104 non-therapeutic agent added to the formulation to provide a desired consistency, viscosity or stabilizing effect.

[0062] The pharmaceutical formulations of this disclosure may, in certain embodiments, be fluid formulations. As used herein, the term fluid formulation means a mixture of at least two components that exists predominantly in the fluid state between about 2 °C and about 45 °C. Fluid formulations include, among others, liquid formulations. Fluid formulations may be of low, moderate, or high viscosity, depending on their specific constituents.

[0063] The term antibody, as used herein, refers to an antigen-binding molecule or molecular complex comprising a set of complementarity-determining regions (CDRs) that specifically bind to or interact with a specific antigen (e.g., Fel d1). The term “antibody,” as used herein, includes immunoglobulin molecules comprising four polypeptide chains, two heavy chains (H) and two light chains (L) interconnected by disulfide bonds, as well as their multimers (e.g., IgM). In a typical antibody, each heavy chain comprises a variable heavy chain region (abbreviated herein as HCVR or VH) and a constant heavy chain region. The constant heavy chain region comprises three domains, CH1, CH2, and CH3. Each light chain comprises a variable light chain region (abbreviated herein as LCVR or VL) and a constant light chain region. The constant light chain region comprises one domain (CL1).The VH and VL regions can be subdivided into regions of hypervariability, called complementarity-determining regions (CDRs), interspersed with more conserved regions, called framework regions (FRs). Each VH and VL is composed of three CDRs and four FRs, arranged from the amino terminal to the carboxy terminal in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. In some modalities, the FRs of... Petition 870250097901, dated 10 / 27 / 2025, p. 22 / 139 / 104 antibody (or its antigen-binding portion) may be identical to human germline sequences or may be modified naturally or artificially. A consensus amino acid sequence may be defined based on a side-by-side analysis of two or more CDRs.

[0064] Unless specifically indicated otherwise, the term “antibody,” as used herein, also includes antigen-binding fragments of complete antibody molecules. The terms “antigen-binding portion” of an antibody, “antigen-binding fragment” of an antibody, “antigen-binding domain,” and the like, as used herein, include any naturally occurring, enzymatically obtained, synthetic, or genetically modified polypeptide or glycoprotein that specifically binds to an antigen to form a complex.Non-limiting examples of antigen-binding fragments include: (i) Fab fragments; (ii) F(ab')2 fragments; (iii) Fd fragments; (iv) Fv fragments; (v) single-chain Fv molecules (scFv); (vi) dAb fragments; and (vii) minimal recognition units consisting of amino acid residues that mimic the hypervariable region of an antibody (e.g., an isolated complementarity-determining region (CDR), such as a CDR3 peptide) or a restricted FR3-CDR3-FR4 peptide. Other engineered molecules, such as domain-specific antibodies, single-domain antibodies, domain-deleted antibodies, chimeric antibodies, CDR-grafted antibodies, diabodies, triabodies, tetrabodies, minibodies, nanobodies (e.g., monovalent nanobodies, bivalent nanobodies, etc.), small modular immunodrugs (SMIPs), and shark variable IgNAR domains, are also encompassed by the expression antigen-binding fragment, as used herein.

[0065] The term “human antibody,” as used herein, is intended to include antibodies with variable and constant regions derived from human germline immunoglobulin sequences. Human antibodies Petition 870250097901, of 10 / 27 / 2025, p. 23 / 139 / 104 of the disclosure may, however, include amino acid residues not encoded by human germline immunoglobulin sequences (e.g., mutations introduced by random or site-specific mutagenesis in vitro or by somatic mutation in vivo), for example in CDRs and in particular in CDR3. However, the term “human antibody,” as used herein, is not intended to include antibodies in which germline-derived CDR sequences from another mammalian species, such as a mouse, have been grafted onto human structural sequences.

[0066] The term “recombinant antibody,” as used herein, is intended to include all antibodies that are prepared, expressed, created, or isolated by recombinant means.The term includes, but is not limited to, antibodies expressed using a recombinant expression vector transfected into a host cell (e.g., Chinese hamster ovary (CHO) cell) or cell expression system, antibodies isolated from a recombinant combinatorial human antibody library, and antibodies isolated from a non-human animal (e.g., a mouse, such as a mouse that is transgenic for human immunoglobulin genes (see, for example, Taylor et al. (1992) Nucl. Acids Res. 20:6287-6295)). In some embodiments, the recombinant antibody is a recombinant human antibody. In some embodiments, recombinant human antibodies possess variable and constant regions derived from human germline immunoglobulin sequences.In certain embodiments, however, such recombinant human antibodies are subjected to in vitro mutagenesis (or, when a transgenic animal for human Ig sequences is used, in vivo somatic mutagenesis) and, therefore, the amino acid sequences of the Vh and Vl regions of the recombinant antibodies are sequences that, although derived from and related to sequences of the human germline Vh and Vl, may not naturally exist in the germline repertoire of human antibodies. Petition 870250097901, dated 10 / 27 / 2025, page 24 / 139 / 104 vivo.

[0067] An isolated antibody refers to an antibody that has been identified and separated and / or recovered from at least one component of its natural environment. For example, an antibody that has been separated or removed from at least one component of an organism, or from a tissue or cell in which the antibody naturally exists or is naturally produced, is an isolated antibody. An isolated antibody also includes an antibody in situ within a recombinant cell. Isolated antibodies are antibodies that have undergone at least one purification or isolation step. According to certain embodiments, an isolated antibody may be substantially free of other cellular materials and / or chemicals.

[0068] The term “specifically binds,” or similar, means that an antibody or antigen-binding fragment forms a complex with an antigen that is relatively stable under physiological conditions. Specific binding can be characterized by an equilibrium dissociation constant of at least about 1x10⁻⁶ M or less, for example, 10⁻⁷ M, 10⁻⁸ M, 10⁻⁹ M, 10⁻¹⁰ M, 10⁻¹¹ M, or 10⁻¹² M (a smaller KD denotes tighter binding). Methods for determining whether an antibody specifically binds to an antigen are known in the art and include, for example, equilibrium dialysis, surface plasmon resonance (e.g., BIACORE™), biolayer interferometry assay (e.g., Octet® HTX biosensor), solution affinity ELISA, and the like. In some embodiments, the specific binding is measured in a surface plasmon resonance assay, for example, at 25°C or 37°C.An antibody or antigen-binding fragment that binds specifically to an antigen of one species may or may not have cross-reactivity with other antigens, such as an orthologous antigen from another species. Anti-Fel dl Antibodies and Their Antigen-Binding Fragments Petition 870250097901, dated 10 / 27 / 2025, page 25 / 139 / 104

[0069] The pharmaceutical formulations of the present disclosure may comprise a human antibody, or an antigen-binding fragment thereof, that binds specifically to the cat allergen Fel d1. In some embodiments, a pharmaceutical formulation of the disclosure comprises one or more (e.g., two, three or more) antibodies that bind specifically to Fel d1. Antibodies to Fel d1 are described, for example, in U.S. Patents Nos. 9,079,948, 10,047,153 and 11,174,305 and in WO 2013 / 166236, each of which is incorporated by reference herein.

[0070] In some embodiments, the pharmaceutical formulation comprises one or more antibodies, or antigen-binding fragments thereof, that bind specifically to Fel d1, wherein the antibody comprises: (a) a heavy chain complementarity determination region 1 (HCDR1) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 4 and 18; (b) a heavy chain complementarity determination region 2 (HCDR2) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 6 and 20; (c) a heavy chain complementarity determination region 3 (HCDR3) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 and 22; (d) a light chain complementarity determination region 1 (LCDR1) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 12 and 26; (e) a light chain complementarity-determining region 2 (LCDR2) comprising an amino acid sequence selected from the group consisting of AAS and KAS; and (f) a light chain complementarity-determining region 3 (LCDR3) comprising an amino acid sequence selected Petition 870250097901, dated 10 / 27 / 2025, page 26 / 139 / 104 of the group consisting of SEQ ID Nos: 14 and 28.

[0071] In some embodiments, the anti-Fel d1 antibody comprises a heavy chain variable region (HCVR) comprising an amino acid sequence that has at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with an amino acid sequence selected from the group consisting of SEQ ID NOs: 2 and 16. In some embodiments, the anti-Fel d1 antibody comprises an HCVR comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 2 and 16.

[0072] In some embodiments, the anti-Fel d1 antibody comprises a variable light chain region (LCVR) comprising an amino acid sequence that has at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with an amino acid sequence selected from the group consisting of SEQ ID NOs: 10 and 24. In some embodiments, the anti-Fel d1 antibody comprises an LCVR comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 10 and 24.

[0073] In some embodiments, a pharmaceutical formulation of the present disclosure comprises an anti-Fel d1 antibody or antigen-binding fragment thereof comprising: (a) an HCDR1 comprising the amino acid sequence of SEQ ID NO:4, an HCDR2 comprising the amino acid sequence of SEQ ID NO:6 and an HCDR3 comprising the amino acid sequence of SEQ ID NO:8, an LCDR1 comprising the amino acid sequence of SEQ ID NO:12, an LCDR2 comprising the amino acid sequence AAS and an LCDR3 comprising the amino acid sequence of SEQ ID Petition 870250097901, dated 10 / 27 / 2025, page 27 / 139 / 104 NO:14; or (b) an HCDR1 comprising the amino acid sequence of SEQ ID NO:18, an HCDR2 comprising the amino acid sequence of SEQ ID NO:20 and an HCDR3 comprising the amino acid sequence of SEQ ID NO:22, an LCDR1 comprising the amino acid sequence of SEQ ID NO:26, an LCDR2 comprising the amino acid sequence KAS and an LCDR3 comprising the amino acid sequence of SEQ ID NO:28.

[0074] In some embodiments, a pharmaceutical formulation of the present disclosure comprises at least two anti-Fel d1 antibodies or antigen-binding fragments thereof. In some embodiments, the pharmaceutical formulation comprises (i) a first antibody that specifically binds to Fel d1, wherein the first antibody comprises an HCDR1 comprising the amino acid sequence SEQ ID NO:4, a HCDR2 comprising the amino acid sequence of SEQ ID NO:6,um HCDR3 comprising the amino acid sequence of SEQ ID NO:8,um LCDR1 comprising the amino acid sequence of SEQ ID NO:12,um (i) an LCDR2 comprising the amino acid sequence AAS, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:14; and (ii) a second antibody that specifically binds to Fel d1, wherein the second antibody comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO:18, an HCDR2 comprising the amino acid sequence of SEQ ID NO:20, an HCDR3 comprising the amino acid sequence of SEQ ID NO:22, an LCDR1 comprising the amino acid sequence of SEQ ID NO:26, an LCDR2 comprising the amino acid sequence KAS, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:28.

[0075] In some embodiments, the anti-Fel d1 antibody comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO:4, Petition 870250097901, dated 10 / 27 / 2025, p. 28 / 139 / 104, an HCDR2 comprising the amino acid sequence of SEQ ID NO:6 and an HCDR3 comprising the amino acid sequence of SEQ ID NO:8, an LCDR1 comprising the amino acid sequence of SEQ ID NO:12, an LCDR2 comprising the amino acid sequence AAS and an LCDR3 comprising the amino acid sequence of SEQ ID NO:14.

[0076] In some embodiments, the anti-Fel d1 antibody comprises an HCVR comprising an amino acid sequence that has at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity with SEQ ID NO:2, and / or an LCVR comprising an amino acid sequence that has at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity with SEQ ID NO:10. In some embodiments, the anti-Fel d1 antibody comprises an HCVR comprising the amino acid sequence of SEQ ID NO:2 and / or an LCVR comprising the amino acid sequence of SEQ ID NO:10.In some embodiments, the anti-Fel d1 antibody comprises an HCVR consisting of the amino acid sequence of SEQ ID NO:2 and / or an LCVR consisting of the amino acid sequence of SEQ ID NO:10.

[0077] In some embodiments, the anti-Fel d1 antibody comprises a heavy chain comprising an amino acid sequence that has at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity with SEQ ID NO:29, and / or a light chain comprising an amino acid sequence that has at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% of Petition 870250097901, dated 10 / 27 / 2025, p. 29 / 139 / 104 sequence identity with SEQ ID NO:30. In some embodiments, the anti-Fel d1 antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:29 and / or a light chain comprising the amino acid sequence of SEQ ID NO:30. In some embodiments, the anti-Fel d1 antibody comprises a heavy chain consisting of the amino acid sequence of SEQ ID NO:29 and / or a light chain consisting of the amino acid sequence of SEQ ID NO:30.

[0078] In some embodiments, the anti-Fel d1 antibody comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO:18, an HCDR2 comprising the amino acid sequence of SEQ ID NO:20 and an HCDR3 comprising the amino acid sequence of SEQ ID NO:22, an LCDR1 comprising the amino acid sequence of SEQ ID NO:26, an LCDR2 comprising the amino acid sequence KAS and an LCDR3 comprising the amino acid sequence of SEQ ID NO:28.

[0079] In some embodiments, the anti-Fel d1 antibody comprises an HCVR comprising an amino acid sequence that has at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity with SEQ ID NO:16, and / or an LCVR comprising an amino acid sequence that has at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity with SEQ ID NO:24. In some embodiments, the antiFel d1 antibody comprises an HCVR comprising the amino acid sequence of SEQ ID NO:16 and / or an LCVR comprising the amino acid sequence of SEQ ID NO:24.In some embodiments, the antiFel d1 antibody comprises an HCVR consisting of the amino acid sequence of SEQ ID NO:16 and / or an LCVR consisting of the amino acid sequence of... Petition 870250097901, dated 10 / 27 / 2025, p. 30 / 139 / 104 SEQ ID NO:24.

[0080] In some embodiments, the anti-Fel dl antibody comprises a heavy chain comprising an amino acid sequence that has at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity with SEQ ID NO:31; and / or a light chain comprising an amino acid sequence that has at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity with SEQ ID NO:32. In some embodiments, the anti-Fel d1 antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:31 and / or a light chain comprising the amino acid sequence of SEQ ID NO:32.In some embodiments, the anti-Fel d1 antibody comprises a heavy chain consisting of the amino acid sequence SEQ ID NO:31 and / or a light chain consisting of the amino acid sequence SEQ ID NO:32.

[0081] In some embodiments, an anti-Fel d1 antibody comprises a selected Fc region from the group consisting of human IgG1, IgG2, IgG3, and IgG4 isotypes. In some embodiments, the anti-Fel d1 antibody comprises a human IgG4 isotype.

[0082] In some embodiments, an anti-Fel d1 antibody or its antigen-binding fragment comprises one or more amino acid substitutions, insertions, and / or deletions in the structure and / or CDR regions of the variable heavy and / or light chain domains, compared to the corresponding germline sequences from which the individual antibodies were derived. Such mutations can be easily verified by comparing the amino acid sequences disclosed here with germline sequences available, for example, in databases. Petition 870250097901, dated 10 / 27 / 2025, p. 31 / 139 / 104 public antibody sequences. The antibodies in this disclosure may comprise antigen-binding fragments that are derived from any of the exemplary amino acid sequences disclosed herein, wherein one or more amino acids within one or more structure and / or CDR regions are mutated to the corresponding residue(s) of the germline sequence from which the antibody was derived, or to the corresponding residue(s) of another human germline sequence, or to a conservative amino acid substitution of the corresponding germline residue(s) (such sequence alterations are referred to herein collectively as germline mutations).One skilled in the art, beginning with the variable region sequences of heavy and light chains disclosed in this document, can easily produce numerous antibodies and antigen-binding fragments comprising one or more individual germline mutations or combinations thereof. In certain embodiments, all structure and / or CDR residues within the VH and / or VL domains are mutated back to the residues found in the original germline sequence from which the antibody was originally derived. In other embodiments, only certain residues are mutated back to the original germline sequence, for example, only the mutant residues found in the first 8 amino acids of FR1 or in the last 8 amino acids of FR4, or only the mutant residues found in CDR1, CDR2, or CDR3.In other embodiments, one or more frame and / or CDR residues are mutated to the corresponding residues of a different germline sequence (i.e., a germline sequence that is different from the germline sequence from which the antibody was originally derived). Furthermore, antibodies or antigen-binding fragments may contain any combination of two or more germline mutations within the frame and / or CDR regions, for example, where... Petition 870250097901, dated 10 / 27 / 2025, page 32 / 139 / 104: certain individual residues are mutated to the corresponding residue of a specific germline sequence, while certain other residues that differ from the original germline sequence are retained or mutated to the corresponding residue of a different germline sequence. Once obtained, antibodies or antigen-binding fragments containing one or more germline mutations can be easily tested for one or more desired properties, such as improved binding specificity, increased binding affinity, improved or increased agonist or antagonist biological properties, reduced immunogenicity, etc. Antibodies and antigen-binding fragments obtained in this manner are generally covered by this disclosure.

[0083] This disclosure also includes antibodies or antigen-binding fragments comprising variants of any of the HCVR, LCVR, and / or CDR amino acid sequences disclosed herein, having one or more conservative substitutions. For example, this disclosure includes antibodies or antigen-binding fragments comprising HCVR, LCVR, and / or CDR amino acid sequences with, for example, 10 or less, 9 or less, 8 or less, 7 or less, 6 or less, 5 or less, 4 or less, 3 or less, 2 or less, or 1 conservative amino acid substitution(s) with respect to any of the HCVR, LCVR, and / or CDR amino acid sequences disclosed herein. A conservative amino acid substitution is one in which an amino acid residue is replaced by another amino acid residue with a side chain (R group) with similar chemical properties (e.g., charge or hydrophobicity).In general, a conservative amino acid substitution will not substantially alter the functional properties of a protein. Examples of amino acid groups that have side chains with similar chemical properties include (1) aliphatic side chains:. Petition 870250097901, of 10 / 27 / 2025, page 33 / 139 / 104 glycine, alanine, valine, leucine and isoleucine; (2) aliphatic hydroxyl side chains: serine and threonine; (3) amide-containing side chains: asparagine and glutamine; (4) aromatic side chains: phenylalanine, tyrosine and tryptophan; (5) basic side chains: lysine, arginine and histidine; (6) acidic side chains: aspartate and glutamate, and (7) sulfur-containing side chains are cysteine ​​and methionine. Preferred conservative amino acid substitution groups are: valine-leucine-isoleucine, phenylalanine-tyrosine, lysine-arginine, alanine-valine, glutamate-aspartate, and asparagine-glutamine. Alternatively, a conservative substitution is any change with a positive value in the PAM250 logarithmic likelihood matrix disclosed in Gonnet et al. (1992) Science 256: 1443-1445.A moderately conservative substitution is any change that has a non-negative value in the log PAM250 probability matrix.

[0084] This disclosure also includes antibodies or antigen-binding fragments comprising an HCVR, LCVR, and / or CDR amino acid sequence that is substantially identical to any of the HCVR, LCVR, and / or CDR amino acid sequences disclosed herein. In some embodiments, an antigen-binding molecule comprises an HCVR, LCVR, and / or CDR amino acid sequence with at least 85% sequence identity, for example, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity, with a sequence disclosed in Table 1.In some embodiments, an antigen-binding molecule comprises HCVR, LCVR, and / or CDR amino acid sequences with at least 85% sequence identity, for example, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity, with a disclosed sequence. Petition 870250097901, dated 10 / 27 / 2025, p. 34 / 139 / 104 in Table 1, where the differences in the amino acid residue(s) in relation to the sequence disclosed in Table 1 are conservative substitutions or moderately conservative substitutions.

[0085] In some embodiments, the antibody or its antigen-binding fragment is chimeric, humanized, or fully human. In some embodiments, the antibody or its antigen-binding fragment is humanized. In some embodiments, the antibody or its antigen-binding fragment is fully human.

[0086] The amount of antibody or antigen-binding fragment (or in the case of two or more antibodies, the amount of each antibody or the total amount of antibody) contained in the pharmaceutical formulations of this disclosure may vary depending on the specific properties desired of the formulations, as well as the particular circumstances and purposes for which the formulations are intended to be used.In certain embodiments, pharmaceutical formulations may contain approximately 1 mg / mL to approximately 500 mg / mL of total antibody; approximately 5 mg / mL to approximately 250 mg / mL of total antibody; approximately 5 mg / mL to approximately 200 mg / mL of total antibody; approximately 15 mg / mL to approximately 250 mg / mL of total antibody; approximately 25 mg / mL to approximately 200 mg / mL of total antibody; approximately 50 mg / mL to approximately 200 mg / mL of total antibody; approximately 100 mg / mL to approximately 200 mg / mL of total antibody; approximately 125 mg / mL to approximately 175 mg / mL of total antibody; or approximately 150 mg / mL to approximately 200 mg / mL of total antibody.For example, the formulations in this disclosure may comprise approximately 5 mg / mL; approximately 10 mg / mL; approximately 15 mg / mL; approximately 20 mg / mL; approximately 25 mg / mL; approximately 30 mg / mL; approximately 35 mg / mL; approximately 40 mg / mL; approximately 45 mg / mL; approximately 50 mg / mL; approximately 55 mg / mL; approximately 60 mg / mL; approximately 65 mg / mL; approximately 70 mg / mL; approximately 75 mg / mL; approximately 80 mg / mL; approximately 85 mg / mL; approximately 90 mg / mL; approximately 95 mg / mL; approximately 100 mg / mL. Petition 870250097901, dated 10 / 27 / 2025, page 35 / 139 / 104 approximately 105 mg / mL; approximately 110 mg / mL; approximately 115 mg / mL; approximately 120 mg / mL; approximately 125 mg / mL; approximately 130 mg / mL; approximately 135 mg / mL; approximately 140 mg / mL; approximately 145 mg / mL; approximately 150 mg / mL; approximately 155 mg / mL; approximately 160 mg / mL; approximately 165 mg / mL; approximately 170 mg / mL; approximately 175 mg / mL; approximately 180 mg / mL; approximately 185 mg / mL; approximately 190 mg / mL; approximately 195 mg / mL; approximately 200 mg / mL; approximately 205 mg / mL; approximately 210 mg / mL; approximately 215 mg / mL; approximately 220 mg / mL; approximately 225 mg / mL; approximately 230 mg / mL; approximately 235 mg / mL; approximately 240 mg / mL; approximately 245 mg / mL; or approximately 250 mg / mL of total antibody or antigen-binding fragment(s) thereof, which bind specifically to Fel d1.In certain embodiments, the pharmaceutical formulations contain approximately 50 ± 5 mg / mL of total antibody, approximately 75 ± 7.5 mg / mL of total antibody, approximately 100 ± 10 mg / mL of total antibody, approximately 120 ± 12 mg / mL of total antibody, approximately 140 ± 14 mg / mL of total antibody, approximately 150 ± 15 mg / mL of total antibody, approximately 170 ± 17 mg / mL of total antibody, or approximately 190 ± 19 mg / mL of total antibody. In certain embodiments, pharmaceutical formulations may contain up to 100 mg / mL, up to 150 mg / mL, up to 200 mg / mL, up to 250 mg / mL, up to 300 mg / mL, up to 400 mg / mL, or up to 500 mg / mL of total antibody.

[0087] For formulations comprising two or more anti-Fel d1 antibodies, in some embodiments each antibody is present in an amount of about 1 mg / mL to about 250 mg / mL, for example, about 5 mg / mL to about 200 mg / mL, about 10 mg / mL to about 150 mg / mL, about 20 mg / mL to about 100 mg / mL, about 50 mg / mL to about 150 mg / mL or about 50 mg / mL to about 100 mg / mL. In some embodiments, each antibody is present in an amount of about 1 mg / mL; about 2 mg / mL; about 5 mg / mL; about 10 mg / mL; about 15 mg / mL; about 20 mg / mL; about 25 mg / mL; about 30 mg / mL; about 35 mg / mL; about 40 mg / mL; about 45 mg / mL; fence Petition 870250097901, dated 10 / 27 / 2025, page 36 / 139 / 104 of 50 mg / mL; approximately 55 mg / mL; approximately 60 mg / mL; approximately 65 mg / mL; approximately 70 mg / mL; approximately 75 mg / mL; approximately 80 mg / mL; approximately 85 mg / mL; approximately 90 mg / mL; approximately 95 mg / mL; approximately 100 mg / mL; approximately 105 mg / mL; approximately 110 mg / mL; approximately 115 mg / mL; approximately 120 mg / mL; approximately 125 mg / mL; approximately 130 mg / mL; approximately 135 mg / mL; approximately 140 mg / mL; approximately 145 mg / mL; approximately 150 mg / mL; approximately 155 mg / mL; approximately 160 mg / mL; approximately 165 mg / mL; approximately 170 mg / mL; approximately 175 mg / mL; approximately 180 mg / mL; approximately 185 mg / mL; approximately 190 mg / mL; approximately 195 mg / mL; or approximately 200 mg / mL. In certain embodiments, the pharmaceutical formulations contain approximately 25 ± 3 mg / mL of each antibody, approximately 50 ± 5 mg / mL of each antibody, approximately 75 ± 7.5 mg / mL of each antibody, or approximately 100 ± 10 mg / mL of each antibody. In some embodiments, each antibody is present in the formulation in the same quantity.In some embodiments, the antibodies are present in the formulation in different quantities. In some embodiments, the antibodies (e.g., REGN1908 and REGN1909) are present in a molecular ratio of 1:1 or a molecular ratio of approximately 1:1. In some embodiments, the antibodies (e.g., REGN1908 and REGN1909) are present in a molecular ratio of approximately 1.5:1 or approximately 1:1.5. In some embodiments, the antibodies (e.g., REGN1908 and REGN1909) are present in a molecular ratio of approximately 2:1 or approximately 1:2. Bioequivalents

[0088] This disclosure covers formulations comprising antibodies with amino acid sequences that differ from those of the antibodies described, but which retain the ability to bind to Fel d1. These variant molecules comprise one or more additions, deletions, or substitutions of amino acids when compared to an original sequence, but exhibit biological activity that is essentially equivalent to that of the Petition 870250097901, dated 10 / 27 / 2025, p. 37 / 139 / 104 antibodies described. Similarly, the nucleic acid sequences encoding the antibodies of this disclosure include sequences comprising one or more nucleotide additions, deletions, or substitutions when compared to the disclosed sequence, but which encode an antibody that is essentially bioequivalent to the antibodies disclosed herein.

[0089] This disclosure includes formulations comprising antibodies that are bioequivalent to any of the exemplary antibodies presented herein. Two antibodies are considered bioequivalent if, for example, they are pharmaceutical equivalents or pharmaceutical alternatives whose rate and extent of absorption do not show a significant difference when administered at the same molar dose under similar experimental conditions, whether in single or multiple doses. Some antibodies will be considered pharmaceutical equivalents or alternatives if they are equivalent in the extent of their absorption but not in their rate of absorption and yet may be considered bioequivalent because such differences in the rate of absorption are intentional and are reflected in the labeling, are not essential for achieving effective body drug concentrations in, for example, chronic use, and are considered clinically insignificant for the specific drug product studied.

[0090] In one embodiment, two antibodies are bioequivalent if there are no clinically significant differences in their safety, purity, and potency.

[0091] In one embodiment, two antibodies are bioequivalent if a patient can be switched one or more times between the first antibody (e.g., reference product) and the second antibody (e.g., biological product) without an expected increase in the risk of adverse effects, including a clinically significant alteration in immunogenicity or decreased efficacy, compared to continued therapy without such switching. Petition 870250097901, dated 10 / 27 / 2025, pages 38 / 139 / 104

[0092] In one embodiment, two antibodies are bioequivalent if both act by a mechanism or mechanisms of action common to the condition or conditions of use, to the extent that such mechanisms are known.

[0093] Bioequivalence can be demonstrated by in vivo and in vitro methods. Non-limiting examples of bioequivalence measures include, for example, (a) an in vivo test in humans or other mammals in which the concentration of the antibody or its metabolites is measured in blood, plasma, serum, or other biological fluid as a function of time; (b) an in vitro test that has been correlated with and is reasonably predictive of human in vivo bioavailability data; (c) an in vivo test in humans or other mammals in which the appropriate acute pharmacological effect of the antibody (or its target) is measured as a function of time; and (d) a well-controlled clinical trial that establishes the safety, efficacy, or bioavailability or bioequivalence of an antibody. Formulation Excipients and pH

[0094] The pharmaceutical formulations of this disclosure comprise one or more excipients. The term excipient, as used herein, means any non-therapeutic agent added to the formulation to provide a desired consistency, viscosity or stabilizing effect.

[0095] The pharmaceutical formulations of this disclosure may also comprise a buffer or buffer system, which serves to maintain a stable pH and help stabilize the anti-Fel d1 antibody or antibodies. In some embodiments, the buffer or buffer system comprises at least one buffer that has a buffering range that fully or partially overlaps the pH range of 5.5 to 6.3 (for example, a histidine buffer or a phosphate buffer). In several embodiments, the pH of the formulation is 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, or 6.3. In some embodiments, the Petition 870250097901, dated 10 / 27 / 2025, page 39 / 139 / 104 formulations have a pH of 5.8 ± 0.3, for example, a pH of 5.8 ± 0.2 or a pH of 5.8 ± 0.1. In some embodiments, the formulations have a pH of 5.9 ± 0.3, for example, a pH of 5.9 ± 0.2 or a pH of 5.9 ± 0.1. In some embodiments, the formulations have a pH of 6.0 ± 0.3, for example, a pH of 6.0 ± 0.2 or a pH of 6.0 ± 0.1.

[0096] In certain embodiments, the buffer comprises histidine. In the context of this disclosure, histidine buffer or buffer comprising histidine is a buffer comprising the amino acid histidine. Examples of histidine buffers include histidine chloride, histidine acetate, histidine phosphate, and histidine sulfate. In one embodiment, the histidine buffer is prepared by dissolving L-histidine and L-histidine hydrochloride (e.g., as monohydrate) in a defined amount and ratio. In another embodiment, the histidine buffer is prepared by titrating L-histidine (free base, solid) with dilute hydrochloric acid. The term histidine is used interchangeably with histidine buffer in this disclosure.In certain embodiments, the buffer (e.g., histidine) is present at a concentration of about 1 mM to about 100 mM, for example, about 1 mM to about 70 mM, about 1 mM to about 40 mM, about 1 mM to about 30 mM, about 5 mM to about 25 mM; or about 5 mM to about 20 mM. In some embodiments, the buffer includes a histidine buffer at a concentration of 5 mM to 15 mM. In some embodiments, the buffer includes a histidine buffer at a concentration of 10 mM ± 2 mM.

[0097] The pharmaceutical formulations of this disclosure may comprise one or more thermal stabilizers. In some embodiments, the term stabilize means maintaining more than about 91% of the antibody in a native conformation when the solution containing the antibody and the thermal stabilizer is incubated at an elevated temperature of about 37°C, about 40°C, or about 45°C for at least 28 days (for example, for Petition 870250097901, of 10 / 27 / 2025, p. 40 / 139 / 104 (one month). In some embodiments, what is meant by “stabilizes” is when less than about 6% (e.g., less than 5%, less than 4%, less than 3%, or less than 2.5% of the antibody is aggregated when the solution containing the antibody and the thermal stabilizer is incubated at an elevated temperature of about 37°C, about 40°C, or about 45°C for at least 28 days (e.g., for one month). As used herein, “native” means the primary or major form of the antibody by size exclusion, which is usually an intact monomer of the antibody. The term native also refers to the non-aggregated and non-degraded form of the antibody.

[0098] In some embodiments, the thermal stabilizer is a polyol, such as sorbitol. In some embodiments, the thermal stabilizer is an amino acid, such as proline. In some aspects, the thermal stabilizer is a sugar, such as sucrose or trehalose. The amount of stabilizer contained in the formulation may vary depending on the specific circumstances and intended purposes for which the formulation is used. In certain embodiments, the thermal stabilizer may be present in the formulation in an amount of about 0.1% to about 20%; about 0.5% to about 20%; about 1% to about 20%; about 1% to about 10%; about 2% to about 15%; about 3% to about 8%; or about 4% to about 6%. For example, the pharmaceutical formulations of this disclosure may comprise about 0.5%; about 1.0%; about 1.5%; around 2.0%; around 2.5%; around 3.0%; around 3.5%; around 4.0%; around 4.5%; around 5.0%; around 5.5%; around 6.0%; around 6.5%; around 7.0%; around 7.5%; around 8.0%; around 8.5%; around 9.0%; around 9.5%; approximately 10.0%; approximately 15%; or approximately 20% of thermal stabilizer (e.g., sucrose). In some embodiments, the formulations contain up to approximately 10% of thermal stabilizer (e.g., sucrose). In some embodiments, the formulations contain from approximately 1% to approximately 10% of thermal stabilizer (e.g., sucrose), for example, approximately 3%, Petition 870250097901, dated 10 / 27 / 2025, p. 41 / 139 / 104 approximately 5%, approximately 7.5% or approximately 10%. In some embodiments, the formulations contain approximately 5% thermal stabilizer (e.g., sucrose). In some embodiments, the formulations contain approximately 5% ± 1% thermal stabilizer (e.g., sucrose). In some embodiments, the formulations contain approximately 5% ± 0.5% thermal stabilizer (e.g., sucrose). Each of the percentages indicated above corresponds to a weight / volume (w / v) percentage.

[0099] The pharmaceutical formulations of this disclosure may comprise one or more viscosity reducers. In some embodiments, the viscosity modifier is an amino acid or a salt. Exemplary amino acids that can be used as viscosity modifiers include, but are not limited to, alanine, proline, arginine, histidine, glycine, and lysine. Exemplary salts (e.g., inorganic salts) that can be used as viscosity modifiers include, but are not limited to, sodium chloride, calcium chloride, magnesium chloride, and calcium acetate. In some embodiments, the viscosity modifier is an amino acid in its salt form (e.g., arginine hydrochloride, histidine hydrochloride, or histidine acetate).

[00100] In certain embodiments, the viscosity modifier is present in an amount of at least 50 mM, for example, at least 60 mM, at least 65 mM, at least 70 mM, or at least 75 mM. In some embodiments, the viscosity modifier is present in an amount of about 50 mM to about 200 mM, for example, from about 50 mM to about 175 mM, from about 60 mM to about 150 mM, or from about 60 mM to about 130 mM. In some embodiments, the viscosity modifier (for example, arginine or arginine hydrochloride, or sodium chloride) is present in an amount of at least 60 mM, for example, at least 65 mM, at least 70 mM, or from about 70 mM to about 120 mM. In certain embodiments, the viscosity modifier is Petition 870250097901, dated 10 / 27 / 2025, p. 42 / 139 / 104 present in an amount of about 0.5% w / v to about 5% w / v, for example, about 1% w / v to about 5% w / v. In one embodiment, the viscosity modifier (e.g., proline) is present in an amount of about 1% w / v to about 5% w / v (e.g., about 1.5% or about 3%).

[00101] The pharmaceutical formulations of this disclosure may also comprise one or more surfactants in a type and amount that stabilizes the anti-Fel d1 antibody or antibodies under conditions of handling or rough shaking. As used herein, the term surfactant refers to a substance that reduces the absorption of hydrophobic antibody patches onto other hydrophobic surfaces and / or reduces the propensity for aggregation at air-water interfaces, where hydrophobic antibody regions would tend to undergo unfolding events. Surfactants may be ionic or non-ionic. Specific non-ionic surfactants that may be included in the formulations of this disclosure include, for example, polysorbates, such as polysorbate 20, polysorbate 28, polysorbate 40, polysorbate 60, polysorbate 65, polysorbate 80, polysorbate 81 and polysorbate 85; poloxamers, such as poloxamer 181, poloxamer 188, poloxamer 407; or polyethylene glycols (PEGs), such as PEG3350.Polysorbate 20 is also known as TWEEN 20, sorbitan monolaurate, or polyoxyethylene sorbitan monolaurate. Poloxamer 188 is also known as KOLLIPHOR® P 188 (BASF) or PLURONIC™ F-68 (Gibco).

[00102] The amount of surfactant contained in the pharmaceutical formulations of this disclosure may vary depending on the specific properties desired of the formulations, as well as the particular circumstances and purposes for which the formulations are to be used. In certain embodiments, the formulations may contain from 0.01% to 0.5% surfactant, for example, from about 0.05% to about 0.5%, from about Petition 870250097901, dated 10 / 27 / 2025, page 43 / 139 / 104, from 0.05% to approximately 0.25%, from approximately 0.075% to approximately 0.25%, or from approximately 0.075% to approximately 0.2%. For example, the formulations of this disclosure may comprise approximately 0.01%; approximately 0.02%; approximately 0.03%; approximately 0.04%; approximately 0.05%; approximately 0.06%; approximately 0.07%; approximately 0.08%; approximately 0.09%; approximately 0.1%; approximately 0.11%; approximately 0.12%; approximately 0.13%; approximately 0.14%; approximately 0.15%; approximately 0.16%; approximately 0.17%; approximately 0.18%; approximately 0.19%; approximately 0.20%; approximately 0.21%; approximately 0.22%; approximately 0.23%; approximately 0.24%; approximately 0.25%; approximately 0.26%; approximately 0.27%; approximately 0.28%; approximately 0.29%; approximately 0.30%; approximately 0.35%; approximately 0.40%; approximately 0.45%; approximately 0.46%; approximately 0.47%; approximately 0.48%; approximately 0.49%; or approximately 0.50% of the surfactant. In some formulations, the surfactant is a polysorbate, for example, polysorbate 20 or polysorbate 80.In some embodiments, the formulations contain approximately 0.1% to approximately 0.2% of polysorbate 20 or polysorbate 80. In some embodiments, the formulations contain approximately 0.1% or approximately 0.15% of polysorbate 20 or polysorbate 80. Each of the percentages indicated above corresponds to a weight / volume (w / v) percentage. Exemplary Formulations

[00103] In some embodiments, a stable liquid pharmaceutical formulation comprises at least one antibody that binds specifically to Fel d1 and a buffer that maintains a stable pH of about 6.0 (e.g., pH 6.0 ± 0.3).

[00104] In some embodiments, a stable liquid pharmaceutical formulation comprises 5-250 mg / mL (e.g., 20 mg / mL, 50 mg / mL, 75 mg / mL, 100 mg / mL, 150 mg / mL, or 200 mg / mL) of at least one antibody that specifically binds to Fel d1 and about 5 mM to about 20 mM of a buffer that maintains a stable pH of about 6.0 (e.g., pH 6.0 ± 0.3). In some embodiments, the buffer is histidine. Petition 870250097901, dated 10 / 27 / 2025, p. 44 / 139 / 104

[00105] In some embodiments, a stable liquid pharmaceutical formulation comprises 5–250 mg / mL (e.g., 20 mg / mL, 50 mg / mL, 75 mg / mL, 100 mg / mL, 150 mg / mL, or 200 mg / mL) of at least one antibody that specifically binds to Fel d1; about 5 mM to about 20 mM of a buffer that maintains a stable pH of about 6.0 (e.g., pH 6.0 ± 0.3); and about 1% to about 10% of a cryoprotectant. In some embodiments, the buffer is histidine. In some embodiments, the cryoprotectant is sucrose, proline, trehalose, or sorbitol.

[00106] In some embodiments, a stable liquid pharmaceutical formulation comprises 5–250 mg / mL (e.g., 20 mg / mL, 50 mg / mL, 75 mg / mL, 100 mg / mL, 150 mg / mL, or 200 mg / mL) of at least one antibody that specifically binds to Fel d1; about 5 mM to about 20 mM of a buffer that maintains a stable pH of about 6.0 (e.g., pH 6.0 ± 0.3); and about 0.01% to about 0.5% of a surfactant. In some embodiments, the buffer is histidine. In some embodiments, the surfactant is a polysorbate, for example, polysorbate 20 or polysorbate 80.

[00107] In some embodiments, a stable liquid pharmaceutical formulation comprises 5–250 mg / mL (e.g., 20 mg / mL, 50 mg / mL, 75 mg / mL, 100 mg / mL, 150 mg / mL, or 200 mg / mL) of at least one antibody that specifically binds to Fel d1; about 5 mM to about 20 mM of a buffer that maintains a stable pH of about 6.0 (e.g., pH 6.0 ± 0.3); and about 50 mM to about 200 mM of a viscosity reducer. In some embodiments, the buffer is histidine. In some embodiments, the viscosity reducer is arginine, histidine, or sodium chloride.

[00108] In some embodiments, a stable liquid pharmaceutical formulation comprises 5-250 mg / mL (for example, 20 mg / mL, 50 mg / mL, 75 mg / mL, 100 mg / mL, 150 mg / mL or 200 mg / mL) of at least Petition 870250097901, dated 10 / 27 / 2025, p. 45 / 139 / 104 an antibody that specifically binds to Fel dl; about 5 mM to about 20 mM of a buffer that maintains a stable pH of about 6.0 (e.g., pH 6.0 ± 0.3); about 1% to about 10% of a cryoprotectant; and about 50 mM to about 200 mM of a viscosity reducer. In some embodiments, the buffer is histidine. In some embodiments, the cryoprotectant is sucrose, proline, trehalose, or sorbitol. In some embodiments, the viscosity reducer is arginine, histidine, or sodium chloride.

[00109] In some embodiments, a stable liquid pharmaceutical formulation comprises 5–250 mg / mL (e.g., 20 mg / mL, 50 mg / mL, 75 mg / mL, 100 mg / mL, 150 mg / mL, or 200 mg / mL) of at least one antibody that specifically binds to Fel d1; about 5 mM to about 20 mM of a buffer that maintains a stable pH of about 6.0 (e.g., pH 6.0 ± 0.3); about 0.01% to about 0.5% of a surfactant; and about 50 mM to about 200 mM of a viscosity reducer. In some embodiments, the buffer is histidine. In some embodiments, the surfactant is a polysorbate, for example, polysorbate 20 or polysorbate 80. In some embodiments, the viscosity reducer is arginine, histidine, or sodium chloride.

[00110] In some embodiments, a stable liquid pharmaceutical formulation comprises 5–250 mg / mL (e.g., 20 mg / mL, 50 mg / mL, 75 mg / mL, 100 mg / mL, 150 mg / mL, or 200 mg / mL) of at least one antibody that specifically binds to Fel d1; about 5 mM to about 20 mM of a buffer that maintains a stable pH of about 6.0 (e.g., pH 6.0 ± 0.3); about 1% to about 10% of a cryoprotectant; about 0.01% to about 0.5% of a surfactant; and about 50 mM to about 200 mM of a viscosity reducer. In some embodiments, the buffer is histidine. In some embodiments, the cryoprotectant is sucrose, proline, trehalose, or sorbitol. In some sports, surfactant is a Petition 870250097901, dated 10 / 27 / 2025, p. 46 / 139 / 104 polysorbate, for example, polysorbate 20 or polysorbate 80. In some embodiments, the viscosity reducer is arginine, histidine or sodium chloride.

[00111] In some embodiments, a stable liquid pharmaceutical formulation comprises 5 mg / mL, 10 mg / mL, 20 mg / mL, 30 mg / mL, 40 mg / mL, 50 mg / mL, 60 mg / mL, 70 mg / mL, 80 mg / mL, 90 mg / mL, 100 mg / mL, 110 mg / mL, 120 mg / mL, 130 mg / mL, 140 mg / mL, 150 mg / mL, 160 mg / mL, 170 mg / mL, 180 mg / mL, 190 mg / mL, or 200 mg / mL of at least one antibody that specifically binds to Fel d1 and a mM histidine buffer that maintains a stable pH of about 6.0 (e.g., pH 6.0 ± 0.3, or a pH of 5.8 or 5.9). In some embodiments, the formulation also comprises 5% (w / v) sucrose. In some embodiments, the formulation also comprises 0.1% (w / v) polysorbate 80.

[00112] In some embodiments, a stable liquid pharmaceutical formulation comprises REGN1908 at a concentration of about 150 mg / mL ± 15 mg / mL and a buffer that maintains a stable pH of about 6.0 (e.g., pH 6.0 ± 0.3, or pH 5.8, or pH 6.2). In some embodiments, the buffer is 10 mM histidine.

[00113] In some embodiments, a stable liquid pharmaceutical formulation comprises REGN1909 at a concentration of about 150 mg / mL ± 15 mg / mL and a buffer that maintains a stable pH of about 6.0 (e.g., pH 6.0 ± 0.6 or pH 5.4, 5.6, 5.8, 6.0, 6.2, or 6.5). In some embodiments, the buffer is 10 mM histidine.

[00114] In some embodiments, a stable liquid pharmaceutical formulation comprises REGN1908 and / or REGN1909 and a viscosity reducer. In some embodiments, the viscosity reducer is arginine HCl, proline, or sodium chloride. In some embodiments, the formulation comprises 70 mM arginine HCl. In some embodiments, the formulation comprises 3% proline. In some embodiments, the formulation Petition 870250097901, dated 10 / 27 / 2025, p. 47 / 139 / 104, comprises 70 mM of sodium chloride.

[00115] In some embodiments, a stable liquid pharmaceutical formulation comprises 150 mg / mL ± 15 mg / mL REGN1908 or REGN1909 and a buffer that maintains a stable pH of about 6.0 (e.g., pH 6.0 ± 0.3, or pH 5.8 or pH 6.2). In some embodiments, the buffer is 10 mM histidine. In some embodiments, the formulation also comprises one of the following: (i) 10 mM histidine (i.e., without viscosity reducer); (ii) 10 mM histidine + 70 mM arginine-HCl; (iii) 100 mM histidine; (iv) 10 mM histidine + 3% proline; or (v) 10 mM histidine + 70 mM sodium chloride. In some embodiments, the formulation comprises 150 mg / mL of REGN1908 and 70 mM arginine, 100 mM histidine, or 70 mM sodium chloride. In some embodiments, the formulation comprises 150 mg / mL of REGN1908 and 70 mM arginine. In some embodiments, the formulation comprises 150 mg / mL of REGN1909 and a viscosity reducer effective in maintaining a viscosity of less than 10 cP in the formulation.

[00116] In some embodiments, a pharmaceutical-grade stable liquid formulation comprises 150 mg / mL REGN1908 or REGN1909 and a buffer that maintains a stable pH of about 6.0 (e.g., pH 6.0 ± 0.3, or pH 5.8 or pH 6.2). In some embodiments, the buffer is 10 mM histidine. In some embodiments, the formulation further comprises a cryoprotectant. In some aspects, the cryoprotectant is 5% w / v or 10% w / v sucrose. In other aspects, the formulation comprises 70 mM arginine-HCl in the presence of sucrose, for example, 5% w / v sucrose.

[00117] In some embodiments, a stable liquid pharmaceutical formulation comprises 175 mg / mL of REGN1908 or REGN1909 and a buffer that maintains a stable pH of about 6.0 (e.g., pH 6.0 ± 0.3, or pH 5.8, or pH 6.2). In some embodiments, the formulation further comprises 10 mM of histidine. In some embodiments, the Petition 870250097901, dated 10 / 27 / 2025, page 48 / 139 / 104, the formulation also includes 70 mM of arginine. In some embodiments, the formulation also includes 5% sucrose.

[00118] In some embodiments, anti-Fel d1 antibodies (e.g., REGN1908 and REGN1909) are individually formulated in an aqueous buffered formulation comprising: (a) 5 mM to 20 mM histidine buffer, (b) 60 mM to 130 mM arginine, and (c) 50 to 200 mg of anti-Fel d1 antibody, at pH 6.0 ± 0.3. In some embodiments, the formulation further comprises 2.5% to 7.5% w / v sucrose and / or 0.01% to 0.5% w / v polysorbate.

[00119] In some embodiments, anti-Fel d1 antibodies (e.g., REGN1908 and REGN1909) are individually formulated in an aqueous buffered formulation comprising: (a) 5 mM to 20 mM histidine buffer, (b) 2.5% to 7.5% w / v sucrose, (c) 60 mM to 130 mM arginine, and (d) 50 to 200 mg anti-Fel d1 antibody, at pH 6.0 ± 0.3. In some embodiments, the formulation further comprises 0.01% to 0.5% w / v polysorbate.

[00120] In some embodiments, an anti-Fel d1 antibody formulation comprises: (a) 10 mM ± 2 mM histidine, (b) 5% ± 1% w / v sucrose, (c) 70 mM ± 14 mM arginine and (d) 190 mg / mL ± 10 mg / mL REGN1908, at pH 6.0 ± 0.3.

[00121] In some embodiments, an anti-Fel d1 antibody formulation comprises: (a) 10 mM ± 2 mM histidine, (b) 5% ± 1% w / v sucrose, (c) 70 mM ± 14 mM arginine, (d) 0.15% ± 0.075% w / v polysorbate 80 and (e) 150 mg / mL ± 15 mg / mL REGN1908, at pH 6.0 ± 0.3.

[00122] In some embodiments, an anti-Fel d1 antibody formulation comprises: (a) 10 mM ± 2 mM histidine, (b) 5% ± 1% w / v sucrose, (c) 70 mM ± 14 mM arginine and (d) 190 mg / mL ± 10 mg / mL REGN1909, at pH 6.0 ± 0.3.

[00123] In some embodiments, an anti-antibody formulation Petition 870250097901, dated 10 / 27 / 2025, page 49 / 139 / 104 Fel dl comprises: (a) 10 mM ± 2 mM histidine, (b) 5% ± 1% w / v sucrose, (c) 70 mM ± 14 mM arginine, (d) 0.15% ± 0.075% w / v polysorbate 80 and (e) 150 mg / mL ± 15 mg / mL REGN1909, at pH 6.0 ± 0.3.

[00124] In some respects, a stable liquid pharmaceutical formulation comprises two anti-Fel d1 antibodies at a total target antibody concentration of 150 mg / mL (75 mg / mL REGN1908 and 75 mg / mL REGN1909) and a buffer that maintains a stable pH of about 6.0 (e.g., pH 6.0 ± 0.3). In some embodiments, the buffer is 10 mM histidine. In some embodiments, the formulation has a pH of 6.1. In some embodiments, the formulation comprises 10 mM histidine and 5% sucrose. In some embodiments, the formulation does not contain arginine or contains 20 mM, 50 mM, 70 mM, 100 mM, or 130 mM arginine.

[00125] In some embodiments, a stable liquid pharmaceutical formulation comprises two anti-Fel d1 antibodies at a total target antibody concentration of 150 mg / mL (75 mg / mL REGN1908 and 75 mg / mL REGN1909) and a buffer that maintains a stable pH of about 6.0 (e.g., pH 6.0 ± 0.3). In some embodiments, the formulation further comprises 10 mM histidine and 70 mM arginine hydrochloride. In some embodiments, the formulation further comprises no polysorbate or polysorbate 20 or polysorbate 80 in an amount of 0.01%, 0.025%, 0.05%, 0.075%, 0.1% or 0.2% (all percentages w / v). In some embodiments, the formulation comprises > 0.05% w / v of polysorbate 20, and / or the formulation comprises > 0.025% w / v or > 0.075% w / v of polysorbate 80.

[00126] In some embodiments, a stable liquid pharmaceutical formulation comprises 150 mg / mL of REGN1908-REGN1909 (75 mg / mL of each antibody), 10 mM histidine, 70 mM arginine hydrochloride, and 0.15% (w / v) polysorbate at pH 6.0. In some embodiments, no cryoprotectant is added. In some embodiments, cryoprotectants are added. Petition 870250097901, dated 10 / 27 / 2025, page 50 / 139 / 104 5% sucrose, 3% proline, 5% trehalose or 2.5% sorbitol (all percentages w / v).

[00127] In some embodiments, a stable liquid pharmaceutical formulation comprises two anti-Fel d1 antibodies in an aqueous buffered formulation comprising: (a) 5 mM to 20 mM histidine buffer, (b) 2.5% to 7.5% w / v sucrose, (c) 60 mM to 130 mM arginine, (d) 0.01% to 0.5% w / v polysorbate, and (e) 50 to 200 mg of total anti-Fel d1 antibody, at pH 6.0 ± 0.3.

[00128] In some embodiments, a stable liquid formulation comprises: (a) 10 mM ± 2 mM histidine, (b) 5% ± 1% w / v sucrose, (c) 70 mM ± 14 mM arginine, (d) 0.15% ± 0.075% w / v polysorbate 80 and (e) 150 mg / mL ± 15 mg / mL REGN1908-REGN1909 (75 mg / mL REGN1908 + 75 mg / mL REGN1909), at pH 6.0 ± 0.3. Characterization of Pharmaceutical Formulations

[00129] In some embodiments, an anti-Fel D1 antibody formulation exhibits one or more of the following attributes:

[00130] A formulation that is stable after being subjected to stress, for example, temperature cycling, extreme temperatures, agitation during transport, etc.

[00131] A formulation with a sufficiently high concentration of anti-Fel D1 antibody / antibodies to support the administration of a single dose of the antibody / antibodies to the patient (e.g., a dose of 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, 500 mg, 550 mg, 600 mg, 650 mg, 700 mg, 750 mg, 800 mg, 850 mg, 900 mg, 950 mg or 1000 mg).

[00132] A formulation with sufficiently low viscosity to be administered by intravenous or subcutaneous injection, even at high antibody concentrations (e.g., an antibody concentration of 100-200 mg / mL or 150-175 mg / mL). Petition 870250097901, dated 10 / 27 / 2025, page 51 / 139 / 104

[00133] A formulation that is at or near physiological osmolality to support administration by intravenous or subcutaneous injection, even at high antibody concentrations (e.g., an antibody concentration of 100-200 mg / mL or 150-175 mg / mL).

[00134] A compliant and stable formulation in Type 1 clear glass vials and standard serum caps as packaging.

[00135] The pharmaceutical formulations of this disclosure generally exhibit high levels of stability. The term stable, as used herein in reference to pharmaceutical formulations, means that the antibodies within the pharmaceutical formulations retain an acceptable degree of chemical structure or biological function after storage under defined conditions. A formulation may be stable even if the antibody contained therein does not retain 100% of its chemical structure or biological function after storage for a defined period of time. Under certain circumstances, the maintenance of approximately 90%, approximately 95%, approximately 96%, approximately 97%, approximately 98%, or approximately 99% of the structure or function of an antibody after storage for a defined period of time may be considered stable.

[00136] In some embodiments, stability refers to physical stability. The physical stability of a formulation refers to properties such as color, appearance, pH, turbidity, and protein concentration. The presence of visible particles in the solution can be detected by visual inspection, while microscopy, light obscuration (HIAC), or microflow imaging (MFI) can be used to measure subvisible particles. A solution passes visual inspection if it is transparent to slightly opalescent, essentially free of visible particles, and colorless to pale yellow. Additionally, turbidity, measured by DO at 405 nm, can also be used to detect particles in the solution. An increase in DO at 405 nm may indicate the presence of particles, an increase in opalescence, or a change in Petition 870250097901, dated 10 / 27 / 2025, page 52 / 139 / 104, color of the test articles. In some embodiments, the antibody protein concentration can be measured by an RP-UPLC assay and reported as a percentage of protein recovery relative to the initial material. In the RP-UPLC assay, the antibody is eluted from the RP column as a single peak. The protein concentration is determined from the total peak area of ​​the antibody by comparing it to a calibration curve generated using antibody standards. The percentage of recovery is calculated based on the measured protein concentration relative to the initial protein concentration. In some embodiments, the antibody protein concentration is measured by SoloVPE (Repligen Corp., Bridgewater, NJ).

[00137] In some embodiments, stability refers to chemical stability. Chemical stability refers to the formation of covalently modified forms (e.g., covalent aggregates, cleavage products, or charge-variant forms) and non-covalently modified forms (e.g., non-covalent aggregates) of proteins. Higher and lower molecular weight degradation products can be separated from the native antibody by methods such as ultra-performance size exclusion liquid chromatography (SE-UPLC) and microchip electrophoresis (MCE-SDS). The percentage of antibodies degraded in the SE-UPLC and MCE-SDS methods is calculated from the ratio of the area of ​​all non-native peaks to the total area of ​​all antibody peaks. Charge-variant forms of antibodies are resolved using CEXUPLC and iCIEF.In the CEX-UPLC method, peaks with retention times before the main peak are labeled as acidic peaks; peaks with retention times after the main peak are labeled as basic peaks. In the iCIEF method, peaks focused at a pI lower than that of the main peak are labeled as acidic peaks, while those focused at a pI higher than that of the main peak are labeled as basic peaks.

[00138] In some modalities, stability is measured under Petition 870250097901, dated 10 / 27 / 2025, page 53 / 139 / 104 stress conditions. For example, the formulation may be subjected to agitation stress (e.g., vortex agitation at 1000 rpm for 5 or 10 minutes, or use of an orbital shaker at 250 rpm for 24 or 48 hours), accelerated stability tests (e.g., subjecting the formulation to high temperature, humidity and / or pH conditions) or thermal stress (e.g., subjecting the formulation to multiple freeze-thaw cycles).

[00139] In some embodiments, stability is measured by determining the percentage of native antibody that remains in the formulation after storage for a defined period of time at a defined temperature. The percentage of native antibody can be determined by, among other methods, size exclusion chromatography (e.g., SE-UPLC), where native means non-aggregated and non-degraded. An acceptable degree of stability, as the phrase is used herein, means that at least 90% of the native form of the antibody can be detected in the formulation after storage for a defined period of time at a defined temperature. In certain embodiments, at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% of the native form of the antibody can be detected in the formulation after storage for a defined period of time at a defined temperature.The defined time period after which stability is measured can be at least 14 days, at least 28 days, at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, at least 7 months, at least 8 months, at least 9 months, at least 10 months, at least 11 months, at least 12 months, at least 18 months, at least 24 months or more. The defined temperature at which the pharmaceutical formulation can be stored when assessing stability can be any temperature from about -80°C to about 60°C, for example, storage at about -80°C, about -30°C, about... Petition 870250097901, dated 10 / 27 / 2025, p. 54 / 139 / 104 20°C, approximately 0°C, approximately 4-8°C, approximately 5°C, approximately 25°C, approximately 35°C, approximately 37°C, approximately 40°C, or approximately 45°C. For example, a pharmaceutical formulation can be considered stable if, after 28 days of storage at 40°C / 75% humidity (RH), more than approximately 95%, 96%, 97%, or 98% of the native antibody is detected by SE-UPLC. A pharmaceutical formulation can be considered stable if, after 12 months of storage at 5°C, more than approximately 95%, 96%, 97%, or 98% of the native antibody is detected by SE-UPLC. A pharmaceutical formulation can also be considered stable if, after 3 months of storage at 25°C, more than approximately 95%, 96%, 97%, or 98% of the native antibody is detected by SE-UPLC. A pharmaceutical formulation can also be considered stable if, after 28 days of storage at 45°C, more than approximately 89%, 90%, 91%, 92%, 93%, 94%, 95%, or 96% of the native antibody is detected by SE-UPLC.A pharmaceutical formulation can also be considered stable if, after 12 months of storage at -20°C, more than approximately 96%, 97%, or 98% of the native antibody is detected by SE-UPLC. A pharmaceutical formulation can also be considered stable if, after 12 months of storage at -30°C, more than approximately 96%, 97%, or 98% of the native antibody is detected by SE-UPLC. A pharmaceutical formulation can also be considered stable if, after 12 months of storage at 80°C, more than approximately 96%, 97%, or 98% of the native antibody is detected by SE-UPLC.

[00140] In some embodiments, stability is measured by determining the percentage of antibody that forms in an aggregate within the formulation after storage for a defined period of time at a defined temperature, wherein stability is inversely proportional to the percentage of aggregate that is formed. The percentage of aggregated antibodies can be determined by: among others, size exclusion chromatography (e.g., SE-UPLC). An acceptable degree of Petition 870250097901, dated 10 / 27 / 2025, page 55 / 139 / 104 stability, as this phrase is used here, means that at most 5% of the antibody is in an aggregated form (also called high molecular weight (HMW) form) detected in the formulation after storage for a defined period of time at a given temperature. In certain embodiments, an acceptable degree of stability means that at most about 5%, 4%, 3%, 2%, 1%, 0.5% or 0.1% of the antibody can be detected in an aggregate in the formulation after storage for a defined period of time at a given temperature.The defined time period after which stability is measured can be at least 2 weeks, at least 28 days, at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, at least 7 months, at least 8 months, at least 9 months, at least 10 months, at least 11 months, at least 12 months, at least 18 months, at least 24 months or more. The temperature at which the pharmaceutical formulation can be stored when assessing stability can be any temperature from about -80°C to about 45°C, for example, storage at about -80°C, about -30°C, about -20°C, about 0°C, about 48°C, about 5°C, about 25°C, about 35°C, about 37°C, about 40°C or about 45°C. For example, a pharmaceutical formulation can be considered stable if, after 12 months of storage at 5°C, less than about 2%, 1%, 0.5% or 0.1% of the antibody is detected in aggregated form.

[00141] In some embodiments, stability is measured by determining the percentage of antibody that migrates in a more acidic fraction during ion exchange (acidic form) than in the main antibody fraction (mainly charged form), where stability is inversely proportional to the fraction of antibody in the acidic form. Although one does not wish to be limited by theory, antibody deamidation can cause the antibody to become more negatively charged and therefore more acidic in Petition 870250097901, of 10 / 27 / 2025, pp. 56 / 139 / 104 regarding non-deamidated antibody (see, for example, Robinson, PNAS, April 16, 2002, 99:5283-5288). The percentage of acidified antibody can be determined, among other things, by ion-exchange chromatography (e.g., ultra-high performance cation-exchange liquid chromatography [CEX-UPLC]). An acceptable degree of stability, as this phrase is used here, means that at most 45% of the antibody is in a more acidic form detected in the formulation after storage for a defined period of time at a defined temperature. In certain embodiments, an acceptable degree of stability means that at most about 40%, 35%, 30%, 25%, 20%, 15%, 10%, 5%, 4%, 3%, 2%, 1%, 0.5% or 0.1% of the antibody can be detected in an acidic form in the formulation after storage for a defined period of time at a given temperature.In one embodiment, an acceptable degree of stability means that less than 30%, 25%, 20%, 15%, 10%, 5%, 4%, 3%, 2%, 1%, 0.5%, or 0.1% of the antibody can be detected in an acidic form in the formulation after storage for a defined period of time at a specified temperature. The defined period of time after which stability is measured may be at least 2 weeks, at least 28 days, at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, at least 7 months, at least 8 months, at least 9 months, at least 10 months, at least 11 months, at least 12 months, at least 18 months, at least 24 months, or more.The temperature at which the pharmaceutical formulation can be stored when assessing stability can be any temperature from approximately -80°C to approximately 45°C, for example, storage at approximately -80°C, approximately -30°C, approximately -20°C, approximately 0°C, approximately 4°C, approximately 5°C, approximately 25°C, or approximately 45°C. For example, a pharmaceutical formulation can be considered stable if, after three months of storage at -80°C, -30°C, or -20°C, it shows less than approximately 30%, 29%, 28%, 27%, 26%, 25%, 24%, 23%, 22%, 21%, 20%, 19%, 18%, 17%, 16% of its components. Petition 870250097901, dated 10 / 27 / 2025, p. 57 / 139 / 104 15%, 14%, 13%, 12%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, or 0.1% of the antibody is in a more acidic form. A pharmaceutical formulation can also be considered stable if, after 12 months of storage at 5°C, less than approximately 32%, 31%, 30%, 29%, 28%, 27%, 26%, 25%, 24%, 23%, 22%, 21%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5% or 0.1% of the antibody is in a more acidic form. A pharmaceutical formulation can also be considered stable if, after 3 months of storage at 25°C, less than approximately 43%, 42%, 41%, 40%, 39%, 38%, 37%, 36%, 35%, 34%, 33%, 32%, 31%, 30%, 29%, 28%, 27%, 26%, 25%, 24%, 23%, 22%, 21%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5% or 0.1% of the antibody is in a more stable form. acidic.A pharmaceutical formulation can also be considered stable if, after 28 days of storage at 45°C, less than approximately 49%, 48%, 47%, 46%, 45%, 44%, 43%, 42%, 41%, 40%, 39%, 38%, 37%, 36%, 35%, 34%, 33%, 32%, 31%, 30%, 29%, 28%, 27%, 26%, 25%, 24%, 23%, 22%, 21%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5% or 0.1% of the antibody can be detected, in a more acidic form.

[00142] Other methods may be used to evaluate the stability of the formulations of the present disclosure, such as, for example, differential scanning calorimetry (DSC) to determine thermal stability, controlled stirring to determine mechanical stability, and absorbance at about 350 nm or about 405 nm to determine the turbidity of the solution. For example, a formulation of the present disclosure may be considered stable if, after 6 or more months of storage at about 5°C to about 25°C, the change in OD405 of the formulation is less than about 0.05 (e.g., 0.04, 0.03, 0.02, 0.01 or less) of the OD405 of the formulation at time zero. Petition 870250097901, dated 10 / 27 / 2025, pp. 58 / 139 / 104

[00143] Measuring the antibody's binding affinity to its target or the antibody's biological activity can also be used to assess stability or potency. For example, a formulation of the present disclosure can be considered stable if, after storage at, for example, 5°C, 25°C, 45°C, etc., for a defined period of time (e.g., 1 to 36 months), the anti-Fel dl antibody or antibodies contained in the formulation bind to the Fel dl antigen with an affinity that is at least 90%, 95%, or more of the antibody's binding affinity prior to said storage. In some embodiments, the potency of an antibody in a formulation is assessed relative to a reference standard (e.g., the antibody or a formulation containing the antibody prior to storage) by ELISA or bioassay, with an acceptance criterion of the test article relative to the reference standard of 50–150% potency.Binding affinity can be determined by, for example, ELISA or surface plasmon resonance. Biological activity (i.e., the antibody's ability to inhibit Fel Dl activity) can be determined by standard in vitro assays or in vivo assays (such as a passive cutaneous anaphylaxis assay, disclosed in WO 2013 / 166236, or a basophil activation test, disclosed in WO 2018 / 118713).

[00144] Additional methods for evaluating the stability of an antibody in the formulation are demonstrated in the Examples presented below.

[00145] The liquid pharmaceutical formulations of this disclosure may, in certain embodiments, exhibit low to moderate levels of viscosity. Viscosity, as used herein, may be kinematic viscosity or absolute viscosity. Kinematic viscosity is a measure of the resistive flow of a fluid under the influence of gravity. When two fluids of equal volume are placed in identical capillary viscometers and allowed to flow by gravity, a viscous fluid takes longer than a less viscous fluid to flow through the capillary. For example, if Petition 870250097901, dated 10 / 27 / 2025, p. 59 / 139 / 104 If one fluid takes 200 seconds to complete its flow and another fluid takes 400 seconds, the second fluid is twice as viscous as the first on a kinematic viscosity scale. Absolute viscosity, sometimes called dynamic or simple viscosity, is the product of kinematic viscosity and the density of the fluid (Absolute Viscosity = Kinematic Viscosity x Density). The dimension of kinematic viscosity is L² / T, where L is a length and T is a time. Commonly, kinematic viscosity is expressed in centistokes (cSt). The SI unit of kinematic viscosity is mm² / s, which is 1 cSt. Absolute viscosity is expressed in centipoise (cP) units. The SI unit of absolute viscosity is millipascal-second (mPa-s), where 1 cP = 1 mPa-s.

[00146] As used herein, a low viscosity level, with reference to a fluid formulation of the present disclosure, will exhibit an absolute viscosity of less than about 20 cPoise (cP). For example, a fluid formulation disclosed herein will be considered to have low viscosity if, when measured using standard viscosity measurement techniques, the formulation exhibits an absolute viscosity of about 20 cP, about 19 cP, about 18 cP, about 17 cP, about 16 cP, about 15 cP, about 14 cP, about 13 cP, about 12 cP, about 11 cP, about 10 cP, about 9 cP, about 8 cP or less. As used in this document, a moderate viscosity level, with reference to a fluid formulation of the present disclosure, will exhibit an absolute viscosity between about 35 cP and about 20 cP.For example, a fluid formulation disclosed herein will be considered to have moderate viscosity if, when measured using standard viscosity measurement techniques, the formulation exhibits an absolute viscosity of about 34 cP, about 33 cP, about 32 cP, about 31 cP, about 30 cP, about 29 cP, about 28 cP, about 27 cP, about 26 cP, about 25 cP, about 24 cP, about 23 cP, about 22 cP, about 21 cP, or about 20 cP. In some embodiments, a formulation provided herein has a... Petition 870250097901, dated 10 / 27 / 2025, p. 60 / 139 / 104 viscosity < 30 cP, for example, < 25 cP. In some embodiments, a formulation provided herein has a viscosity < 20 cP, for example, < 15 cP. Containers and Methods of Administration

[00147] The pharmaceutical formulations of this disclosure may be contained in any suitable container for storing medicines and other therapeutic compositions. For example, the pharmaceutical formulations may be contained in a sealed and sterilized plastic or glass container with a defined volume, such as a vial, ampoule, syringe, cartridge, bottle, or IV bag. Different types of containers may be used to contain the formulations of this disclosure, including, for example, clear and opaque (e.g., amber-colored glass or plastic bottles). Similarly, any type of syringe may be used to contain and / or administer the pharmaceutical formulations of this disclosure. In some embodiments, the pharmaceutical formulation is contained in a pre-filled syringe. In some embodiments, the pharmaceutical formulation is contained in a pre-filled needle syringe.In some embodiments, the pharmaceutical formulation is contained in a container selected from the group consisting of a glass vial, a syringe, a pre-filled syringe, a pen-type administration device, and an autoinjector.

[00148] The pharmaceutical formulations of this disclosure may be contained in normal tungsten syringes or low-tungsten syringes. As will be appreciated by persons skilled in the art, the manufacturing process of glass syringes generally involves the use of a hot tungsten rod that functions to pierce the glass, thereby creating an orifice from which liquids can be withdrawn and expelled from the syringe. This process results in the deposition of traces of tungsten on the inner surface of the syringe. Subsequent washing and other processing steps may be used to reduce the amount of tungsten in the Petition 870250097901, dated 10 / 27 / 2025, p. 61 / 139 / 104 syringe. As used herein, the term normal tungsten means that the syringe contains more than 500 parts per billion (ppb) of tungsten. The term low tungsten means that the syringe contains less than 500 ppb of tungsten. For example, a low-tungsten syringe, according to this disclosure, may contain less than about 490, 480, 470, 460, 450, 440, 430, 420, 410, 390, 350, 300, 250, 200, 150, 100, 90, 80, 70, 60, 50, 40, 30, 20, 10 or less ppb of tungsten.

[00149] The rubber plungers used in syringes and the rubber stoppers used to close the openings of vials may be coated to prevent contamination of the medicinal contents of the syringe or vial and / or to preserve their stability. Thus, the pharmaceutical formulations of the present disclosure, according to certain embodiments, may be contained within a syringe comprising a coated plunger, or within a vial that is sealed with a coated rubber stopper. For example, the plunger or stopper may be coated with a fluorocarbon film. Examples of coated stoppers and / or plungers suitable for use with vials and syringes containing the pharmaceutical formulations of the present disclosure are mentioned in, for example, U.S. Patents Nos. 4,997,423; 5,908,686; 6,286,699; 6,645,635; and 7,226,554, the contents of which are incorporated herein in their entirety by reference.Particular exemplary rubber-coated stoppers and plungers that may be used in the context of this disclosure are commercially available under the trade name FluroTec®, available from West Pharmaceutical Services, Inc. (Lionville, PA). According to certain embodiments of this disclosure, the pharmaceutical formulations may be contained in a low-concentration tungsten syringe comprising a fluorocarbon-coated plunger. In some embodiments, the container is a syringe, such as an Ompi EZ-Fill™ syringe or a BD Neopak™ syringe. In some cases, the syringe is a 1 mL long glass syringe with a 1 mL West plunger. Petition 870250097901, dated 10 / 27 / 2025, page 62 / 139 / 104, a 27G thin-walled needle and an FM30 or BD260 needle shield. In some cases, the syringe is a 2.25 mL glass syringe (e.g., Nuova Ompi). In various forms, the syringe is available in sizes of 0.5 mL, 0.6 mL, 0.7 mL, 0.8 mL, 0.9 mL, 1.0 mL, 1.1 mL, 1.2 mL, 1.3 mL, 1.4 mL, 1.5 mL, 1.6 mL, 1.7 mL, 1.8 mL, 1.9 mL, 2.0 mL, 2.1 mL, 2.2 mL, 2.3 mL, 2.4 mL, 2.5 mL, 2.6 mL, 2.7 mL, 2.8 mL, 2.9 mL, 3.0 mL, 3.5 mL, 4.0 mL, 4.5 mL, 5.0 mL, 5.5 mL, 6.0 mL, 6.5 mL, 7.0 mL, 7.5 mL, 8.0 mL, 8.5 mL. 9.0 mL, 9.5 mL, or 10 mL (for example, a glass syringe).

[00150] Pharmaceutical formulations can be administered to a patient via parenteral routes, such as injection (e.g., subcutaneous, intravenous, intramuscular, intraperitoneal, etc.) or percutaneous, mucosal, nasal, pulmonary and / or oral administration. Numerous reusable pen and / or autoinjector delivery devices can be used to subcutaneously administer the pharmaceutical formulations of this disclosure. Examples include, but are not limited to, AUTOPEN™ (Owen Mumford, Inc., Woodstock, United Kingdom), DISETRONIC™ pen (Disetronic Medical Systems, Bergdorf, Switzerland), HUMALOG MIX 75 / 25™ pen, HUMALOG™ pen, HUMALIN 70 / 30™ pen (Eli Lilly and Co., Indianapolis, IN), NOVOPEN™ I, II and III (Novo Nordisk, Copenhagen, Denmark), NOVOPEN JUNIOR™ (Novo Nordisk, Copenhagen, Denmark), BD™ pen (Becton Dickinson, Franklin Lakes, NJ), OPTIPEN™, OPTIPEN PRO™, OPTIPEN STARLET™ and OPTICLIK™ (sanofi-aventis, Frankfurt, Germany), to name just a few.Examples of disposable pen and / or autoinjector delivery devices with applications for subcutaneous administration of a pharmaceutical composition of this disclosure include, but are not limited to, the SOLOSTAR™ pen (Sanofi-Aventis), the FLEXPEN™ (Novo Nordisk) and the KWIKPEN™ (Eli Lilly), the SURECLICK™ Autoinjector (Amgen, Thousand Oaks, CA), the PENLET™ (Haselmeier, Stuttgart, Germany), the EPIPEN (Dey, LP) and the HUMIRA™ pen (Abbott). Petition 870250097901, dated 10 / 27 / 2025, page 63 / 139 / 104 Labs, Abbott Park, IL), to name just a few. In some cases, the pharmaceutical formulation is contained in a syringe specifically adapted for use with an autoinjector. Subcutaneous injections can be administered using a 20-30 gauge needle or a 25-30 gauge needle. In some cases, subcutaneous injections can be administered using a 25 gauge needle. In some cases, subcutaneous injections can be administered using a 27 gauge needle. In some cases, subcutaneous injections can be administered using a 29 gauge needle.

[00151] Another type of delivery device may include a safety system. Such devices may be relatively inexpensive and function to manually or automatically extend a safety sleeve over a needle once the injection is complete. Examples of safety systems may include the ERIS device from West Pharmaceutical or the UltraSafe device from Becton Dickinson. In addition, the use of a large-volume device (“LVD”), or bolus injector, to administer the pharmaceutical formulations of this disclosure is also contemplated herein. In some cases, the LVD or bolus injector may be configured to inject a drug into a patient. For example, an LVD or bolus injector may be configured to administer a large volume of medication (typically about 2 mL to about 10 mL).

[00152] The pharmaceutical formulations of this disclosure may also be contained in a unit dosage form. The term unit dosage form, as used herein, refers to a physically discrete unit suitable as a unit dosage for the patient to be treated, each unit containing a predetermined amount of active compound calculated to produce the desired therapeutic effect in association with the necessary carrier, diluent, or pharmaceutical excipient. In various embodiments, the unit dosage form is contained within Petition 870250097901, dated 10 / 27 / 2025, page 64 / 139 / 104, a container as discussed in this document. The actual dosage levels of the active ingredient (e.g., an anti-Fel dl antibody) in the formulations of this disclosure may be varied in order to obtain an amount of the active ingredient that is effective in achieving the desired therapeutic response for a specific patient, composition, and route of administration, without adverse effects on the patient.The dosage level selected will depend on a variety of pharmacokinetic factors, including the activity of the specific compositions of this disclosure employed, the route of administration, the time of administration, the excretion rate of the specific compound employed, the duration of treatment, other medications, compounds and / or materials used in combination with the specific compositions employed, the age, sex, weight, condition, general health and previous medical history of the patient being treated, and similar factors well known in medical techniques. The term diluent, as used herein, refers to a solution suitable for altering or achieving an exemplary or appropriate concentration or concentrations, as described herein.

[00153] In several embodiments, the unit dosage form contains an amount of the active ingredient or ingredients (e.g., one or more anti-Fel d1 antibodies) intended for a single use. In several embodiments, the amount of the active ingredient(s) in the unit dosage form is from about 0.1 mg to about 5,000 mg, from about 25 mg to about 1,000 mg, from about 50 mg to about 500 mg, or from about 100 to 750 mg, or ranges or intervals thereof. For example, it is desirable to include ranges of values ​​that use a combination of any of the values ​​mentioned above (or values ​​contained within the ranges mentioned above) as upper and / or lower limits. In a particular embodiment, the formulation is often provided as a liquid in unit dosage form. In some embodiments, the form of Petition 870250097901, dated 10 / 27 / 2025, page. 65 / 139 / 104 unit dosage contains approximately 25 mg, approximately 50 mg, approximately 75 mg, approximately 100 mg, approximately 125 mg, approximately 150 mg, approximately 175 mg, approximately 200 mg, approximately 250 mg, approximately 300 mg, approximately 350 mg, approximately 400 mg, approximately 450 mg, approximately 500 mg, approximately 550 mg, approximately 600 mg, approximately 650 mg, approximately 700 mg, approximately 750 mg, approximately 800 mg, approximately 850 mg, approximately 900 mg, approximately 950 mg or approximately 1000 mg of the active ingredient(s). In some embodiments, the unit dosage form contains two anti-Fel d1 antibodies and contains approximately 25 mg, approximately 50 mg, approximately 75 mg, approximately 100 mg, approximately 125 mg, approximately 150 mg, approximately 175 mg, approximately 200 mg, approximately 250 mg, approximately 300 mg, approximately 350 mg, or approximately 400 mg of each antibody. In some embodiments, a unit dosage form according to this disclosure is suitable for subcutaneous or intravenous administration to a patient.

[00154] This disclosure also includes methods for preparing a unit dosage form. In an exemplary embodiment, a method for preparing a unit pharmaceutical dosage form includes combining the formulation of any of the preceding embodiments in a suitable container (for example, those containers discussed herein). Kits

[00155] Kits are also provided comprising one or more components which include, but are not limited to, a stable liquid pharmaceutical formulation comprising at least one antibody that binds specifically to Fel d1, alone or in combination with one or more additional components, including, but not limited to, an additional therapeutic agent, as discussed herein. The stable liquid pharmaceutical formulation and / or the additional therapeutic agent may be formulated as a single composition or separately in two or more compositions, for example, with a pharmaceutically acceptable vehicle, in a pharmaceutical composition. Petition 870250097901, dated 10 / 27 / 2025, page 66 / 139 / 104

[00156] Illustratively, the kit may comprise a stable liquid pharmaceutical formulation comprising: an antibody that binds specifically to Fel d1, wherein the antibody comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO:4, an HCDR2 comprising the amino acid sequence of SEQ ID NO:6, an HCDR3 comprising the amino acid sequence of SEQ ID NO:8, an LCDR1 comprising the amino acid sequence of SEQ ID NO:12, an LCDR2 comprising the amino acid sequence AAS and an LCDR3 comprising the amino acid sequence of SEQ ID NO:14.

[00157] In some embodiments, the kit may comprise a stable liquid pharmaceutical formulation comprising: an antibody that binds specifically to Fel d1, wherein the antibody comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO:18, an HCDR2 comprising the amino acid sequence of SEQ ID NO:20, an HCDR3 comprising the amino acid sequence of SEQ ID NO:22, an LCDR1 comprising the amino acid sequence of SEQ ID NO:26, an LCDR2 comprising the amino acid sequence KAS and an LCDR3 comprising the amino acid sequence of SEQ ID NO:28.

[00158] In some embodiments, the kit may comprise a stable liquid pharmaceutical formulation comprising:

[00159] a first antibody that specifically binds to Fel d1, wherein the first antibody comprises an HCVR comprising the amino acid sequence of SEQ ID NO:2 and an LCVR comprising the amino acid sequence of SEQ ID NO:10, wherein the concentration of the first antibody is up to about 100 mg / mL (e.g., 50 mg / mL ± 5 mg / mL or 75 mg / mL ± 10 mg / mL); and

[00160] a second antibody that binds specifically to Fel d1, wherein the second antibody comprises an HCVR comprising the amino acid sequence of SEQ ID NO:16 and an LCVR comprising the sequence Petition 870250097901, dated 10 / 27 / 2025, p. 67 / 139 / 104 of amino acids from SEQ ID NO: 24, where the concentration of the second antibody is up to approximately 100 mg / mL (e.g., 50 mg / mL ± 5 mg / mL or 75 mg / mL ± (10 mg / mL)).

[00161] In one embodiment, the kit includes a stable liquid pharmaceutical formulation in a container (e.g., in a sterile glass or plastic bottle). In another embodiment, the kit further includes an additional therapeutic agent in another container (e.g., in a sterile glass or plastic bottle).

[00162] In another embodiment, the kit comprises a combination of a stable liquid pharmaceutical formulation in combination with one or more other therapeutic agents formulated together, optionally, in a pharmaceutical composition, in a single common container.

[00163] If the kit includes the stable liquid pharmaceutical formulation for parenteral or subcutaneous administration to a subject, the kit may include a device (e.g., an injection device) to perform such administration. For example, the kit may include one or more hypodermic needles or other injection devices, as discussed above, containing the stable liquid pharmaceutical formulation.

[00164] The kit may include an information leaflet with information about the stable liquid pharmaceutical formulation and dosage forms in the kit. In general, such information assists patients and physicians in the effective and safe use of the included pharmaceutical compositions and dosage forms. For example, the following information may be provided in the leaflet: pharmacokinetics, pharmacodynamics, clinical studies, efficacy parameters, indications and use, contraindications, warnings, precautions, adverse reactions, overdose, proper dosage and administration, as supplied, proper storage conditions, references, manufacturer / distributor information, and patent information. In some embodiments, the kit includes instructions for the use of the formulation in Petition 870250097901, dated 10 / 27 / 2025, page 68 / 139 / 104 treatment of a disease, disorder or condition associated with the expression or activity of Fel dl, for example, as disclosed here. Therapeutic Uses

[00165] The pharmaceutical formulations of this disclosure are useful, among other things, for the treatment, prevention and / or improvement of any disease, disorder or condition associated with the expression or activity of Fel d1.

[00166] The therapeutic methods of this disclosure comprise administering to a subject any formulation comprising one or more anti-Fel d1 antibodies, as disclosed herein. The subject to whom the pharmaceutical formulation is administered may be, for example, any human or non-human animal that requires such treatment, prevention and / or improvement. This disclosure further includes the use of any of the pharmaceutical formulations disclosed herein in the manufacture of a medicament for the treatment, prevention and / or improvement of any disease or disorder associated with the expression or activity of Fel d1.

[00167] In some embodiments, the pharmaceutical formulations of this disclosure are used to treat, prevent, or improve one or more symptoms associated with exposure to the cat allergen Fel d1. In some embodiments, the pharmaceutical formulations of this disclosure are used to treat patients allergic to cats, for example, patients suffering from allergies to cat dander or patients who demonstrate sensitivity to the Fel d1 allergen. In some embodiments, the pharmaceutical formulations of this disclosure are used to prevent an intensified response to Fel d1 after secondary exposure, or the symptoms associated with the allergy, or to decrease the severity and / or duration of the allergic response associated with primary exposure to a cat harboring the Fel d1 allergen or with the recurrence of symptoms after secondary exposure.In some embodiments, the pharmaceutical formulations of this disclosure are used to treat or prevent asthma triggered by cat allergens. Petition 870250097901, dated 10 / 27 / 2025, p. 69 / 139 / 104

[00168] In some embodiments, a patient to be treated with a pharmaceutical formulation as disclosed herein is sensitized to the Fel d1 antigen or to cat dander. In some embodiments, the patient is allergic to cats. In some embodiments, the patient is allergic to cats, with conjunctivitis and rhinitis. In some embodiments, the patient is allergic to cats and has rhinitis with or without symptoms of conjunctivitis. In some embodiments, the patient is a cat-allergic patient with rhinitis with or without symptoms of conjunctivitis and with or without asthma. In some embodiments, the patient is a cat-allergic patient with asthma (e.g., mild asthma). In some embodiments, the patient is >12 years of age. In some embodiments, the patient is >18 years of age.

[00169] In some embodiments, treatment with a pharmaceutical formulation as disclosed herein results in a reduction in the severity and / or duration of at least one symptom or complication associated with an allergic reaction to the Fel d1 allergen. In some embodiments, the symptom or complication associated with the allergic reaction is sneezing, rhinorrhea, nasal itching, or nasal congestion. In some embodiments, treatment results in a reduction in allergic rhinitis, allergic conjunctivitis, rhinoconjunctivitis, allergic asthma, asthma exacerbations, or an anaphylactic response following the patient's exposure to an allergen.

[00170] In some embodiments, treatment with a pharmaceutical formulation as disclosed herein results in one or more of the following: (a) reduction in the total daily nasal symptom score (TNSS); (b) reduction in the daily eye symptom score (TOSS); (c) reduction in the total daily symptom score (TSS), calculated as the sum of TNSS and TOSS; (d) reduction in daily medication score (DMS); Petition 870250097901, of 10 / 27 / 2025, page 70 / 139 / 104 (e) reduction in the combined daily symptom and medication score (CSMS), calculated as the daily TSS plus DMS; and / or (f) reduction in the mean wheal diameter in a cat skin prick test (CPT).

[00171] In some embodiments, the pharmaceutical formulations of this disclosure are used in combination with a second therapeutic agent. For example, in some embodiments, the pharmaceutical formulation is used in combination with one or more other fractions or therapeutic modalities known in the art to treat, prevent or reduce the severity of allergies, such as, but not limited to, treatment with antihistamines, corticosteroids, epinephrine, anti-IgE antibodies (e.g., omalizumab) or allergen-specific immunotherapy (e.g., SCIT or SLIT).

[00172] A summary of the sequences and the corresponding SEQ ID NOs referenced here are shown in Table 1 below. Table 1: Informal Sequence Listing SEQ ID NO Sequence Description 1 gaggtgcagc tggtggagtc tgggggaggc ctggtcaagc ctggggggtc cctgagactc tcctgtgcag cctctggatt caccttcaga aactataaca taaactgggt ccgccaggct ccagggaagg ggctggagtg ggtctcactc atcagtggta gtagtagtta catatattac gcagactcag tgaagggccg attcaccgtc tccagagaca acgccaagaa ctcactgtat ctgcaaatga acagcctgag agccgaggac acggctgtgt attactgtgc gaggcggaca ttaagctact acgttatgga cgtctggggc caagggacca cggtcaccgt ctcctca Nucleic acid sequence of HCVR of REGN1908 2 EVQLVESGGGLVKPGGSLRLSCAASGFTFRNYNINWVRQ APGKGLEWVSLISGSSSYIYYADSVKGRFTVSRDNAKNSL YLQMNSLRAEDTAVYYCARRTLSYYVMDVWGQGTTVT VSS Amino acid sequence of HCVR of REGN1908 3 ggattcacct tcagaaacta taac Nucleic acid sequence HCDR1 of REGN1908 4 GFTFRNYN Amino acid sequence of HCDR1 of REGN1908 5 atcagtggta gtagtagtta cata Nucleic acid sequence HCDR2 of REGN1908 6 ISGSSSYI Amino acid sequence of HCDR2 of REGN1908 7 gcgaggcgga cattaagcta ctacgttatg gacgtc Sequencenucleic acid sequence HCDR2 from REGN1908 8 ARRTLSYYVMDV Amino acid sequence of HCDR3 from REGN1908 Petition 870250097901, dated 10 / 27 / 2025, p. 71 / 139 / 104 SEQ ID NO Sequence Description 9 gacatccagg tgacccagtc tccatccccc ctgtctgcat ctgtaggaga cagagtcacc atcacttgcc gggcgagtca gggcattagc aattatttag cctggtatca gcagaaacca gggagagttc ctcagctcct gatctatgct gcatccactt tgcaatcagg ggtcccatct cggttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct gaagatgttg caacttatta ctgtcaaaag tataacagtg ccccgtacac ttttggccag gggaccaagc tggagatcaa a nucleic acid sequence of LCVR from REGN1908 10 DIQVTQSPSPLSASVGDRVTITCRASQGISNYLAWYQQKP GRVPQLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPED VATYYCQKYNSAPYTFGQGTKLEIK Amino acid sequence of LCVR from REGN1908 11 cagggcatta gcaattat Nucleic acid sequence of LCDR1 from REGN1908 12 QGISNY Amino acid sequence of LCDR1 from REGN1908 gctgcatcc Nucleic acid sequence of LCDR2 from REGN1908 AAS Amino acid sequence of LCDR2 from REGN1908 13 caaaagtata acagtgcccc gtacact Nucleic acid sequence of LCDR3 from REGN1908 14 QKYNSAPYT Amino acid sequence of LCDR3 from REGN1908 15 gaggtgcagc tggtggagtc tgggggaggcttggtacagc ctggggggtc cctgagactc tcctgtgcag cctctggatt cacctttagc agttatgcca tgagctgggt ccgccaggct ccagggaagg ggctggagtg ggtctcagct attagtggtc gtggttataa cgcagactac gcagactccg tgaagggccg gttcaccatc tccagggaca attccaagaa cacgctgtat ctgcaaatga acagcctgag agccgaagac acggccgtat attactgtgc gaaattggaa tactttgact actggggcca gggaaccctg gtcactgtct cctca HCVR nucleic acid sequence from REGN1909 16 EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQ APGKGLEWVSAISGRGYNADYADSVKGRFTISRDNSKNT LYLQMNSLRAEDTAVYYCAKLEYFDYWGQGTLVTVSS Amino acid sequence of HCVR from REGN1909 17 ggattcacct ttagcagtta tgcc Nucleic acid sequence of REGN1909 HCDR1 18 GFTFSSYA Amino acid sequence of HCDR1 from REGN1909 19 attagtggtc gtggttataa cgca Nucleic acid sequence of REGN1909 HCDR2 20 ISGRGYNA Amino acid sequence of HCDR2 from REGN1909 21 gcgaaattgg aatactttga ctac Nucleic acid sequence of REGN1909 HCDR2 22 AKLEYFDY Amino acid sequence of HCDR3 from REGN1909 23 gacatccaga tgacccagtc tccttccacc ctgtctgcatctgtaggaga cagagtcacc atcacttgcc gggccagtca gagtattagt agctggttgg cctggtatca gcagaaacca gggaaagccc ctaagctcct gatctataag gcgtctagtt tagaaagtgg ggtcccatca aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgaggcct gaagattttg caacttatta ctgccaacag tataatagtt accctctgac tttcggcgga gggaccaagg tggagateaa a Nucleic acid sequence of LCVR from REGN1909 Petition 870250097901, dated 10 / 27 / 2025, p. 72 / 139 68 / 104 SEQ ID NO Sequence Description 24 DIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKP GKAPKLLIYKASSLESGVPSRFSGSGSGTDFTLTISSLRPED FATYYCQQYNSYPLTFGGGTKVEIK Amino acid sequence of LCVR from REGN1909 25 cagagtatta gtagctgg Nucleic acid sequence of REGN1909 LCDR1 26 QSISSW Amino acid sequence of REGN1909 LCDR1 aaggcgtct Nucleic acid sequence of REGN1909 LCDR2 KAS Amino acid sequence of REGN1909 LCDR2 27 caacagtata atagttaccc tctgact Nucleic acid sequence of REGN1909 LCDR3 28 QQYNSYPLT Amino acid sequence of REGN1909 LCDR3 29 EVQLVESGGGLVKPGGSLRLSCAASGFTFRNYNINWVRQ APGKGLEWVSLISGSSSYIYYADSVKGRFTVSRDNAKNSL YLQMNSLRAEDTAVYYCARRTLSYYVMDVWGQGTTVT VSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGT KTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGP SVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQFNWY VDGVEVHNAKTKPREEQFNSTYRWSVLTVLHQDWLNG KEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEE MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP VLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK Heavy chain amino acid sequence REGN1908 30 DIQVTQSPSPLSASVGDRVTITCRASQGISNYLAWYQQKP GRVPQLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPED VATYYCQKYNSAPYTFGQGTKLEIKRTVAAPSVFIFPPSD EQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQ ESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQ GLSSPVTKSFNRGEC Light chain amino acid sequence REGN1908 31 EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQ APGKGLEWVSAISGRGYNADYADSVKGRFTISRDNSKNT LYLQMNSLRAEDTAVYYCAKLEYFDYWGQGTLVTVSSA STKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSW NSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTKTY TCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVF LFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQFNWYVD GVEVHNAKTKPREEQFNSTYRWSVLTVLHQDWLNGKE YKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEM TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV LDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHY TQKSLSLSLGK Heavy chain amino acid sequence REGN1909 32 DIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKP GKAPKLLIYKASSLESGVPSRFSGSGSGTDFTLTISSLRPED FATYYCQQYNSYPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQE SVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQG LSSPVTKSFNRGEC Amino acid sequence of the REGN1909 light chain EXAMPLES

[00173] The following examples are presented in order to provide those with common knowledge in the area with a complete disclosure and description of how to make and use the methods and compositions of disclosure, and Petition 870250097901, dated 10 / 27 / 2025, p. 73 / 139 / 104, does not intend to limit the scope of what the inventors consider to be their invention. Efforts have been made to ensure accuracy with respect to the numbers used (e.g., quantities, temperature, etc.), but some experimental errors and deviations should be considered. Unless otherwise indicated, parts are parts by weight, molecular weight is weight-average molecular weight, temperature is in degrees Celsius, and pressure is or is close to atmospheric. Example 1: Antibodies to Fel dl

[00174] Specific antibodies for Fel d1 were generated as described in US 9,079,948, incorporated herein by reference. Exemplary fully human anti-Fel d1 antibodies (i.e., antibodies possessing both human variable domains and human constant domains) that were generated include H4H1232N (REGN1908) and H4H2636P (REGN1909). The nucleic acid and amino acid sequences of the CDRs, variable heavy chain regions, and variable light chain regions of these antibodies are presented in Table 1. Tables 2-3 below present the amino acid sequence identifiers (Table 2) and nucleic acid sequence identifiers (Table 3) of these antibodies. Table 2: Amino Acid Sequence Identifiers___________________ SEQ ID Nos: Antibody Name HCVR HCDR1 HCDR2 HCDR3 LCVR LCDR1 LCDR2 LCDR3 REGN1908 2 4 6 8 10 12 - 14 REGN1909 16 18 20 22 24 26 - 28 Table 3: Nucleic Acid Sequence Identifiers SEQ ID Nos: Antibody Name HCVR HCDR1 HCDR2 HCDR3 LCVR LCDR1 LCDR2 LCDR3 REGN1908 1 3 5 7 9 11 - 13 REGN1909 15 17 19 21 23 25 - 27 Example 2: Identification of buffer, pH and excipients suitable for individual anti-Fel d1 antibodies.

[00175] Initial formulation development activities involved screening buffer and pH conditions which demonstrated a Petition 870250097901, dated 10 / 27 / 2025, page 74 / 139 / 104 good balance of physical and chemical stability for each of the anti-Fel dl antibodies REGN1908 and REGN1909. The anti-Fel D1 antibody (REGN1908 or REGN1909) at a concentration of 5 mg / mL was incubated in phosphate buffer at pH 6.0, 6.5, 7.0, 7.5 or 8.0, in histidine buffer at pH 5.5, 6.0 or 6.5, or acetate buffer at pH 4.5, 5.0 or 5.5. The formulations were subjected to a shaking test and evaluated for the formation of aggregates and variant charge species. It was found that 10 mM of histidine conferred the best stability to REGN1908 and REGN1909. In the agitation test, formulations REGN1908 > pH 6.0 and formulations REGN1909 > pH 6.0 and < pH 5.5 failed the agitation tests. REGN1908 was determined to be the most stable with respect to aggregate formation in the pH range of 5.5-6.0 and with respect to charge variants at pH 5.0-6.0.REGN1909 was determined to be the most stable with respect to aggregate formation in the pH range of 6.06.5 and with respect to charge variants at pH 5.5. Thus, it was determined that a pH of 5.8 provided a good balance of physical and chemical stability for both molecules.

[00176] Formulations containing REGN1908 or REGN1909 at a concentration of 20 mg / mL in a 10 mM histidine buffer at pH 6.0 were evaluated for thermal stability in the absence or presence of a cryoprotectant. It was determined that both antibodies were stable in formulations containing 5% (w / v) sucrose as a cryoprotectant, but an increase in the percentage of high molecular weight species was observed in control formulations without the sucrose cryoprotectant.

[00177] Formulations containing REGN1908 or REGN1909 were also evaluated for the effects of a surfactant on agitation stability and thermal stability. Agitation stress was applied to all formulations by vortexing at 1000 rpm for 120 minutes. Thermal stability was evaluated by incubating all formulations under accelerated conditions of 45°C for 28 days. Polysorbate 20 (0.1% w / v), polysorbate 80 Petition 870250097901, dated 10 / 27 / 2025, page 75 / 139 / 104 (0.1% w / v), PEG 3350 (0.5% w / v) and PEG 3350 (1.5% w / v) were all tested in formulations containing REGN1908 or REGN1909 at a concentration of 20 mg / mL, 5% (w / v) sucrose and 10 mM histidine buffer at pH 6.0. All surfactants tested provided protection against agitation. In a thermal stability assay, REGN1908 was found to have lower thermal stability with polysorbate 20 compared to polysorbate 80 (thermal stability rating: 0.1% PS80 > 0.5% PEG > 1.5% PEG > 0.1% PS20). REGN1909 was thermally stable with all surfactants tested.

[00178] Based on these initial formulation development activities, it was determined that a formulation comprising 10 mM histidine, 5% (w / v) sucrose and 0.1% (w / v) polysorbate 80 at pH 5.8 was suitable for formulating REGN1908 or REGN1909. Example 3: Formulation of High Concentration Anti-Fel dl Antibodies

[00179] Subsequent formulation development activities included formulating anti-Fel d1 antibodies individually at higher concentrations, which is desirable to minimize the volume of medication administered to the patient. However, it is known in the art that as the antibody concentration increases, the viscosity of the formulation also increases. In turn, higher viscosity can lead to challenges in manufacturing and patient administration.

[00180] REGN1908 at a concentration of 150 mg / mL was formulated with 10 mM histidine at different pHs ranging from 5.4 to 6.5. The formulations were evaluated by SE-UPLC for aggregate formation under two different conditions: after incubation at 45°C for 28 days and after incubation at 25°C for 2 months. As shown in Figure 1A, unfavorable levels of HMW aggregates were observed with the pH 5.4 formulation after incubation at 45°C for 28 days. After incubation at 45°C for 28 Petition 870250097901, dated 10 / 27 / 2025, page 76 / 139 / 104 days, the lowest levels of HMW species were observed for the formulation at pH 6.0 (Figure 1A), while after incubation at 25°C for 2 months, the lowest levels of HMW species were observed for the formulations at pH 5.8, 6.0 and 6.2 (Figure 1B).

[00181] REGN1908 formulations were also evaluated for viscosity at 20°C. As shown in Figure 2, REGN1908 at 150 mg / mL and formulated at pH 5.4 showed the lowest viscosity, while formulations at pH 6.2 or 6.5 showed viscosity > 20 cP.

[00182] As shown in Table 4 below, the 150 mg / mL REGN1908 formulation at pH 6.0 achieved the best balance between acceptable viscosity and low HMW aggregate formation. Formulations at pH 6.0 were then tested to determine the effects of further increasing the REGN1908 concentration on viscosity. As shown in Figure 3, it was found that although 150 mg / mL REGN1908 had a low viscosity of 19.7 cP, higher concentrations resulted in formulations with a viscosity > 20 cP. Table 4: Viscosity and Aggregation of High Concentration Formulations REGN1908_________________________________________ pH Viscosity HMW Aggregation 45°C, 28 days HMW Aggregation 25°C, 2 months 5.4 + - NA 5.6 0 0 0 5.8 0 0 + 6.0 0 + + 6.2 - 0 + 6.5 - 0 0 + favorable; 0 neutral; - unfavorable; NA not available

[00183] REGN1909 at a concentration of 150 mg / mL was formulated with 10 mM histidine at different pHs ranging from 5.4 to 6.8. The formulations were evaluated by SE-UPLC for aggregate formation under two different conditions: after incubation at 45°C for 28 days and after incubation at 25°C for 2 months. As shown in Figure 1A, unfavorable levels of HMW aggregates were observed with the pH 5.4 formulation after incubation at 45°C for 28 days. After incubation at 45°C for 28 Petition 870250097901, dated 10 / 27 / 2025, page 77 / 139 / 104 days, the lowest levels of HMW species were observed for the formulation at pH 6.2 and 6.5 (Figure 1A). After incubation at 25°C for 2 months, the lowest levels of HMW species were observed for the formulations at pH 5.4, 5.6, 5.8 and 6.0 (Figure 1B).

[00184] REGN1909 formulations at different pHs were evaluated for viscosity at 20 °C. As shown in Figure 2, REGN1908 at 150 mg / mL and formulated at pH 5.4 showed the lowest viscosity, although all formulations tested had a viscosity < 20 cP.

[00185] As shown in Table 5 below, the 150 mg / mL REGN1909 formulation at a pH of 5.6 to 6.0 achieved the best balance between acceptable viscosity and low HMW aggregate formation. Formulations at pH 6.0 were then tested to determine the effects of further increasing the REGN1909 concentration on viscosity. As shown in Figure 3, 150 mg / mL REGN1909 was found to have a viscosity of 11.8 cP. Higher concentrations up to approximately 180 mg / mL still exhibited acceptable viscosity. Table 5: Viscosity and Aggregation of High Concentration Formulations REGN1909_________________________________________ pH Viscosity HMW Aggregation 45°C, 28 days HMW Aggregation 25°C, 2 months 5.4 + - + 5.6 + 0 + 5.8 + 0 + 6.0 + 0 + 6.2 + + 0 6.5 + + 0 6.8 + 0 0 + favorable; 0 neutral; - unfavorable

[00186] The effects of four different viscosity reducers on high concentration formulations of REGN1908 or REGN1909 were also tested. REGN1908 or REGN1909 at 150 mg / mL was formulated at pH 6.0 and the following excipients: (i) 10 mM histidine (i.e., without viscosity reducer); (ii) 10 mM histidine + 70 mM arginine-HCl; Petition 870250097901, dated 10 / 27 / 2025, page 78 / 139 / 104 (iii) 100 mM histidine; (iv) 10 mM histidine + 3% proline; or (v) 10 mM histidine + 70 mM sodium chloride. The formulations were evaluated for viscosity at 20 °C. As shown in Figure 4 and Table 6 below, 70 mM arginine was the most effective in reducing the viscosity of REGN1908 (the most viscous of the two antibodies). For REGN1908, a viscosity < 10 cP was obtained using 70 mM arginine, 100 mM histidine, or 70 mM sodium chloride as a viscosity reducer. For REGN1909, each of the viscosity reducers tested resulted in a formulation with a viscosity < 10 cP. Table 6: Effects of Viscosity Reducers Formulation % reduction of cP for REGN1908 % reduction of cP for REGN1909 10 mM histidine, without reducing agent 0% 0% 100 mM histidine 55% 13% 10 mM histidine, 70 mM arginine 60% 15% 10 mM histidine, 3% proline 22.5% 20% 10 mM histidine, 70 mM NaCl 52.5% 4%

[00187] The effects of the cryoprotectant on viscosity were tested for REGN1908 and REGN1909. REGN1908 or REGN1909 was formulated at a target concentration of 150 mg / mL with 10 mM histidine at pH 6.0. As shown in Figure 5, the viscosity of REGN1909 was not essentially affected by the addition of the sucrose cryoprotectant at 5% w / v or 10% w / v. However, the viscosity of REGN1908 was approximately 20 cP in the presence of 5% sucrose and increased to 30 cP in the presence of 10% sucrose. Further tests were performed with REGN1908 to determine the effects on viscosity of the inclusion of 70 mM arginine-HCl in the presence of sucrose.As shown in Figure 6, it was determined that 70 mM arginine-HCl was able to reduce the viscosity of a REGN1908 formulation at a concentration of ~140 mg / mL with 5% w / v sucrose; the formulation with 70 mM arginine-HCl and 5% sucrose had a viscosity of about 8 cP at 20 °C, versus a viscosity of about 24 cP in the absence of arginine and sucrose (Figure 6) or a viscosity of about 20 cP in the presence of 5% sucrose (Figure 5). Petition 870250097901, dated 10 / 27 / 2025, pp. 79 / 139 / 104

[00188] Table 7 below shows seven formulations for REGN1908 and REGN1909 that were evaluated for stability at a target protein concentration of 175 mg / mL; this higher antibody concentration was chosen in case of potential need for high doses of the antibody or antibodies in clinical trials. As shown in Table 7 below, in the absence of a viscosity reducer or sucrose, the REGN1908 formulation had a viscosity of 34.8 cP. The REGN1908 formulation with 10 mM histidine and 70 mM arginine, without sucrose or with 5% sucrose, resulted in formulations with the lowest viscosity (13.7 cP and 18.0 cP, respectively). The REGN1908 formulation with 80 mM histidine without sucrose resulted in a formulation with a viscosity of 15.8 cP; The addition of 5% or 10% sucrose increased the viscosity to 20.5 cP or 23.3 cP, respectively. For the REGN1909 formulations, all formulations tested had a viscosity < 20 cP. Table 7: Viscosity of Formulations of 175 mg / mL of REGN1908 or REGN1909_____________________________________________ Formulation Base Histidine (mM) Arginine (mM) Sucrose (% w / v) Viscosity (cP) of REGN1908 at 20 °C Viscosity (cP) of REGN1909 at 20 °C 175 mg / ml of REGN1908 or REGN1909 pH 6.0, Polysorbate 80 at 0.1% 10 - - 34.8 19.0 80 - - 15.8 11.1 80 - 5 20.5 15.8 80 - 10 23.3 16.9 10 70 - 13.7 13.9 10 70 5 18.0 15.8* 10 70 10 21.1 14.9 * The measured concentration of REGN1909 for this sample was 183 mg / mL. For the other samples, the concentration was approximately 175 mg / mL. Example 4: Exemplary Formulations of Individual Antibodies

[00189] In certain embodiments, anti-Fel d1 antibodies (e.g., REGN1908 and REGN1909) are individually formulated in an aqueous buffered formulation comprising: (a) 5 mM to 20 mM histidine buffer, (b) 60 mM to 130 mM arginine, and (c) 50 to 200 mg of anti-Fel d1 antibody, at pH 6.0 ± 0.3. In some embodiments, the formulation further comprises: 2.5% to 7.5% w / v sucrose and / or 0.01% to 0.5% w / v polysorbate. Petition 870250097901, dated 10 / 27 / 2025, pages 80 / 139 / 104

[00190] In certain embodiments, anti-Fel dl antibodies (e.g., REGN1908 and REGN1909) are individually formulated in an aqueous buffered formulation comprising: (a) 5 mM to 20 mM histidine buffer, (b) 2.5% to 7.5% w / v sucrose, (c) 60 mM to 130 mM arginine, and (d) 50 to 200 mg anti-Fel d1 antibody, at pH 6.0 ± 0.3. In some embodiments, the formulation further comprises 0.01% to 0.5% w / v polysorbate.

[00191] In an exemplary embodiment, an anti-Fel d1 antibody formulation comprises: (a) 10 mM ± 2 mM histidine, (b) 5% 1% w / v sucrose, (c) 70 mM ± 14 mM arginine and (d) 190 mg / mL ± 10 mg / mL REGN1908, at pH 6.0 ± 0.3.

[00192] In an exemplary embodiment, an anti-Fel d1 antibody formulation comprises: (a) 10 mM ± 2 mM histidine, (b) 5% ± 1% w / v sucrose, (c) 70 mM ± 14 mM arginine, (d) 0.15% ± 0.075% w / v polysorbate 80 and (e) 150 mg / mL ± 15 mg / mL REGN1908, at pH 6.0 ± 0.3.

[00193] In an exemplary embodiment, an anti-Fel d1 antibody formulation comprises: (a) 10 mM ± 2 mM histidine, (b) 5% ± 1% w / v sucrose, (c) 70 mM ± 14 mM arginine and (d) 190 mg / mL ± 10 mg / mL REGN1909, at pH 6.0 ± 0.3.

[00194] In an exemplary embodiment, an anti-Fel d1 antibody formulation comprises: (a) 10 mM ± 2 mM histidine, (b) 5% ± 1% w / v sucrose, (c) 70 mM ± 14 mM arginine, (d) 0.15% ± 0.075% w / v polysorbate 80 and (e) 150 mg / mL ± 15 mg / mL REGN1909, at pH 6.0 ± 0.3. Example 5: Stability Studies for REGN1908 Formulations

[00195] REGN1908 was formulated at a concentration of ~150 mg / mL or ~190 mg / mL for various long-term stability studies. REGN1908 Formulation No. 1 contained 191.2 mg / mL of REGN1908, 10 mM histidine, 70 mM arginine-HCl, and 5% (w / v) sucrose at pH 6.0. Petition 870250097901, dated 10 / 27 / 2025, p. 81 / 139 / 104 Formulation REGN1908 No. 2 contained 155.7 mg / mL of REGN1908, 10 mM histidine, 70 mM arginine-HCl, 5% (w / v) sucrose and 0.15% (w / v) super-refined polysorbate 80, at pH 6.0. Stability studies of formulation REGN1908 No. 1 and No. 2 were performed in 5 mL polycarbonate bottles. REGN1908 Formulation No. 1

[00196] For stability studies of Formulation No. 1 REGN1908, long-term storage conditions were -80°C or -30°C for 0, 1, 3, 6, 9, 12, 18, and 24 months. Accelerated conditions were -20°C for 0, 1, 3, and 6 months; 5°C for 0, 0.5, 1, 3, and 6 months; or 25°C / 60% RH for 0, 0.5, 1, 3, and 6 months. Thermal stress conditions were 40°C / 75% RH for 0, 0.25, 0.5, 1, and 3 months. Stability under physical stresses, including agitation and freeze / thaw cycles, was also evaluated. For the agitation tests, samples were agitated at 1000 RPM for 0, 5, and 10 minutes. For freeze / thaw tests, samples were frozen at -30°C and thawed at room temperature for 0, 2, and 4 cycles.

[00197] 12 months of storage stability data are available for REGN1908 Formulation No. 1. No appreciable change in the physical or chemical stability of Formulation No. 1 REGN1908 was detected when stored at -80 °C and -30 °C for up to 24 months (Table 8 and Table 9). All attributes examined met the quality target under the storage conditions. These results indicate that Formulation No. 1 REGN1908 is stable for at least 24 months when frozen under storage conditions of -30 °C or -80 °C.

[00198] Research stability studies indicated that Formulation No. 1 REGN1908 was physically and chemically stable when incubated at -20 °C for up to 6 months, 5 °C for up to 6 months, and at 25 °C / 60% RH for up to 0.5 months (Table 10), with no significant changes observed in any of the monitored stability attributes. At 25°C / 60% RH, 6 months of Petition 870250097901, dated 10 / 27 / 2025, page 82 / 139 / 104 storage, a 1.1% increase in HMW species was observed by SE-UPLC and an 8.8% increase in Region 1 (acidic variants) without significant changes in Region 3 (basic variants) was observed by iCIEF.

[00199] After incubation at 40°C / 75% RH for 3 months, a 14.7% increase in HMW species was observed by SE-UPLC. A 35.8% increase in Region 1 (acid charge variants) was observed by iCIEF (Table 10). A concomitant 31.8% decrease in Region 2 (main peak), without any significant change in Region 3 (base charge variants), was observed by iCIEF.

[00200] Formulation REGN1908 No. 1 was chemically stable when vortexed for 5 or 10 minutes (Table 11). However, after 5 and 10 minutes of extreme vortex stress conditions, the formulation showed an increase of 0.3% and 0.5% in HMW species, respectively. Formulation REGN1908 No. 1 was physically and chemically stable when subjected to 4 freeze-thaw cycles (Table 11). No appreciable changes in physical or chemical stability were detected in any of the monitored attributes. Table 8: Stability of REGN1908 Formulation No. 1 at -80°C Assay Storage Duration (months) 0 12 24 Visual Appearance (changes from clear, colorless to light yellow, essentially free of visible particles) Approved Approved Approved pH 6.0 6.0 6.0 Total Protein (mg / mL) 197 199.7 203.1 Purity by SE-UPLC % principal 98.5 98.4 98.5 % LMW species 0.0 0.1 0.0 % HMW species 1.5 1.6 1.5 Charge Variant Analysis by iCIEF % acid (Region 1) 32.8 35.5 35.0 % principal (Region 2) 54.1 51.0 52.2 % basic (Region 3) 13.2 13.5 12.8 Particulate Matter (MFI) - Unfiltered > 2 to < 10 gm (particles / ml) 576 1118 570 > 10 gm (particles / mL) 25 40 50 > 25 gm (particles / mL) 2 0 3 NP = not performed Petition 870250097901, dated 10 / 27 / 2025, pp. 83 / 139 / 104 Table 9: Stability of Formulation No. 1 REGN1908 at -30°C Assay Storage Duration (months) 0 12 24 Visual Appearance (changes from clear, colorless to light yellow, essentially free of visible particles) Approved Approved Approved pH 6.0 6.0 6.1 Total Protein (mg / mL) 197 201.5 205.0 Purity by SE-UPLC % principal 98.5 98.4 98.5 % LMW species 0.0 0.1 0.0 % HMW species 1.5 1.6 1.5 Charge Variant Analysis by iCIEF % acid (Region 1) 32.8 35.3 35.2 % principal (Region 2) 54.1 50.9 51.6 % basic (Region 3) 13.2 13.8 13.2 Particulate Matter (MFI) Unfiltered > 2 to < 10 µm (particles / mL) 576 2198 609 > 10 µm (particles / mL) 25 50 23 > 25 µm (particles / mL) 2 6 3 NP = not performed Petition 870250097901, dated 10 / 27 / 2025, pages 84 / 139 / 104 Table 10: Stability of REGN1908 Formulation No. 1 incubated at -20°C, 5°C, 25°C / 60% RH and 40°C / 75% RH Petition 870250097901, dated 10 / 27 / 2025, page 85 / 139 / 104 Table 11: Stability of REGN1908 Formulation No. 1 - Effect of Agitation and Freezing / Thawing from page 86 / 139 / 104 Formulation No. 2 REGN1908

[00201] For stability studies of Formulation No. 2 REGN1908, long-term storage conditions were -80°C or -30°C for 0, 1, 3, 6, 9, 12, 18, and 24 months. Accelerated conditions were -20°C for 0, 1, 3, and 6 months; 5°C for 0, 0.5, 1, 3, and 6 months; or 25°C / 60% RH for 0, 0.5, 1, 3, and 6 months. Thermal stress conditions were 40°C / 75% RH for 0, 0.25, 0.5, 1, and 3 months. Stability under physical stresses, including agitation and freeze / thaw cycles, was also evaluated. For the agitation tests, samples were agitated at 1000 RPM for 0, 30, and 60 minutes. For freeze / thaw tests, samples were frozen at -30°C and thawed at room temperature for 0, 2, and 4 cycles.

[00202] 24-month storage stability data are available for Formulation No. 2 REGN1908. No appreciable change in the physical or chemical stability of Formulation No. 2 REGN1908 was detected when stored at -80°C and -30°C for up to 24 months (Table 12 and Table 13). All attributes examined met the quality target under the storage conditions. These results indicate that Formulation No. 2 REGN1908 is stable for at least 24 months when frozen under storage conditions.

[00203] Research stability studies indicated that Formulation No. 2 REGN1908 was physically and chemically stable when incubated at -20°C for up to 6 months, 5°C for up to 6 months, and at 25°C / 60% RH for up to 0.5 months (Table 14), with no significant changes observed in any of the monitored stability attributes. At 25°C / 60% RH after 6 months of storage, a 0.8% increase in HMW species was observed by SE-UPLC and a 7.6% increase in Region 1 (acidic variants) with no significant changes observed in Region 3 (basic variants) by iCIEF.

[00204] After incubation at 40°C / 75% RH for 3 months, a 13.1% increase in HMW species was observed by SE-UPLC. An increase of Petition 870250097901, dated 10 / 27 / 2025, page 87 / 139 / 104 A 34.8% decrease in Region 1 (acid charge variants) was observed by iCIEF (Table 14). A concomitant decrease of 31.1% in Region 2 (main peak), without any significant change in Region 3 (base charge variants), was observed by iCIEF.

[00205] Formulation REGN1908 No. 2 was physically and chemically stable when agitated for 60 or 120 minutes (Table 15). No appreciable change in physical or chemical stability was detected in any of the monitored attributes. Formulation No. 2 REGN1908 was physically and chemically stable when subjected to up to 4 freeze-thaw cycles (Table 15). No appreciable change in physical or chemical stability was detected in any of the monitored attributes. Table 12: Stability of Formulation No. 2 REGN1908 at -80°C Assay Storage Duration (months) 0 12 24 Visual Appearance (changes from clear, colorless to light yellow, essentially free of visible particles) Approved Approved Approved pH 6.0 6.04 6.0 Total Protein (mg / mL) 154.6 158 153.6 Purity by SE-UPLC % principal 98.5 98.6 98.6 % of LMW species 0.0 0.0 0.0 % of HMW species 1.5 1.4 1.4 Charge Variant Analysis by iCIEF % acid (Region 1) 33.5 34.0 34.2 % principal (Region 2) 53.3 52.9 52.6 % basic (Region 3) 13.2 13.1 13.2 Particulate Matter (MFI) unfiltered > 2 to < 10 gm (particles / ml) 177 179 186 > 10 gm (particles / mL) 21 19 11 > 25 gm (particles / mL) 0 2 0 Table 13: Stability of Formulation No. 2 REGN1908 at -30°C Assay Storage Duration (months) 0 12 24 Visual Appearance (changes from clear, colorless to light yellow, essentially free of visible particles) Approved Approved Approved pH 6.0 6.0 6.0 Total Protein (mg / mL) 154.6 160.9 154.9 Purity by SE-UPLC % principal 98.5 98.5 98.6 % LMW species 0.0 0.0 0.0 % HMW species 1.5 1.4 1.4 Charge Variant Analysis by iCIEF % acid (Region 1) 33.5 35.6 34.7 % principal (Region 2) 53.3 51.1 52.1 % basic (Region 3) 13.2 13.3 13.2 Particulate Matter (MFI) - unfiltered > 2 to < 10 gm (particles / ml) 177 313 82 > 10 gm (particles / mL) 21 23 9 > 25 gm (particles / mL) 0 4 5 Petition 870250097901, dated 10 / 27 / 2025, pages 88 / 139 / 104 Table 14: Stability of REGN1908 formulation no. 2 incubated at -20°C, 5°C, 25°C / 60% RH and 40°C / 75% RH Petition 870250097901, dated 10 / 27 / 2025, pages 89 / 139 / 104 Table 15: Stability of Formulation No. 2 REGN1908 - Effect of Agitation and Freezing / Thawing Petition 870250097901, dated 10 / 27 / 2025, pp. 90 / 139 / 104 Example 6: Stability Studies for REGN1909 Formulations

[00206] REGN1909 was formulated at a concentration of ~150 mg / mL or ~190 mg / mL for various long-term stability studies. Formulation REGN1909 No. 1 contained 189.4 mg / mL of REGN1909, 10 mM histidine, 70 mM arginine-HCl, and 5% (w / v) sucrose at pH 6.0. Formulation REGN1909 No. 2 contained 152.6 mg / mL of REGN1909, 10 mM histidine, 70 mM arginine-HCl, 5% (w / v) sucrose, and 0.15% (w / v) super-refined polysorbate 80 at pH 6.0. Stability studies of formulations REGN1909 No. 1 and No. 2 were performed in 5 mL polycarbonate bottles. REGN1909 Formulation No. 1

[00207] For stability studies of Formulation No. 1 REGN1909, long-term storage conditions were -80°C or -30°C for 0, 1, 3, 6, 9, 12, 18, and 24 months. Accelerated conditions were -20°C for 0, 1, 3, and 6 months; 5°C for 0, 0.5, 1, 3, and 6 months; or 25°C / 60% RH for 0, 0.5, 1, 3, and 6 months. Thermal stress conditions were 40°C / 75% RH for 0, 0.25, 0.5, 1, and 3 months. Stability under physical stresses, including agitation and freeze / thaw cycles, was also evaluated. For the agitation tests, samples were agitated at 1000 RPM for 0, 5, and 10 minutes. For freeze / thaw tests, samples were frozen at -30°C and thawed at room temperature for 0, 2, and 4 cycles.

[00208] 24 months of storage stability data are available for Formulation No. 1 REGN1909. No appreciable change in the physical or chemical stability of Formulation No. 1 REGN1909 was detected when stored at -80°C and -30°C for up to 24 months (Table 16 and Table 17). All attributes examined met the quality target under the storage conditions. These results indicate that Formulation No. 1 REGN1909 is stable for at least 24 months when frozen under storage conditions of -30°C or -80°C. Petition 870250097901, dated 10 / 27 / 2025, pp. 91 / 139 / 104

[00209] Research stability studies indicated that Formulation No. 1 REGN1909 was physically and chemically stable when incubated at -20 °C for up to 6 months, 5 °C for up to 6 months, and at 25 °C / 60% RH for up to 0.5 months (Table 18), with no significant changes observed in any of the monitored stability attributes. At 25°C / 60% RH, 6 months of storage, a 1.8% increase in HMW species was observed by SE-UPLC and an 8.8% increase in Region 1 (acidic variants) without significant changes in Region 3 (basic variants) was observed by iCIEF.

[00210] Following incubation at 40°C / 75% RH for 3 months, a 6.4% increase in HMW species was observed by SE-UPLC. A 28.4% increase in Region 1 (acid charge variants) was observed by iCIEF (Table 18). A concomitant 28.8% decrease in Region 2 (main peak), without any significant change in Region 3 (base charge variants), was observed by iCIEF.

[00211] Formulation REGN1909 No. 1 was physically and chemically stable when agitated for 5 minutes (Table 19). However, after 10 minutes of extreme vortex agitation stress, Formulation REGN1909 No. 1 became chemically stable but not physically stable, as there was a 0.3% increase in HMW species. Formulation REGN1909 No. 1 was physically and chemically stable when subjected to 4 freeze-thaw cycles (Table 19). No appreciable changes in physical or chemical stability were detected in any of the monitored attributes. Table 16: Stability of Formulation No. 1 REGN1909 at -80°C Assay Storage Duration (months) 0 12 24 Visual Appearance (changes from clear, colorless to light yellow, essentially free of visible particles) Approved Approved Approved pH 6.0 6.0 5.9 Total Protein (mg / mL) 196.0 200.3 195.8 Purity by SE-UPLC % principal 98.5 98.6 98.6 % of LMW species 0.0 0.1 0.0 % of HMW species 1.5 1.4 1.4 Charge Variant Analysis by iCIEF % acid (Region 1) 38.5 40.1 40.7 % principal (Region 2) 53.6 52.9 52.4 Petition 870250097901, dated 10 / 27 / 2025, pp. 92 / 139 / 104 Basic % (Region 3) 7.9 7.0 6.9 Particulate matter (MFI) - unfiltered > 2 to < 10 µm (particles / mL) 964 1560 201 > 10 µm (particles / mL) 31 77 3 > 25 µm (particles / mL) 4 15 0 Table 17: Stability of Formulation No. 1 REGN1909 at -30°C Assay Storage Duration (months) 0 12 24 Visual Appearance (changes from clear, colorless to light yellow, essentially free of visible particles) Approved Approved Approved pH 6.0 6.0 5.9 Total Protein (mg / mL) 196.0 206.1 199.1 Purity by SE-UPLC % principal 98.5 98.6 98.4 % LMW species 0.0 0.0 0.0 % HMW species 1.5 1.4 1.6 Charge Variant Analysis by iCIEF % acid (Region 1) 38.5 39.8 41.5 % principal (Region 2) 53.6 53.0 51.5 % basic (Region 3) 7.9 7.2 7.1 Particulate Matter (MFI) - Unfiltered > 2 to < 10 µm (particles / mL) 964 5403 159 > 10 µm (particles / mL) 31 177 11 > 25 µm (particles / mL) 4 29 7 Petition 870250097901, dated 10 / 27 / 2025, pp. 93 / 139 / 104 Table 18: Stability of REGN1909 Formulation No. 1 incubated at -20°C, 5°C, 25°C / 60% RH and 40°C / 75% RH Petition 870250097901, dated 10 / 27 / 2025, pp. 94 / 139 / 104 Table 19: Stability of REGN1909 Formulation No. 1 - Effect of Agitation and Freezing / Thawing Petition 870250097901, dated 10 / 27 / 2025, pp. 95 / 139 / 104 REGN1909 Formulation No. 2

[00212] For stability studies of Formulation No. 2 REGN1909, long-term storage conditions were -80°C or -30°C for 0, 1, 3, 6, 9, 12, 18, and 24 months. Accelerated conditions were -20°C for 0, 1, 3, and 6 months; 5°C for 0, 0.5, 1, 3, and 6 months; or 25°C / 60% RH for 0, 0.5, 1, 3, and 6 months. Thermal stress conditions were 40°C / 75% RH for 0, 0.25, 0.5, 1, and 3 months. Stability under physical stresses, including agitation and freeze / thaw cycles, was also evaluated. For the agitation tests, samples were agitated at 1000 RPM for 0, 30, and 60 minutes. For freeze / thaw tests, samples were frozen at -30°C and thawed at room temperature for 0, 2, and 4 cycles.

[00213] 24-month storage stability data are available for Formulation No. 2 REGN1909. No appreciable change in the physical or chemical stability of Formulation No. 2 REGN1909 was detected when stored at 80°C and -30°C for up to 24 months (Table 20 and Table 21). These results indicate that Formulation No. 2 REGN1909 is stable for at least 24 months when stored frozen at -30°C or 80°C.

[00214] Research stability studies indicated that Formulation No. 2 REGN1909 was physically and chemically stable when incubated at -20 °C for up to 6 months, 5 °C for up to 6 months, and at 25 °C / 60% RH for up to 0.5 months (Table 22), with no significant changes observed in any of the monitored stability attributes. At 25 °C / 60% RH after 6 months of storage, a 1.5% increase in HMW species was observed by SE-UPLC and an 11.0% increase in Region 1 (acidic variants) with no significant changes in Region 3 (basic variants) was observed by iCIEF.

[00215] After incubation at 40 °C / 75% RH for 3 months, a 5.4% increase in HMW species was observed by SE-UPLC. An increase of Petition 870250097901, dated 10 / 27 / 2025, pages 96 / 139 / 104 A 31.3% decrease in Region 1 (acid charge variants) was observed by iCIEF (Table 22). A concomitant decrease of 29.6% in Region 2 (main peak), without any significant change in Region 3 (base charge variants), was observed by iCIEF.

[00216] Formulation REGN1909 No. 2 was physically and chemically stable when agitated for 60 or 120 minutes (Table 23). Larger than normal subvisible particles were observed after 120 minutes of vortex agitation. However, no increase in % HMW was observed. More extensive agitation of Formulation No. 2 was performed using an orbital shaker for 24 and 48 hours. After 48 hours in the orbital shaker, a 0.1% increase in HMW species was observed with low subvisible particles in the 10 and 25 tim ranges (255 and 21 particles / mL, respectively). No appreciable change in physical or chemical stability was detected in any of the other monitored attributes. Formulation REGN1909 No. 2 was physically and chemically stable when subjected to up to 4 freeze-thaw cycles (Table 23). No appreciable changes in physical or chemical stability were detected in any of the monitored attributes. Table 20: Stability of Formulation No. 2 REGN1909 at -80°C Assay Storage Duration (months) 0 12 24 Visual Appearance (changes from clear, colorless to light yellow, essentially free of visible particles) Approved Approved Approved pH 6.0 6.0 5.9 Total Protein (mg / mL) 152.6 148.4 152.1 Purity by SE-UPLC % principal 98.7 98.7 98.6 % LMW species 0.0 0.0 0.1 % HMW species 1.3 1.3 1.3 Charge Variant Analysis by iCIEF % acid (Region 1) 35.9 41.3 41.0 % principal (Region 2) 56.0 51.1 51.8 % basic (Region 3) 8.0 7.6 7.2 Particulate Matter (MFI) no Filtered > 2 to < 10 gm (particles / ml) 11 819 73 > 10 µm (particles / mL) 4 54 3 > 25 µm (particles / mL) 0 4 0 Petition 870250097901, dated 10 / 27 / 2025, pages 97 / 139 / 104 Table 21: Stability of Formulation No. 2 REGN1909 at -30°C Assay Storage Duration (months) 0 12 24 Visual Appearance (changes from clear, colorless to light yellow, essentially free of visible particles) Approved Approved Approved pH 6.0 6.0 5.9 Total Protein (mg / mL) 152.6 150.9 148.7 Purity by SE-UPLC % principal 98.7 98.7 98.6 % LMW species 0.0 0.0 0.1 % HMW species 1.3 1.3 1.3 Charge Variant Analysis by iCIEF % acid (Region 1) 35.9 40.0 40.3 % principal (Region 2) 56.0 52.7 52.6 % basic (Region 3) 8.0 7.3 7.1 Particulate Matter (MFI) - unfiltered > 2 to < 10 μm (particles / ml) 11 190 234 > 10 μm (particles / mL) 4 19 19 > 25 μm (particles / mL) 0 6 3 Petition 870250097901, dated 10 / 27 / 2025, pages 98 / 139 / 104 Table 22: Stability of REGN1909 formulation no. 2 incubated at -20°C, 5°C, 25°C / 60% RH and 40°C / 75% RH Petition 870250097901, dated 10 / 27 / 2025, pp. 99 / 139 / 104 Table 23: Stability of REGN1909 Formulation No. 2 - Effect of Agitation and Freezing / Thawing Petition 870250097901, dated 10 / 27 / 2025, pages 100 / 139 / 104 Example 7: Co-Formulation of Anti-Fel dl Antibodies

[00217] In circumstances where multiple antibodies must be administered simultaneously to a patient, it may be beneficial to formulate the antibodies together in a single formulation (e.g., to facilitate administration to the patient and increase patient adherence). Development activities have been initiated for the co-formulation of a fixed-dose combination of REGN1908 and REGN1909. For the co-formulation of REGN1908 and REGN1909, histidine buffer at pH 6.0 was selected; as shown in Tables 4 and 5 above, pH 6.0 was the ideal pH to achieve acceptable viscosity and low or low / intermediate aggregation stability of REGN1908 and REGN1909.

[00218] As disclosed in Example 3 above, REGN1908 was found to be more viscous than REGN1909 in identical formulations. Formulations comprising REGN1908 and REGN1909 were tested to determine whether co-formulation of REGN1908 and REGN1909 increased the formulation viscosity. Formulations containing a total target antibody concentration of 150 mg / mL (approximately 75 mg / mL REGN1908 and approximately 75 mg / mL REGN1909) were formulated at pH 6.1 with 10 mM histidine and 5% sucrose, and without arginine or with 20, 50, 70, 100, or 130 mM arginine. Co-formulations containing at least 50 mM arginine showed viscosity similar to that of REGN1908 or REGN1909 formulated separately (Figure 7A-7C). Significant differences in viscosity were observed in formulations without arginine or with 20 mM arginine (Figure 7A-7C).

[00219] REGN1908 and REGN1909 were co-formulated in the absence or presence of a polysorbate surfactant to evaluate the effects on stability. Starting with a basic formulation containing a total target antibody concentration of 150 mg / mL REGN1908-REGN1909 (approximately 75 mg / mL of each antibody), 10 mM histidine, and 70 mM of Petition 870250097901, dated 10 / 27 / 2025, page 101 / 139 / 104 arginine hydrochloride at pH 6.0, no polysorbate was added, or polysorbate 20 or polysorbate 80 were added in an amount of 0.01%, 0.025%, 0.05%, 0.075%, 0.1% or 0.2% (all percentages w / v). The formulations were subjected to agitation stress induced by orbital shaking at 250 rpm for 24 or 48 hours. As shown in Figure 8, formulations containing > 0.05% w / v of polysorbate 20 were protected from aggregation formation (Fig. 8A), while formulations containing > 0.075% w / v of polysorbate 80 were protected from aggregation formation (Fig. 8B). Furthermore, the presence of subvisible particles was determined using microfluidic imaging (MFI) at >10 microns and >25 microns for 48-hour samples.As shown in Figure 9, both polysorbate 20 and polysorbate 80 were effective at > 0.025% w / v; however, polysorbate 80 resulted in lower particle counts in the 10-micron and 25-micron compartments compared to polysorbate 20.

[00220] Co-formulations containing polysorbate 20 or polysorbate 80 and further comprising a cryoprotectant were generated and tested for stability under accelerated stability storage conditions (40°C at 75% relative humidity) and under repeated freeze-thaw conditions. Starting with a base formulation containing a total target antibody concentration of 150 mg / mL REGN1908-REGN1909 (approximately 75 mg / mL each antibody), 10 mM histidine, 70 mM arginine hydrochloride and 0.15% (w / v) polysorbate at pH 6.0, no cryoprotectant was added, or 5% sucrose, 3% proline, 5% trehalose or 2.5% sorbitol were added (all percentages w / v).

[00221] Figures 10A-10B show stability data for co-formulations containing polysorbate 20, while Figures 10C-10D show stability data for co-formulations containing polysorbate 80. Figures 10A and 10C show that the aggregation formation rates (slopes) for cryoprotectants were higher in the presence of polysorbate. Petition 870250097901, dated 10 / 27 / 2025, pp. 102 / 139 / 104 than for polysorbate 80, suggesting a better stability profile for polysorbate 80 formulations. As shown in Figures 10B and 10D, the presence of cryoprotectant protected against HMW formation after 8 freeze / thaw cycles, both for formulations containing polysorbate 20 and for formulations containing polysorbate 80. Example 8: Characterization of Co-Formulation (DoE)

[00222] Design of Experiments (DoE) analysis was conducted on components of an exemplary formulation, scaled over a wider range than typical manufacturing specifications. Table 24 below shows the factors and ranges that were investigated. REGN1908 and REGN1909 were co-formulated in a ratio of approximately 1:1. Table 24: Factors investigated by the DoE Factor Description Target Range Lower Level Upper Level Concentration REGN1908- REGN1909 (mg / mL) Protein 150 ± 10% 135 165 pH pH 6 ± 0.3 5.7 6.3 Histidine (mM) Buffer 10 ± 40% 6 14 Polysorbate 80 (% w / v) Surfactant 0.15 0.075 - 0.2 0.075 0.2 Arginine (mM) Viscosity reducer 70 ± 40% 42 98 Sucrose (% w / v) Thermal stabilizer 5 ± 40% 3 7

[00223] Figure 11 shows the predicted responses of the formulation at 40°C as a function of the variation of the formulation components. Positive or negative slopes on the range of a component (x-axis) indicate the response of a formulation attribute (y-axis) to that change; vertical dashed lines indicate the target value chosen for each component of the formulation. Most trends in the thermal profiler are stable, indicating that the protein and formulation are thermally stable across the entire functional range of the components. Most responses (y-axis) are minimally affected, except as a function of pH, indicating that protein stability is affected by the formulation pH.

[00224] Figure 12 shows the predicted responses of the formulation under agitation as a function of the variation of the formulation components. Most Petition 870250097901, dated 10 / 27 / 2025, pp. 103 / 139 / 104: The trends in the agitation profiler are practically stable throughout the range, indicating that the protein and the formulation are thermally stable throughout the functional range of the components. However, significant reductions in particle formation are predicted with increasing sucrose concentration.

[00225] Figure 13 shows the predicted responses of the formulation under repeated freeze-thaw cycles as a function of the variation of the formulation components. Most trends in the freeze-thaw profiler are practically stable across the range, indicating that the protein and formulation are stable to freeze-thaw stress across the entire functional range of the components. Significant increases in particle formation are predicted with increasing pH, although particle counts are very low at the target pH of 6.0.

[00226] Figure 14 shows the predicted osmolality and viscosity responses as a function of variations in the formulation components. Most trends in the t=0 profiler are stable throughout the range, indicating that the protein formulations do not undergo significant changes in viscosity and osmolality across the functional range of the components. For viscosity, a significant increase in viscosity is predicted with an increase in protein concentration, and a significant decrease in viscosity is predicted with an increase in the viscosity reducer (arginine). For osmolality, a significant increase in osmolality is predicted with an increase in arginine and sucrose concentrations, although these predicted changes do not fall outside the manufacturing range or beyond physiological tolerability. Example 9: Stability Studies for Co-Formulations REGN1908REGN1909

[00227] In certain modalities, two anti-Fel d1 antibodies are Petition 870250097901, dated 10 / 27 / 2025, pp. 104 / 139 100 / 104 co-formulated in an aqueous buffered formulation comprising: (a) 5 mM to 20 mM histidine buffer, (b) 2.5% to 7.5% w / v sucrose, (c) 60 mM to 130 mM arginine, (d) 0.01% to 0.5% w / v polysorbate and (e) 50 to 200 mg total anti-Fel d1 antibody, at pH 6.0 ± 0.3.

[00228] In an exemplary embodiment, an anti-Fel d1 antibody formulation comprises: (a) 10 mM ± 2 mM histidine, (b) 5% ± 1% w / v sucrose, (c) 70 mM ± 14 mM arginine, (d) 0.15% ± 0.075% w / v polysorbate 80 and (e) 150 mg / mL ± 15 mg / mL REGN1908-REGN1909 (75 mg / mL REGN1908 + 75 mg / mL REGN1909), at pH 6.0 ± 0.3.

[00229] REGN1908 and REGN1909 were co-formulated at a concentration of ~150 mg / mL of total antibody (approximately a 1:1 ratio of REGN1908:REGN1909, with approximately 75 mg / mL of REGN1908 and approximately 75 mg / mL of REGN1909) in 10 mM histidine, 70 mM arginine-HCl, 5% (w / v) sucrose, and 0.15% (w / v) super-refined polysorbate 80 at pH 6.0 for various long-term stability studies. Stability studies on the REGN1908-1909 co-formulation were performed in glass vials and pre-filled syringes (PFS).

[00230] As shown in Tables 25 and 26 below, research stability studies indicated that the REGN1908-1909 coformulation was physically and chemically stable when incubated at 5°C for up to 24 months when stored in glass vials or in PFS, with no significant changes observed in any monitored stability attributes. The stability of the vial and PFS were comparable.

[00231] After incubation at 40°C / 75% RH for 3 months, a 10.9% increase in HMW species was observed by SE-UPLC for the REGN1908-1909 co-formulation stored in glass vials, and a 9.8% increase in HMW species was observed for the co-formulation stored in PFS. See Tables 27 and 28.

[00232] The REGN1908-1909 co-formulation was physically and chemically Petition 870250097901, dated 10 / 27 / 2025, pp. 105 / 139 101 / 104 stable under agitation stress (see Tables 29 and 30) and when subjected to 4 freeze-thaw cycles (Table 29). No appreciable change in physical or chemical stability was detected in any of the monitored attributes. Table 25: Drug Stability in Bottle for Co-formulation REGN1908-1909 at 5°C Assay Storage Duration (months) 0 12 24 Visual Appearance (changes from clear, colorless to light yellow, essentially free of visible particles) Approved Approved Approved pH 6.0 6.0 5.9 Total Protein (mg / mL) 155 157 151 Purity by SE-UPLC % principal 98.2 97.6 97.5 % of LMW species 0.0 0.0 0.0 % of HMW species 1.8 2.4 2.5 Load Variant Analysis by iCIEF % R1909 Principal (A+B) 28.4 29.8 27.0 % R1908 Principal 21.1 23.2 20.3 Particulate Matter (MFI) - unfiltered > 2 to < 10 μm (particle / ml) 1093 716 1266 > 10 pm (particle / mL) 105 15 28 > 25 pm (particle / mL) 3 7 3 Light obscuration, HIAC > 10 μm (no. particle / container), < 6000 particles / container 64 64 24 > 25 μm (no. particle / container), < 600 particles / container 1 0 1 Table 26: Stability of the PFS drug of the REGN19081909 co-formulation at 5°C Assay Storage Duration (months) 0 12 24 Visual Appearance (changes from clear, colorless to light yellow, essentially free of visible particles) Approved Approved Approved pH 6.0 6.0 6.0 Total Protein (mg / mL) 155 158 156 Purity by SE-UPLC % principal 98.2 97.6 97.5 % of LMW species 0.0 0.0 0.0 % of HMW species 1.8 2.4 2.5 Load Variant Analysis poi iCIEF % R1909 Principal (A+B) 28.3 30.4 28.0 % R1908 Principal 20.7 23.5 20.4 Particulate Matter (MFI) - unfiltered > 2 to < 10 μm (particle / ml) 4020 12201 3216 > 10 pm (particles / mL) 177 25 1333 > 25 pm (particles / mL) 0 2 6 Filtered Particulate Matter (MFI) (Aspect Ratio AR<0.85) > 2 to < 10 μm (particles / mL) 1464 10054 1956 > 10 pm (particles / mL) 15 8 21 > 25 pm (particles / mL) 0 2 4 Petition 870250097901, dated 10 / 27 / 2025, pp. 106 / 139 102 / 104 Test Duration of Storage (months) 0 12 24 Visual appearance (changes from clear, colorless to light yellow, essentially free of visible particles) Approved Approved Approved Light obscuration, HIAC > 10 μm (number of particles / container), < 6000 particles / container 29 127 96 > 25 μm (number of particles / container), < 600 particles / container 0 3 3 Table 27: Drug Stability in Co-formulation Bottle REGN1908-1909 at 25°C / 60% RH and 40°C / 75% RH___________________ Storage conditions No storage Storage at 25°C / 60% RH (months) Storage at 40°C / 75% RH (months) Assay 0 6 3 Visual appearance (changes from clear, colorless to light yellow, essentially free of visible particles) Approved Approved Approved pH 6.0 6.0 6.0 Total protein (mg / mL) 155 164 148 Purity by SE-UPLC % principal 98.2 96.9 88.8 % LMW species 0.0 0.1 0.3 % HMW species 1.8 3.1 10.9 Load variant analysis by iCIEF % R1909 Principal (A+B) 28.4 23.6 14.2 % R1908 Principal 21.1 20.3 9.4 Particulate matter (MFI) - unfiltered > 2 to < 10 μm (particles / ml) 1093 2231 1562 > 10 pm (particles / mL) 104 46 33 > 25 pm (particles / mL) 2 6 8 Table 28: Stability of the PFS drug of the REGN19081909 co-formulation at 25°C / 60% RH and 40°C / 75% RH____________________________ Storage conditions No storage Storage at 25°C / 60% RH (months) Storage at 40°C / 75% RH (months) Assay 0 6 3 Visual appearance (changes from clear, colorless to light yellow, essentially free of visible particles) Approved Approved Approved pH 6.0 6.0 6.0 Total protein (mg / mL) 155 157 151 Purity by SE-UPLC % principal 98.2 96.9 90.0 % LMW species 0.0 0.1 0.2 % HMW species 1.8 3.1 9.8 Load variant analysis by iCIEF % R1909 Principal (A+B) 28.4 23.7 14.3 % R1908 Principal 21.1 20.1 9.7 Particulate matter (MFI) - unfiltered > 2 to < 10 μm (particles / ml) 1093 4099 22725 > 10 pm (particles / mL) 104 81 621 > 25 pm (particles / mL) 2 2 21 Petition 870250097901, dated 10 / 27 / 2025, pp. 107 / 139 103 / 104 Table 29: Drug stability in co-formulation vial REGN1908-1909 under agitation and freezing / thawing Storage conditions No storage Orbital Shakers (h) Freeze / Thaw Cycles Assay 0 48 4 Visual appearance (changes from clear, colorless to light yellow, essentially free of visible particles) Approved Approved Approved pH 6.0 6.0 6.0 Total protein (mg / mL) 155 159 151 Purity by SEUPLC % principal 98.2 98.2 98.0 % of LMW species 0.0 0.0 0.0 % of HMW species 1.8 1.8 2.0 Load variant analysis by iCIEF % R1909 Principal (A+B) 28.4 28.5 28.2 % R1908 Principal 21.1 21.4 20.8 Particulate matter (MFI) - unfiltered > 2 to < 10 μm (particle / ml) 1093 1437 940 > 10 gm (particle / mL) 104 90 63 > 25 gm (particle / mL) 2 6 2 Table 30: Stability of the REGN1908-1909 PFS co-formulation. Drug agitation. Storage conditions No storage Tamvor (hours) Assay 0 48 Visual appearance (changes from clear, colorless to light yellow, essentially free of visible particles) Approved Approved pH 6.0 6.1 Total protein (mg / mL) 155 153 Purity by SE-UPLC % principal 98.1 98.1 % of LMW species 0.0 0.0 % of HMW species 1.9 1.9 Charge variant analysis by iCIEF % R1909 Principal (A+B) 28.3 28.5 % R1908 Principal 20.7 21.3 Unfiltered particulate matter (MFI) > 2 to < 10 μm (particle / mL) 3181 3087 > 10 gm (particle / mL) 86 81 > 25 gm (particles / mL) 0 8

[00233] The present invention should not be limited in scope by the specific embodiments described herein. In fact, various modifications of the invention, in addition to those described herein, will become apparent to those skilled in the art from the preceding description and the accompanying figures. Such modifications and variations are intended to be within the scope of the appended claims. Disclosures of all patents and Petition 870250097901, dated 10 / 27 / 2025, pp. 108 / 139 104 / 104 Distinguished patent literature cited in this document is expressly incorporated in full by reference. Petition 870250097901, dated 10 / 27 / 2025, pp. 109 / 139

Claims

1 / 9 CLAIMS 1. Stable liquid pharmaceutical formulation, characterized in that it comprises: (a) at least one antibody that specifically binds to Fel d1, wherein the antibody is selected from the group consisting of: (i) an antibody comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:4, an HCDR2 comprising the amino acid sequence of SEQ ID NO:6, an HCDR3 comprising the amino acid sequence of SEQ ID NO:8, an LCDR1 comprising the amino acid sequence of SEQ ID NO:12, an LCDR2 comprising the amino acid sequence AAS and an LCDR3 comprising the amino acid sequence of SEQ ID NO:14;and (ii) an antibody comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:18, an HCDR2 comprising the amino acid sequence of SEQ ID NO:20, an HCDR3 comprising the amino acid sequence of SEQ ID NO:22, an LCDR1 comprising the amino acid sequence of SEQ ID NO:26, an LCDR2 comprising the amino acid sequence KAS and an LCDR3 comprising the amino acid sequence of SEQ ID NO:28; (b) a buffer containing histidine; (c) a thermal stabilizer; and (d) a surfactant; wherein the formulation has a pH of 6.0 ± 0.

3.

2. Stable liquid pharmaceutical formulation according to claim 1, characterized in that it comprises (i) a first antibody that specifically binds to Fel d1, wherein the first antibody comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO:4, an HCDR2 comprising the amino acid sequence of SEQ ID NO:6, an HCDR3 comprising the amino acid sequence of SEQ Petition 870250097901, of 10 / 27 / 2025, p.110 / 139 2 / 9 ID NO:8, an LCDR1 comprising the amino acid sequence of SEQ ID NO:12, an LCDR2 comprising the amino acid sequence AAS, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:14; and (ii) a second antibody that specifically binds to Fel d1, wherein the second antibody comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO:18, an HCDR2 comprising the amino acid sequence of SEQ ID NO:20, an HCDR3 comprising the amino acid sequence of SEQ ID NO:22, an LCDR1 comprising the amino acid sequence of SEQ ID NO:26, an LCDR2 comprising the amino acid sequence KAS, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:

28.

3. Stable liquid pharmaceutical formulation according to claim 2, characterized in that the first antibody comprises a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO:2 and a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO:

10.

4. Stable liquid pharmaceutical formulation according to claim 2, characterized in that the second antibody comprises an HCVR comprising the amino acid sequence of SEQ ID NO:16 and an LCVR comprising the amino acid sequence of SEQ ID NO:

24.

5. Stable liquid pharmaceutical formulation according to any one of claims 1 to 4, characterized in that the total antibody concentration is from 5 mg / mL to 200 mg / mL.

6. Stable liquid pharmaceutical formulation according to claim 5, characterized in that the total antibody concentration is 150 mg / mL ± 15 mg / mL.

7. Stable liquid pharmaceutical formulation according to any one of claims 2 to 6, characterized in that the first antibody and the second antibody are present in the formulation in a molecular ratio of about 1:

1.

8. Stable liquid pharmaceutical formulation according to any one of claims 2 to 7, characterized in that the first antibody is present at a concentration of 75 mg / mL ± 7.5 mg / mL and the second antibody is present at a concentration of 75 mg / mL ± 7.5 mg / mL.

9. Stable liquid pharmaceutical formulation according to any one of claims 1 to 8, characterized in that the buffer comprises histidine at a concentration of 5 mM to 25 mM.

10. Stable liquid pharmaceutical formulation according to claim 9, characterized in that histidine is present at a concentration of 10 mM ± 2 mM.

11. Stable liquid pharmaceutical formulation according to any one of claims 1 to 10, characterized in that the thermal stabilizer comprises sucrose, trehalose, proline or sorbitol.

12. Stable liquid pharmaceutical formulation according to claim 11, characterized in that the thermal stabilizer comprises sucrose at a concentration of 2.5% w / v 7.5% w / v.

13. Stable liquid pharmaceutical formulation according to claim 12, characterized in that sucrose is present at a concentration of 5% w / v ± 1% w / v.

14. Stable liquid pharmaceutical formulation according to any one of claims 1 to 13, characterized in that it further comprises a viscosity reducer.

15. Stable liquid pharmaceutical formulation according to claim 14, characterized in that the viscosity reducer comprises arginine.

16. Stable liquid pharmaceutical formulation according to Petition 870250097901, dated 10 / 27 / 2025, page 112 / 139 4 / 9 claim 15, characterized in that arginine is present in a concentration of 60 mM to 130 mM.

17. Stable liquid pharmaceutical formulation according to claim 15, characterized in that arginine is present at a concentration of at least 70 mM.

18. Stable liquid pharmaceutical formulation according to claim 15, characterized in that arginine is present at a concentration of 70 mM ± 14 mM.

19. Stable liquid pharmaceutical formulation according to any one of claims 1 to 18, characterized in that the surfactant comprises polysorbate 20 or polysorbate 80.

20. Stable liquid pharmaceutical formulation according to claim 19, characterized in that polysorbate 20 or polysorbate 80 is present at a concentration of 0.05% w / v or 0.2% w / v.

21. Stable liquid pharmaceutical formulation according to claim 19, characterized in that the surfactant comprises polysorbate 80 at a concentration of 0.15% w / v ± 0.075% w / v.

22. Stable liquid pharmaceutical formulation according to any one of claims 1 to 21, characterized in that it comprises: histidine at a concentration of 10 mM ± 2 mM; sucrose at a concentration of 5% w / v ± 1% w / v; arginine at a concentration of 70 mM ± 14 mM; polysorbate 80 at a concentration of 0.15% w / v ± 0.075% w / v; wherein the total antibody concentration in the formulation is 150 mg / mL ± 15 mg / mL, and wherein the formulation has a pH of 6.0 ± 0.

3.

23. Stable liquid pharmaceutical formulation according to any one of claims 1 to 22, characterized in that the formulation has a viscosity < 25 cP at 20°C. Petition 870250097901, dated 10 / 27 / 2025, pp. 113 / 139 5 / 9 24. Stable liquid pharmaceutical formulation according to claim 23, characterized in that the formulation has a viscosity < 15 cP at 20°C.

25. Stable liquid pharmaceutical formulation according to any one of claims 1 to 24, characterized in that the formulation comprises: an anti-Fel D1 antibody comprising an HCVR comprising the amino acid sequence SEQ ID NO:2 and an LCVR comprising the amino acid sequence SEQ ID NO:10, wherein the antibody concentration is from 50 mg / mL to 190 mg / mL; histidine at a concentration of 10 mM ± 2 mM; sucrose at a concentration of 5% w / v ± 1% w / v; arginine at a concentration of 70 mM ± 14 mM; and polysorbate 80 at a concentration of 0.15% w / v ± 0.075% w / v; wherein the formulation has a pH of 6.0 ± 0.

3.

26. Stable liquid pharmaceutical formulation according to any one of claims 1 to 24, characterized in that the formulation comprises: an anti-Fel D1 antibody comprising an HCVR comprising the amino acid sequence of SEQ ID NO:16 and an LCVR comprising the amino acid sequence of SEQ ID NO:24, wherein the antibody concentration is from 50 mg / mL to 190 mg / mL; histidine at a concentration of 10 mM ± 2 mM; sucrose at a concentration of 5% w / v ± 1% w / v; and polysorbate 20 or polysorbate 80 at a concentration of 0.15% w / v ± 0.075% w / v; wherein the formulation has a pH of 6.0 ± 0.

3.

27. Stable liquid pharmaceutical formulation according to claim 26, characterized in that it further comprises a viscosity reducer. Petition 870250097901, dated 10 / 27 / 2025, page 114 / 139 6 / 9 28. Stable liquid pharmaceutical formulation according to claim 27, characterized in that the viscosity reducer is arginine at a concentration of 70 mM ± 14 mM.

29. Stable liquid pharmaceutical formulation according to any one of claims 1 to 24, characterized in that the formulation comprises: a first antibody that binds specifically to Fel d1, wherein the first antibody comprises an HCVR comprising the amino acid sequence of SEQ ID NO:2 and an LCVR comprising the amino acid sequence of SEQ ID NO:10, wherein the concentration of the first antibody is 75 mg / mL ± 10 mg / mL; a second antibody that binds specifically to Fel d1, wherein the second antibody comprises an HCVR comprising the amino acid sequence of SEQ ID NO:16 and an LCVR comprising the amino acid sequence of SEQ ID NO:24, wherein the concentration of the second antibody is 75 mg / mL ± 10 mg / mL; histidine at a concentration of 10 mM ± 2 mM; sucrose at a concentration of 5% w / v ± 1% w / v; arginine at a concentration of 70 mM ± 14 mM; and polysorbate 80 at a concentration of 0.15% w / v ± 0.075% w / v; wherein the formulation has a pH of 6.0 ± 0.

3.

30. Stable liquid pharmaceutical formulation, characterized in that it comprises: (a) an antibody that specifically binds to Fel d1, wherein the antibody comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO:4, an HCDR2 comprising the amino acid sequence of SEQ ID NO:6, an HCDR3 comprising the amino acid sequence of SEQ ID NO:8, an LCDR1 comprising the amino acid sequence of SEQ ID NO:12, an LCDR2 comprising the amino acid sequence AAS and an LCDR3 comprising the amino acid sequence of SEQ ID NO:14; (b) a buffer containing histidine; (c) a thermal stabilizer; and (d) a surfactant; wherein the formulation has a pH of 6.0 ± 0.

3.

31. Stable liquid pharmaceutical formulation according to claim 30, characterized in that the antibody comprises an HCVR comprising the amino acid sequence of SEQ ID NO:2 and an LCVR comprising the amino acid sequence of SEQ ID NO:

10.

32. Stable liquid pharmaceutical formulation according to any one of claims 30 or 31, characterized in that the formulation comprises: an anti-Fel D1 antibody comprising an HCVR comprising the amino acid sequence of SEQ ID NO:2 and an LCVR comprising the amino acid sequence of SEQ ID NO:10, wherein the antibody concentration is from 50 mg / mL to 190 mg / mL; histidine at a concentration of 10 mM ± 2 mM; sucrose at a concentration of 5% w / v ± 1% w / v; and polysorbate 80 at a concentration of 0.15% w / v ± 0.075% w / v; wherein the formulation has a pH of 6.0 ± 0.

3.

33. Stable liquid pharmaceutical formulation, characterized in that it comprises: (a) an antibody that binds specifically to Fel d1, wherein the antibody comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO:18, an HCDR2 comprising the amino acid sequence of SEQ ID NO:20, an HCDR3 comprising the amino acid sequence of SEQ ID NO:22, an LCDR1 comprising the amino acid sequence of SEQ ID NO:26, an LCDR2 comprising the amino acid sequence KAS and an LCDR3 comprising the amino acid sequence of SEQ ID NO:28; (b) a buffer containing histidine; (c) a thermal stabilizer; and (d) a surfactant; wherein the formulation has a pH of 6.0 ± 0.

3.

34. Stable liquid pharmaceutical formulation according to claim 33, characterized in that the antibody comprises an HCVR comprising the amino acid sequence of SEQ ID NO:16 and an LCVR comprising the amino acid sequence of SEQ ID NO:

24.

35. Stable liquid pharmaceutical formulation according to any one of claims 33 or 34, characterized in that the formulation comprises: an anti-Fel D1 antibody comprising an HCVR comprising the amino acid sequence of SEQ ID NO:16 and an LCVR comprising the amino acid sequence of SEQ ID NO:24, wherein the antibody concentration is from 50 mg / mL to 190 mg / mL; histidine at a concentration of 10 mM ± 2 mM; sucrose at a concentration of 5% w / v ± 1% w / v; and polysorbate 20 or polysorbate 80 at a concentration of 0.15% w / v ± 0.075% w / v; wherein the formulation has a pH of 6.0 ± 0.

3.

36. Stable liquid pharmaceutical formulation according to claim 35, characterized in that it further comprises a viscosity reducer.

37. Stable liquid pharmaceutical formulation according to claim 36, characterized in that the viscosity reducer is arginine at a concentration of 70 mM ± 14 mm. Petition 870250097901, dated 10 / 27 / 2025, pp. 117 / 139 9 / 9 38. Stable liquid pharmaceutical formulation according to any one of claims 1 to 37, characterized in that it is contained in a container selected from the group consisting of a glass vial, a syringe, a pre-filled syringe, a pen-type administration device and an autoinjector administration device.

39. Stable liquid pharmaceutical formulation according to any one of claims 1 to 37, characterized in that it is contained in a large volume device or bolus injector.

40. Container, characterized in that it contains the stable liquid pharmaceutical formulation according to any one of claims 1 to 37.

41. Kit, characterized in that it comprises: (i) a container containing the stable liquid pharmaceutical formulation according to any one of claims 1 to 37; and (ii) markings for use of the pharmaceutical formulation.

42. Kit according to claim 41, characterized in that the marking indicates subcutaneous or intravenous administration of the pharmaceutical formulation. Petition 870250097901, dated 10 / 27 / 2025, pp. 118 / 139

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